Informed Consent Form for PTSD Treatment Study - Transcend Therapeutics PDF

Transcend Therapeutics, Inc. Page 1 of 24 Protocol Number TSND201-PTSD-202, Part A ICF, USA V2.0 04June2024 Part A: Informed Consent Form and Authorization to Use and Disclose...

Transcend Therapeutics, Inc. Page 1 of 24 Protocol Number TSND201-PTSD-202, Part A ICF, USA V2.0 04June2024 Part A: Informed Consent Form and Authorization to Use and Disclose Protected Health Information CONFIDENTIAL Sponsor / Study Title: Transcend Therapeutics, Inc. / “An Evaluation of the Safety and Efficacy of Methylone for the Treatment of PTSD IMPACT-2 (Investigation of Methylone for Post-Traumatic Stress Disorder [PTSD])” Protocol Number: TSND201-PTSD-202 Principal Investigator: Rishi Kakar, M.D. (Study Doctor) Telephone: 954-990-6326 1-800-730-7692 (24 Hours) Address: Innovative Clinical Research, Inc. 7481 W. Oakland Park Blvd. Suite 205 & 307 Lauderhill, FL 33319 Introduction You have been invited to take part in a research study because you have post-traumatic stress disorder (PTSD). The study is organized and funded by Transcend Therapeutics (the “Sponsor”). Transcend Therapeutics is a pharmaceutical company that is working to develop a new treatment for PTSD. During this study, you will be given a new drug called “methylone” (the “study drug”), which is somewhat similar to MDMA (also known as “ecstasy”), but methylone is likely to have milder effects. Before you decide whether to take part in this research study, you need to understand why the research is being done, what it would involve for you, how your information will be used and the possible benefits, risks, and discomforts. The study doctor, or a member of the study staff, will go through this informed consent form with you and answer any questions you may have. Please take time to read the following information carefully. You may talk to your own family doctor or family/relatives/friends about the study if you wish. This informed consent form will be split into the following parts: Part 1 tells you the purpose of this study and what will happen to you if you take part. Part 2 gives you more detailed information about the conduct of the study. Rishi Kakar, M.D. Advarra IRB Approved Version 11 Jun 2024 Revised 27 Jun 2024  Transcend Therapeutics, Inc. Page 2 of 24 Protocol Number TSND201-PTSD-202, Part A ICF, USA V2.0 04June2024 This consent may contain words you do not understand. Please ask the study doctor or study staff to explain any words or information that you do not understand or if you would like more information. Part 1 What is clinical research? Clinical research is a way to bring about progress in medicine. Clinical research makes it possible to scientifically assess the properties of a drug, to demonstrate whether the study drug is effective in treating or managing a specific disease/condition, or to demonstrate the safety of the study drug or to learn more about a disease/condition. What is the purpose of this study? The purpose of this study is to test a drug called methylone (the “study drug”) that is being developed for the treatment of PTSD. PTSD is an anxiety disorder caused by very stressful, frightening, or distressing events. PTSD can develop immediately after someone experiences a disturbing event, or it can occur weeks, months, or even years later. Someone with PTSD often relives the traumatic event through nightmares and flashbacks, and may experience feelings of isolation, irritability, and guilt. They may also have problems sleeping, such as insomnia, find concentrating difficult and avoid situations that trigger flashbacks. These symptoms are often severe and keep happening often enough to have a significant impact on the person’s day to day life. Unfortunately, many people suffering from PTSD either do not receive treatment or do not respond well to currently available treatments. This is a two-part study. Part A is open-label, which means everyone (approximately 15 participants) will get the study drug called methylone. Part B of the study is placebo-controlled. A placebo looks like the active study drug, but contains no active ingredients (i.e., “sugar pill”). Placebo-controlled means that half of the participants will get methylone and half will get placebo (up to 64 participants may be enrolled in Part B). You are being invited to take part in Part A, which means you will get methylone. Methylone is a controlled study drug (which means that it is a drug that may be abused). Methylone is a psychoactive compound. This means it affects how the brain works, which can cause changes in mood, awareness, thoughts, feelings, or behavior. Recently, it has been shown that methylone may help in managing the symptoms of PTSD and the Sponsor wishes to investigate this further. Methylone can create a strong sense of emotional openness, reduced fear, and increased understanding of feelings, which could be well suited to be given for PTSD. Methylone is an experimental treatment. This means that it is not an approved treatment by the US Food and Drug Administration (FDA) for PTSD. The main aims of this part of the study are: To assess the safety and tolerability of methylone. To assess the efficacy of methylone on PTSD symptoms. Rishi Kakar, M.D. Advarra IRB Approved Version 11 Jun 2024 Revised 27 Jun 2024  Transcend Therapeutics, Inc. Page 3 of 24 Protocol Number TSND201-PTSD-202, Part A ICF, USA V2.0 04June2024 You must have a diagnosis of severe PTSD to take part in this study and have PTSD symptoms for at least 6 months before Screening. During this study, you will attend the clinic for study treatment once a week for 3 weeks. During each dosing session, you will be administered 3 capsules of the study drug. Throughout the study, information on the safety of the study drug will be reviewed by a group of people called the Data Safety and Monitoring Board. Why have I been invited to participate? You have been invited to participate in this study because you are a healthy adult, between 18 and 70 years of age, with a diagnosis of severe PTSD. To participate in this study, you need to have not responded to a prior course of treatment – that could be either a medicine, such as sertraline or paroxetine (a type of antidepressant sometimes called an “SSRI”), or a course of psychotherapy. There are no official recommendations about what an adequate study of such treatments is, but your mental healthcare provider will have discussed this with you. You should not discontinue the treatment or therapy that you are responding to in order to participate in this study. Do I have to take part? No, it is your choice whether or not to take part in this study. Your decision will not result in any penalty or loss of benefits to which you are otherwise entitled. You should not feel pressured into joining the study. You do not have to decide today. You are free to leave and think about taking part. You may also discuss it with your own doctor or family/relatives/friends. You may stop taking part at any time. You do not have to give a reason why. This will not affect your regular treatment from your doctor. What are the alternatives if I don’t want to take part? You do not have to be in this study to receive treatment for your PTSD. Your other options may include: Meeting with a therapist A medicine such as sertraline or paroxetine (an SSRI) Please talk to the study doctor about your options before you decide whether or not you will take part in this study. What are the side effects of the study drug? All drugs can cause side effects in some people. You may have none, some or all of the effects listed below, and they may be mild, moderate or severe. If you have any of these side effects, or you are worried about them, talk with your study doctor. Your study doctor will also be looking out for side effects. You must tell the study doctor or study staff about any side effects that you may experience. Rishi Kakar, M.D. Advarra IRB Approved Version 11 Jun 2024 Revised 27 Jun 2024  Transcend Therapeutics, Inc. Page 4 of 24 Protocol Number TSND201-PTSD-202, Part A ICF, USA V2.0 04June2024 In order to ensure your safety, the study drug will only be administered in the clinic where you will be looked after and receive psychological support from a Mentor (who is a person specially trained to work with methylone). Your Mentor will be with you at all times during the dosing sessions and will be able to help you if you do get anxious or distressed. There will be another observer either in the room or remotely watching the session. You will be given the study drug in a quiet, calm, and private environment. You will be checked for well-being before being allowed to go home. Side effects occurring in Transcend-sponsored clinical studies that may or may not be caused by methylone: Side Effect Number (out of 14) and percent of participants reported by Headache 6 (42.9%) Decreased appetite 4 (28.6%) Non-heart chest pain 3 (21.4%) Tiredness 3 (21.4%) Teeth grinding/clenching 2 (14.3%) Dizziness 2 (14.3%) Excessive sweating 2 (14.3%) Flu-like illness 2 (14.3%) Trouble sleeping 2 (14.3%) Stuffy nose 2 (14.3%) Potential side effects of methylone (or similar drugs, like MDMA) based on published literature include: Short-term psychological distress or symptoms. Psychological distress is a state of intense emotional reaction, in which people can experience a range of emotions, including sadness, anxiety, fear, anger and moodiness. Although unlikely, someone may experience strong effects like hallucinations (hearing, seeing, feeling, smelling or even tasting things that are not real), delusions (false beliefs that conflict with reality) and confused and disturbed thoughts (which is when someone perceives reality in a very different way from people around them). Suicidal thoughts or suicide attempts are not expected to be caused by methylone. However, both are recognized problems of PTSD. You will be closely monitored throughout the study, and questions about suicidal thoughts and feelings will be frequently asked. If you are having suicidal thoughts or feel in crisis, call the study doctor at the telephone number listed on the first page of this form. You can also call or text the National Suicide & Crisis Lifeline at 9-8-8 or 1-800-273-TALK (8255). The Lifeline numbers are answered 24 hours a day every day of the year by a skilled, trained counselor. You can also present to a healthcare provider, your local emergency room, or call 9-1-1 to be connected to local emergency services. Increases in your heart rate and blood pressure may occur, which might cause dizziness. Your heart rate and blood pressure will be frequently monitored throughout the study. Rishi Kakar, M.D. Advarra IRB Approved Version 11 Jun 2024 Revised 27 Jun 2024  Transcend Therapeutics, Inc. Page 5 of 24 Protocol Number TSND201-PTSD-202, Part A ICF, USA V2.0 04June2024 Rises in body temperature may occur following administration of the study drug. If your body temperature rises, attempts will be made to lower your temperature. Your temperature will be frequently monitored throughout the study. Dehydration has happened after people use MDMA (a similar drug), however it is unlikely in the clinic. Water will be allowed throughout the dosing session; however, you should not drink more than 3 liters (about 12 cups) of water or clear fluids. The study drug’s effect on the body may change when the drug is taken at the same time as another drug, which can result in either a decrease or increase in the effects. This could cause side effects. The study staff will carefully evaluate any medicines (prescription or non-prescription) that you are taking at the first visit, which is known as your Screening visit. They will also inform you of any medications you will not be permitted to take during the study. Methylone is a controlled study drug, which may mean there is risk that you can become dependent or desire to seek it out. Early research has shown that it may not be as addictive as other common drugs of abuse. If you begin to feel this way, we will ensure that you are properly supported. Although rare, there have been instances of death associated with methylone when used as a street drug, commonly with other abused drugs. As with any drug, side effects that were not previously described may occur. You could also have an allergic reaction to the study drug. If you have a very serious allergic reaction, you may be at risk of death. Some symptoms of allergic reactions are: Rash Wheezing and difficulty breathing Dizziness and fainting Swelling around the mouth, throat or eyes A fast pulse Sweating Please seek treatment immediately and tell the study doctor and study staff if you have any of these symptoms. It is important that you report to your study doctor all symptoms and side effects that you may experience, as soon as they appear, whether or not you think they are related to the study drug and whether good or bad. If a side effect occurs, you might need to be admitted into a hospital. Depending on the type of side effect, a medical specialist would be asked to take over your care. What if something goes wrong? In the unlikely event that something goes wrong with your health after being given methylone, you will be looked after by study staff who will be present during the clinic visits. If something Rishi Kakar, M.D. Advarra IRB Approved Version 11 Jun 2024 Revised 27 Jun 2024  Transcend Therapeutics, Inc. Page 6 of 24 Protocol Number TSND201-PTSD-202, Part A ICF, USA V2.0 04June2024 was to happen which required emergency care, you would be looked after by the study staff who are trained in emergency procedures. We will give you a “contact card” containing the contact details of the key members of the study staff for during office hours. We will also provide you with an out of hours emergency phone number for the on-call doctor who is knowledgeable about the study. You should keep this card and phone number handy at all times. If any problems arise outside of the study (for example, a failed drug test), you may contact the study staff for advice and support. If your mental health was to deteriorate significantly during any point of the study and we had serious concerns about your safety, you may be withdrawn from the study and we will ensure that you are properly looked after. What will happen to me if I take part? If you agree to take part in this study, it will take up to 13 weeks to complete, including up to a 4-week screening period, 3-week study treatment period, and 6-week follow-up period. You may be asked to stop taking certain medications before you enroll in the study or before dosing sessions. Instructions for how and when to stop taking certain medications will be given by the study doctor. Do not stop taking medications without instruction from the study doctor and/or the doctor that prescribed the medication. If needed, the screening period may be extended to allow time to discontinue medications. There are a total of 17 study visits during this study. Some of them may be conducted remotely. At a minimum, you will attend at least 7 visits on-site (these study visits will take place at the study site) and other visits may be conducted via videoconference or telephone. The 7 on-site visits include the screening visit, baseline-preparation visit, the three study treatment visits, and two follow-up visits. An overview of the scheduled study visits is illustrated below: The study visits will consist of: Screening Visit o Prior to any study-related procedures taking place, you will be asked to sign this form saying that you agree to take part in the study (informed consent). o This visit will last about 5-6 hours. Rishi Kakar, M.D. Advarra IRB Approved Version 11 Jun 2024 Revised 27 Jun 2024 Transcend Therapeutics, Inc. Page 7 of 24 Protocol Number TSND201-PTSD-202, Part A ICF, USA V2.0 04June2024 o In order to understand if you are suitable to enroll in this study, your medical history will be collected; this includes information about your physical and mental health and whether you have ever had a diagnosis of hepatitis or HIV. You will also be asked questions about any prior or current medications you are taking, age, sex, and race. A physical examination (a medical check-up by the study doctor) including height and weight will be performed. o A urine sample will be taken to test for the use of drugs of abuse. The use of these substances can influence the effect of the study treatment and may put you in danger. o Blood and urine samples will be taken to check that you are healthy, and (for some females) to confirm that you are not pregnant. If you are female, depending on your age, the study doctor may decide to perform an additional blood test to assess your menopausal status. o You will complete a series of questionnaires to evaluate your PTSD history and current symptoms. o Psychiatric assessments will be performed, including an assessment of the severity of your PTSD symptoms where prior traumatic experiences that have occurred during your life will be discussed. These assessments will be completed by an independent clinician (a clinician who is not involved in the day-to-day study activities) via videoconference.  The independent clinician sessions may be recorded. The purpose of the recordings is for training and quality verification purposes. The recordings will be securely stored and will only be accessible to the staff of independent clinicians. You may choose to opt out of the recording and still participate in the study. o Blood pressure, heart rate, respiratory rate, and temperature (vital signs) will be measured. o A painless recording will be made of the electrical activity of your heart (electrocardiogram [ECG]), which checks for any irregularities. Ten stickers with wires will be temporarily applied to your chest, arms and legs. o Your healthcare provider will be contacted (with your permission) and asked to supply your medical history. After your Screening visit, a study doctor will look at the results of all these tests and then decide if it is okay for you to take part in the study. If it is, you will be asked to return to the clinic for the Baseline/Preparatory Session. Baseline/Preparatory Session o You will also be required to attend the clinic for a Baseline/preparatory session. This visit will last about 4 hours. o You will meet your Mentor (a specialist in mental health) who will explain to you the feelings you may experience after receiving the study drug and help you to get ready for the study treatment. Rishi Kakar, M.D. Advarra IRB Approved Version 11 Jun 2024 Revised 27 Jun 2024 Transcend Therapeutics, Inc. Page 8 of 24 Protocol Number TSND201-PTSD-202, Part A ICF, USA V2.0 04June2024 o The severity of your PTSD symptoms will be assessed. This will be completed by an independent clinician via videoconference and may be recorded for training and verification purposes. o You will also be asked complete a series of questionnaires, which will assess your PTSD symptoms, mood, and sleep. o Blood pressure, heart rate, respiratory rate, and temperature (vital signs) will be measured. o A urine sample will be taken to test for the use of drugs of abuse. Your blood pressure and heart rate (vital signs) will be measured. Study Treatment Period o Dosing Sessions  You will attend the clinic on Days 1, 8, and 15 for study treatment. The overall visits will last about 9 hours (the dosing sessions will be about 8 hours). The dosing sessions may be video recorded. The purpose of the video recordings is for training and verification purposes. The recordings will be securely stored, anonymized, and will only be accessible to study staff, the Sponsor, and its designated representatives. You may choose to opt out of the video recording and still participate in the study.  You will be asked to fast (not eat or drink anything except water) for 2 hours before until 2 hours after you take the study drug. You should not drink any alcohol for 24 hours before coming to the clinic or have xanthine (used in treatments for asthma, bronchitis, and COPD) or caffeine for at least 2 hours prior to dosing until at least 8 hours after the dose.  A urine pregnancy test (some females only) will be performed prior to dosing.  A urine drugs of abuse test will be performed prior to dosing.  You will be given the study drug by mouth. Your Mentor will be present for the full duration of your dosing session to provide support.  You will be asked to stay in the clinic until at least 8 hours after dosing or until all effects have resolved (whichever is longer) on each visit.  While you are in the clinic, measurements of your blood pressure, heart rate, and temperature and ECG recording will be performed, and you will be asked questions about your health and medicines you have taken.  If a study doctor thinks it is necessary, you may be asked to remain in the unit for further observation until any symptoms or test results have returned to normal. Rishi Kakar, M.D. Advarra IRB Approved Version 11 Jun 2024 Revised 27 Jun 2024 Transcend Therapeutics, Inc. Page 9 of 24 Protocol Number TSND201-PTSD-202, Part A ICF, USA V2.0 04June2024  If you experience any emotional distress or other symptoms after leaving the site, contact the study staff or study doctor, who will ensure you are looked after and supported. o The Day After Each Study Treatment  You will be contacted by telephone 1 day after each dosing session to check up on you. You will be asked questions about your health and medicines you have taken. o Two Days After Each Study Treatment  You will also be asked to attend a study visit (either in-clinic or via videoconference) 2 days after each dosing session to answer questions about your health and any medicines you have taken. This visit will last about 2-3 hours.  The severity of your PTSD symptoms will be assessed. This will be completed by an independent clinician via videoconference and may be recorded for training and verification purposes.  You will also be asked to complete a series of questionnaires, which will assess your PTSD symptoms, mood, and sleep. Follow-up Sessions o One Week After Your Last Study Treatment  You will be asked to attend the clinic on Day 22 (1 week after your final study treatment). This visit will last about 3 hours.  Blood pressure, heart rate, and temperature (vital signs) will be measured.  The severity of your PTSD symptoms will be assessed. This will be completed by an independent clinician via videoconference and may be recorded for training and verification purposes.  You will also be asked complete a series of questionnaires, which will assess your PTSD symptoms, mood, and sleep.  Blood and urine samples will be taken to check that you are healthy, and (for some females) to confirm that you are not pregnant. ECG recordings will also be performed.  You will also be asked questions about your health and medicines you have taken.  If needed, your Mentor will be available to speak with you about your experiences following the dosing sessions. o Two Weeks After Your Last Study Treatment  You will also be asked to attend a study visit (either in-clinic or via videoconference) on Day 29 (2 weeks after your final study treatment). This visit will last about 2 hours. Rishi Kakar, M.D. Advarra IRB Approved Version 11 Jun 2024 Revised 27 Jun 2024 Transcend Therapeutics, Inc. Page 10 of 24 Protocol Number TSND201-PTSD-202, Part A ICF, USA V2.0 04June2024  The severity of your PTSD symptoms will be assessed. This will be completed by an independent clinician via videoconference and may be recorded for training and verification purposes.  You will also be asked complete a series of questionnaires, which will assess your mood and sleep.  You will also be asked questions about your health and medicines you have taken.  If needed, your Mentor will be available to speak with you about your experiences following the dosing sessions. o Three Weeks After Your Last Study Treatment  You will be contacted by phone on Day 36 to check up on you. You will be asked questions about your health and medicines you have taken. This call will last about 20 minutes. o Four Weeks After Your Last Study Treatment  You will also be asked to attend a study visit (either in-clinic or via videoconference) on Day 43 (4 weeks after your final study treatment). This visit will last about 2 hours.  The severity of your PTSD symptoms will be assessed. This will be completed by an independent clinician via videoconference and may be recorded for training and verification purposes.  You will also be asked to complete a series of questionnaires, which will assess your mood, and sleep.  You will also be asked questions about your health, and medicines you have taken.  If needed, your Mentor will be available to speak with you about your experiences following the dosing sessions. o Five Weeks After Your Last Study Treatment  You will be contacted by phone on Day 50 to check up on you. You will be asked questions about your health and medicines you have taken. This call will last about 20 minutes. o Six Weeks After Your Last Study Treatment  You will be asked to attend the clinic for an end-of-study visit on Day 57. This visit will last about 3 hours.  A physical examination will be performed.  Blood pressure, heart rate, and temperature (vital signs) will be measured.  Blood and urine samples will be taken to check that you are healthy, and (for some females) to confirm that you are not pregnant. ECG recordings will also be performed. Rishi Kakar, M.D. Advarra IRB Approved Version 11 Jun 2024 Revised 27 Jun 2024  Transcend Therapeutics, Inc. Page 11 of 24 Protocol Number TSND201-PTSD-202, Part A ICF, USA V2.0 04June2024  You will be asked questions about your health and medicines you have taken.  The severity of your PTSD symptoms will be assessed. This will be completed by an independent clinician via videoconference and may be recorded for training and verification purposes.  You will also be asked complete a series of questionnaires, which will assess your PTSD symptoms, mood, and sleep. If you withdraw from the study prior to attending all scheduled visits, you will be asked to return for a visit, which will be the same as the “Six Weeks After Your Last Study Treatment” visit. This request will be made even if you stop the study drug. At the end of the study, whether you complete or withdraw, you will be given an Exit Plan, which provides information about the study treatment, your current medications and contact information regarding the study. Will there be any additional tests or visits? On each visit you will be asked about your general condition and any problems you might experience (for example possible side effects of the study drug). If your problems require further investigation, additional tests may be done, and additional visits (so called “unscheduled visits”) might also be planned by your study doctor. Please report all unusual experiences, even positive ones, since they may be important. What samples will be taken from me during the study? Both blood and urine samples will be collected for a number of different tests. Blood will be collected at 3 timepoints (approximately 8 mL [approximately 1.5 teaspoons] per time). The total amount of blood that will be taken from you during the study is approximately 24 mL (approximately 5 teaspoons). What will happen to the blood and urine samples that are collected from me? The blood and urine samples that are collected during the study will be analyzed following collection and discarded after analysis. Will I have to undergo genetic testing? There is no genetic testing in this study. What do I have to do if I participate in the study? You must agree to the following in order to participate in the study: Study visits – You should attend all planned study visits. Administration of study drug – Study drug will be administered during the visit on Day 1, Day 8, and Day 15 (Visits 3, 6, and 9). Previous medical history - You must tell your study doctors and staff everything about your health history in an open and honest manner. Rishi Kakar, M.D. Advarra IRB Approved Version 11 Jun 2024 Revised 27 Jun 2024 Transcend Therapeutics, Inc. Page 12 of 24 Protocol Number TSND201-PTSD-202, Part A ICF, USA V2.0 04June2024 Use of medications o Before the study – Please inform your study doctor about all the medications that you take, including herbal preparations and even those that you buy without a prescription (over-the-counter). You may not be suitable to participate in the study if you use certain medications. o If you are suitable to participate, you will be asked to refrain from taking any new prescription or over-the-counter medications, or any prohibited medications, throughout the study. In addition, you will be asked to not visit any other doctors about your PTSD. Please consult with your study doctor before taking any medications, either bought by yourself or prescribed by your healthcare provider before or during the study. o During the study – During every visit, your study doctor or a member of the clinical staff will ask you whether you have taken any medications since the last visit. Certain medications are not allowed, as they may affect your safety or the interpretation of the study results. Your study doctor will check this and will explain what is allowed and what is not allowed. Lifestyle – please avoid major changes in your exercise, diet, and drinking habits during the study. You must not do strenuous exercise (e.g., heavy lifting, weight training, aerobics) for 24 hours before each dosing session, and while in the clinic. You must also not operate any motor vehicle or heavy machinery for at least 24 hours after each dosing visit. The site staff will ensure you have transportation organized (e.g., a friend or family member to pick you up) after leaving the unit on dosing days. Diet – You will be asked to fast (refrain from eating or drinking anything except water) for 2 hours before and 2 hours after taking the study drug at each dosing visit. The following are also restricted during the study: o Water and clear fluids will be encouraged up to a maximum fluid intake of 3 liters during the dosing session. o As poppy seeds can sometimes cause a positive result on the drugs of abuse test, you should avoid eating poppy seeds/food containing poppy seeds for at least 48 hours before attending any visits which include a drugs of abuse test. o Avoid all xanthine and caffeine or caffeine-containing products for 2 hours prior to dosing and until 8 hours after receiving the study drug. Alcohol – You will be required to refrain from drinking alcohol for 24 hours prior to Screening and each dosing session until discharged from the unit. You must not drink an excessive amount of alcohol for the duration of the study. Smoking – You must refrain from smoking for 2 hours before taking the study drug and until 8 hours after on each dosing day. Rishi Kakar, M.D. Advarra IRB Approved Version 11 Jun 2024 Revised 27 Jun 2024  Transcend Therapeutics, Inc. Page 13 of 24 Protocol Number TSND201-PTSD-202, Part A ICF, USA V2.0 04June2024 Recreational drugs – You will be required to refrain from any illegal recreational drugs during the study from the very first visit until the end-of-study visit (Day 57) is completed. Could there be any harm to an unborn child or nursing infant? Contraception It is unknown if methylone can harm an unborn child. For this reason, you will be asked to use very effective contraception during the study. If you are a male with a female sexual partner of childbearing potential, you must agree to use one of the highly effective contraceptive methods (please see the list below) for the duration of the study and for at least 90 days after the final dose of study drug. Additionally, you must not donate sperm until 90 days after final dosing. The following are acceptable contraceptive methods: Female use of hormonal contraceptives and a male condom Either you or your partner is surgically sterilized Abstinence If you are a female of childbearing potential (your study doctor will tell you), you must use a highly effective method of contraception for the duration of the study until 1 month following final dosing. The following are considered forms of highly effective contraception: Estrogen and progesterone hormonal contraception (oral, intravaginal, transdermal). Progesterone-only hormone contraception (oral, injectable, implantable). Intrauterine hormone-releasing system (IUS) or an intrauterine device (IUD). Bilateral tubal occlusion Sterile male partner (vasectomized for at least 6 months prior to the first dose). Abstinence The female condom is not an acceptable method of contraception. If you, or your female partner, does become pregnant during the course of the study, we would ask you to tell your study doctor immediately. We will ask if we can collect information on the pregnancy and newborn child until 12 months following delivery or termination. What are the possible disadvantages and risks of taking part? Please see the “What are the side effects of the study drug?” section, which details potential side effects of the study drug, methylone. Risks associated with drawing blood As is common with drawing blood, you may feel some discomfort when the needle goes into your vein. In addition, you may experience light headedness or irritation, such as redness, tenderness (pain), bleeding, and bruising, at the sites used to obtain blood. These problems Rishi Kakar, M.D. Advarra IRB Approved Version 11 Jun 2024 Revised 27 Jun 2024  Transcend Therapeutics, Inc. Page 14 of 24 Protocol Number TSND201-PTSD-202, Part A ICF, USA V2.0 04June2024 usually clear up within a few days. Blood tests can also make you feel faint, so you’ll have the option to lie down when we take your blood. The swelling of a vein or in very rare cases a blood clot cannot be entirely ruled out. Infection is rare but could occur. Risks associated with ECG An ECG is a completely safe test. You may experience local skin irritations and redness from the stickers on your skin that will recover quickly. Risks associated with Psychological Interviews / Questionnaires You will be asked to talk about and report on your past traumas, your PTSD symptoms, your mood, and other elements of your mental health. This could be distressing to discuss difficult moments in your past. The independent clinician and site staff will support you if you feel distressed. Risks associated with Stopping Antidepressants If you are currently receiving antidepressants, you will be asked to discontinue them prior to taking part in this research study. Your study doctor will provide you the details of how to stop taking your antidepressant medication in order to reduce side effects. Sometimes people who stop taking antidepressants can experience the following side effects: anxiety, irritability, mood changes, headaches, insomnia, nausea, electric shock sensations, and/or return of depression symptoms. Your study doctor will monitor you closely to help reduce any of these symptoms. Risks associated with Videorecording The dosing sessions and videoconference assessments may be recorded, so there is the risk that someone may recognize you or your voice. What are the possible benefits of taking part? There may not be any benefit to you, but you are contributing to the scientific knowledge which may lead to the expansion of treatment options for people with PTSD. After completion of this study, you will need to return to treatment with your own mental health provider. The Sponsor of this study is unable to continue study treatment with methylone after you have completed the study, even if you showed or felt improvement, as it is not approved for use and cannot be prescribed. In addition, the need for, or frequency of, additional treatment with methylone, or the safety of taking methylone time after time over long periods is still not known. This study will help design further studies to answer these questions. This completes Part 1. If the information in Part 1 has interested you and you are considering taking part, please read the additional information in Part 2 before making any decision. Rishi Kakar, M.D. Advarra IRB Approved Version 11 Jun 2024 Revised 27 Jun 2024  Transcend Therapeutics, Inc. Page 15 of 24 Protocol Number TSND201-PTSD-202, Part A ICF, USA V2.0 04June2024 PART 2 What if new information becomes available? During the course of the research study, new information may become available about the drug that is being studied, which might influence your willingness to participate in the study. If this happens, your study doctor will tell you about it and discuss it with you as to whether you wish to continue in the study. If you decide to continue in the study, you will be asked to sign an updated consent form. Also, on receiving new information, your study doctor might consider it to be in your best interest to withdraw you from the study. Your study doctor would explain the reasons and arrange for your care to continue. What will happen if I don’t want to carry on with the study? You can stop taking part in this study at any time without any consequences for you. No pressure will be exerted on you if you decide to stop participating at any moment. If you decide to stop being part of the study, you should tell the study doctor immediately, who will ask you to come back to the clinic for a final visit. Should you withdraw from the study then your information will still be processed along with any other data collected while in the study. Under what circumstances would study treatment be stopped? Your study doctor can take you out of the study even if you wanted to continue taking part if: The study doctor thinks that stopping study treatment is in your best interests You need certain medication that is not allowed in the study If you become pregnant during the course of this study The Sponsor decides to stop the study You are not cooperating, or you have not followed the directions given by the study doctor If study treatment is stopped, you may still be asked to continue to be followed. What if there is a problem? Concerns If you have a concern about any aspect of this study, you should ask to speak to a member of the study staff who will do their best to answer your questions (see contact numbers provided at the end of this sheet and on your card). Harm If you become ill or are injured while you are in the study, get the medical care that you need right away. You should inform the healthcare professional treating you that you are participating Rishi Kakar, M.D. Advarra IRB Approved Version 11 Jun 2024 Revised 27 Jun 2024  Transcend Therapeutics, Inc. Page 16 of 24 Protocol Number TSND201-PTSD-202, Part A ICF, USA V2.0 04June2024 in this study. If you tell the study staff that you think you have been injured then they will help you get the care you need. If you are injured as a result of taking the study drug or from procedures done for the purpose of this study, the Sponsor will pay for those medical expenses necessary to treat your injury that are not covered by your medical insurance or any other third-party coverage. By signing this document, you will not lose any of your legal rights or release anyone involved in the research from responsibility for mistakes. To pay medical expenses, the Sponsor will need to know some information about you like your name, date of birth, and Medicare Beneficiary Identifier (MBI). This is because the Sponsor has to check to see if you receive Medicare and if you do, report the payment it makes to Medicare. DATA PRIVACY AND CONFIDENTIALITY How will we use information about you? We will need to use information from you and from your medical records for this research study. This information will include your Identification Data: Name, sex, ethnicity, address, date of birth, contact number, email address Unique participant identification code Demographic data General information relating to your PTSD or medical history Biological samples (blood and urine) Health information such as current medications and medical histories The study doctor, the Sponsor or persons working on behalf of the Sponsor, and under certain circumstances, the United States Food and Drug Administration (FDA) and the Institutional Review Board (IRB) will use this information to do the research or to check your records to make sure that the research is being done properly. While every effort will be made to protect the confidentiality of your information, absolute confidentiality cannot be guaranteed. People who do not need to know who you are will not be able to see your name or contact details. Your data will have a code number instead. We will keep all information about you safe and secure. Once the study is finished, some of the data will be kept so the results can be checked. Reports will be written in a way that no one can work out that you took part in the study. What are your choices about how your information is used? You can stop being part of the study at any time, without giving a reason, but we will keep information about you that we already have. Rishi Kakar, M.D. Advarra IRB Approved Version 11 Jun 2024 Revised 27 Jun 2024  Transcend Therapeutics, Inc. Page 17 of 24 Protocol Number TSND201-PTSD-202, Part A ICF, USA V2.0 04June2024 We need to manage your records in specific ways for the research to be reliable. This means that we won’t be able to let you see or change the data we hold about you. Will my healthcare provider be informed? Your healthcare provider may be informed of your participation in this study, and we would request information relating to your medical records from them. If appropriate, your healthcare provider may be consulted about any new treatments during the study. Can I take part in more than one study? You are not allowed to take part in this study if you are already taking part in another study involving an investigational medication. Business confidentiality The information and any materials or items that you are given during the study - such as information identifying the research unit, the Sponsor, any study drug(s), and/or the type of study being performed - should be considered confidential business information of the Sponsor. You are of course free to discuss such information under confidence with your doctor or with your friends and family while considering whether to participate in this study or at any time when discussing your present or future healthcare. However, distributing confidential business information as described above to the media or posting it on the internet is strictly prohibited. What will happen to the results of the research study? The information about you will be kept anonymous. The results of this study will be used to understand the study drug and may be used to inform future scientific research into PTSD, and yet undefined issues. The results of this study will be available publicly at the end of the study, and if you wish, you can be provided a copy of the summary of results. The results may be published in the scientific press; however, you will not be identified by these results or within any published scientific literature. A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by U.S. Law. This Web site will not include any information that can identify you. At most, the Web site will include a summary of the results. You can search this Web site anytime. Will it cost me anything to participate in the study? There will be no charge to you for your participation in this study. The study drug, study-related procedures, and study visits will be provided at no charge to you or your insurance company. Rishi Kakar, M.D. Advarra IRB Approved Version 11 Jun 2024 Revised 27 Jun 2024  Transcend Therapeutics, Inc. Page 18 of 24 Protocol Number TSND201-PTSD-202, Part A ICF, USA V2.0 04June2024 Will I be compensated for my participation in the study? You will be paid according to the following visit schedule: Visit / Day / Week Period Patient Stipend Screening/ Visit 1/ Day -28 to -5 Screening Period $325.00 Baseline/ Visit 2/ Day -4 to -1 Randomization $200.00 Treatment Period Pre-Dose $125.00 Visit 3/ Day 1 (Dose 1) Post-Dose $375.00 Visit 4/ Day 2/ TC Phone Call $38.00 Visit 5/ Day 3 $150.00 Pre-Dose $125.00 Visit 6/ Day 8 (Dose 2) Post-Dose $375.00 Visit 7/ Day 9/ TC Phone Call $38.00 Visit 8/ Day 10 $150.00 Pre-Dose $125.00 Visit 9/ Day 15 (Dose 3) Post-Dose $375.00 Visit 10/ Day 16/ TC Phone Call $38.00 Visit 11/ Day 17 $150.00 End of Treatment Period Visit 12/ Day 22/ FU1 $150.00 Follow-Up Visit 13/ Day 29/ FU2 $150.00 Visit 14/ Day 36/ TC Phone Call $38.00 Visit 15/ Day 43/ FU3 Follow-Up $150.00 Visit 16/ Day 50/ TC Phone Call $38.00 End of Study/ Visit 17/ Day 57/ EOS/ET $300.00 Early Termination Total Compensation: Up to $3,415.00 Conditional Stipends Unscheduled Visit (If needed) $100.00 You will receive payment for visits performed within a week from visit completion. If you do not finish the study, you will only be paid for completed visits. We offer transportation services under certain circumstances. Your study doctor can discuss this with you further. If your test results show you are taking drugs that are not allowed during the screening process and throughout study participation, or, if you are discovered participating in any other study during a visit, the visit is considered incomplete. As a result, you will not be paid for that visit and may be terminated from the study. Rishi Kakar, M.D. Advarra IRB Approved Version 11 Jun 2024 Revised 27 Jun 2024  Transcend Therapeutics, Inc. Page 19 of 24 Protocol Number TSND201-PTSD-202, Part A ICF, USA V2.0 04June2024 Further information and contact details Thank you for reading this information sheet. Remember, you do not have to take part in this research if you do not want to and you can stop taking part at any time. If there is anything you do not understand or if you have any other questions, please ask your study doctor or a member of the site staff. Whom to contact about this study During the study, if you experience any medical problems, suffer a research-related injury, or have questions, concerns or complaints about the study such as: Whom to contact in the case of a research-related injury or illness; Payment or compensation for being in the study, if any; Your responsibilities as a research participant; Eligibility to participate in the study; The study doctor’s or study site’s decision to withdraw you from participation; Results of tests and/or procedures; Please contact the study doctor at the telephone number listed on the first page of this consent document. If you seek emergency care, or hospitalization is required, alert the treating physician that you are participating in this research study. An institutional review board (IRB) is an independent committee established to help protect the rights of research participants. If you have any questions about your rights as a research participant, contact: By mail: Study Subject Adviser Advarra IRB 6100 Merriweather Dr., Suite 600 Columbia, MD 21044 or call toll free: 877-992-4724 or by email: [email protected] Please reference the following number when contacting the Study Subject Adviser: Pro00076615. All spoken and written information and discussions about this study will be in English. Do not sign the consent form unless you have had the chance to ask any questions that you may have and have received satisfactory answers. If you agree to take part in this study, you will receive a signed and dated copy of this information sheet and consent form for your records. The original signed version will be maintained at the research site and a copy will be enclosed in your medical records. Rishi Kakar, M.D. Advarra IRB Approved Version 11 Jun 2024 Revised 27 Jun 2024  Transcend Therapeutics, Inc. Page 20 of 24 Protocol Number TSND201-PTSD-202, Part A ICF, USA V2.0 04June2024 Thank you for taking the time to read this information. Rishi Kakar, M.D. Advarra IRB Approved Version 11 Jun 2024 Revised 27 Jun 2024  Transcend Therapeutics, Inc. Page 21 of 24 Protocol Number TSND201-PTSD-202, Part A ICF, USA V2.0 04June2024 INFORMED CONSENT SIGNATURE PAGE Participant I confirm the following: Initials I understand that the dosing sessions will be video recorded for training and verification purposes. The recordings will be securely stored, and only be accessible to the study staff, Sponsor, and its designated representatives. Please select the appropriate option. I agree I do not agree I understand that the independent clinician sessions will be recorded for training and quality verification purposes. The recordings will be securely stored and only be accessible to a staff of independent clinicians. The recordings may be stored up to 3 months after your participation in the study. Please select the appropriate option. I agree I do not agree Informing Your Healthcare Provider I agree to my healthcare provider being informed of my participation in the study. YES NO Name and address of Name: healthcare provider: Address: Telephone and Fax Tel: Number: Fax: Rishi Kakar, M.D. Advarra IRB Approved Version 11 Jun 2024 Revised 27 Jun 2024  Transcend Therapeutics, Inc. Page 22 of 24 Protocol Number TSND201-PTSD-202, Part A ICF, USA V2.0 04June2024 I agree to take part in the above-mentioned study. I confirm with my signature that I have had enough time to read and understand the above information, and my questions have been answered to my satisfaction. I have the right to ask further questions as they come up during the study. I voluntarily agree to participate in this study until I decide otherwise. I do not give up any of my legal rights by signing this consent document. I will receive a copy of this signed consent document. Written Informed Consent: PARTICIPANT: Printed Name:................................................................................................................................................. Signature:................................................................................................................................................. Time:......:...... Date:....../....../...... PERSON OBTAINING INFORMED CONSENT: Printed Name:................................................................................................................................................. Signature:................................................................................................................................................. Time:......:...... Date:....../....../...... Rishi Kakar, M.D. Advarra IRB Approved Version 11 Jun 2024 Revised 27 Jun 2024 Transcend Therapeutics, Inc. Page 23 of 24 Protocol Number TSND201-PTSD-202, Part A ICF, USA V2.0 04June2024 AUTHORIZATION TO USE AND DISCLOSE PROTECTED HEALTH INFORMATION If you decide to be in this study, the study doctor and study staff will use and share health data about you to conduct the study. Health data may include: Your name. Address. Phone number. Date of birth. Medical history. Information from your study visits, including all test results. Health data may come from your study records or from existing records kept by your doctor or other health care workers. For this study, the study staff may share health data about you with authorized users. Authorized users may include: Representatives of Transcend Therapeutics. Representatives of Advarra IRB (an Institutional Review Board that reviews this study). The Food and Drug Administration (FDA) and other US federal and state agencies. Government agencies to whom certain diseases (like HIV, hepatitis, and STDs) must be reported. Governmental agencies of other countries. Outside individuals and companies, such as laboratories and data storage companies, that work with the researchers and Sponsor and need to access your information to conduct this study. Other study doctors and medical centers participating in this study, if applicable. A data safety monitoring board which oversees this study. Your health data will be used to conduct and oversee the research, including for instance: To see if the study drug works and is safe. Rishi Kakar, M.D. Advarra IRB Approved Version 11 Jun 2024 Revised 27 Jun 2024  Transcend Therapeutics, Inc. Page 24 of 24 Protocol Number TSND201-PTSD-202, Part A ICF, USA V2.0 04June2024 To compare the study drug to other drugs. For other research activities related to the study drug. Once your health data has been shared with authorized users, it may no longer be protected by federal privacy law and could possibly be used or disclosed in ways other than those listed here. Your permission to use and share health data about you will end in 50 years unless you revoke it (take it back) sooner. You may revoke (take back) your permission to use and share health data about you at any time by writing to the study doctor at the address listed on the first page of this form. If you do this, you will not be able to stay in this study. No new health data that identifies you will be gathered after your written request is received. However, health data about you that has already been gathered may still be used and given to others as described in this form. Your right to access your health data in the study records will be suspended during the study to keep from changing the study results. When the study is over, you can access your study health data. If you decide not to sign this form, you will not be able to take part in the study. STATEMENT OF AUTHORIZATION I have read this form and its contents were explained. My questions have been answered. I voluntarily agree to allow study staff to collect, use and share my health data as specified in this form. I will receive a signed and dated copy of this form for my records. I am not giving up any of my legal rights by signing this form. PARTICIPANT: Printed Name:.................................................................................................................................. Signature:.................................................................................................................................. Time:......:...... Date:....../....../...... Rishi Kakar, M.D. Advarra IRB Approved Version 11 Jun 2024 Revised 27 Jun 2024