BugSpeak Protocol (09-Sep-2024) PDF

Protocol No.: PRPL-BUGSPEAKS-01-2024 Version No.: 1.0 Date: 09-Sep-2024 Sponsor: LEUCINE RICH BIO PVT LTD medical condition(s), physical examination and/or laboratory data shall be recorded as an AE....

Protocol No.: PRPL-BUGSPEAKS-01-2024 Version No.: 1.0 Date: 09-Sep-2024 Sponsor: LEUCINE RICH BIO PVT LTD medical condition(s), physical examination and/or laboratory data shall be recorded as an AE. QOL, stool collection, Visit schedule Chemoradiotherapy Comments personalized nutrition Chemo cycle 1 + Day 1 Screening Visit 1 Radio Day 2 Radio QOL/ Visit 2 Day 3 Radio Randomization If holiday, Stool will be Day 4 Radio collection collected next day Day 5 Radio Sample will Day 6 Gap reach the Lab Day 7 Gap Chemo cycle 2+ Day 8 Visit 3 Radio Day 9 Radio Day 10 Radio Day 11 Radio Day 12 Radio Day 13 Gap Day 14 Gap Chemo cycle 3 + Day 15 Radio Day 16 Radio Day 17 Radio Confidential Page 11 of 48 Protocol No.: PRPL-BUGSPEAKS-01-2024 Version No.: 1.0 Date: 09-Sep-2024 Sponsor: LEUCINE RICH BIO PVT LTD Day 18 Radio Bugspeaks Day 19 Radio personalized nutrition Day 20 Gap Day 21 Gap Chemo cycle 4 + Day 22 Radio Day 23 Radio Day 24 Radio Visit 4 Day 25 Radio Day 26 Radio Day 27 Gap Day 28 Gap Chemo cycle 5 + Day 29 Radio Day 30 Radio Day 31 Radio Day 32 Radio End of the Day 33 Radio QOL Treatment Visit 5 Day 34 Day 45 Visit 6 Day 60 QOL Visit 7 QOL, Stool End of the Day 90 Collection Study Clinical Primary Outcome will be measured using - QoL outcome: Primary outcome Questionnaire at day 3 or 4, day 34, day 60 and day 90. Secondary NA outcome Confidential Page 12 of 48 Protocol No.: PRPL-BUGSPEAKS-01-2024 Version No.: 1.0 Date: 09-Sep-2024 Sponsor: LEUCINE RICH BIO PVT LTD Based on the recording and classification of adverse events (AEs) using CTCAE v 5.0 criteria, vital signs Safety outcome monitoring, physical examination, and clinical laboratory investigations. Site of the study: Department of Radiation Oncology, AIIMS, Raipur Pre-treatment Investigations: 1. Complete Blood Count (CBC) 2. Liver Function Tests (LFT) 3. Kidney Function Tests (KFT) During Treatment: List of clinical investigations: 1. Weekly CBC 2. Stool (Visit 3) Post Concurrent Chemo-radiotherapy Follow-up: 1. Clinical examination 2. As per requirement: a. Chest X-ray b. Ultrasound (USG) of the abdomen 3. Stool (visit 7) Study Improvement in quality-of-life parameters as endpoint adjudged based on clinically proven QOL Primary endpoint questionnaire in the Intervention arm as compared to the control arm. Secondary Improvement in efficacy of the treatment endpoint Confidential Page 13 of 48 Protocol No.: PRPL-BUGSPEAKS-01-2024 Version No.: 1.0 Date: 09-Sep-2024 Sponsor: LEUCINE RICH BIO PVT LTD Exploratory NA endpoint Safety endpoint NA Statistical and analytical plan Will be included in the protocol Publication policy Will be included in the protocol ABBREVIATIONS Confidential Page 14 of 48 Protocol No.: PRPL-BUGSPEAKS-01-2024 Version No.: 1.0 Date: 09-Sep-2024 Sponsor: LEUCINE RICH BIO PVT LTD AE Adverse Event CFR Code of Federal Regulation CRO Contract Research Organization EDC Electronic Data Capture EC Ethics Committee eCRFs Electronic Case Report Forms EOS End of Study GCP Good Clinical Practice ICH International Conference on Harmonisation IRB Institutional Review Board MedDRA Medical Dictionary for Regulatory Activities NCI-CTCAE National Cancer Institute- The Common Terminology Criteria for Adverse Events PT Protocol SAE Serious Adverse Event SOPs Standard Operating Procedures SOC System Organ Class TEAE Treatment Emergent Adverse Event Confidential Page 15 of 48  Protocol No.: PRPL-BUGSPEAKS-01-2024 Version No.: 1.0 Date: 09-Sep-2024 Sponsor: LEUCINE RICH BIO PVT LTD BACKGROUND AND RATIONALE Malnutrition and muscle wasting are frequently reported in cancer patients, either linked to the tumour itself or caused by oncologic therapies. Understanding the value of nutritional care during cancer treatment remains crucial. In fact, cancer-associated sarcopenia plays a key role in determining higher rates of morbidity, mortality, treatment- induced toxicities, prolonged hospitalizations and reduced adherence to anticancer treatment, worsening quality of life and survival. Since many cancer patients suffer weight loss and are poorly nourished or initially sarcopenic, the importance of screening patients for malnutrition from the beginning of their treatment is well established, as lack of proper nutritional management may limit the response to even the most effective therapy [1,2]. More especially, muscle wasting, resulting from mechanical and functional disorders including the imbalance between catabolic and anabolic pathways, is associated with increased surgical complications, poor prognosis, greater treatment related toxicities, a poorer response to anti-cancer therapies, worse quality of life and length hospital stay [3,4,5]. On the other hand, cancer therapies may affect the function and composition of gut microbiota, and can trigger dysbiosis affecting multiple metabolic pathways, thus weakening the immune response. We will outline the role of gut microbiota in cancer therapies in terms of toxicity and treatment response and, in turn, how cancer therapies could impact gut microbiota composition and function. In this context, we will explore the potential implications of various nutritional interventions such as prebiotics, dietary changes, and dietary restrictions on the modulation of gut microbiota during cancer therapies. In this study, we discuss on the role of detecting malnutrition early, and how to prevent this condition actively throughout the oncological care path. Malnutrition is a multifactorial effect experienced by cancer-patients due to inflammation, imbalance between anabolic and catabolic pathways, anti-cancer toxicities, inadequate food intake and hormonal abnormalities. To fight against malnutrition remains a common goal of all who make up the patients’ care team. Therefore, a close collaboration among experts and nutritional societies is necessary to promote pragmatic screening tools and guidelines to better define the timing of nutritional intervention in malnourished patients. Confidential Page 16 of 48  Protocol No.: PRPL-BUGSPEAKS-01-2024 Version No.: 1.0 Date: 09-Sep-2024 Sponsor: LEUCINE RICH BIO PVT LTD Test Product Diet plays an important role in shaping the composition of the gut microbiota thereby influencing the host’s health status. Various diet forms are found to influence the specific compositional patterns of the gut microbiota. The gut microbiome has also been shown to be linked with certain chronic diseases such as IBD, type 2 diabetes, non-alcoholic fatty acid liver disease (NAFLD), cancer patients etc. Because of such significant impact, manipulation of the gut microbiome (composition, abundance, and diversity) has been deemed to significantly influence our physiological functions, through immune and metabolic regulation. Gut microbiome is now area of interest worldwide relates to health of every human. In studies major factors responsible for change in gut microbiome in healthy person reported as per geographic location, age, lifestyle and diet. Gastrointestinal tract (GI) contains various types of microorganisms, collectively called as microbiome or microbiota. On the other words microbiome is the collection of genomes (contains all of the information needed to build and maintain that organism) from all the microorganisms found in a particular environment or specific area. Healthy Gut Microbiome helps in metabolism and energy regulation in humans. Alteration in these microbiomes due to change in habitat may lead to different changes in GI tract. Recent reports have even suggested that these microbial communities within the gut, can modify (both potentiate and weaken) the drugs consumed to treat specific disease conditions. This has started a dialogue on the need for in-depth knowledge of the impact of the microbiome on therapeutic strategies and have gained huge momentum with the precision medicine domain. BugSpeaks®, is a non-invasive gut microbiota profiling test which profiles the gut microbiota and provides personalized nutritional recommendation based on the gut microbiota. Diet especially, personalized, may improve prophylaxis and can be thoughtfully administered to patients undergoing concurrent Chemoradiotherapy for Carcinoma Cervix to accelerate recovery and improve clinical outcomes. Confidential Page 17 of 48  Protocol No.: PRPL-BUGSPEAKS-01-2024 Version No.: 1.0 Date: 09-Sep-2024 Sponsor: LEUCINE RICH BIO PVT LTD Risk/Benefits Assessment This trial will be conducted by strictly complying ICH-GCP principles and ethical guidelines laid down by Indian Council of Medical Research [ICMR]. The planned procedures in this trial pose no special risk to the participating human subjects. Based on the data available for safety and adverse events of BugSpeaks®, Based personalized Nutrition. STUDY OBJECTIVE Primary Objective To study the effects of microbiota based personalized diet on quality-of-life parameters of cervical cancer patients undergoing concurrent chemoradiotherapy. Secondary Objective To evaluate the Adverse events, discomforts arise with BugSpeaks®, based personalized nutrition. STUDY END POINT Primary end point 1. Improvement in quality-of-life parameters as adjudged based on clinically proven QOL questionnaire in the Intervention arm as compared to the control arm at visit 2(day 3), visit 5 (day 33), visit 6(day 60) and visit 7(day 90). Secondary end point 1. Improvement in efficacy of the treatment. Confidential Page 18 of 48  Protocol No.: PRPL-BUGSPEAKS-01-2024 Version No.: 1.0 Date: 09-Sep-2024 Sponsor: LEUCINE RICH BIO PVT LTD 2. Safety evaluation, as measured by AEs, Adverse Reactions (ARs), SAEs, Serious ARs (SARs) [Time Frame: Throughout the study]. STUDY DESIGN General Design This will be an Open Label, controlled, randomized, comparative, parallel group study to determine the Safety and efficacy of BugSpeaks®, based personalized nutrition on patients with cervical cancer undergoing concurrent chemoradiotherapy. The trial will be conducted 1 site in India, having qualified Investigator. Total duration for each subject: 90 days (Screening Period: 30 days, Assessment Period of 90 Days, Follow Up Period: at day 1, 3, 4, 19(+/-2 days), day 35(+/-2), day 60 and day 90 The study will be initiated only after the receipt of ethics committee (EC) approval. After obtaining the informed consent, Subjects will be screened by undergoing various assessments as mentioned in Schedule of Assessment and after confirming eligibility, eligible Subjects will be randomized to either control arm or test arm for 90 days treatment. During the study, Specimen collection and Body vitals will be monitored as per site practice. During the study, assessments will be performed as mentioned in Schedule of Assessment (Protocol Appendix 1). Study Methodology: This is an Open Label, controlled, randomized, comparative, parallel group study. The study will be conducted at 1 site in India, having qualified Investigator. The study will be initiated only after the receipt of ethics committee (EC) approval. After obtaining the informed consent, patients will be screened by undergoing various assessments as mentioned in flow chart and after confirming eligibility, eligible patients will be randomized to either BugSpeaks®®, based personalized nutrition or to continue routine nutrition. 30 patients will be enrolled in this study. Patients will participate in the study approximately 90 days. Confidential Page 19 of 48  Protocol No.: PRPL-BUGSPEAKS-01-2024 Version No.: 1.0 Date: 09-Sep-2024 Sponsor: LEUCINE RICH BIO PVT LTD STUDY ASSESSMENTS Informed Consent Voluntary written/audio or video recorded informed consent must be obtained from each subject (or their LAR) prior to performing any study-related procedures. Demographics Demographic variables such as age, gender will be recorded at Screening Day Medical /Surgery history and Prior medications Any clinical event, including diagnosis, condition, or surgery, that occurred prior to allocation to treatment, is to be recorded on the Medical History form. In case a clinical event concerns a chronic disorder, which means it started in the past and it is still present at the Screening, it should also be recorded on the Medical History Form. Worsening of the pre-existing medical condition will be recorded as an AE by the treating physicians. Medications taken by Subjects prior to screening will also be recorded on the Medical History form. Vital Signs and Body Temperature Vital signs will include measurements of respiratory rate (breaths/min), pulse rate (beats/min), and systolic and diastolic blood pressure (mmHg), and body temperature (°F). Vital signs will be assessed from V-1 to V- 6. Physical Examination A complete physical examination includes general appearance, skin, head, neck, ear- nose-throat (ENT), heart, lungs, abdomen, extremities, neurological, musculoskeletal, and lymph nodes and will be performed at Screening Day. The physical examination conducted at the scheduled visit will be recorded in the case report form (CRF). Pregnancy Test For women of childbearing potential, a serum/urine pregnancy test will be performed at Screening/Baseline visit (if applicable). Blood Analysis Blood samples will be collected at every week- Complete Blood Count, liver function test, kidney function test, Confidential Page 20 of 48