PDF of Trial CTRI Website URL - http://ctri.nic.in Clinical Trial Details (PDF Generation Date :- Fri, 01 Oct 2021 07:55:31 GMT) CTRI Number CTRI/2020/07/026529 [Registered on: 13/07/2020] - Trial Registered Prospectively Last Modified On 13/07/2020 Post Graduate Thesis No Type of Trial Interventional Type of Study Drug Study Design Randomized, Parallel Group, Multiple Arm Trial Public Title of Study A Study to evaluate the safety and efficacy of Eflornithine against the standard of care in human adult hospitalized COVID-19 patients Scientific Title of An open label, randomized, three treatment, three arm, parallel group, investigator initiated, Study comparative clinical trial to evaluate the safety and efficacy of Eflornithine against the standard of care in human adult hospitalized COVID-19 patients Secondary IDs if Any Secondary ID Identifier NIL NIL Details of Principal Details of Principal Investigator Investigator or overall Name Dr Abhay Vispute Shantaram Trial Coordinator (multi-center study) Designation Director and physician Affiliation SRV Hospital Address Medicine department SRV Hospital Dr Mandakini Parihar Marg opposite Lokmanya Tilak Terminus, Tilak Nagar, Chembur, Mumbai, Maharashtra Mumbai MAHARASHTRA 400089 India Phone 9819428656 Fax Email [email protected] Details Contact Details Contact Person (Scientific Query) Person (Scientific Name Dr Abhay Vispute Shantaram Query) Designation Director and Physician Affiliation Dept. of Medicine, SRV Hospital Address SRV Hospital Dr Mandakini Parihar Marg opposite Lokmanya Tilak Terminus, Tilak Nagar, Chembur, Mumbai, Maharashtra Mumbai MAHARASHTRA 400089 India Phone 9819428656 Fax Email [email protected] Details Contact Details Contact Person (Public Query) Person (Public Query) Name Dr Abhay Vispute Shantaram Designation Director and Physician Affiliation Dept. of Medicine, SRV Hospital Address SRV Hospital Dr Mandakini Parihar Marg opposite Lokmanya Tilak Terminus, Tilak Nagar, Chembur, Mumbai, Maharashtra Mumbai MAHARASHTRA 400089 page 1 / 6 PDF of Trial CTRI Website URL - http://ctri.nic.in India Phone 9819428656 Fax Email [email protected] Source of Monetary or Source of Monetary or Material Support Material Support > Dept. of Medicine, SRV Hospital, Dr Mandakini Parihar Marg, opposite Lokmanya Tilak Terminus, Tilak Nagar, Chembur, Mumbai, Maharashtra 400089 Primary Sponsor Primary Sponsor Details Name Dr Abhay Vispute Shantaram Address SRV Hospital Dr Mandakini Parihar Marg, opposite Lokmanya Tilak Terminus, Tilak Nagar, Chembur, Mumbai, Maharashtra 400089 Type of Sponsor Other [Self] Details of Secondary Name Address Sponsor NIL NIL Countries of List of Countries Recruitment India Sites of Study Name of Principal Name of Site Site Address Phone/Fax/Email Investigator Dr Abhay Vispute SRV Hospital Dept. of Medicine Dr 9819428656 Shantaram Mandakini Parihar Marg, opposite [email protected] Lokmanya Tilak Terminus, Tilak Nagar, Chembur 400089 Mumbai MAHARASHTRA Details of Ethics Name of Committee Approval Status Date of Approval Is Independent Ethics Committee Committee? New Healthcare Approved 28/06/2020 Yes Nursing Home Regulatory Clearance Status Date Status from DCGI Not Applicable No Date Specified Health Condition / Health Type Condition Problems Studied Patients Coronavirus as the cause of diseases classified elsewhere Patients Other infectious disease Intervention / Type Name Details Comparator Agent Comparator Agent Standard Of Care (SoC) SoC including antimalarials, antivirals and macrolides. Intervention Eflornithine Treatment arm 1: Dose 2.5g, Oral solution administered every 6 hours + Standard of Care (SoC) excluding antimalarials and antivirals Treatment arm 2: Dose 5.0, oral solution administered every 6 hours + Standard of Care (SoC) excluding antimalarials and antivirals. Inclusion Criteria Inclusion Criteria Age From 18.00 Year(s) page 2 / 6 PDF of Trial CTRI Website URL - http://ctri.nic.in Age To 85.00 Year(s) Gender Both Details 1. Has laboratory-confirmed positive COVID-19 infection as determined by RT-PCR or other commercial or public health assay in any specimen, an RT-PCR (Nasopharynx and Throat) test shall be repeated to assess eligibility.<br/> 2. Symptomatic male or non-pregnant female adult requiring hospitalization, with or without comorbidities between the age group of 18-85 years of age at time of enrollment.<br/> 3. Illness or condition of any duration, and at least one of the following:<br/> - Fever defined as temperature greater than or equal to 36.6C (98.4F) measured by an infrared body temperature detection device.<br/> - Radiographic infiltrates by imaging (chest x-ray, CT scan, etc.), OR<br/> - Clinical assessment (evidence of rales/crackles on exam) AND SpO2 less than or equal to 94% on room air, OR<br/> - Requiring supplemental oxygen, OR<br/> - Requiring mechanical ventilation.<br/> 4. Women of childbearing potential must agree to either abstain or use at<br/> least one primary form of contraception not including hormonal contraception from the time of screening to the end of study (Day 28 or live hospital discharge, whichever is earlier).<br/> 5. Agrees to not participate in another clinical trial for the treatment of COVID-19 until the end of study (Day 28 or live hospital discharge, whichever is earlier).<br/> 6. Subject (or legally authorized representative) providing written informed consent prior to initiation of any study procedures.<br/> 7. Has a personal (mobile/cellular) phone, and is able to nominate at least one locator individual (e.g. a family member, friend or recovery mentor) with a verifiable address and a telephone number to assist with the arrangement of follow-up appointments as required.<br/> Exclusion Criteria Exclusion Criteria Details 1. Testing positive for HIV, HbsAg and HCV infection. 2. Females who are currently pregnant or breastfeeding. 3. Allergy or other contraindication to one of the investigational products. 4. Has received Eflornithine within the last 10 days. 5. Has received anti-viral, anti-malarial or anti-bacterial within the last 14 days. 6. Alanine Aminotransferase (ALT) or aspartate aminotransferase (AST) > 5 X upper limit of normal (ULN). 7. QTc interval ? 500ms. 8. Recent Myocardial Infarction (within last 6 months). 9. Known case of (K/C/O) Congestive heart failure. 10. K/C/O Chronic Kidney Disease. 11. K/C/O active Tuberculosis. 12. History of drug or alcohol dependence in the past 6 months. 13. In the opinion of the clinical team, progression to death is imminent and inevitable within the next 24 hours, irrespective of the provision of treatments. 14. Anticipated transfer to another hospital which is not a study site within 72 hours. 15. K/C/O of epilepsy. Method of Generating Stratified block randomization Random Sequence Method of An Open list of random numbers Concealment page 3 / 6 PDF of Trial CTRI Website URL - http://ctri.nic.in Blinding/Masking Open Label Primary Outcome Outcome Timepoints Time to Negative Viral Test: will be assessed by 1, 4, 7, 14, 21 and 28 days the time taken from initiation of the study treatment (i.e. the first study dose) to the day when the RT-PCR test results are first shown to be negative from samples collected from all of the below: a) Nasopharynx b) Throat An ICMR approved RT-PCR test resulting negative in the first instance, will be reconfirmed ? 24 hours apart with fresh samples from the same sites (a) Nasopharynx and (b) Throat. Secondary Outcome Outcome Timepoints 1. Time to Clinical Improvement (TTCI) 1, 4, 7, 14, 21 and 28 days 2. Eight-point ordinal 14-day analysis 3. Eight-point ordinal 28-day analysis 4. Oxygen free days 5. Duration of hospitalization in survivors and non-survivors 6. Subject 14-day mortality 7. Subject 28-day mortality 8. Time to death 9. Percentage Change in Biochemical Analysis Safety Endpoints: i) Cumulative incidence of Grade 3 and 4 adverse events (AEs) and Serious Adverse Events (SAEs) ii)Cumulative incidence of Hearing Impairment Target Sample Size Total Sample Size=18 Sample Size from India=18 Final Enrollment numbers achieved (Total)=Applicable only for Completed/Terminated trials Final Enrollment numbers achieved (India)=Applicable only for Completed/Terminated trials Phase of Trial Phase 2/ Phase 3 Date of First 20/07/2020 Enrollment (India) Date of First No Date Specified Enrollment (Global) Estimated Duration of Years=0 Trial Months=3 Days=0 Recruitment Status of Not Applicable Trial (Global) Recruitment Status of Not Yet Recruiting Trial (India) Publication Details Will be published in Pubmed indexed journal Brief Summary page 4 / 6 PDF of Trial CTRI Website URL - http://ctri.nic.in Based on the fact that Eflornithine has shown in vitro viral load reduction in MERS-CoV, it is hypothesized that the primary efficacy endpoint (time to viral load clearance by way of a negative RT-PCR test for COVID-19 infection) in patients of the Eflornithine treatment arms (Arms 1 & 2) will be statistically superior to the comparator arm (Arm 3) wherein the patient will receive antimalarials/ antivirals/ macrolides as a part of standard of care. Further, it is hypothesized that the primary efficacy endpoint (time to viral load clearance by way of a negative RT-PCR test for COVID-19 infection) in patients of the Eflornithine treatment arm 2 will be statistically superior to the treatment arms 1. It is also hypothesized that the Eflonrithine treatment arms (Arms 1 & 2) will have a faster time to clinical improvement, a fewer incidence of deaths on day 14 & 28, a lesser duration of hospitalization and more number of oxygen free days as compred to the comparator arm (Arm 3). It is also hypothesized that the Eflonrithine treatment arm 2 will have a faster time to clinical improvement, a fewer incidence of deaths on day 14 & 28, a lesser duration of hospitalization and more number of oxygen free days as compred to the treatment arm 1. Treatment arm 1: Eflornithine Granules (2.5 g) (Orange Flavour; Sugar Free) for oral solution administered every 6 hours + Standard of Care (SoC) excluding antimalarials and antivirals. Treatment arm 2: Eflornithine Granules (5.0 g) (Orange Flavour; Sugar Free) for oral solution administered every 6 hours + Standard of Care (SoC) excluding antimalarials and antivirals.