CTRI Number	CTRI/2021/08/035424 [Registered on: 04/08/2021] Trial Registered Prospectively
Last Modified On:	03/08/2021
Post Graduate Thesis	No
Type of Trial	Interventional
Type of Study	Drug
Study Design	Randomized, Parallel Group, Multiple Arm Trial
Public Title of Study Modification(s)	Study to evaluate the efficacy and safety of Molnupiravir capsules Compare with the with Standard of Care Medications Care alone in patients who are suffering with Moderate COVID-19 disease
Scientific Title of Study	A Phase 3, Prospective, Open Label, Randomized, Multicenter, Parallel Study to evaluate the efficacy and safety of Molnupiravir capsules when administered along with Standard of Care compared to Standard of Care alone in Indian patients with Moderate COVID-19 disease
Secondary IDs if Any Modification(s)	Secondary ID  Registry  CR217-21   Protocol Number  Version 2.0 Dated 08 Jun 2021  Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)	Name  Dr Subhra Lahiri  Address  AXIS Clinicals Ltd 1-121/1, Miyapur, Hyderabad Telangana INDIA AXIS Clinicals Ltd 1-121/1, Miyapur, Hyderabad Telangana INDIA Hyderabad TELANGANA 500049 India  Phone  8886221089   Fax  40408060   Email  Subhra.L@axisclinicals.com
Details Contact Person Scientific Query	Name  Dr Subhra Lahiri  Address  AXIS Clinicals Ltd 1-121/1, Miyapur, Hyderabad Telangana INDIA AXIS Clinicals Ltd 1-121/1, Miyapur, Hyderabad Telangana INDIA Hyderabad TELANGANA 500049 India  Phone  8886221089   Fax  40408060   Email  Subhra.L@axisclinicals.com
Details Contact Person Public Query	Name  Dr Subhra Lahiri  Address  AXIS Clinicals Ltd 1-121/1, Miyapur, Hyderabad Telangana INDIA AXIS Clinicals Ltd 1-121/1, Miyapur, Hyderabad Telangana INDIA Hyderabad TELANGANA 500049 India  Phone  8886221089   Fax  40408060   Email  Subhra.L@axisclinicals.com
Source of Monetary or Material Support Modification(s)	APL Research Centre-II, Aurobindo Pharma Limited, Sy No. 71&72, Indrakaran (V), Sangareddy (M), Medak Dist-502329, Telangana, India.
Primary Sponsor	Name  Aurobindo Pharma Limited  Address  Aurobindo Pharma Limited Sy No71&72Indrakaran (V)SangareddyM Medak Dist 50 2329Telangana, India  Type of Sponsor  Pharmaceutical industry-Indian
Details of Secondary Sponsor	Name  Address  NIL  NIL
Countries of Recruitment	India
Sites of Study Modification(s)	No of Sites = 6   Contact Person  Name of Site  Site Address  Phone/Fax/Email  Dr Pramod Sonba Atole  Baramati Hospitals Pvt.Ltd  Behind Kavivarya Moropant Natyamandir, Ring Road, Baramati-413102 Pune   9970997767 drpramodatole@gmail.com  DrSoumik Chowdhury  Health Point Hospital  21, Prannath Pandit Street, Opposite Lansdown Padmapukur, Kolkata -700025 Kolkata   9432164842 shoumikchowdhary0@gmail.com  Dr Vaibhav Lotke  Pulse Multispeciality Hospital  Vishwa Arcade, Near Bombay Bangalore Highway, Narhe, Pune, 411041 Maharashtra, India Pune   8552003274 drlotke.pulse@gmail.com  Dr Vijaykumar Barge  RCSM Govt. Medical College and CPR Hospital  Dasara Chowk, Bhausingji Road, Town HallKolhapur-416012 Kolhapur   9011066766 drvijaybarge12@gmail.com  Dr A Venkatshwar Rao  St Theresas Hospital  Sanathnagar, Hyderabad-500018 Hyderabad   9440040662 drvenkateshwarraoavula@gmail.com  Dr Abhishek Mahadev Karmalkar  Vedant Multispeciality Hospital  Sambhaji Nagar, Chinchwad, Pune 411019 Maharashtra Pune   9850337271 dr.karmalkar@gmail.com
Details of Ethics Committee Modification(s)	No of Ethics Committees= 6   Name of Committee  Approval Status  Ethics committee of Baramati hospital  Approved  Ethics committee of Pulse Multispecialty hospital   Approved  Ethics committee St.Theresa’s hospital  Approved  Health Point Ethics Committee  Approved  IEC of Vedant multispecialty hospital  Approved  Kolhapur Institutional Ethics committee 2( RCSMGMCIEC2)   Approved
Regulatory Clearance Status from DCGI	Status  Approved/Obtained
Health Condition / Problems Studied Modification(s)	Health Type  Condition  Patients  Acute upper respiratory infection,unspecified  Patients  Coronavirus as the cause of diseases classified elsewhere
Intervention / Comparator Agent Modification(s)	Type  Name  Details  Intervention  Molnupiravir capsules  05 Days treatment. 1600 mgs/twice a day/Oral   Comparator Agent  Standard of Care Therapy   Standard of Care Therapy as per the Institution Practice and Based on Patient condition
Inclusion Criteria	Age From  18.00 Year(s) Age To  60.00 Year(s) Gender  Both  Details  1. Male and/or female patients aged ≥ 18 and ≤ 60 years of age (both inclusive). 2. Patients and LAR willing to comply with study protocol requirements and voluntarily able to provide written informed consent. 3. Patients with positive for SARS-CoV-2 confirmed by RT-PCR in nasopharyngeal and/or oropharyngeal swabs within 5 days prior to randomization. 4. Patients with presence of clinical features of dyspnea and or hypoxia, fever, cough, including one of the following symptoms at the time of screening and randomization. a. Respiratory rate ≥ 24/min, breathlessness b. SpO2: 90% to ≤ 93% on room air 5. Patients with a risk factor for progressing to severe COVID-19 (i.e., who have co-morbid conditions diabetes, hypertension and so on). 6. Male patients must agree to either abstain from sexual intercourse or to use contraception during the entire study duration and for a period of at least 04 days after the last dose of study medication or after the early withdrawal visit. 7. Female patients of childbearing potential must agree to either abstain from sexual intercourse or to use acceptable contraceptive method during the entire study duration and for a period of at least 04 days after the last dose of study medication or after the early withdrawal visit and must have negative urine pregnancy test prior to randomization. Medically acceptable forms of contraceptive include: a. Hormonal contraceptives (at least 1 month before screening visit) b. Double barrier methods (e.g., diaphragm with spermicide; or condoms with spermicide) c. Intrauterine device (IUD)
ExclusionCriteria	Details  Inclusion Criteria: 1. Male and/or female patients aged ≥ 18 and ≤ 60 years of age (both inclusive). 2. Patients and LAR willing to comply with study protocol requirements and voluntarily able to provide written informed consent. 3. Patients with positive for SARS-CoV-2 confirmed by RT-PCR in nasopharyngeal and/or oropharyngeal swabs within 5 days prior to randomization. 4. Patients with presence of clinical features of dyspnea and or hypoxia, fever, cough, including one of the following symptoms at the time of screening and randomization. a. Respiratory rate ≥ 24/min, breathlessness b. SpO2: 90% to ≤ 93% on room air 5. Patients with a risk factor for progressing to severe COVID-19 (i.e., who have co-morbid conditions diabetes, hypertension and so on). 6. Male patients must agree to either abstain from sexual intercourse or to use contraception during the entire study duration and for a period of at least 04 days after the last dose of study medication or after the early withdrawal visit. 7. Female patients of childbearing potential must agree to either abstain from sexual intercourse or to use acceptable contraceptive method during the entire study duration and for a period of at least 04 days after the last dose of study medication or after the early withdrawal visit and must have negative urine pregnancy test prior to randomization. Medically acceptable forms of contraceptive include: a. Hormonal contraceptives (at least 1 month before screening visit) b. Double barrier methods (e.g., diaphragm with spermicide; or condoms with spermicide) c. Intrauterine device (IUD) Exclusion Criteria: 1. Patients with known hypersensitivity to any of the excipients of the study medication or to any other similar class of drugs. 2. Patients who participated in any other clinical trial of an experimental treatment for COVID-19 within 90 days prior to randomization. 3. Patients infected post vaccination of either 1st or 2nd dose. 4. Patients with pulse rate < 50 beats per minute at rest at the time of screening and randomization. 5. Patient with severe COVID-19 with any of the following: respiratory failure (including endotracheal intubation and mechanical ventilation, oxygen delivered by high-flow nasal cannula (flow rates >20L/min with fraction of delivered oxygen ≥0.5), noninvasive positive pressure ventilation, or extracorporeal membrane oxygenation (ECMO). 6. Patients have hepatitis B virus (HBV) or hepatitis C virus (HCV) with cirrhosis, end-stage liver disease, hepatocellular carcinoma, aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 3X upper limit of normal at screening. 7. Patients with platelet count <100,000/μL or received a platelet transfusion within 5 days prior to randomization. 8. Patients with AIDS-defining illness in the past 6 months. 9. Patients with uncontrolled co-morbid conditions such as hypertension, diabetes, cardiovascular disease, chronic lung/ liver/ kidney disease, cerebro-vascular disease as per the investigator’s discretion. 10. Patients currently administering or anticipated to require Favipiravir, Oseltamivir or any other anti-viral treatments during study participation. 11. Patients with Absolute Neutrophil Count (ANC) < 500 mm3. 12. Patients currently administering immunosuppressive treatments within 30 days of prior to randomization. 13. Female patients who are pregnant and/ or breast feeding. 14. Patients who have any medical condition(s) or has any medical condition(s) which would likely interfere with the conduct or interpretation of the study as per the investigator’s discretion.
Method of Generating Random Sequence	Stratified block randomization
Method of Concealment	An Open list of random numbers
Blinding/Masking	Open Label
Primary Outcome Modification(s)	Outcome  TimePoints  Proportion of patients with clinical improvement at Day 14. Clinical improvement is defined as 2-point decrease in clinical progression scale as recommended by WHO.   Day 28
Secondary Outcome Modification(s)	Outcome  TimePoints  • Proportion of patients with clinical improvement at Day 28. • Time to clinical improvement from randomization up to 28 days. • Mortality rate at Day 28. • Rate of SARS-CoV2 RT-PCR negativity in nasopharyngeal and/or oropharyngeal swab at the end of treatment, Day 14 and Day 28. • Change in SARS CoV-2 viral load (Cycle Threshold (CT) value of RT-PCR test) from baseline to end of the treatment, Day 14 and Day 28.   Day 28
Target Sample Size Modification(s)	Total Sample Size="100" Sample Size from India="100"
Phase of Trial	Phase 3
Date of First Enrollment (India)	10/08/2021
Date of First Enrollment (Global)	No Date Specified
Estimated Duration of Trial	Years="0" Months="3" Days="0"
Recruitment Status of Trial (Global)	Not Applicable
Recruitment Status of Trial (India)	Not Yet Recruiting
Publication Details	No
Brief Summary	This is a phase 3, prospective, open-label, randomized, multicentre, a parallel study in patients with Moderate COVID-19 disease. This study will be conducted in two parts. In part 1, the study will be conducted on 100 patients. Part 2 of this study will be continued to complete the enrollment of remaining patients to achieve the randomization of 1284 patients considering two parts. The total duration of study for each patient will be approximately 5 weeks including a screening period. This study will be conducted in approximately 20 sites across India.