CTRI Number	CTRI/2020/09/027817 [Registered on: 15/09/2020] Trial Registered Prospectively
Last Modified On:	11/02/2021
Post Graduate Thesis	No
Type of Trial	Interventional
Type of Study	Drug Ayurveda
Study Design	Randomized, Parallel Group, Active Controlled Trial
Public Title of Study Modification(s)	A Phase III Clinical Study to assess the Safety and Efficacy of Ayurvedic Tablets combined with the current available medicine and its impact on lab parameters in Subjects with Uncomplicated Moderate COVID-19 infection.
Scientific Title of Study	A Multi-center, Randomized, Double-Blind, Placebo-Controlled Phase III Clinical Study to assess the Safety and Efficacy of BV-4051 Tablets combined with the Current Standard of Care and its impact on Inflammatory Biomarkers in Subjects with Uncomplicated Moderate SARS-CoV-2 infections (COVID-19)
Secondary IDs if Any	Secondary ID  Registry  NIL  NIL
Details of Principal Investigator or overall Trial Coordinator (multi-center study) Modification(s)	Name  DrN Kumarasamy  Address  VHS infectious disease medical centre Department of Infectious disease First Floor, SH 49A, Pallipattu, Tharamani, Chennai, Tamil Nadu VHS infectious disease medical centre Department of Infectious disease First Floor SH 49A, Pallipattu, Tharamani, Chennai, Tamil Nadu Chennai TAMIL NADU 600113 India  Phone  9769545533   Fax     Email  Kumarasamy@cartcrs.org
Details Contact Person Scientific Query	Name  Dr Sujay Patil  Address  KlinEra Global Services 801, Neelkanth Corporate Park Near Vidhyavihar Station Vidhyavihar West, Mumbai Mumbai MAHARASHTRA 400 086 India  Phone  8291279069   Fax  912225091476   Email  sujay.patil@Klinera.com
Details Contact Person Public Query Modification(s)	Name  Rajeev Singh  Address  KlinEra Global Services 801, Neelkanth Corporate Park Near Vidhyavihar Station Vidhyavihar West, Mumbai KlinEra Global Services 801, Neelkanth Corporate Park Near Vidhyavihar Station Vidhyavihar West, Mumbai Mumbai MAHARASHTRA 400 086 India  Phone  7045324601   Fax  912225091476   Email  rsingh@klinera.com
Source of Monetary or Material Support Modification(s)	Bioved Pharmaceuticals Pvt.Ltd., Unit 5, Survey No 12 (Part) Near Lokmat, Vadgaon Khurd Pune 411041
Primary Sponsor	Name  Bioved Pharmaceuticals Pvt Ltd  Address  5-6/12, Vadgaon Khurd, Pune, Maharashtra 411041  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 Prashant Rahate  Seven Star Hospital  Seven Star Hospital, 324/1, Jagnade Square, Great Nag Road, Nandanvan, Nagpur- 440009. Nagpur   9890198013 prashantrahate84@yahoo.com  Dr Jagdish Rawat  Shri Mahant Indiresh Hospital  Shri Guru Ram Rai Institute of Health and Medical Sciences, Shri Mahant Indiresh Hospital, Patel Nagar, Dehradun 248001. Dehradun   01356673400 drjagdishrawat@yahoo.com  Dr Amol Gitte  Siddhivinayak Hospital  Siddhivinayak Hospital Maternity ward S1, 2nd floor, Vedant Complex,, Above Nisarg Hotel, Vartak Nagar, Thane (W, Thane, Maharashtra 400606 Thane   9769545533 smghthane@yahoo.com  Dr Rahul Tulle  Vedant Hospital  Vedant Hospital,Department of General Medicines Ground floor, Research room Ghodbunder Rd, Kasarvadavali, Thane West, Thane, Maharashtra 400615 Thane   9823317762 Clinicalresearch@vedanthospital.com  Dr N Kumarasamy  VHS infectious disease medical centre  VHS infectious disease medical centre Department of Infectious disease First Floor, SH 49A, Pallipattu, Tharamani, Chennai, Tamil Nadu Chennai   9176912007 Kumarasamy@cartcrs.org  Dr Namdev Jagtap  VishwaRaj Hospital  VishwaRaj Hospital, Ground floor OPD 01 Solapur Rd, Rajbaug, Loni Kalbhor, Maharashtra 412201 Pune   9823914414 dr.jagtapdev@gmail.com
Details of Ethics Committee Modification(s)	No of Ethics Committees= 6   Name of Committee  Approval Status  Institutional Ethics Committee Maeers Vishwaraj Hospital  Approved  Institutional Ethics Committee Rahate Surgical hospital  Approved  Institutional Ethics CommitteeShri Guru Ram Rai Institute of Medical & Health Science  Submittted/Under Review  Vedant Hospital Institutional Ethics Committee  Approved  Vedant Hospital Institutional Ethics Committee  Approved  VHS Institutional Ethics Committee  Submittted/Under Review
Regulatory Clearance Status from DCGI	Status  Not Applicable
Health Condition / Problems Studied Modification(s)	Health Type  Condition  Patients  Coronavirus as the cause of diseases classified elsewhere
Intervention / Comparator Agent Modification(s)	Type  Name  Details  Comparator Agent  680 mg of Active or Placebo ingredient  Each tablet contains 444 mg of herbal extracts and 231 mg starch and aerosil (excipients or fillers)to be taken 04 tablets twice orally for 14 days  Intervention  680 mg of Active or Placebo ingredient   Each tablet contains 444 mg of herbal extracts and 231 mg starch and aerosil (excipients or fillers) to be taken 04 tablets twice orally for 14 days
Inclusion Criteria Modification(s)	Age From  18.00 Year(s) Age To  65.00 Year(s) Gender  Both  Details  1. Male, Female 2. 18 to 65 years 3. Subjects with acute uncomplicated moderate Corona infections needing hospitalization with temperature ≥ 38 ℃ (100.4 °F); plus at least one respiratory symptom (nasal congestion, sore throat, cough, breathing difficulty {Respiratory Rate ≥24 breaths per minute or Saturation of Oxygen (SpO2) <94% on room air}); and at least one constitutional symptom (aches or pains, fatigue, headache, chills or sweats). If antipyretics were taken, may wait at least 4 hours after dosing to determine if a qualifying temperature is observed. 4. Subjects with laboratory confirmed SARS-CoV-2 infection (COVID-19) as determined by the Reverse Transcription Polymerase Chain Reaction (RT-PCR) or other approved commercially available or public health assay prior to Visit 1. 5. Onset of symptoms at least 48 hours before Visit 1 (Screening; study drug administration visit). The onset of symptoms is defined as either: 1. Time of the first increase in body temperature to ≥ 38 ℃ (100.4 °F); or 2. Time when the subject experiences at least one general or respiratory symptom. 6. Subjects who are able to understand and willing to sign the informed consent form (ICF). 7. Subjects who are willing and able to comply with all scheduled visits, treatment plans, laboratory tests, lifestyle considerations and other study procedures. 8. All female subjects of child-bearing potential must have a negative urine pregnancy test result. All female subjects of child-bearing potential and male subjects and their spouse/partner must agree to use a medically acceptable method of contraception (e.g., abstinence, an intrauterine device, a double barrier method such as condom + spermicidal or condom + diaphragm with spermicidal, a contraceptive implant, an oral contraceptive or have a vasectomized partner with confirmed azoospermia) throughout the entire study period, and for 30 days for females and 90 days for males after study drug discontinuation.
ExclusionCriteria	Details  1. Subjects with severe COVID-19 infection requiring intensive inpatient treatment. 2. Subjects requiring mechanical ventilation or ECMO at the time of randomization on Day 1. 3. 3. Subjects with severe symptoms such as respiratory rate > 30 breaths per minute or saturation of oxygen (SpO2) < 90% on room air. 4. Subjects with other concurrent infections requiring systemic antimicrobial and/or antiviral therapy prior to screening. 5. Administration of immunomodulators, interferon inducers, homeopathic, hormonal other than hormone replacement therapy, antiviral and antibacterial drugs during the previous 4 weeks before the first dose. Use of corticosteroids as part of the current standard of care is permitted. 6. Subjects who have any of the following documented conditions: uncontrolled hypertension systolic blood pressure greater than 140 mm Hg or diastolic blood pressure greater than 90 mm Hg, diabetes, asthma any current or recent, not childhood if resolved, COPD any, cardiac, hepatic, renal including eGFRless than60 and hematopoietic disorders, bleeding tendency or hemorrhagic disease, neurological system disease, compromised immune system including patients receiving immunosuppressant therapy, or those with cancer within the past 5 years or human immunodeficiency virus HIV infection, endocrine disorders including thyroid disorders. 7. Subjects with anatomical nasal obstruction or gross anatomical abnormalities. For example, nasal polyps or significant nasal septal deviation. 8. Clinically obese subjects with BMI less than or equal to 40. 9. Subjects with recent history within 6 months of alcoholism or substance abuse. 10. Participation in other clinical trial within 1 month, or during the study. 11. Pregnant or breast-feeding female subjects 12. Allergy or known allergy to components of study medication. 13. Previous history of difficulty swallowing capsules. 14. Any other associated disease or condition which, in the opinion of the investigator, might restrict or impede participation in the study or affect the study results.
Method of Generating Random Sequence	Random Number Table
Method of Concealment	Sequentially numbered, sealed, opaque envelopes
Blinding/Masking	Double Blind Double Dummy
Primary Outcome Modification(s)	Outcome  TimePoints  To investigate clinical efficacy of BV-4051 tablets in alleviation of fever and other symptoms including breathing difficulty, nasal congestion, sore throat, cough, headache, body ache, fatigue, chills or sweats, diarrhea, vomiting, taste and smell disorders in subjects with uncomplicated moderate SARS-CoV-2 infections (COVID-19).  Day 7 and Day 14
Secondary Outcome	Outcome  TimePoints  1. Duration of viral shedding: defined as the time from treatment initiation to the time of first negative COVID-19 virus RNA by RT-PCR and/or to the time of first negative COVID-19 virus using other approved commercially available or public health assay. 2. Reduction in Inerleukin-6, TNF-Alpha, Erythrocyte Sedimentation Rate, C-Reactive Protein and LDH from baseline to Day 7 or Early Discharge Visit Day and Day 14 post treatment initiation.   Day 14 post treatment initiation.
Target Sample Size	Total Sample Size="180" Sample Size from India="180"
Phase of Trial	Phase 3
Date of First Enrollment (India) Modification(s)	18/09/2020
Date of First Enrollment (Global)	No Date Specified
Estimated Duration of Trial	Years="0" Months="3" Days="0"
Recruitment Status of Trial (Global) Modification(s)	Not Applicable
Recruitment Status of Trial (India)	Open to Recruitment
Publication Details Modification(s)	NIL
Brief Summary	This phase III clinical study is designed to be conducted in India in about 3-5 clinical research centers during the third quarter in 2020.  Approximately 180 subjects with newly diagnosed moderate COVID-19 will be enrolled in this study. Total of three (3) visits will be scheduled for all subjects during this study: visit 1 on day 1, visit 2 on day 7, and visit 3 on day 14.  The GCP, ICH (Declaration of Helsinki) and other government and local regulations will be strictly followed throughout the study. Subjects with moderate COVID-19 symptoms onset, at least 48 hours of prior to presentation will be screened against inclusion/exclusion criteria after signing informed consent. Eligible subjects will be randomized to one of two study groups. All subjects will be required to take study medication twice daily for 14 days from the day of randomization. From day 1 to day 14, self-assessment shall be completed by subject and recorded on the “symptoms assessment card” twice per day of their symptoms and temperature during the past 12 hours period and body temperature, and the other card of “quality of life” once per day prior to the evening dose. Any medications other than permitted by the current standard of care are prohibited throughout the study. All female subjects and male subjects and their partner/spouse must agree to use a medically acceptable method of contraception (e.g., abstinence, an intrauterine device, a double-barrier method such as condom + spermicidal or condom + diaphragm with spermicidal, a contraceptive implant, an oral contraceptive or have a vasectomized partner with confirmed azoospermia) throughout the entire study period and for 30 days for females and 90 days for males after study drug discontinuation. COVID-19 virus testing will be performed by RT-PCR or other approved commercially available or public health assay on day 1. If documented evidence of virus diagnostic test results are available prior to the screening process; the results are acceptable and the virus diagnostic test may not be conducted for these subjects at the screening visit on day 1. On Day 7 and Day 14, the virus testing will be repeated utilizing the same test method used on day 1. The primary endpoint is to assess the time of alleviation of COVID-19 symptoms. Approximately 180 subjects with newly diagnosed moderate COVID-19 will be randomized in this 2-arm study with BV-4051 tablets + the current standard of care and placebo + the current standard of care, respectively. Subjects will be randomized to one of the two arms according to the randomization scheme on Day 1 in the ratio of 1:1.