A randomized, double-blind, placebo-controlled, parallel group, phase 2/3, multicenter trial investigating the efficacy and safety of C21 as add on to standard of care in adult subjects with COVID-19.
Trial Acronym
ATTRACT Trial
Secondary IDs if Any
Secondary ID
Identifier
VP-C21-008 Version 3.0 dated 02 Jul 2021
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Kartikeya Parmar
Designation
Assistant Professor
Affiliation
Civil Hospital and B J Medical College
Address
Department of Medicine Civil Hospital and B J Medical College Asarwa Ahmadabad GUJARAT 380016 India
Phone
9924643799
Fax
Email
drkartik@gmail.com
Details of Contact Person Scientific Query
Name
Mr Yadvendra Singh Raghuvanshi
Designation
Clinical Project Manager
Affiliation
Orphan Reach
Address
Clinical Operations QED Clinical Services India Private Limited, Office number B-209, Westgate Besides YMCA Club S. G. Highway Ahmadabad GUJARAT 380015 India
Phone
9619579849
Fax
Email
yraghuvanshi@orphan-reach.com
Details of Contact Person Public Query
Name
Mr Gajendrasinh Chanchu
Designation
Director
Affiliation
Orphan Reach
Address
Clinical Operations QED Clinical Services India Private Limited, Office number B-209, Westgate Besides YMCA Club S. G. Highway Ahmadabad GUJARAT 380015 India
Phone
8511048026
Fax
Email
gchanchu@orphan-reach.com
Source of Monetary or Material Support
Vicore Pharma AB Kronhusgatan 11 SE-411 05 Göteborg Sweden
Primary Sponsor
Name
Vicore Pharma AB
Address
Kronhusgatan 11, SE-411 05 Göteborg, Sweden
Type of Sponsor
Pharmaceutical industry-Global
Details of Secondary Sponsor
Name
Address
NIL
NIL
Countries of Recruitment
Argentina Brazil Colombia Czech Republic India Peru Philippines Poland Russian Federation Ukraine United States of America
Department of Pulmonology, Aakash Healthcare Private Limited, Hospital Plot, Road No. 201, Sector 3, Dwarka New Delhi DELHI
9893322007
dr.akshaybudhraja@gmail.com
Dr MD Sabah Siddiqui
All India Institute of Medical Sciences
General Medicine OPD, All India Institute of Medical Sciences, Room No. 1111, 1st Floor, College Building, Department of General Medicine, All India Institute of Medical Sciences, Gate No. 5, GE Road, Tatibandh Raipur CHHATTISGARH
8518881911
dr.sabahsiddiqui@gmail.com
Dr Kartikeya Parmar
B J Medical College and Civil Hospital
Department of Medicine, B J Medical College and Civil Hospital, Asarwa Ahmadabad GUJARAT
9924643799
drkartik@gmail.com
Dr Mohan M E
BGS Global Institute of Medical Sciences
Principles office, BGS Global Institute of Medical Sciences, No. 67, BGS Health and Education city, Uttarahalli Main road, Kengeri Bangalore KARNATAKA
9845125293
drmohanbgsresearch@gmail.com
Dr Arunkumar Radhakrishnan
Chettinad Hospital and Research Institute
Department of general medicine, Chettinad Hospital and Research Institute, SH 49A Kelambakkam Chennai TAMIL NADU
04447411000
drarunresearch2020@gmail.com
Dr Rohit Parate
Chirayu Medical College
Department of General Medicine, Chirayu Medical College and Hospital, Bhopal Indore Highway, Near Bairagarh Bhopal MADHYA PRADESH
9630033341
rohitparate963@gmail.com
Dr Shibu Raj
Dr SMCSI Medical college
Department of Medicine, Dr. SMCSI Medical college, Parassala Vellarada Road, Karakonam Thiruvananthapuram KERALA
04712250233
drshiburajps21@gmail.com
Dr Vinod P B
Elite Mission Hospital
Department of Medicine, Elite Mission Hospital, Koorkenchery Rd, Koorkenchery Thrissur KERALA
8589951229
drvinodpbaburajan1989@gmail.com
Dr Atul Rajkondawar
Government Medical College and Hospital
Department of Medicine, Government Medical College and Hospital, Near Hanuman Nagar, Medical Square Ajani Road Nagpur MAHARASHTRA
9373215775
atul.rajkondawar@gmail.com
Prof Dr Lokeshwar Singh Kumuckcham
Jawaharlal Nehru Institute of Medical Sciences
Department of Medicine, Jawaharlal Nehru Institute of Medical Sciences, PorompatDepartment Imphal East MANIPUR
8258919544
lokeshwarsingh57@gmail.com
Dr Mohammed Mirvaz Zulfikar
Malabar Medical College Hospital and Research Centre
Department of Medicine, Malabar Medical College Hospital And Research Centre, MMC Campus, Ulliyeri Kozhikode KERALA
04962701800
mohammedmzulfikar@gmail.com
Dr Ajay Bulle
Meditrina Institute of Medical Sciences
Department of Medicine, Meditrina Institute of Medical Sciences, 278, central baazar road, Ramdaspeth Nagpur MAHARASHTRA
9921981109
ajaybulle@yahoo.com
Dr Reema Kashiva
Noble Hospital PVT LTD
Department of Diabetes and Obesity, Noble Hospital PVT LTD, 153, Magarpatta, City Road, HadapsarDepartment Pune MAHARASHTRA
8240213193
reemakashiva@gmail.com
Dr Mahesh Ramesh More
Rajiv Gandhi Medical College and Chhatrapati Shivaji Maharaja Hospital
Department of General Medicine, Rajiv Gandhi Medical College and Chhatrapati Shivaji Maharaja Hospital, Old Thane – Belapur Road, Kalwa Thane MAHARASHTRA
7725859185
maheshmore007@gmail.com
Dr Nirav Bhalani
Rhythm Heart Institute
Department of Cardiology, Rhythm Heart Institute – A Unit of SLPL, Nr Siddharth Bunglows, Sama – Savli Road Vadodara GUJARAT
8128995863
trial@rhythmheart.com
Dr Kapil Zirpe
Ruby Hall Clinic
Neuro Trauma Intensive Care Unit, Ruby Hall Clinic, 59/6, Disney Park, Azad Nagar, Wanowrie Pune MAHARASHTRA
9822844212
kapilzirpe@gmail.com
Dr Mayank Thakkar
Shree Giriraj Multispecialty Hospital
Department of Medicine, Shree Giriraj Multispecialty Hospital, 27- Navjyot Park Corner, 150 Feet Ring Road Rajkot GUJARAT
9909971118
drmayankthakker@gmail.com
Dr Himanshu Pophale
Smt. Kashibai Navale Medical College and General Hospital
Department of Pulmonology, Smt. Kashibai Navale Medical College and General Hospital, S. No. 4911, Off Westerly Bypass Highway, Mumbai Pune Bypass, Narhe (Ambegaon), Haveli Pune MAHARASHTRA
7738363741
himanshupophale@yahoo.co.in
Dr Dilip Gude
Virinchi Hospital
General Medicine OPD, Virinchi Hospital (A Unit of Virinchi Health Care Pvt. Ltd), Door No: 8-2-672/5&6, Road No. 1, Banjara Hills Hyderabad TELANGANA
Institutional Ethics Committee, Malabar Medical College Hospital and Research Centre
Approved
Institutional Human Ethics Committee
Approved
Meditrina Institute Ethics Committee
Approved
Noble Hospital Institutional Ethics Committee
Approved
Rhythm Heart Institute Ethics Committee
Approved
Shree Giriraj Hospital Research Ethics Committee
Approved
Virinchi Hospitals Institutional Ethics Committee
Approved
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
(1) ICD-10 Condition: B972||Coronavirus as the cause of diseases classified elsewhere,
Intervention / Comparator Agent
Type
Name
Details
Intervention
C21
IMP will be administered twice daily orally for 14 days from Visit 2 to Visit 15 as follows: 1. Morning dose: Two 50 mg capsules to be taken with a glass of water after minimum 2 hours fasting 2 Afternoon/evening dose: Two 50 mg capsules to be taken with a glass of water after minimum 2 hours fasting Subjects will be required not to eat anything for 1 hour after taking the IMP.
Comparator Agent
Placebo
IMP will be administered twice daily orally for 14 days from Visit 2 to Visit 15 as follows: 1. Morning dose: Two 50 mg capsules to be taken with a glass of water after minimum 2 hours fasting 2 Afternoon/evening dose: Two 50 mg capsules to be taken with a glass of water after minimum 2 hours fasting Subjects will be required not to eat anything for 1 hour after taking the IMP.
Inclusion Criteria
Age From
18.00 Year(s)
Age To
65.00 Year(s)
Gender
Both
Details
1. Age ≥18 years or the legal age of consent in the jurisdiction in which the trial is taking place at the time of signing the informed consent. (Specific for India; Age ≥18 at the time of signing the informed consent to ≤65 years.)
2. Hospitalized due to SARS-CoV-2 infection confirmed by polymerase chain reaction (PCR) test, documented by either of the following:
a. PCR positive in sample collected <72 hours prior to randomization (Visit 2); OR
b. PCR positive in sample collected ≥72 hours and ≤7 days prior to randomization, documented inability to obtain a repeat sample AND progressive disease suggestive of ongoing SARS-CoV-2 infection.
3. A score of 5 or 6 on the 8-point ordinal scale:
a. Score 5: Hospitalized, requiring supplemental oxygen.
b. Score 6: Hospitalized, on non-invasive ventilation or high-flow oxygen device.
4. Contraceptive use by men and women of childbearing potential consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
5. Written informed consent, consistent with International Council for Harmonization (ICH Good Clinical Practice (GCP) R2 and local laws, obtained before the initiation of any trial-related procedure.
6. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
7. Specific for India: For subjects with an ordinal scale score of 5, moderate to severe COVID-19 disease confirmed by at an SpO2 ≤ 93 % or a respiratory rate ≥ 24/min on room air. Note: If a subject is on supplemental oxygen with SpO2 >93% and respiratory rate <24/min, but desaturation to ≤ 93 % or increase of respiratory rate to ≥ 24/min on lower supplemental oxygen or room air is documented during screening, the inclusion criterion is considered to be met.
ExclusionCriteria
Details
1. Concurrent serious medical condition which in the opinion of the investigator constitutes a risk or a contraindication for the participation in the trial or that could interfere with the trial objectives, conduct or evaluation.
2. Known, active tuberculosis, active hepatitis B, C, or human immunodeficiency virus (HIV) infection (i.e., HIV with a CD4 count <500 cells/mm³).
3. Impaired hepatic function (i.e., Child-Pugh class B or C).
4. Severe renal impairment (i.e., estimated glomerular filtration rate (eGFR) ≤30 ml/min/1.73 m2).
5. COVID-19 symptom onset >14 days prior to screening (Visit 1).
6. Hospitalized due to COVID-19 for >72 hours at screening (Visit 1).
7. Invasive mechanical ventilation or ECMO within 72 hours of screening (Visit 1)
8. Expected need for invasive mechanical ventilation or ECMO in <48 hours in the opinion of the investigator.
9. Moderate to severe ARDS (e.g., same-day PaO2/FiO2 ≤200 mmHg; or SpO2/FiO2 ≤232 if arterial blood gas test is not available), if on non-invasive mechanical ventilation or high-flow oxygen.
10. Pregnant or breast-feeding female subjects.
11. Any previous and concurrent experimental treatment for COVID-19 that is not considered local SoC.
12. Treatment with the medications listed below within 1 week prior to screening (Visit 1) or anticipated need for such medication during the participation in this trial:
a. Strong Cytochrome P450 (CYP) 3A4 inducers.
b. P-glycoprotein (P-gp) substrates with narrow therapeutic index.
c. High dose BCRP sensitive substrates.
d. Warfarin.
e. Sulphasalazine or rosuvastatin.
13. Current or previous participation in any other clinical trial where the subject has received a dose of IMP within 1 month or 5 half-lives of the IMP, whichever is longest, prior to screening (Visit 1).
14. Positive pregnancy test
15. Abnormal laboratory value at screening (Visit 1) indicating a potential risk for the subject if enrolled in the trial as evaluated by the investigator.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Centralized
Blinding/Masking
Participant and Investigator Blinded
Primary Outcome
Outcome
TimePoints
Proportion of subjects discharged from hospital and free of supplemental oxygen at Day 15.
Proportion of subjects discharged from hospital and free of supplemental oxygen at Day 15.
Secondary Outcome
Outcome
TimePoints
Supplemental oxygen free days up to Day 29.
Will be assessed upto days 29
Proportion of subjects free of respiratory failure, defined as an 8-point ordinal scale score more than 6, at Day 15.
Will be assessed on days 15
Time to sustained hospital discharge up to Day 60
Will be assessed upto days 60
All-cause mortality up to Day 60
Will be assessed upto days 60
Adverse events (AE)s
During study participation
Serious AEs (SAE)s
During study participation
Changes in safety laboratory assessments
During study participation
Withdrawals due to AEs
During study participation
PK profile of C21 in subjects with COVID-19
Will be assessed on visit 2
Proportion of subjects discharged from hospital and free of supplemental oxygen at Days 8, 22 and 29.
Will be assessed on days 8, 22 & 29
Proportion of hospitalized subjects on non-invasive, invasive mechanical ventilation, extra corporeal membrane oxygenation (ECMO) or supplemental oxygen use at Days 8, 15, 22, 29 and 60.
Will be assessed on days 8, 15, 22, 29 & 60
Proportion of subjects in each category of the 8-point ordinal scale at Days 8, 15, 22, 29 and 60
Will be assessed on days 8, 15, 22, 29 & 60
Duration of hospitalization, including re-hospitalization, up to Day 60
Will be assessed upto days 60
Proportion of subjects needing intensive care unit stay at Days 8, 15, 22, 29 and 60
Will be assessed on days 8, 15, 22, 29 & 60
Duration of intensive care unit stay, including re-admission, up to Day 60.
Will be assessed upto days 60
Proportion of subjects on invasive mechanical ventilation or ECMO at Days 8, 15, 22, 29 and 60, and duration of use up to Day 60.
Will be assessed upto days 60
Proportion of subjects free of respiratory failure at Days 8, 22, 29 and 60, and respiratory failure free days up to Day 60.
Will be assessed upto days 60
All-cause mortality up to Days 8, 15, 22 and 29
Will be assessed upto days 29
Change from baseline in peripheral capillary oxygen saturation (SpO2) / fraction of inspired oxygen (FiO2) at Day 15
Will be assessed on days 15
Change from baseline in CRP at Day 15
Will be assessed on days 15
Change from baseline in lactate dehydrogenase (LDH) at Day 15
Will be assessed on days 15
Target Sample Size
Total Sample Size="600" Sample Size from India="80" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
A randomized, double-blind, placebo-controlled trial evaluating the efficacy and safety of C21 200 mg daily dose (100 mg b.i.d) as add on to standard of care in adult subjects with COVID-19 for 14 days. Approximately 600 subjects with COVID-19 infection will be randomized 1:1 to receive either standard of care and C21 or standard of care and placebo. All subjects will be followed-up on day 22, 29 & 60. The primary objective is to investigate the efficacy of C21 200 mg daily dose (100 mg b.i.d.) on COVID-19 infection not requiring mechanical invasive or non-invasive ventilation.
Rationale for trial:
The corona virus disease 2019 (COVID-19) is an ongoing pandemic caused by severe acute respiratory syndrome corona virus 2 (SARS-CoV-2). Although several therapeutic agents have been evaluated for the treatment of COVID-19, the morbidity and mortality are still significant. The need for safe, effective, and convenient COVID-19 drugs is likely to remain even after the launch of vaccine programs. The safety and efficacy of C21 in subjects with COVID-19 have been investigated in a phase 2 trial. The results show that C21, as add on to standard of care (SoC), reduced the need for extended oxygen supplementation and had a favorable benefit/risk profile. The rationale for conducting this phase 2/3 trial is to confirm the efficacy of C21 in subjects with COVID-19.