Study assessing the safety and anti-coronavirus response of brequinar combined with dipyridamole in patients with mild to moderate SARS-CoV-2 infection
Scientific Title of Study
A phase II, randomized, assessor-blind, multicenter, multi-dose, placebo-controlled study assessing the safety and anti-coronavirus response of brequinar combined with dipyridamole in patients with mild to moderate SARS-CoV-2 infection.
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
21-VIN-0372 version 02 dated 30 Sep 2021
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Sumit Arora
Designation
Vice President Clinical Operations
Affiliation
Veeda Clinical Research Ltd.
Address
Veeda Clinical Research Ltd.,
Shivalik Plaza, Near I.I.M.,
Ambawadi, Ahmedabad 380 015, India
Ahmadabad GUJARAT 380015 India
Phone
7930013000
Fax
7930013010
Email
Sumit.arora@veedacr.com
Details of Contact Person Scientific Query
Name
Dr Ravi Alamchandani
Designation
General Manager
Affiliation
Veeda Clinical Research Ltd.
Address
Veeda Clinical Research Ltd.,
Shivalik Plaza, Near I.I.M.,
Ambawadi, Ahmedabad 380 015, India
Ahmadabad GUJARAT 380015 India
Phone
7930013000
Fax
7930013010
Email
Ravi.A1950@veedacr.com
Details of Contact Person Public Query
Name
Dr Ravi Alamchandani
Designation
General Manager
Affiliation
Veeda Clinical Research Ltd.
Address
Veeda Clinical Research Ltd.,
Shivalik Plaza, Near I.I.M.,
Ambawadi, Ahmedabad 380 015, India
GUJARAT 380015 India
Phone
7930013000
Fax
7930013010
Email
Ravi.A1950@veedacr.com
Source of Monetary or Material Support
Clear Creek Bio, Inc.
585 Massachusetts Ave., 4th Floor
Cambridge, MA 02139 USA
Primary Sponsor
Name
Clear Creek Bio Inc
Address
585 Massachusetts Ave., 4th Floor
Cambridge, MA 02139 USA
Type of Sponsor
Pharmaceutical industry-Global
Details of Secondary Sponsor
Name
Address
Veeda Clinical Research Ltd
Shivalik Plaza, Near I.I.M.,
Ambawadi, Ahmedabad 380 015, India
RIMS, Government medical college & Government General Hospital
Department of General medicine, Govt. Medical college & Govt. General hospital, (Old RIMSGGH), Srikakulam-532001, Andhra Pradesh, India. Srikakulam ANDHRA PRADESH
BGS Global Institute of Medical Sciences and Hospital
2nd Floor - Clinical Research Department,College Building, BGS Global Institute of Medical Sciences, 67 BGSHealth and EducationCity Uttarahali road,Kengeri, Bengaluru, Karnataka 560060 Bangalore KARNATAKA
9964319375 08026984801 vveena67@yahoo.com
Dr Milan Dhaduk
Global Hospital
4th Floor, Global Point,Beside Navjivan Sarthana Jakatnaka, Surat-395006, Gujarat Surat GUJARAT
8866683338
drmilandhadukcr@gmail.com
Dr Kapil Zirpe
Grant Medical Foundation Ruby Hall Clinic
Grant Medical Foundation Ruby Hall Clinic, 40 Sassoon Road, Main Building, Sassoon road, Pune, Maharashtra, India. Pune MAHARASHTRA
9822844212
kapilzirpe@gmail.com
Dr Sandhiya Selvaranjan
Jawaharlal Institute of Postgraduate Medical Education and Research
3rd Block, Department of Clinical Research, Pharmacology Institute Jawaharlal Institute of Postgraduate Medical Education and Research
(JIPMER), Dhanvantari nagar, Puducherry- 605006 Pondicherry PONDICHERRY
9443492922
sandhivaselvaraian@jjniail.com
Dr Y Gnana Sundara Raju
King George Hospital
KGH Down Rd, Opp. KGH OP Gate, Maharani Peta, Visakhapatnam, Andhra Pradesh 531011 Visakhapatnam ANDHRA PRADESH
(1) ICD-10 Condition: B972||Coronavirus as the cause of diseases classified elsewhere,
Intervention / Comparator Agent
Type
Name
Details
Intervention
brequinar 50 mg & dipyridamole 75 mg
brequinar 50 mg OD & dipyridamole 75 mg Three times a day) for 5 days
Comparator Agent
Not applicable
Not applicable
Inclusion Criteria
Age From
18.00 Year(s)
Age To
65.00 Year(s)
Gender
Both
Details
1. Willing and able to provide informed consent for the trial, written, electronic, verbal, or other method deemed acceptable by the institution and IRB.
2. Subjects between ≥18 and ≤65 years of age.
3. Subjects found positive for SARS-CoV-2 either by rapid antigen test or by reverse transcription polymerase chain reaction (RT-PCR) using ICMR-validated kit.
Note: Test need not be repeated in those with possession of confirmed positive report but positive result test date must be ≤5 days of first dose of study drug.
4. Mild or Moderate COVID-19 as per latest updated version of CLINICAL MANAGEMENT PROTOCOL for COVID-19 (in Adults) released by Government of India Ministry of Health and Family Welfare Directorate General of Health Services (EMR Division).
5. The effects of brequinar on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men and women treated or enrolled on this protocol must also agree to use adequate contraception for the duration of study participation, and for 90 days after completion of brequinar administration.
6. Male subjects must agree to refrain from sperm donation and female subjects must agree to refrain from ovum donation from initial study drug administration until 90 days after the last dose of brequinar.
7. At least one non-respiratory COVID-19 symptom characterized as mild to moderate by the Investigator including but not limited to fatigue, chills, fever, body aches, nasal congestion, nausea, vomiting, or other sign or symptom commonly associated with COVID-19 in the opinion of the investigator. Symptom onset must be ≤5 days prior to first dose. Subject must have one or more signs/symptoms present at first dose.
8. Willing to participate in the PK subset if at one of the identified sites.
9. Able to swallow capsules.
ExclusionCriteria
Details
1. Have an oxygen saturation of <90% while breathing ambient air.
2. Any physical examination findings and/or history of any illness that, in the opinion of the study investigator, might confound the results of the study or pose an additional risk to the subject.
3. Nursing women or women of childbearing potential (WOCBP) with a positive pregnancy test.
4. Treatment with another DHODH inhibitor (e.g., leflunomide, teriflunomide) or other agents known to cause bone marrow suppression leading to thrombocytopenia.
5. Ongoing treatment with aspirin and or dipyridamole, famotidine or cimetidine. Remdesivir and ivermectin are prohibited through Study Day 8. Steroids are permitted per the guidelines.
6. Platelets less than or equal to 125,000 cell/mm3.
7. Hemoglobin less than 10 gm/dL.
8. Absolute neutrophil count less than 1000 cells/mm3.
9. Renal dysfunction, i.e., creatinine clearance less than 30 mL/min.
10. AST or ALT more than 3 x ULN, or total bilirubin more than ULN. Gilbert’s Syndrome is allowed.
11. Bleeding disorders or blood loss requiring transfusion in the six weeks preceding enrollment.
12. Ongoing gastrointestinal ulcer, or gastrointestinal bleeding within 6 weeks of first dose.
13. Chronic hepatitis B infection, active hepatitis C infection, active liver disease and/or cirrhosis per subject report.
14. Heart failure, current uncontrolled cardiovascular disease, including unstable angina, uncontrolled arrhythmias, major adverse cardiac event within 6 months (e.g., stroke, myocardial infarction, hospitalization due to heart failure, or revascularization procedure).
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
On-site computer system
Blinding/Masking
Participant Blinded
Primary Outcome
Outcome
TimePoints
To characterize the safety and tolerability of the brequinar-dipyridamole combination in COVID-19 subjects as measured by frequencies of grade 3 and 4 toxicities and serious adverse events (SAEs) considered by the investigator to be related to the combination.
qPCR SARS-CoV-2 levels through Day 29 and at days 4, 8, 12, 15, 22, and 29
Secondary Outcome
Outcome
TimePoints
Reduction of SARS-CoV-2 levels using qPCR through Day 29 and at days 4, 8, 12, 15, 22, and 29;
Reduction in time to symptom improvement;
Reduction in percentage of subjects requiring hospital admission/re-admission as an in-patient for 24 hours;
Reduction in percentage of subjects requiring medical attended visits, e.g., hospitalization, emergency room visits, Urgent Care/Family Doctor visits;
Reduction in percentage of subjects requiring supplemental support such as oxygen.
qPCR SARS-CoV-2 levels through Day 29 and at days 4, 8, 12, 15, 22, and 29
Time to symptom improvement through Day 29;
Percentage of subjects requiring hospital admission/re-admission as an in-patient for 24 hours through Day 29;
Percentage of subjects requiring medical attended visits, e.g., hospitalization, emergency room visits, Urgent Care/Family Doctor visits through Day 29;
Percentage of subjects requiring supplemental support such as oxygen through Day 29.
Target Sample Size
Total Sample Size="112" Sample Size from India="112" 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
The first part of
the study will be a phase II, randomized, assessor-blind, multicenter,
multi-dose, placebo-controlled study in approximately 64 subjects with mild to
moderate COVID-19 infection confirmed by a positive SARS-CoV-2 RT-PCR
qualitative test /rapid antigen test and who have at least mild to moderate
signs and/or symptoms ongoing at study entry.
Approximately 32 subjects
(50% of subjects per arm per cohort) at selected sites will be invited to
participate in the “PK†arm of the study until approximately 8 subjects in each
cohort have been recruited after providing written informed consent for the
same. PK includes brequinar and dipyridamole plasma concentrations.
If a particular
cohort meets study stopping criteria (as defined in section “Safety Criteriaâ€)
or is found to be unsafe by DSMB members, then the study will not proceed with
enrollment of subsequent cohorts.
An expansion
cohort of approximately 48 subjects will be added to the cohort with the
highest brequinar dose that meets safety criteria.
All subjects will
receive SOC as per relevant guidelines for treatment of patients with mild to
moderate COVID-19 infection.