Brequinar Combined With Dipyridamole in Patients With Mild to Moderate SARS-CoV-2 Infection.

• Status: Not yet recruiting
• Trial end date: 2022-07-01
• Target enrollment: 0
• Participant gender: All

Summary

A Phase 2 multi-center, assessor-blind, randomized study to assess the safety, tolerability, and antiviral activity of brequinar in combination with dipyridamole.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Clear Creek Bio, Inc.
• Treatments: Brequinar; Dipyridamole

Criteria

Inclusion Criteria:

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.

Exclusion Criteria:

• 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 ≤125,000 cell/mm3. 7. Hemoglobin <10 gm/dL. 8. Absolute neutrophil count <1000 cells/mm3. 9. Renal dysfunction, i.e., creatinine clearance <30 mL/min. 10. AST or ALT >3 x ULN, or total bilirubin >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).