Brequinar Combined With Dipyridamole in Patients With Mild to Moderate COVID-19

NCT05166876 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: CCB-CRISIS-04
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 7

Brief Summary

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

Conditions

COVID-19

Keywords

SARS-CoV-2; Oral antiviral; DHODH Inhibitor; brequinar

Outcome Measures

Primary Outcomes (1)

• Safety and Tolerability of the Brequinar-dipyridamole Combination in COVID-19 Subjects

  There were no subjects who experienced grade 3 and 4 toxicities and serious adverse events (SAEs) considered by the investigator to be related to the combination, brequinar alone or placebo alone. therefore frequencies of these events could not be compared.

  Day 29

Secondary Outcomes (5)

• Reduction of SARS-CoV-2 Levels Using qPCR Through Day 29 and at Days 4, 8, 12, 15, 22, and 29

  Day 29

• Reduction in Time to Symptom Improvement

  Day 29

• Reduction in Percentage of Subjects Requiring Hospital Admission/Re-admission as an In-patient for >24 Hours

  Day 29

• Reduction in Percentage of Subjects Requiring Medical Attended Visits, e.g., Hospitalization, Emergency Room Visits, Urgent Care/Family Doctor Visits

  Day 29

• Reduction in Percentage of Subjects Requiring Supplemental Support Such as Oxygen

  Day 29

Study Arms (3)

Brequinar monotherapy

EXPERIMENTAL

Brequinar oral capsules will be administered once daily for 5 days using a dose-escalation approach. Planned doses include 50 mg, 100 mg, 150 mg, and 200 mg. Dosing will start at 50 mg and be escalated to the next higher dose if cohort stopping rules are not met.

Drug: Brequinar Sodium

Placebo

PLACEBO COMPARATOR

Placebo matching brequinar oral capsules will be administered once daily for 5 days using a dose-escalation approach. Planned doses include 50 mg, 100 mg, 150 mg, and 200 mg. Dosing will start at 50 mg and be escalated to the next higher dose if cohort stopping rules are not met.

Drug: Placebo

Brequinar-Dipyridamole Combination

EXPERIMENTAL

Brequinar oral capsules will be administered once daily for 5 days using a dose-escalation approach. Planned doses include 50 mg, 100 mg, 150 mg, and 200 mg. Dosing will start at 50 mg and be escalated to the next higher dose if cohort stopping rules are not met. All subjects assigned to this arm will also receive dipyridamole 75 mg tablets TID.

Drug: Brequinar Sodium; Drug: Dipyridamole 75 MG

Interventions

Brequinar Sodium DRUG

50 mg, 100 mg, 150 mg, 200 mg x 5 days

Brequinar monotherapy; Brequinar-Dipyridamole Combination

Dipyridamole 75 MG DRUG

75 mg TID for 5 days

Brequinar-Dipyridamole Combination

Placebo DRUG

50 mg, 100 mg, 150 mg, 200 mg x 5 days

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Willing and able to provide informed consent for the trial, written, electronic, verbal, or other method deemed acceptable by the institution and IRB.
• Subjects between ≥18 and ≤65 years of age.
• 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.
• 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).
• 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.
• 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.
• 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.
• Willing to participate in the PK subset if at one of the identified sites.
• Able to swallow capsules.

You may not qualify if:

• \. 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.
• \. Nursing women or women of childbearing potential (WOCBP) with a positive pregnancy test.
• \. Treatment with another DHODH inhibitor (e.g., leflunomide, teriflunomide) or other agents known to cause bone marrow suppression leading to thrombocytopenia.
• \. 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.
• \. 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.
• \. Bleeding disorders or blood loss requiring transfusion in the six weeks preceding enrollment.
• \. Ongoing gastrointestinal ulcer, or gastrointestinal bleeding within 6 weeks of first dose.
• \. Chronic hepatitis B infection, active hepatitis C infection, active liver disease and/or cirrhosis per subject report.
• \. 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).

Sponsors & Collaborators

• Clear Creek Bio, Inc.: lead

Study Sites (7)

RIMS - Government Medical College

Srikakulam, Andhra Pradesh, 532001, India

Location

King George Hospital

Visakhapatnam, Andhra Pradesh, 531011, India

Location

Global Hospital

Surat, Gujarat, 395006, India

Location

Rajarajeshwari Medical College and Hospital

Bangalore, Karnataka, 560060, India

Location

JIPMER Hospital

Puducherry, Puducherry, 605006, India

Location

Noble Hospital

Hadapsar, Pune, 411013, India

Location

Panimalar Hospital

Chennai, Tamil Nadu, 600123, India

Location

MeSH Terms

Conditions

COVID-19

Interventions

brequinar; Dipyridamole

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Vikram Sheel Kumar
• Organization: Clear Creek Bio, Inc.

kumar@clearcreekbio.com

(617) 765-2252

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: All staff will be blinded to treatment with the exception of the pharmacist and any staff recording study drug administration.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: All subjects will receive standard of care. In addition, subjects will be randomly assigned to one of 3 treatments: brequinar (50 mg, 100 mg, 150 mg, or 200 mg), placebo (50 mg, 100 mg, 150 mg, or 200 mg), or brequinar + dipyridamole (75 mg TID) in a 2:1:1 ratio in Part 1 of the study using a dose escalation approach. An expansion cohort is planned with the highest safe brequinar dose.

Study Record Dates

• First Submitted: December 16, 2021
• First Posted: December 22, 2021
• Study Start: February 1, 2022
• Primary Completion: June 4, 2022
• Study Completion: June 4, 2022
• Last Updated: November 7, 2023
• Results First Posted: February 6, 2023

Record last verified: 2023-10

Locations

IN (7)