CRISIS2: A Phase 2 Study of the Safety and Antiviral Activity of Brequinar in Non-hospitalized Pts With COVID-19

NCT04575038 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: CCB-CRISIS-02
• Study Type: interventional
• Target: 115
• Locations: 1 country
• Sites: 14

Brief Summary

This study will assess the efficacy and safety of DHODHi (brequinar) as an antiviral via 5 days of treatment of participants with positive COVID-19 and at least one symptom of COVI019 in an out-patient setting. The study is multi-center, randomized, and placebo-controlled.

Conditions

COVID-19 Infection

Outcome Measures

Primary Outcomes (1)

• Log10 SARS-CoV-2 Viral Load

  Median Change from Baseline in Quantitative Log10 SARS-CoV-2 viral load at Days 4, 8, 12, 15, 22, and 29.

  Days 4, 8, 12, 15, 22, and 29

Secondary Outcomes (3)

• Rates of AEs and SAEs Including Laboratory Assessments

  Through Day 29

• Viral Shedding Duration

  Through Day 36

• Hospital Admission

  Day 29

Study Arms (2)

Brequinar 100 mg

EXPERIMENTAL

Brequinar oral capsules 100 mg x 5 days

Drug: Brequinar

Placebo

PLACEBO COMPARATOR

Placebo for Brequinar capsules x 5 days

Drug: Placebo

Interventions

Brequinar DRUG

Dihydroorotate dehydrogenase inhibitor (DHODHi)

Brequinar 100 mg

Placebo DRUG

Placebo capsules

Placebo

Eligibility Criteria

• Age: 18 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.
• years of age or older.
• Laboratory-confirmed SARS-CoV-2 infection as determined by real time polymerase chain reaction (RT-PCR) or other FDA-approved commercial or public health assay.
• Out-patient (never hospitalized as an in-patient for COVID-19 or was evaluated/treated for COVID-19 only in the Emergency Room with a stay of \< 24 hours)
• 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.
• Must have at least one COVID-19 symptom including but not limited to fever, cough, sore throat, malaise, headache, muscle pain, gastrointestinal symptoms, shortness of breath, dyspnea, anosmia, dysgeusia, or other symptom commonly associated with COVID-19 in the opinion of the investigator. Symptom onset must be ≤7 days prior to first dose. Subject must have one or more symptoms at first dose.
• Able to swallow capsules.

You may not qualify if:

• 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 patient
• 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
• Platelets ≤150,000 cell/mm3
• Hemoglobin \< 10 gm/dL
• Absolute neutrophil count \< 1500 cells/mm3
• Renal dysfunction, i.e., creatinine clearance \< 30 mL/min
• AST or ALT \> 2 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 randomization.
• 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 (14)

Central Alabama Research

Homewood, Alabama, 35209, United States

Location

Ark Clinical Research

Long Beach, California, 90806, United States

Location

Doral Medical Research

Doral, Florida, 33166, United States

Location

South Jersey Infectious Disease

Somers Point, New Jersey, 08244, United States

Location

Monroe Biomedical Research

Monroe, North Carolina, 28112, United States

Location

Wilmington Health

Wilmington, North Carolina, 28401, United States

Location

Remington-Davis, Inc.

Columbus, Ohio, 43215, United States

Location

Toledo Institute of Clinical Research

Toledo, Ohio, 43617, United States

Location

VitaLink - Gaffney

Gaffney, South Carolina, 29615, United States

Location

Self Regional Healthcare Research Center - Self Medical Group

Greenwood, South Carolina, 29646, United States

Location

VitaLink Research

Spartanburg, South Carolina, 29303, United States

Location

Clinical Trials Center of Middle Tennessee

Franklin, Tennessee, 37067, United States

Location

Centex Studies, Inc. - McAllen

McAllen, Texas, 78504, United States

Location

Synexus Clinical Research US, Inc. - Olympus Family Medicine

Salt Lake City, Utah, 84117, United States

Location

MeSH Terms

Conditions

COVID-19

Interventions

brequinar

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

Results Point of Contact

• Title: Barbara Powers, Vice President Clinical Operations
• Organization: Clear Creek Bio, Inc.

clinical@clearcreekbio.com

16177652252

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomized 1:1 brequinar 100 mg or placebo

Study Record Dates

• First Submitted: October 1, 2020
• First Posted: October 5, 2020
• Study Start: November 19, 2020
• Primary Completion: April 28, 2021
• Study Completion: April 28, 2021
• Last Updated: April 19, 2022
• Results First Posted: April 19, 2022

Record last verified: 2022-04

Locations

US (14)