Safety and Anti-coronavirus Response of Suppression of Host Nucleotide Synthesis in Patients With COVID-19

NCT04425252 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: CCB-CRISIS-01
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 5

Brief Summary

This will be a phase 1a randomized, open label, multi-center study with approximately 24 subjects. All subjects will receive standard of care (SOC) per institutional guidelines for treatment of hospitalized patients with COVID-19 infection. In addition to SOC, the brequinar group will receive 5 daily doses of brequinar 100 mg.

Conditions

COVID-19

Keywords

DHODH inhibition; antiviral; coronavirus; SARS-CoV-2

Outcome Measures

Primary Outcomes (3)

• Safety/Tolerability Assessed by Rates of Grade 3 or 4 Post Randomization Adverse Events

  Safety/tolerability as assessed by number of participants with Grade 3 or 4 post randomization adverse events.

  Through Day 15.

• Safety/Tolerability as Assessed by Rates of Serious Adverse Events (SAEs).

  Safety/tolerability as assessed by number of participants with Serious Adverse Events (SAEs).

  Through Day 15

• Safety/Tolerability Measured by Mortality at Day 29

  Safety/tolerability as measured by mortality at Day 29

  Through Day 29

Secondary Outcomes (3)

• Hospitalization Status

  Days 3, 5, 7, and 15

• Duration of Hospitalization

  Through Day 15

• NEWS2 Score

  Baseline, Days 3, 5, 7, and 15.

Study Arms (2)

Standard of Care

OTHER

Subjects are hospitalized for COVID-19 and will receive all supportive/interventional care per institutional guidelines.

Other: Standard of Care

Brequinar

EXPERIMENTAL

Subjects will receive standard of care plus brequinar 100 mg daily (Study Days 1-5).

Drug: Brequinar

Interventions

Brequinar DRUG

DHODH inhibitor, 100 mg daily x 5 days

Also known as: Standard of Care + Brequinar

Brequinar

Standard of Care OTHER

Standard of Care per institutional guidelines for COVID-19 patients

Standard of Care

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.
• If discharged from the hospital prior to Study Day 15 or if follow up is needed for study drug-related adverse event, willing to go to an outpatient facility if feasible or be in contact with the study team (phone call or other digital media) for remaining study assessments.
• Laboratory-confirmed SARS-CoV-2 infection as determined by real time polymerase chain reaction (RT-PCR) or other Food and Drug Administration (FDA)-cleared commercial or public health assay.
• Hospitalized (in patient with expected duration ≥ 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 from initial study drug administration until 90 days after the last dose of brequinar.
• ≤ 10 days since first COVID-19 symptom as determined by treating clinician.
• Able to swallow capsules.
• 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, dysgeusia, or other symptom commonly associated with COVID-19.

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.
• Active malignancy other than squamous cell carcinoma; anticancer treatment such as chemotherapy or radiation therapy within the past month.
• Nursing women or women of childbearing potential (WOCBP) with a positive pregnancy test.
• Treatment with another DHODH inhibitor (e.g., leflunomide or teriflunomide), tacrolimus, sirolimus.
• 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 and/or ALT \> 1.5 ULN, or total bilirubin \> ULN
• History of bleeding disorders or recent surgery in the six weeks preceding enrollment
• Concomitant use of agents known to cause bone marrow suppression leading to thrombocytopenia
• History of gastrointestinal ulcer, or history of gastrointestinal bleeding.
• History of hepatitis B and/or C infection, active liver disease and/or cirrhosis.
• 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).
• Life expectancy of \< 5 days in the judgment of the treating clinician.

Sponsors & Collaborators

• Clear Creek Bio, Inc.: lead

Study Sites (5)

Hartford Hospital

Hartford, Connecticut, 06102, United States

Location

Baptist Medical Center

Jacksonville, Florida, 32207, United States

Location

University of South Florida/Tampa General

Tampa, Florida, 33606, United States

Location

University of New Mexico

Albuquerque, New Mexico, 87106, United States

Location

Temple University

Philadelphia, Pennsylvania, 19140, United States

Location

MeSH Terms

Conditions

COVID-19; Coronavirus Infections

Interventions

brequinar; Standard of Care

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Limitations and Caveats

CCB-CRISIS-01 was a small, open-label study with small numbers of subjects analyzed. In addition, the study was conducted prior to availability of COVID-19 vaccinations and there were many missed visits and assessments due to COVID-19 restrictions in place at the time that prohibited return visits to the hospital or clinic. Standard of care for these hospitalized subjects included remdesivir and steroids.

Results Point of Contact

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

clinical@clearcreekbio.com

(617) 765-2252

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomized 1:2 to standard of care (SOC) alone or SOC + brequinar

Study Record Dates

• First Submitted: June 9, 2020
• First Posted: June 11, 2020
• Study Start: August 19, 2020
• Primary Completion: December 29, 2020
• Study Completion: January 12, 2021
• Last Updated: February 17, 2022
• Results First Posted: February 16, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)