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

NCT ID: NCT04425252

Last Updated: 2022-02-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-08-19
• Study Completion Date: 2021-01-12

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.

Detailed Description

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 SARS-CoV-2 infection. Subjects will be randomly assigned in a 1:2 ratio to SOC alone or SOC plus brequinar. The SOC plus brequinar group will receive 5 daily doses of brequinar 100 mg on Days 1 - 5 in addition to SOC. Physical examinations, vital signs, laboratory assessments, SARS-CoV-2 testing, and other observations will be conducted by experienced personnel throughout the study based on the Schedule of Events. Blood chemistry tests include blood urea nitrogen (BUN), creatinine, alkaline phosphatase (ALP), alanine amino transferase (ALT), aspartate amino transferase (AST), bilirubin, total protein, albumin, glucose, serum electrolytes (sodium, potassium, chloride, carbon dioxide/bicarbonate, and calcium), lactate dehydrogenase (LDH). Plasma will be collected for inflammatory markers such as D-dimer, ferritin, c-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). Pro-inflammatory markers will be measured. Serum is to be collected for research purposes. Hematology tests include hemoglobin, hematocrit, complete blood count with full differential, and platelet count. Nasopharyngeal swabs for viral load will be collected Days 1, 3, 5, 7, and 15. Survival will be assessed through Day 29.

Conditions

COVID-19

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Standard of Care

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

Group Type: OTHER

Standard of Care

Intervention Type: OTHER

Standard of Care per institutional guidelines for COVID-19 patients

Brequinar

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

Group Type: EXPERIMENTAL

Brequinar

Intervention Type: DRUG

DHODH inhibitor, 100 mg daily x 5 days

Interventions

Brequinar

DHODH inhibitor, 100 mg daily x 5 days

Intervention Type: DRUG

Standard of Care

Standard of Care per institutional guidelines for COVID-19 patients

Intervention Type: OTHER

Other Intervention Names

Standard of Care + Brequinar

Eligibility 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. 18 years of age or older.

3. 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.

4. 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.

5. Hospitalized (in patient with expected duration ≥ 24 hours)

6. 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.

7. Male subjects must agree to refrain from sperm donation from initial study drug administration until 90 days after the last dose of brequinar.

8. ≤ 10 days since first COVID-19 symptom as determined by treating clinician.

9. Able to swallow capsules.

10. 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.

Exclusion Criteria

1. 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.

2. Active malignancy other than squamous cell carcinoma; anticancer treatment such as chemotherapy or radiation therapy within the past month.

3. Nursing women or women of childbearing potential (WOCBP) with a positive pregnancy test.

4. Treatment with another DHODH inhibitor (e.g., leflunomide or teriflunomide), tacrolimus, sirolimus.

5. Platelets ≤150,000 cell/mm3.

6. Hemoglobin < 10 gm/dL

7. Absolute neutrophil count < 1500 cells/mm3

8. Renal dysfunction, i.e., creatinine clearance < 30 mL/min

9. AST and/or ALT > 1.5 ULN, or total bilirubin > ULN

10. History of bleeding disorders or recent surgery in the six weeks preceding enrollment

11. Concomitant use of agents known to cause bone marrow suppression leading to thrombocytopenia

12. History of gastrointestinal ulcer, or history of gastrointestinal bleeding.

13. History of hepatitis B and/or C infection, active liver disease and/or cirrhosis.

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).

15. Life expectancy of < 5 days in the judgment of the treating clinician.

16. Evidence of critical illness defined by at least one of the following:

a. Respiratory failure requiring at least one of the following: i. Endotracheal intubation and mechanical ventilation, noninvasive positive pressure ventilation, ECMO, or clinical diagnosis of respiratory failure (i.e., clinical need for one of the preceding therapies, but preceding therapies may not be able to be administered in setting of resource limitation) ii. Shock (defined by systolic blood pressure < 90 mm Hg, or diastolic blood pressure < 60 mm Hg or requiring vasopressors) b. Multi-organ dysfunction/failure.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Clear Creek Bio, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Hartford Hospital

Hartford, Connecticut, United States

Baptist Medical Center

Jacksonville, Florida, United States

University of South Florida/Tampa General

Tampa, Florida, United States

University of New Mexico

Albuquerque, New Mexico, United States

Temple University

Philadelphia, Pennsylvania, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

CCB-CRISIS-01

Identifier Type: -

Identifier Source: org_study_id