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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04575038
Recruitment Status : Recruiting
First Posted : October 5, 2020
Last Update Posted : January 19, 2021
Sponsor:
Information provided by (Responsible Party):
Clear Creek Bio, Inc.

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.

Condition or disease Intervention/treatment Phase
COVID-19 Infection Drug: Brequinar Drug: Placebo Phase 2

Detailed Description:

Brequinar is a potent DHODH inhibitor that has been previously studied in more than 1,000 cancer, psoriasis, and organ transplant patients. Brequinar has been found to have potent in vitro antiviral activity against many RNA viruses including SARS-CoV-2. The antiviral activity of brequinar against SARS-CoV-2 is likely due to DHODH inhibition and shows nanomolar potency and a high selectivity index in inhibiting viral replication in in vitro studies.

The CRISIS2 trial will study out-patients (non-hospitalized patients) who have a positive SARS-CoV-2 test and are symptomatic. Subjects will be randomized to receive standard of care (SOC) + 5 days of brequinar or SOC + 5 days of placebo. The purpose of this study is to determine if the in vitro antiviral activity of brequinar can be duplicated in patients infected with SARS-CoV-2 by measuring the effect of brequinar on viral shedding. Importantly, the safety and tolerability of brequinar will also be determined in these patients. The results of this proof-of-concept study will inform future studies that will help determine if brequinar is a safe and effective drug for the treatment of SARS-CoV-2 infection.

This will be a phase II randomized, placebo-controlled, double blind, multi-center study with approximately 100 subjects. All subjects will receive standard of care (SOC) per institutional guidelines for treatment of patients with COVID-19 infection. In addition to SOC, the subjects will self-administer one capsule once daily for 5 days.

Subjects will have a Screening Visit followed as soon as possible with Study Day 1. Study visits (virtual or in person) will take place at Screening and on specified days. The visits that include bloodwork must be conducted at the study site or arrangements made for sample collection at the subject's home or other appropriate location. Other visits/visit activities for that visit may be conducted remotely using telemedicine or other remote technique. Subjects are to self-collect a viral load sample, obtain their respiratory rate, heart rate, body temperature and SpO2, and complete a symptom assessment checklist on specified days.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Randomized 1:1 brequinar 100 mg or placebo
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Double blind
Primary Purpose: Treatment
Official Title: The CRISIS2 Study: A Phase 2, Randomized, Double Blind, Placebo-controlled, Multi-center Study Assessing the Safety and Anti-coronavirus Response of Suppression of Host Nucleotide Synthesis in Out-patient Adults With SARS-CoV-2
Actual Study Start Date : November 19, 2020
Estimated Primary Completion Date : February 28, 2021
Estimated Study Completion Date : February 28, 2021

Arm Intervention/treatment
Experimental: Brequinar 100 mg
Brequinar oral capsules 100 mg x 5 days
Drug: Brequinar
Dihydroorotate dehydrogenase inhibitor (DHODHi)

Placebo Comparator: Placebo
Placebo for Brequinar capsules x 5 days
Drug: Placebo
Placebo capsules




Primary Outcome Measures :
  1. SARS-CoV-2 viral load [ Time Frame: Day 29 ]
    Quantitative SARS-CoV-2 viral load


Secondary Outcome Measures :
  1. Rates of AEs and SAEs including laboratory assessments [ Time Frame: Day 29 ]
    Safety measured by rates of AEs and SAEs including laboratory assessments

  2. Viral shedding duration [ Time Frame: Day 29 ]
    Duration of viral shedding

  3. Hospital Admission [ Time Frame: Day 29 ]
    Percentage of subjects requiring admission as an inpatient for >24 hours



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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. 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.
  4. 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)
  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. 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.
  8. Able to swallow capsules.

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. Nursing women or women of childbearing potential (WOCBP) with a positive pregnancy test
  3. Treatment with another DHODH inhibitor (e.g., leflunomide, teriflunomide) or other agents known to cause bone marrow suppression leading to thrombocytopenia
  4. Platelets ≤150,000 cell/mm3
  5. Hemoglobin < 10 gm/dL
  6. Absolute neutrophil count < 1500 cells/mm3
  7. Renal dysfunction, i.e., creatinine clearance < 30 mL/min
  8. AST or ALT > 2 x ULN, or total bilirubin > ULN. Gilbert's Syndrome is allowed.
  9. Bleeding disorders or blood loss requiring transfusion in the six weeks preceding enrollment
  10. Ongoing gastrointestinal ulcer, or gastrointestinal bleeding within 6 weeks of randomization.
  11. Chronic hepatitis B infection, active hepatitis C infection, active liver disease and/or cirrhosis per subject report.
  12. 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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04575038


Contacts
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Contact: Barbara L Powers, PhD (617) 765-2252 clinical@clearcreekbio.com

Locations
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United States, Alabama
Central Alabama Research Recruiting
Homewood, Alabama, United States, 35209
Contact: Barry McLean, PD, Ph.D.    205-949-1906    bmclean@centralalabamaresearch.com   
United States, California
Ark Clinical Research Recruiting
Long Beach, California, United States, 90806
Contact: Akanksha Nanda, MD    562-997-1000    info@arkclinicalresearch.com   
United States, Florida
Doral Medical Research Recruiting
Doral, Florida, United States, 33166
Contact: Antonio Nava    305-821-6112    andoralmedresearch@gmail.com   
United States, Georgia
IACT Health Recruiting
Columbus, Georgia, United States, 31904
United States, New Jersey
South Jersey Infectious Disease Recruiting
Somers Point, New Jersey, United States, 08244
Contact: Christopher Lucasti, DO, FACOI    609-927-6662    infect123@aol.com   
United States, North Carolina
Monroe Biomedical Research Recruiting
Monroe, North Carolina, United States, 28112
Contact: Suvi Gross    704-283-7359    suvi.gross@monroeresearch.com   
Wilmington Health Recruiting
Wilmington, North Carolina, United States, 28401
Contact: Joy Jurnak, RN, CCRC    910-815-3680    jjurnack@wilmingtonhealth.com   
United States, Ohio
Remington-Davis, Inc. Recruiting
Columbus, Ohio, United States, 43215
Contact: Study Team    614-487-2560    info@remdavis.com   
Toledo Institute of Clinical Research Recruiting
Toledo, Ohio, United States, 43617
Contact: Rabia Gilani, PhD    419-843-8815    rabia.gilani@ohmiallergy.com   
United States, South Carolina
VitaLink - Gaffney Recruiting
Gaffney, South Carolina, United States, 29615
Contact: David R Erb, MD, FCCP    864-488-1283    derb.md@vitalinkresearch.com   
Self Regional Healthcare Research Center - Self Medical Group Recruiting
Greenwood, South Carolina, United States, 29646
Contact: Heather Rich    864-943-2416    Heather.Rich@selfregional.org   
VitaLink Research Recruiting
Spartanburg, South Carolina, United States, 29303
Contact: Gregory Feldman, MD    864-515-0092    gfeldman.md@vitalinkresearch.com   
United States, Tennessee
Clinical Trials Center of Middle Tennessee Recruiting
Franklin, Tennessee, United States, 37067
Contact: Alex J Slandzicki, MD    615-205-8350    jslandzicki@ctcmidtn.com   
United States, Texas
Centex Studies, Inc. - McAllen Recruiting
McAllen, Texas, United States, 78504
Contact: Joel Solis, MD    956-540-7170    jsolis@centexstudies.com   
United States, Utah
Synexus Clinical Research US, Inc. - Olympus Family Medicine Recruiting
Salt Lake City, Utah, United States, 84117
Contact: David Garcia    385-367-6166    davidgarcia@cctresearch.com   
Sponsors and Collaborators
Clear Creek Bio, Inc.
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Responsible Party: Clear Creek Bio, Inc.
ClinicalTrials.gov Identifier: NCT04575038    
Other Study ID Numbers: CCB-CRISIS-02
First Posted: October 5, 2020    Key Record Dates
Last Update Posted: January 19, 2021
Last Verified: January 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Brequinar
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs