COVID-19 InfectionPhase 2CRISIS2NCT04575038

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

A Phase 2 study testing Brequinar in people with COVID-19 Infection, run by Clear Creek Bio, Inc. at 14 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: COVID-19 Infection
What is being tested?: Brequinar
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 115 participants
Where: 14 sitesUnited States
Study dates: 19 Nov 2020to 28 Apr 2021
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Willing and able to provide informed consent for the trial, written, electronic, verbal or other method deemed acceptable by the institution and IRB.
18 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.

Who cannot join

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

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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).

Trial locations and contacts

14 sites in 1 country.

City, postcode or hospital

14 sites in 1 country

United States14 sites

Remington-Davis, Inc.
Columbus, Ohio, 43215
Doral Medical Research
Doral, Florida, 33166
Clinical Trials Center of Middle Tennessee
Franklin, Tennessee, 37067
VitaLink - Gaffney
Gaffney, South Carolina, 29615
Self Regional Healthcare Research Center - Self Medical Group
Greenwood, South Carolina, 29646
Central Alabama Research
Homewood, Alabama, 35209
Ark Clinical Research
Long Beach, California, 90806
Centex Studies, Inc. - McAllen
McAllen, Texas, 78504
Monroe Biomedical Research
Monroe, North Carolina, 28112
Synexus Clinical Research US, Inc. - Olympus Family Medicine
Salt Lake City, Utah, 84117
South Jersey Infectious Disease
Somers Point, New Jersey, 08244
VitaLink Research
Spartanburg, South Carolina, 29303
Toledo Institute of Clinical Research
Toledo, Ohio, 43617
Wilmington Health
Wilmington, North Carolina, 28401

Other trials in United States

About this study

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

Read the 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.

Conditions: COVID-19 Infection
Being tested: Brequinar, Placebo
Medical subject headings: COVID-19

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

BrequinarDrug
Dihydroorotate dehydrogenase inhibitor (DHODHi)
PlaceboDrug
Placebo capsules

Study groups in NCT04575038
Study group	Role	What they receive
Brequinar 100 mg	Experimental	Brequinar oral capsules 100 mg x 5 days Receives: Drug: Brequinar
Placebo	Placebo comparator	Placebo for Brequinar capsules x 5 days Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: Days 4, 8, 12, 15, 22, and 29

Secondary outcomes (3)

Rates of AEs and SAEs Including Laboratory Assessments
Safety measured by number of participants with AEs and SAEs including laboratory assessments.
Measured: Through Day 29
Viral Shedding Duration
Duration of viral shedding was defined as the time to viral clearance (two consecutive negative test results) for the Microbiology Evaluable Set population.
Measured: Through Day 36
Hospital Admission
Percentage of subjects requiring admission as an inpatient for >24 hours
Measured: Day 29

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

19 Nov 202028 Apr 2021

First posted5 Oct 2020
Study start19 Nov 2020
Primary completion28 Apr 2021
Study completion28 Apr 2021

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for COVID-19 InfectionStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Model description: Randomized 1:1 brequinar 100 mg or placebo
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 115 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04575038
Sponsor's protocol ID: CCB-CRISIS-02
Acronym: CRISIS2
Status last verified: Apr 2022
First submitted: 1 Oct 2020
Last updated: 19 Apr 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 19 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT04575038
Acronym / sponsor ID: CRISIS2 / CCB-CRISIS-02
Conditions: COVID-19 Infection
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 115 participants (actual)
Lead sponsor: Clear Creek Bio, Inc.Industry (pharma, biotech, devices)
Study start: 19 Nov 2020 (actual)
Primary completion: 28 Apr 2021 (actual)
Study completion: 28 Apr 2021 (actual)
First posted: 5 Oct 2020 (actual)
Results: Posted 19 Apr 2022

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2
Model description: Randomized 1:1 brequinar 100 mg or placebo

Arm	Type	Receives
Brequinar 100 mg	Experimental	Drug: BrequinarBrequinar oral capsules 100 mg x 5 days
Placebo	Placebo comparator	Drug: PlaceboPlacebo for Brequinar capsules x 5 days

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (8 listed)

Willing and able to provide informed consent for the trial, written, electronic, verbal or other method deemed acceptable by the institution and IRB.
18 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.

Key exclusion criteria (12 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
BrequinarDihydroorotate dehydrogenase inhibitor (DHODHi)	Drug	Brequinar 100 mg
PlaceboPlacebo capsules	Drug	Placebo

Primary outcome

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

3 secondary outcomes

Rates of AEs and SAEs Including Laboratory Assessments
Time frame: Through Day 29
Viral Shedding Duration
Time frame: Through Day 36
Hospital Admission
Time frame: Day 29

Results and safety

Results posted to the registry on 19 Apr 2022, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Standard of Care + Brequinar 100 mg	56	55
Standard of Care + Placebo	59	58

Primary outcome: Log10 SARS-CoV-2 Viral Load

Time frame: Days 4, 8, 12, 15, 22, and 29. Median (Full Range). Unit: Log 10 SARS-CoV-2 Viral Load Copies/mL

Measure	Standard of Care + Brequinar 100 mg n = 43	Standard of Care + Placebo n = 45
Baseline	5.056 (3.14 to 7.96)	5.110 (3.14 to 8.22)
Day 4 Change from Baseline	-1.651 (-7.94 to 0.87)	-1.881 (-7.21 to 0.93)
Day 8 Change from Baseline	-2.413 (-7.94 to 1.85)	-3.231 (-7.78 to 0.12)
Day 12 Change from Baseline	-3.907 (-7.94 to 0.45)	-3.514 (-7.78 to 0.00)
Day 15 Change from Baseline	-4.140 (-7.94 to 0.20)	-3.143 (-7.78 to 1.40)
Day 22 Change from Baseline	-4.874 (-7.94 to 0.26)	-3.575 (-7.78 to -0.31)
Day 29 Change from Baseline	-4.170 (-7.94 to 3.09)	-3.839 (-7.78 to -1.20)

Population analysed: Microbiology Evaluable Set (MES) consisted of all randomized subjects with detectable Log10 SARS-CoV-2 viral load at baseline and at least one non-missing postbaseline viral load assessment. Microbiology evaluable subjects were analyzed according to their randomized treatment. SARS-CoV-2 viral load (log 10 copies/mL) was reported as below. * Number of copies/mL; * \<Number of copies/mL, if detected but under the lower limit of quantification (LLOQ); * No SARS-CoV-2 detected, if not detected.

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: 29 Days. Other adverse events reported at 2% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Standard of Care + Brequinar 100 mg	1 of 56 (1.8%)	3 of 56 (5.4%)	0 of 56
Standard of Care + Placebo	0 of 59 (0%)	4 of 59 (6.8%)	0 of 59

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 19 Apr 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

14 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Brequinar in people with COVID-19 Infection, run by Clear Creek Bio, Inc. at 14 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 14 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Apr 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Log10 SARS-CoV-2 Viral Load (time frame: Days 4, 8, 12, 15, 22, and 29). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04575038.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Apr 2022.