COVID-19Phase 1/2CRISISNCT04425252

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

A Phase 1/2 study testing Brequinar in people with COVID-19, run by Clear Creek Bio, Inc. at 5 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

Who is it for?: Ages 18 years and older
Conditions the study is for: COVID-19
What is being tested?: Brequinar
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 25 participants
Where: 5 sitesUnited States
Study dates: 19 Aug 2020to 12 Jan 2021
Phase: Phase 1/2
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.
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.

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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.

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.
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

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

Trial locations and contacts

5 sites in 1 country.

City, postcode or hospital

5 sites in 1 country

United States5 sites

University of New Mexico
Albuquerque, New Mexico, 87106
Hartford Hospital
Hartford, Connecticut, 06102
Baptist Medical Center
Jacksonville, Florida, 32207
Temple University
Philadelphia, Pennsylvania, 19140
University of South Florida/Tampa General
Tampa, Florida, 33606

Other trials in United States

About this study

Official title: The CRISIS Study: A Randomized Open-label Study Assessing the Safety and Anti-coronavirus Response of Suppression of Host Nucleotide Synthesis in Hospitalized Adults With Coronavirus-19 (COVID-19)

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.

Read the 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
Being tested: Brequinar, Standard of Care
Keywords: DHODH inhibition, antiviral, coronavirus, SARS-CoV-2
Medical subject headings: COVID-19, Coronavirus Infections

What participants receive

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

BrequinarDrug
Also called Standard of Care + Brequinar
DHODH inhibitor, 100 mg daily x 5 days
Standard of CareOther
Standard of Care per institutional guidelines for COVID-19 patients

Study groups in NCT04425252
Study group	Role	What they receive
Standard of Care	Other	Subjects are hospitalized for COVID-19 and will receive all supportive/interventional care per institutional guidelines. Receives: Other: Standard of Care
Brequinar	Experimental	Subjects will receive standard of care plus brequinar 100 mg daily (Study Days 1-5). Receives: Drug: Brequinar

What is being measured

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

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.
Measured: 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).
Measured: Through Day 15
Safety/Tolerability Measured by Mortality at Day 29
Safety/tolerability as measured by mortality at Day 29
Measured: Through Day 29

Secondary outcomes (3)

Hospitalization Status
All participants were hospitalized at time of study entry. This outcome measures participant hospitalization status at Days 3, 5, 7, and 15 in terms of: hospitalized in intensive care unit (ICU), hospitalized as part of initial admission, re-hospitalized (had been discharged from initial hospitalization and was re-admitted to the hospital) or was dead at the time of the assessment.
Measured: Days 3, 5, 7, and 15
Duration of Hospitalization
Duration in number of days from admission to discharge; days counted as an integer only.
Measured: Through Day 15
NEWS2 Score
Measure Description: National Early Warning Score (NEWS) 2. Composite score of respiratory rate, oxygen saturation, systolic blood pressure, pulse, consciousness, and temperature. The NEWS2 provides a score of illness severity based on respiratory rate, SpO2, whether the patient is breathing room air or on oxygen, systolic blood pressure, heart rate, consciousness, and body temperature. The scale ranges from 20 (worst/sickest) to 0 (all measurements in a normal range). The NEWS2 was assessed at baseline, Days 3, 5, 7, and 15.
Measured: Baseline, Days 3, 5, 7, and 15.

Timeline

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

19 Aug 202012 Jan 2021

First posted11 Jun 2020
Study start19 Aug 2020
Primary completion29 Dec 2020
Study completion12 Jan 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-19Studies 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 1/2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Model description: Randomized 1:2 to standard of care (SOC) alone or SOC + brequinar
Masking: None (open label)
Enrolment: 25 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04425252
Sponsor's protocol ID: CCB-CRISIS-01
Acronym: CRISIS
Status last verified: Feb 2022
First submitted: 9 Jun 2020
Last updated: 17 Feb 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: 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?

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Study at a glance

From the registry record, last updated by the sponsor on 17 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: The CRISIS Study: A Randomized Open-label Study Assessing the Safety and Anti-coronavirus Response of Suppression of Host Nucleotide Synthesis in Hospitalized Adults With Coronavirus-19 (COVID-19)
ClinicalTrials.gov ID: NCT04425252
Acronym / sponsor ID: CRISIS / CCB-CRISIS-01
Conditions: COVID-19
Keywords: DHODH inhibition, antiviral, coronavirus, SARS-CoV-2
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 25 participants (actual)
Lead sponsor: Clear Creek Bio, Inc.Industry (pharma, biotech, devices)
Study start: 19 Aug 2020 (actual)
Primary completion: 29 Dec 2020 (actual)
Study completion: 12 Jan 2021 (actual)
First posted: 11 Jun 2020 (actual)
Results: Posted 16 Feb 2022

Clinical summary

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

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.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2
Model description: Randomized 1:2 to standard of care (SOC) alone or SOC + brequinar

Arm	Type	Receives
Standard of Care	Other	Other: Standard of CareSubjects are hospitalized for COVID-19 and will receive all supportive/interventional care per institutional guidelines.
Brequinar	Experimental	Drug: BrequinarSubjects will receive standard of care plus brequinar 100 mg daily (Study Days 1-5).

Who may qualify

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

Key inclusion criteria (10 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.
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)

Key exclusion criteria (17 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.
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.

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
BrequinarAlso: Standard of Care + BrequinarDHODH inhibitor, 100 mg daily x 5 days	Drug	Brequinar
Standard of CareStandard of Care per institutional guidelines for COVID-19 patients	Other	Standard of Care

Primary outcome

Safety/Tolerability Assessed by Rates of Grade 3 or 4 Post Randomization Adverse Events
Time frame: Through Day 15.
Safety/tolerability as assessed by number of participants with Grade 3 or 4 post randomization adverse events.
Safety/Tolerability as Assessed by Rates of Serious Adverse Events (SAEs).
Time frame: Through Day 15
Safety/tolerability as assessed by number of participants with Serious Adverse Events (SAEs).
Safety/Tolerability Measured by Mortality at Day 29
Time frame: Through Day 29
Safety/tolerability as measured by mortality at Day 29

3 secondary outcomes

Hospitalization Status
Time frame: Days 3, 5, 7, and 15
Duration of Hospitalization
Time frame: Through Day 15
NEWS2 Score
Time frame: Baseline, Days 3, 5, 7, and 15.

Results and safety

Results posted to the registry on 16 Feb 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	8	4
Standard of Care + Brequinar	15	13

Primary outcome: Safety/Tolerability Assessed by Rates of Grade 3 or 4 Post Randomization Adverse Events

Time frame: Through Day 15.. Count of participants. Unit: Participants

Measure	Standard of Care n = 8	Standard of Care + Brequinar n = 15
Value	1	1

Population analysed: All subjects in the Modified Intent-to-Treat Population included those with at least one post randomization assessment.

Primary outcome: Safety/Tolerability as Assessed by Rates of Serious Adverse Events (SAEs).

Time frame: Through Day 15. Count of participants. Unit: Participants

Measure	Standard of Care n = 8	Standard of Care + Brequinar n = 15
Value	1	3

Population analysed: Modified intent-to-treat population included all subjects with at least one post randomization assessment.

Primary outcome: Safety/Tolerability Measured by Mortality at Day 29

Time frame: Through Day 29. Count of participants. Unit: Participants

Measure	Standard of Care n = 8	Standard of Care + Brequinar n = 15
Value	0	0

Population analysed: Modified intent-to-treat population included all participants with at least one post-randomization assessment.

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: 29 days. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Standard of Care	1 of 8 (12.5%)	0 of 8 (0%)	0 of 8
Standard of Care + Brequinar	3 of 15 (20%)	3 of 15 (20%)	0 of 15

Limitations and caveats (from the sponsor): 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.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 17 Feb 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

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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.

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

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Brequinar in people with COVID-19, run by Clear Creek Bio, Inc. at 5 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 10 inclusion and 17 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 17 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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 16 Feb 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?

Safety/Tolerability Assessed by Rates of Grade 3 or 4 Post Randomization Adverse Events (time frame: Through Day 15.). The study lists 3 primary outcomes in all. 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 NCT04425252.

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 17 Feb 2022.