Trial Outcomes & Findings for CRISIS2: A Phase 2 Study of the Safety and Antiviral Activity of Brequinar in Non-hospitalized Pts With COVID-19 (NCT NCT04575038)
NCT ID: NCT04575038
Last Updated: 2022-04-19
Results Overview
Median Change from Baseline in Quantitative Log10 SARS-CoV-2 viral load at Days 4, 8, 12, 15, 22, and 29.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
115 participants
Primary outcome timeframe
Days 4, 8, 12, 15, 22, and 29
Results posted on
2022-04-19
Participant Flow
Subjects were all confirmed to be positive for COVID-19 by means of either a rapid antigen or RT-PCR test. Subjects were out-patients (not hospitalized) at the time of study entry. The first subject was enrolled on 19-NOV-2020; the last subject completed the study on 29-MAR-2021.
A total of 182 subjects were screened for the study at 14 centers in the US. The Screening period was not more than 7 days in order to provide subjects the earliest possible opportunity for antiviral treatment. The primary screen fail reason was failure to meet one of the laboratory eligibility criteria including low hemoglobin, low platelets, low neutrophil count, and elevated liver function test. Qualifying subjects were enrolled into the study and randomized on the same day.
Participant milestones
| Measure |
Standard of Care + Brequinar 100 mg
Standard of Care + Brequinar oral capsules 100 mg x 5 days
Brequinar: Dihydroorotate dehydrogenase inhibitor (DHODHi)
|
Standard of Care + Placebo
Standard of Care + Placebo for Brequinar oral capsules x 5 days
Placebo: Placebo capsules
|
|---|---|---|
|
Overall Study
STARTED
|
56
|
59
|
|
Overall Study
COMPLETED
|
55
|
58
|
|
Overall Study
NOT COMPLETED
|
1
|
1
|
Reasons for withdrawal
| Measure |
Standard of Care + Brequinar 100 mg
Standard of Care + Brequinar oral capsules 100 mg x 5 days
Brequinar: Dihydroorotate dehydrogenase inhibitor (DHODHi)
|
Standard of Care + Placebo
Standard of Care + Placebo for Brequinar oral capsules x 5 days
Placebo: Placebo capsules
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
1
|
1
|
Baseline Characteristics
CRISIS2: A Phase 2 Study of the Safety and Antiviral Activity of Brequinar in Non-hospitalized Pts With COVID-19
Baseline characteristics by cohort
| Measure |
Standard of Care + Brequinar 100 mg
n=56 Participants
Standard of Care + Brequinar oral capsules 100 mg x 5 days
Brequinar: Dihydroorotate dehydrogenase inhibitor (DHODHi)
|
Standard of Care + Placebo
n=59 Participants
Standard of Care + Placebo for Brequinar oral capsules x 5 days
Placebo: Placebo capsules
|
Total
n=115 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
0 Participants
n=35 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
53 Participants
n=39 Participants
|
52 Participants
n=41 Participants
|
105 Participants
n=35 Participants
|
|
Age, Categorical
>=65 years
|
3 Participants
n=39 Participants
|
7 Participants
n=41 Participants
|
10 Participants
n=35 Participants
|
|
Age, Continuous
|
46.5 years
n=39 Participants
|
45.0 years
n=41 Participants
|
46.0 years
n=35 Participants
|
|
Sex: Female, Male
Female
|
37 Participants
n=39 Participants
|
22 Participants
n=41 Participants
|
59 Participants
n=35 Participants
|
|
Sex: Female, Male
Male
|
19 Participants
n=39 Participants
|
37 Participants
n=41 Participants
|
56 Participants
n=35 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
18 Participants
n=39 Participants
|
18 Participants
n=41 Participants
|
36 Participants
n=35 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
38 Participants
n=39 Participants
|
41 Participants
n=41 Participants
|
79 Participants
n=35 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
0 Participants
n=35 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
0 Participants
n=35 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
0 Participants
n=35 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
1 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
1 Participants
n=35 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=39 Participants
|
12 Participants
n=41 Participants
|
14 Participants
n=35 Participants
|
|
Race (NIH/OMB)
White
|
53 Participants
n=39 Participants
|
45 Participants
n=41 Participants
|
98 Participants
n=35 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
0 Participants
n=35 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=39 Participants
|
2 Participants
n=41 Participants
|
2 Participants
n=35 Participants
|
|
Region of Enrollment
United States
|
56 participants
n=39 Participants
|
59 participants
n=41 Participants
|
115 participants
n=35 Participants
|
|
Detectable Log 10 SARS-CoV-2 Viral Load
Detectable
|
43 Participants
n=39 Participants
|
45 Participants
n=41 Participants
|
88 Participants
n=35 Participants
|
|
Detectable Log 10 SARS-CoV-2 Viral Load
Undetectable
|
7 Participants
n=39 Participants
|
12 Participants
n=41 Participants
|
19 Participants
n=35 Participants
|
|
Detectable Log 10 SARS-CoV-2 Viral Load
Inconclusive
|
0 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
0 Participants
n=35 Participants
|
|
Detectable Log 10 SARS-CoV-2 Viral Load
Missing
|
6 Participants
n=39 Participants
|
2 Participants
n=41 Participants
|
8 Participants
n=35 Participants
|
|
Body Temperature
|
36.7 Degrees Celsius
n=39 Participants
|
36.7 Degrees Celsius
n=41 Participants
|
36.7 Degrees Celsius
n=35 Participants
|
|
SpO2
|
98.0 Percentage of blood oxygen saturation
n=39 Participants
|
97.0 Percentage of blood oxygen saturation
n=41 Participants
|
98.0 Percentage of blood oxygen saturation
n=35 Participants
|
|
Respiratory Rate
|
16.0 Breaths per minute
n=39 Participants
|
16.0 Breaths per minute
n=41 Participants
|
16.0 Breaths per minute
n=35 Participants
|
|
COVID-19 Symptom Type
Cough
|
43 Participants
n=39 Participants
|
44 Participants
n=41 Participants
|
87 Participants
n=35 Participants
|
|
COVID-19 Symptom Type
Headache
|
44 Participants
n=39 Participants
|
40 Participants
n=41 Participants
|
84 Participants
n=35 Participants
|
|
COVID-19 Symptom Type
Malaise
|
44 Participants
n=39 Participants
|
39 Participants
n=41 Participants
|
83 Participants
n=35 Participants
|
|
COVID-19 Symptom Type
Sore Throat
|
28 Participants
n=39 Participants
|
34 Participants
n=41 Participants
|
62 Participants
n=35 Participants
|
|
COVID-19 Symptom Type
Anosmia
|
25 Participants
n=39 Participants
|
28 Participants
n=41 Participants
|
53 Participants
n=35 Participants
|
|
COVID-19 Symptom Type
Muscle Pain
|
23 Participants
n=39 Participants
|
22 Participants
n=41 Participants
|
45 Participants
n=35 Participants
|
|
COVID-19 Symptom Type
Gastrointestinal Symptoms
|
22 Participants
n=39 Participants
|
21 Participants
n=41 Participants
|
43 Participants
n=35 Participants
|
|
COVID-19 Symptom Type
Fever
|
18 Participants
n=39 Participants
|
23 Participants
n=41 Participants
|
41 Participants
n=35 Participants
|
|
COVID-19 Symptom Type
Shortness of Breath
|
19 Participants
n=39 Participants
|
22 Participants
n=41 Participants
|
41 Participants
n=35 Participants
|
|
COVID-19 Symptom Type
Dysgeusia
|
18 Participants
n=39 Participants
|
17 Participants
n=41 Participants
|
35 Participants
n=35 Participants
|
|
COVID-19 Symptom Type
Chills/Rigors
|
17 Participants
n=39 Participants
|
15 Participants
n=41 Participants
|
32 Participants
n=35 Participants
|
|
COVID-19 Symptom Type
Nasal Congestion
|
6 Participants
n=39 Participants
|
10 Participants
n=41 Participants
|
16 Participants
n=35 Participants
|
|
COVID-19 Symptom Type
Dyspnea
|
5 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
5 Participants
n=35 Participants
|
|
COVID-19 Symptom Type
Fatigue
|
5 Participants
n=39 Participants
|
4 Participants
n=41 Participants
|
9 Participants
n=35 Participants
|
|
COVID-19 Symptom Type
Body Aches
|
0 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
0 Participants
n=35 Participants
|
|
COVID-19 Symptom Type
Other
|
12 Participants
n=39 Participants
|
13 Participants
n=41 Participants
|
25 Participants
n=35 Participants
|
|
WHO Ordinal Scale
WHO Score of 0
|
0 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
0 Participants
n=35 Participants
|
|
WHO Ordinal Scale
WHO Score of 1
|
0 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
0 Participants
n=35 Participants
|
|
WHO Ordinal Scale
WHO Score of 2
|
52 Participants
n=39 Participants
|
52 Participants
n=41 Participants
|
104 Participants
n=35 Participants
|
|
WHO Ordinal Scale
WHO Score of 3
|
0 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
0 Participants
n=35 Participants
|
|
WHO Ordinal Scale
Missing
|
4 Participants
n=39 Participants
|
7 Participants
n=41 Participants
|
11 Participants
n=35 Participants
|
PRIMARY outcome
Timeframe: Days 4, 8, 12, 15, 22, and 29Population: 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.
Median Change from Baseline in Quantitative Log10 SARS-CoV-2 viral load at Days 4, 8, 12, 15, 22, and 29.
Outcome measures
| Measure |
Standard of Care + Brequinar 100 mg
n=43 Participants
Standard of Care + Brequinar oral capsules 100 mg x 5 days
Brequinar: Dihydroorotate dehydrogenase inhibitor (DHODHi)
|
Standard of Care + Placebo
n=45 Participants
Standard of Care + Placebo for Brequinar oral capsules x 5 days
Placebo: Placebo capsules
|
|---|---|---|
|
Log10 SARS-CoV-2 Viral Load
Baseline
|
5.056 Log 10 SARS-CoV-2 Viral Load Copies/mL
Interval 3.14 to 7.96
|
5.110 Log 10 SARS-CoV-2 Viral Load Copies/mL
Interval 3.14 to 8.22
|
|
Log10 SARS-CoV-2 Viral Load
Day 4 Change from Baseline
|
-1.651 Log 10 SARS-CoV-2 Viral Load Copies/mL
Interval -7.94 to 0.87
|
-1.881 Log 10 SARS-CoV-2 Viral Load Copies/mL
Interval -7.21 to 0.93
|
|
Log10 SARS-CoV-2 Viral Load
Day 8 Change from Baseline
|
-2.413 Log 10 SARS-CoV-2 Viral Load Copies/mL
Interval -7.94 to 1.85
|
-3.231 Log 10 SARS-CoV-2 Viral Load Copies/mL
Interval -7.78 to 0.12
|
|
Log10 SARS-CoV-2 Viral Load
Day 12 Change from Baseline
|
-3.907 Log 10 SARS-CoV-2 Viral Load Copies/mL
Interval -7.94 to 0.45
|
-3.514 Log 10 SARS-CoV-2 Viral Load Copies/mL
Interval -7.78 to 0.0
|
|
Log10 SARS-CoV-2 Viral Load
Day 15 Change from Baseline
|
-4.140 Log 10 SARS-CoV-2 Viral Load Copies/mL
Interval -7.94 to 0.2
|
-3.143 Log 10 SARS-CoV-2 Viral Load Copies/mL
Interval -7.78 to 1.4
|
|
Log10 SARS-CoV-2 Viral Load
Day 22 Change from Baseline
|
-4.874 Log 10 SARS-CoV-2 Viral Load Copies/mL
Interval -7.94 to 0.26
|
-3.575 Log 10 SARS-CoV-2 Viral Load Copies/mL
Interval -7.78 to -0.31
|
|
Log10 SARS-CoV-2 Viral Load
Day 29 Change from Baseline
|
-4.170 Log 10 SARS-CoV-2 Viral Load Copies/mL
Interval -7.94 to 3.09
|
-3.839 Log 10 SARS-CoV-2 Viral Load Copies/mL
Interval -7.78 to -1.2
|
SECONDARY outcome
Timeframe: Through Day 29Population: The Safety Analysis Set (Safety) consisted of all subjects who received at least one dose of study drug. Safety analysis subjects were analyzed according to their actual treatment received.
Safety measured by number of participants with AEs and SAEs including laboratory assessments.
Outcome measures
| Measure |
Standard of Care + Brequinar 100 mg
n=56 Participants
Standard of Care + Brequinar oral capsules 100 mg x 5 days
Brequinar: Dihydroorotate dehydrogenase inhibitor (DHODHi)
|
Standard of Care + Placebo
n=59 Participants
Standard of Care + Placebo for Brequinar oral capsules x 5 days
Placebo: Placebo capsules
|
|---|---|---|
|
Rates of AEs and SAEs Including Laboratory Assessments
Maximum Grade 4 AE
|
0 Participants
|
0 Participants
|
|
Rates of AEs and SAEs Including Laboratory Assessments
Any AE
|
10 Participants
|
13 Participants
|
|
Rates of AEs and SAEs Including Laboratory Assessments
Maximum Grade 1 AE
|
8 Participants
|
8 Participants
|
|
Rates of AEs and SAEs Including Laboratory Assessments
Maximum Grade 2 AE
|
1 Participants
|
2 Participants
|
|
Rates of AEs and SAEs Including Laboratory Assessments
Maximum Grade 3 AE
|
1 Participants
|
3 Participants
|
|
Rates of AEs and SAEs Including Laboratory Assessments
Maximum Grade 5 AE
|
0 Participants
|
0 Participants
|
|
Rates of AEs and SAEs Including Laboratory Assessments
Study Drug-Related AE
|
3 Participants
|
3 Participants
|
|
Rates of AEs and SAEs Including Laboratory Assessments
AE Leading to Study Drug Discontinuation
|
0 Participants
|
0 Participants
|
|
Rates of AEs and SAEs Including Laboratory Assessments
Severity Grade 3 or Higher Study Drug Related AE
|
0 Participants
|
0 Participants
|
|
Rates of AEs and SAEs Including Laboratory Assessments
SAE
|
1 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Through Day 36Population: 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.
Duration of viral shedding was defined as the time to viral clearance (two consecutive negative test results) for the Microbiology Evaluable Set population.
Outcome measures
| Measure |
Standard of Care + Brequinar 100 mg
n=43 Participants
Standard of Care + Brequinar oral capsules 100 mg x 5 days
Brequinar: Dihydroorotate dehydrogenase inhibitor (DHODHi)
|
Standard of Care + Placebo
n=45 Participants
Standard of Care + Placebo for Brequinar oral capsules x 5 days
Placebo: Placebo capsules
|
|---|---|---|
|
Viral Shedding Duration
|
12.0 Days
Interval 4.0 to 29.0
|
8.0 Days
Interval 4.0 to 36.0
|
SECONDARY outcome
Timeframe: Day 29Population: Intent-to-treat population
Percentage of subjects requiring admission as an inpatient for \>24 hours
Outcome measures
| Measure |
Standard of Care + Brequinar 100 mg
n=56 Participants
Standard of Care + Brequinar oral capsules 100 mg x 5 days
Brequinar: Dihydroorotate dehydrogenase inhibitor (DHODHi)
|
Standard of Care + Placebo
n=59 Participants
Standard of Care + Placebo for Brequinar oral capsules x 5 days
Placebo: Placebo capsules
|
|---|---|---|
|
Hospital Admission
|
1 Participants
|
0 Participants
|
Adverse Events
Standard of Care + Brequinar 100 mg
Serious events: 1 serious events
Other events: 3 other events
Deaths: 0 deaths
Standard of Care + Placebo
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Standard of Care + Brequinar 100 mg
n=56 participants at risk
Standard of Care + Brequinar oral capsules 100 mg x 5 days
Brequinar: Dihydroorotate dehydrogenase inhibitor (DHODHi)
|
Standard of Care + Placebo
n=59 participants at risk
Standard of Care + Placebo for Brequinar oral capsules x 5 days
Placebo: Placebo capsules
|
|---|---|---|
|
Infections and infestations
COVID-19 Pneumonia
|
1.8%
1/56 • Number of events 1 • 29 Days
|
0.00%
0/59 • 29 Days
|
Other adverse events
| Measure |
Standard of Care + Brequinar 100 mg
n=56 participants at risk
Standard of Care + Brequinar oral capsules 100 mg x 5 days
Brequinar: Dihydroorotate dehydrogenase inhibitor (DHODHi)
|
Standard of Care + Placebo
n=59 participants at risk
Standard of Care + Placebo for Brequinar oral capsules x 5 days
Placebo: Placebo capsules
|
|---|---|---|
|
Gastrointestinal disorders
Nausea
|
3.6%
2/56 • Number of events 2 • 29 Days
|
3.4%
2/59 • Number of events 2 • 29 Days
|
|
Skin and subcutaneous tissue disorders
Rash
|
1.8%
1/56 • Number of events 1 • 29 Days
|
3.4%
2/59 • Number of events 2 • 29 Days
|
Additional Information
Barbara Powers, Vice President Clinical Operations
Clear Creek Bio, Inc.
Phone: 16177652252
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place