Trial Outcomes & Findings for Safety and Anti-coronavirus Response of Suppression of Host Nucleotide Synthesis in Patients With COVID-19 (NCT NCT04425252)

NCT ID: NCT04425252

Last Updated: 2022-02-17

Results Overview

Safety/tolerability as assessed by number of participants with Grade 3 or 4 post randomization adverse events.

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 25 participants
• Primary outcome timeframe: Through Day 15.
• Results posted on: 2022-02-17

Participant Flow

First Patient Enrolled: 19 AUG 2020 Last Patient Completed the study: 12 JAN 2021 Patients were hospitalized with COVID-19 and were recruited at the hospital where they were being treated as in-patients.

All subjects were hospitalized as in-patients as part of the inclusion criteria. 25 patients were enrolled, but 2 withdrew consent prior to treatment and had no post-randomization assessments for a total of 23 subjects randomized in the study and included in the modified intent-to-treat population.

Participant milestones

Measure	Standard of Care Subjects were hospitalized for COVID-19 and received standard of care per institutional guidelines for COVID-19 patients.	Standard of Care + Brequinar Subjects were hospitalized for COVID-19 and received standard of care per institutional guidelines for COVID-19 patients plus brequinar 100 mg daily x 5 days.
Overall Study STARTED	8	15
Overall Study COMPLETED	4	13
Overall Study NOT COMPLETED	4	2

Reasons for withdrawal

Measure	Standard of Care Subjects were hospitalized for COVID-19 and received standard of care per institutional guidelines for COVID-19 patients.	Standard of Care + Brequinar Subjects were hospitalized for COVID-19 and received standard of care per institutional guidelines for COVID-19 patients plus brequinar 100 mg daily x 5 days.
Overall Study Withdrawal by Subject	2	1
Overall Study Lost to Follow-up	1	0
Overall Study Subject did not return due to COVID-19 restrictions.	1	1

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Standard of Care n=8 Participants Subjects were hospitalized with COVID-19 and received institutional standard of care for COVID-19.	Standard of Care + Brequinar n=15 Participants Subjects were hospitalized with COVID-19 and received institutional standard of care for COVID-19 plus brequinar 100 mg daily x 5 days.	Total n=23 Participants Total of all reporting groups
Age, Continuous	51.38 years STANDARD_DEVIATION 16.02 • n=5 Participants	55.59 years STANDARD_DEVIATION 14.78 • n=7 Participants	54.24 years STANDARD_DEVIATION 15.63 • n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	7 Participants n=7 Participants	11 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	8 Participants n=7 Participants	12 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) White	7 Participants n=5 Participants	8 Participants n=7 Participants	15 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	4 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	8 participants n=5 Participants	15 participants n=7 Participants	23 participants n=5 Participants

PRIMARY outcome

Timeframe: Through Day 15.

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

Safety/tolerability as assessed by number of participants with Grade 3 or 4 post randomization adverse events.

Outcome measures

Measure	Standard of Care n=8 Participants Subjects were hospitalized for COVID-19 and received standard of care per institutional guidelines for COVID-19 patients.	Standard of Care + Brequinar n=15 Participants Subjects were hospitalized for COVID-19 and received standard of care per institutional guidelines for COVID-19 patients plus brequinar 100 mg daily x 5 days.
Safety/Tolerability Assessed by Rates of Grade 3 or 4 Post Randomization Adverse Events	1 Participants	1 Participants

PRIMARY outcome

Timeframe: Through Day 15

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

Safety/tolerability as assessed by number of participants with Serious Adverse Events (SAEs).

Outcome measures

Measure	Standard of Care n=8 Participants Subjects were hospitalized for COVID-19 and received standard of care per institutional guidelines for COVID-19 patients.	Standard of Care + Brequinar n=15 Participants Subjects were hospitalized for COVID-19 and received standard of care per institutional guidelines for COVID-19 patients plus brequinar 100 mg daily x 5 days.
Safety/Tolerability as Assessed by Rates of Serious Adverse Events (SAEs).	1 Participants	3 Participants

PRIMARY outcome

Timeframe: Through Day 29

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

Safety/tolerability as measured by mortality at Day 29

Outcome measures

Measure	Standard of Care n=8 Participants Subjects were hospitalized for COVID-19 and received standard of care per institutional guidelines for COVID-19 patients.	Standard of Care + Brequinar n=15 Participants Subjects were hospitalized for COVID-19 and received standard of care per institutional guidelines for COVID-19 patients plus brequinar 100 mg daily x 5 days.
Safety/Tolerability Measured by Mortality at Day 29	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Days 3, 5, 7, and 15

Population: Modified intent-to-treat population which includes all participants with at least one post-randomization study assessment.

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.

Outcome measures

Measure	Standard of Care n=8 Participants Subjects were hospitalized for COVID-19 and received standard of care per institutional guidelines for COVID-19 patients.	Standard of Care + Brequinar n=15 Participants Subjects were hospitalized for COVID-19 and received standard of care per institutional guidelines for COVID-19 patients plus brequinar 100 mg daily x 5 days.
Hospitalization Status Day 7 Hospitalized	1 Participants	0 Participants
Hospitalization Status Day 3 Died	0 Participants	0 Participants
Hospitalization Status Day 3 Discharged	5 Participants	3 Participants
Hospitalization Status Day 5 Died	0 Participants	0 Participants
Hospitalization Status Day 7 Discharged	7 Participants	15 Participants
Hospitalization Status Day 15 Died	0 Participants	0 Participants
Hospitalization Status Day 15 Hospitalized in ICU	0 Participants	0 Participants
Hospitalization Status Day 15 Hospitalized	1 Participants	1 Participants
Hospitalization Status Day 15 Discharged	6 Participants	14 Participants
Hospitalization Status Day 15 Missing	1 Participants	0 Participants
Hospitalization Status Day 3 Hospitalized in ICU	0 Participants	3 Participants
Hospitalization Status Day 3 Hospitalized	3 Participants	9 Participants
Hospitalization Status Day 5 Hospitalized in ICU	0 Participants	1 Participants
Hospitalization Status Day 5 Hospitalized	3 Participants	4 Participants
Hospitalization Status Day 5 Discharged	5 Participants	10 Participants
Hospitalization Status Day 7 Died	0 Participants	0 Participants
Hospitalization Status Day 7 Hospitalized in ICU	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Through Day 15

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

Duration in number of days from admission to discharge; days counted as an integer only.

Outcome measures

Measure	Standard of Care n=8 Participants Subjects were hospitalized for COVID-19 and received standard of care per institutional guidelines for COVID-19 patients.	Standard of Care + Brequinar n=15 Participants Subjects were hospitalized for COVID-19 and received standard of care per institutional guidelines for COVID-19 patients plus brequinar 100 mg daily x 5 days.
Duration of Hospitalization	2 days Interval 1.5 to 4.0	4 days Interval 3.0 to 5.0

SECONDARY outcome

Timeframe: Baseline, Days 3, 5, 7, and 15.

Population: Participants with at least one post randomization assessment who were able to return to the clinic for a study visit. Multiple subjects were unable to return for scheduled study assessments at various time points due to COVID-19 restrictions in place at the institutions where the study was conducted.

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.

Outcome measures

Measure	Standard of Care n=8 Participants Subjects were hospitalized for COVID-19 and received standard of care per institutional guidelines for COVID-19 patients.	Standard of Care + Brequinar n=13 Participants Subjects were hospitalized for COVID-19 and received standard of care per institutional guidelines for COVID-19 patients plus brequinar 100 mg daily x 5 days.
NEWS2 Score Day 7	3.3 units on a scale Standard Error 1.03	3.8 units on a scale Standard Error 1.75
NEWS2 Score Day 15	0.00 units on a scale Standard Error 0.00	2.6 units on a scale Standard Error 0.97
NEWS2 Score Baseline (Day 1 pre dose)	1.9 units on a scale Standard Error 0.69	3.9 units on a scale Standard Error 0.80
NEWS2 Score Day 3	3.0 units on a scale Standard Error 1.15	2.8 units on a scale Standard Error 0.47
NEWS2 Score Day 5	2.5 units on a scale Standard Error 1.55	3.8 units on a scale Standard Error 1.07

Adverse Events

Standard of Care

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Standard of Care + Brequinar

Serious events: 3 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Measure	Standard of Care n=8 participants at risk Subjects were hospitalized with COVID-19 and received institutional standard of care for COVID-19.	Standard of Care + Brequinar n=15 participants at risk Subjects were hospitalized with COVID-19 and received institutional standard of care for COVID-19 plus brequinar 100 mg daily x 5 days.
Cardiac disorders Angina pectoris	0.00% 0/8 • 29 days Events that occurred prior to informed consent were entered as medical history; AEs that occurred after informed consent were entered on the AE form. Subjects were questioned and observed for evidence of AEs, whether or not judged by the Investigator or designated person to be related to study drug.	6.7% 1/15 • Number of events 1 • 29 days Events that occurred prior to informed consent were entered as medical history; AEs that occurred after informed consent were entered on the AE form. Subjects were questioned and observed for evidence of AEs, whether or not judged by the Investigator or designated person to be related to study drug.
Cardiac disorders Atrial fibrillation	12.5% 1/8 • Number of events 1 • 29 days Events that occurred prior to informed consent were entered as medical history; AEs that occurred after informed consent were entered on the AE form. Subjects were questioned and observed for evidence of AEs, whether or not judged by the Investigator or designated person to be related to study drug.	0.00% 0/15 • 29 days Events that occurred prior to informed consent were entered as medical history; AEs that occurred after informed consent were entered on the AE form. Subjects were questioned and observed for evidence of AEs, whether or not judged by the Investigator or designated person to be related to study drug.
Infections and infestations COVID-19 pneumonia	0.00% 0/8 • 29 days Events that occurred prior to informed consent were entered as medical history; AEs that occurred after informed consent were entered on the AE form. Subjects were questioned and observed for evidence of AEs, whether or not judged by the Investigator or designated person to be related to study drug.	6.7% 1/15 • Number of events 1 • 29 days Events that occurred prior to informed consent were entered as medical history; AEs that occurred after informed consent were entered on the AE form. Subjects were questioned and observed for evidence of AEs, whether or not judged by the Investigator or designated person to be related to study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/8 • 29 days Events that occurred prior to informed consent were entered as medical history; AEs that occurred after informed consent were entered on the AE form. Subjects were questioned and observed for evidence of AEs, whether or not judged by the Investigator or designated person to be related to study drug.	6.7% 1/15 • Number of events 1 • 29 days Events that occurred prior to informed consent were entered as medical history; AEs that occurred after informed consent were entered on the AE form. Subjects were questioned and observed for evidence of AEs, whether or not judged by the Investigator or designated person to be related to study drug.
Injury, poisoning and procedural complications Fall	12.5% 1/8 • Number of events 1 • 29 days Events that occurred prior to informed consent were entered as medical history; AEs that occurred after informed consent were entered on the AE form. Subjects were questioned and observed for evidence of AEs, whether or not judged by the Investigator or designated person to be related to study drug.	0.00% 0/15 • 29 days Events that occurred prior to informed consent were entered as medical history; AEs that occurred after informed consent were entered on the AE form. Subjects were questioned and observed for evidence of AEs, whether or not judged by the Investigator or designated person to be related to study drug.
Vascular disorders Orthostatic hypotension	12.5% 1/8 • Number of events 1 • 29 days Events that occurred prior to informed consent were entered as medical history; AEs that occurred after informed consent were entered on the AE form. Subjects were questioned and observed for evidence of AEs, whether or not judged by the Investigator or designated person to be related to study drug.	0.00% 0/15 • 29 days Events that occurred prior to informed consent were entered as medical history; AEs that occurred after informed consent were entered on the AE form. Subjects were questioned and observed for evidence of AEs, whether or not judged by the Investigator or designated person to be related to study drug.

Other adverse events

Measure	Standard of Care n=8 participants at risk Subjects were hospitalized with COVID-19 and received institutional standard of care for COVID-19.	Standard of Care + Brequinar n=15 participants at risk Subjects were hospitalized with COVID-19 and received institutional standard of care for COVID-19 plus brequinar 100 mg daily x 5 days.
Endocrine disorders Hyperglycemia	0.00% 0/8 • 29 days Events that occurred prior to informed consent were entered as medical history; AEs that occurred after informed consent were entered on the AE form. Subjects were questioned and observed for evidence of AEs, whether or not judged by the Investigator or designated person to be related to study drug.	20.0% 3/15 • Number of events 3 • 29 days Events that occurred prior to informed consent were entered as medical history; AEs that occurred after informed consent were entered on the AE form. Subjects were questioned and observed for evidence of AEs, whether or not judged by the Investigator or designated person to be related to study drug.
Investigations Alanine aminotransferase increased	0.00% 0/8 • 29 days Events that occurred prior to informed consent were entered as medical history; AEs that occurred after informed consent were entered on the AE form. Subjects were questioned and observed for evidence of AEs, whether or not judged by the Investigator or designated person to be related to study drug.	13.3% 2/15 • Number of events 2 • 29 days Events that occurred prior to informed consent were entered as medical history; AEs that occurred after informed consent were entered on the AE form. Subjects were questioned and observed for evidence of AEs, whether or not judged by the Investigator or designated person to be related to study drug.

Additional Information

Vice President Clinical Operations

Clear Creek Bio, Inc.

Phone: (617) 765-2252

Email: clinical@clearcreekbio.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place