Severe Acute Respiratory Syndrome
Conditions
Brief summary
To determine if the reduction in TMPRSS2 activity via direct inhibition with Camostat mesilate combined with standard of care (SOC) treatment will increase the proportion of patients alive and free from respiratory failure at Day 28 in SARS-CoV-2 as compared to SOC treatment with placebo.
Interventions
Given PO
OTHERStandard of Care
At Investigator discretion
Sponsors
Alan Bryce
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Laboratory confirmed SARS-CoV-2 infection * Admitted to hospital for management of SARS-CoV-2 * Age ≥18 * Subject or legal representative able to give informed consent * Ability to take all study drugs * Respiratory status of 3 or greater on the WHO ordinal scale * ALT or AST ≤5 x ULN * Creatinine clearance ≥50 mL/min using the Cockroft-Gault formula * Willingness to provide mandatory specimens for correlative research and banking
Exclusion criteria
* Women who are pregnant or breastfeeding * Known hypersensitivity to the study drug, the metabolites or formulation excipient
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Patients Alive and Free From Respiratory Failure | 28 Days | To determine if the reduction in TMPRSS2 activity via direct inhibition with Camostat mesilate combined with standard of care (SOC) treatment will change the proportion of patients alive and free from respiratory failure at Day 28 in SARS-CoV-2 as compared to SOC treatment with placebo. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Patients Alive and Free of Ventilator Use or ECMO | 28 Days | To determine if reduction in TMPRSS2 activity via direct inhibition with Camostat mesilate combined with SOC treatment will change the proportion of patients alive and free of ventilator use or ECMO at Day 28 as compared to SOC treatment combined with placebo. |
| Mortality Rate | 28 Days | To determine if the combination of Camostat mesilate combined with SOC treatment will result in a changed mortality rate at 28 days as compared to SOC treatment combined with placebo. |
| Clinical Change | 28 Days | Clinical change will be defined as a 2 or more point decease on the WHO ordinal scale. The WHO ordinal scale ranges from 0, the best status, to 8, death. Time to clinical improvement will be calculated as the number of days from study entry until the earliest date of clinical change. |
| Adverse Event Grade 3 Plus Rate | 28 days | Analyses for safety will include all participants who are randomized and received at least 1 dose of study treatment. Participants will be grouped according to the treatment to which they were randomized. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Standard of Care will be defined by the investigators in collaboration with the sponsor on the basis of the best available evidence at the time of study initiation with placebo. | 50 |
| Camostat Patient will receive SOC tablets and Camostat mesilate 200 mg four times a day after each meal with Standard of Care treatment. | 50 |
| Total | 100 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 4 | 6 |
Baseline characteristics
| Characteristic | Camostat | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 57.1 years STANDARD_DEVIATION 18.4 | 57.7 years STANDARD_DEVIATION 17 | 58.3 years STANDARD_DEVIATION 15.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 9 Participants | 15 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 39 Participants | 80 Participants | 41 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 5 Participants | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 5 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 5 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 6 Participants | 3 Participants |
| Race (NIH/OMB) White | 41 Participants | 81 Participants | 40 Participants |
| Sex: Female, Male Female | 18 Participants | 34 Participants | 16 Participants |
| Sex: Female, Male Male | 32 Participants | 66 Participants | 34 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 4 / 50 | 3 / 50 |
| other Total, other adverse events | 16 / 50 | 21 / 50 |
| serious Total, serious adverse events | 4 / 50 | 2 / 50 |
Outcome results
Primary
Proportion of Patients Alive and Free From Respiratory Failure
To determine if the reduction in TMPRSS2 activity via direct inhibition with Camostat mesilate combined with standard of care (SOC) treatment will change the proportion of patients alive and free from respiratory failure at Day 28 in SARS-CoV-2 as compared to SOC treatment with placebo.
Time frame: 28 Days
Population: All patients that submitted day 28 outcome data
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Proportion of Patients Alive and Free From Respiratory Failure | .891 Proportion of patients |
| Camostat | Proportion of Patients Alive and Free From Respiratory Failure | .884 Proportion of patients |
Secondary
Adverse Event Grade 3 Plus Rate
Analyses for safety will include all participants who are randomized and received at least 1 dose of study treatment. Participants will be grouped according to the treatment to which they were randomized.
Time frame: 28 days
Population: All treated patients that were evaluated for adverse events.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Adverse Event Grade 3 Plus Rate | .17 proportion of participants |
| Camostat | Adverse Event Grade 3 Plus Rate | .20 proportion of participants |
Secondary
Clinical Change
Clinical change will be defined as a 2 or more point decease on the WHO ordinal scale. The WHO ordinal scale ranges from 0, the best status, to 8, death. Time to clinical improvement will be calculated as the number of days from study entry until the earliest date of clinical change.
Time frame: 28 Days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Clinical Change | 4 Days |
| Camostat | Clinical Change | 4 Days |
Secondary
Mortality Rate
To determine if the combination of Camostat mesilate combined with SOC treatment will result in a changed mortality rate at 28 days as compared to SOC treatment combined with placebo.
Time frame: 28 Days
Population: All patients that submitted day 28 outcome data
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Mortality Rate | .061 proportion of participants |
| Camostat | Mortality Rate | .070 proportion of participants |
Secondary
Proportion of Patients Alive and Free of Ventilator Use or ECMO
To determine if reduction in TMPRSS2 activity via direct inhibition with Camostat mesilate combined with SOC treatment will change the proportion of patients alive and free of ventilator use or ECMO at Day 28 as compared to SOC treatment combined with placebo.
Time frame: 28 Days
Population: All patients that submitted day 28 outcome data
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Proportion of Patients Alive and Free of Ventilator Use or ECMO | .891 Proportion of patients |
| Camostat | Proportion of Patients Alive and Free of Ventilator Use or ECMO | .883 Proportion of patients |