Covid19
Conditions
Brief summary
This study will evaluate the efficacy of oral Foipan® (camostat mesilate) compared with the current standard of care in reducing the duration of viral shedding of SARS-CoV-2 virus in patients with mild-moderate COVID-19 disease. Patients will attend 4 study visits over a period of up to 28 days.
Interventions
Camostat Mesilate administered as oral tablets
DRUGPlacebo
Placebo to match camostat mesilate
OTHERStandard of Care Treatment
Standard of Care Treatment for COVID-19 Infection
Sponsors
Stanford University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of COVID-19 disease as presence of mild-moderate symptoms without signs of respiratory distress, with FDA-cleared molecular diagnostic assay positive for SARS-CoV-2 within 72 hours prior to informed consent * Males must be sterile, OR agree not to donate semen AND agree to strictly adhere to contraceptive measures during the study and for seven days following the last dose of study medication * Females must be unable to bear children, OR ensure that their male partner is incapable of fathering a child, OR, if of childbearing potential will strictly adhere to contraceptive measures during the study and for seven days following the last dose of study medication * Females must agree to stop breast-feeding prior to first dose of study drug and through seven days after completing therapy * Females must have a negative pregnancy test at screening * Participant agrees to maintain home or other quarantine as recommended by the study physician, except to visit the study site as required by the protocol
Exclusion criteria
* Concomitant bacterial respiratory infection documented by respiratory culture. NOTE: Subjects on empirical antibiotic treatment for possible but unproven bacterial pneumonia, but who are positive for SARS-CoV-2, are allowed in the study. * Previous use of antiviral drugs that may be active against Covid-19. * Abnormal laboratory test results at screening: * Use of adrenocorticosteroids (except topical or inhaled preparations or oral preparations equivalent to or less than 10 mg of oral prednisone) or immunosuppressive or immunomodulatory drugs (e.g., immunosuppressants, anticancer drugs, interleukins, interleukin antagonists or interleukin receptor blockers). NOTE: Treatment of study participants following institutional COVID-19 treatment policies or guidelines, including the use of immunomodulatory medications, is permitted. This excludes treatment with agents that have the potential for direct antiviral activity, including convalescent plasma and NO, and co-enrollment into other clinical studies that evaluate investigational agents for COVID-19. * Serious chronic disease (e.g., human immunodeficiency virus \[HIV\], cancer requiring chemotherapy within the preceding 6 months, and/or moderate or severe hepatic insufficiency). * Previously received camostat mesilate within the past 30 days. * Advanced kidney disease * Advanced liver disease * History of alcohol or drug abuse in the previous 6 months. * Psychiatric illness that is not well controlled (defined as stable on a regimen for more than one year). * Taken another investigational drug within the past 30 days. * Seemed by the Investigator to be ineligible for any reason.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve (AUC) of Shedding of SARS-CoV-2 Virus | Days 1-10 | AUC of shedding of SARS-CoV-2 virus calculated using the reverse transcription-polymerase chain reaction (RT-PCR) measures of viral load from self-collected nasal swabs on days 1-10. AUC was defined by a single participant's cycle threshold (Ct) from nasal swabs collected and calculated by the trapezoidal rule, using exact times of collection of each swab. Ct denotes how many PCR cycles are required before the SARS-CoV-2 viral RNA reached a detectable level. Higher Ct values correspond to lower viral copy numbers. For reference, Ct values of 20 correspond to \ 2.12 x 106 viral copies per milliliter, while a Ct value of 40 is undetectable and is considered the lower limit of detection of this RT-PCR test for SARS-CoV-2. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time Until Cessation of Shedding of SARS-CoV-2 Virus | Up to 28 days | This outcome is defined as the time in days from randomization to the first negative RT-PCR result of self-collected nasal swabs that is followed by only negative results (i.e. no later positive results are observed). |
| Clinical Worsening of COVID-19 Disease in Symptomatic Patients | Up to 28 days | Number of symptomatic patients with clinical worsening, defined as the development of respiratory distress or symptoms that require hospitalization. |
| AUC of Shedding of SARS-CoV-2 Virus | Days 1-10, 14, 21, and 28 | AUC of shedding of SARS-CoV-2 virus calculated using the RT-PCR measures of viral load from self-collected nasal swabs on days 1-10, 14, 21, and 28. AUC was defined by a single participant's Ct from nasal swabs collected and calculated by the trapezoidal rule, using exact times of collection of each swab. Ct denotes how many PCR cycles are required before the SARS-CoV-2 viral RNA reached a detectable level. Higher Ct values correspond to lower viral copy numbers. For reference, Ct values of 20 correspond to \ 2.12 x 106 viral copies per milliliter, while a Ct value of 40 is undetectable and is considered the lower limit of detection of this RT-PCR test for SARS-CoV-2. |
| Development of Antibodies to SARS-CoV-2 | Up to 28 days | Number of patients that develop antibodies to SARS-CoV-2. |
| Drug Level on Day Five, One Hour After a Dose Taken on an Empty Stomach | Day 5, 1 hour post dose | — |
| Time Until Resolution of Symptoms | Up to 28 days | This outcome is defined as absence of moderate or severe symptoms for at least 24 hours for those reporting moderate or severe symptoms at baseline. |
Countries
United States
Participant flow
Recruitment details
After 49 participants were enrolled, this trial was subsumed into a pragmatic platform trial (the COVID-19 Outpatient Pragmatic Platform Study (COPPS) - Camostat Sub-Protocol (NCT04662073). Additional subjects subsequently consented for camostat in the platform study. Their results are not included here.
Participants by arm
| Arm | Count |
|---|---|
| Camostat Mesilate Camostat mesilate for 10 days in addition to standard of care treatment. | 25 |
| Placebo Placebo to match camostat mesilate for 10 days in addition to standard of care treatment. | 24 |
| Total | 49 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 2 |
Baseline characteristics
| Characteristic | Camostat Mesilate | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 37.88 years STANDARD_DEVIATION 13.47 | 39.18 years STANDARD_DEVIATION 13.79 | 40.54 years STANDARD_DEVIATION 14.27 |
| Alanine Aminotransferase | 25.00 units/L | 29.00 units/L | 34.50 units/L |
| Anterior nares RT-PCR Ct | 19.40 cycles | 20.87 cycles | 21.58 cycles |
| Aspartate Aminotransferase | 25.00 units/L | 27.00 units/L | 30.00 units/L |
| Body Mass Index | 27.81 kg/m^2 | 27.81 kg/m^2 | 28.00 kg/m^2 |
| Creatinine | 0.87 mg/dL | 0.87 mg/dL | 0.86 mg/dL |
| Duration of Symptoms | 5.00 days | 5.00 days | 4.50 days |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 15 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 18 Participants | 31 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Number of Symptoms | 6 symptoms | 6 symptoms | 6 symptoms |
| Race/Ethnicity, Customized American Indian/Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 5 Participants | 9 Participants | 4 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized More than one race | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 2 Participants | 8 Participants | 6 Participants |
| Race/Ethnicity, Customized Unknown | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 12 Participants | 19 Participants | 7 Participants |
| Region of Enrollment United States | 25 Participants | 49 Participants | 24 Participants |
| Sex: Female, Male Female | 10 Participants | 17 Participants | 7 Participants |
| Sex: Female, Male Male | 15 Participants | 32 Participants | 17 Participants |
| Uric acid | 5.10 mg/dL | 5.10 mg/dL | 5.00 mg/dL |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 25 | 0 / 24 |
| other Total, other adverse events | 2 / 25 | 10 / 24 |
| serious Total, serious adverse events | 0 / 25 | 3 / 24 |
Outcome results
Primary
Area Under the Curve (AUC) of Shedding of SARS-CoV-2 Virus
AUC of shedding of SARS-CoV-2 virus calculated using the reverse transcription-polymerase chain reaction (RT-PCR) measures of viral load from self-collected nasal swabs on days 1-10. AUC was defined by a single participant's cycle threshold (Ct) from nasal swabs collected and calculated by the trapezoidal rule, using exact times of collection of each swab. Ct denotes how many PCR cycles are required before the SARS-CoV-2 viral RNA reached a detectable level. Higher Ct values correspond to lower viral copy numbers. For reference, Ct values of 20 correspond to \ 2.12 x 106 viral copies per milliliter, while a Ct value of 40 is undetectable and is considered the lower limit of detection of this RT-PCR test for SARS-CoV-2.
Time frame: Days 1-10
Population: Patients with nasal swab data are included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Camostat Mesilate | Area Under the Curve (AUC) of Shedding of SARS-CoV-2 Virus | 95.3 cycles*days |
| Placebo | Area Under the Curve (AUC) of Shedding of SARS-CoV-2 Virus | 93 cycles*days |
p-value: 0.8995% CI: [-8.14, 9.32]Regression, Linear
Secondary
AUC of Shedding of SARS-CoV-2 Virus
AUC of shedding of SARS-CoV-2 virus calculated using the RT-PCR measures of viral load from self-collected nasal swabs on days 1-10, 14, 21, and 28. AUC was defined by a single participant's Ct from nasal swabs collected and calculated by the trapezoidal rule, using exact times of collection of each swab. Ct denotes how many PCR cycles are required before the SARS-CoV-2 viral RNA reached a detectable level. Higher Ct values correspond to lower viral copy numbers. For reference, Ct values of 20 correspond to \ 2.12 x 106 viral copies per milliliter, while a Ct value of 40 is undetectable and is considered the lower limit of detection of this RT-PCR test for SARS-CoV-2.
Time frame: Days 1-10, 14, 21, and 28
Population: Patients with nasal swab data are included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Camostat Mesilate | AUC of Shedding of SARS-CoV-2 Virus | 116 cycles*days |
| Placebo | AUC of Shedding of SARS-CoV-2 Virus | 124 cycles*days |
p-value: 0.0295% CI: [2.98, 34.83]Regression, Linear
Secondary
Clinical Worsening of COVID-19 Disease in Symptomatic Patients
Number of symptomatic patients with clinical worsening, defined as the development of respiratory distress or symptoms that require hospitalization.
Time frame: Up to 28 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Camostat Mesilate | Clinical Worsening of COVID-19 Disease in Symptomatic Patients | 2 Participants |
| Placebo | Clinical Worsening of COVID-19 Disease in Symptomatic Patients | 0 Participants |
p-value: 0.49Fisher Exact
Secondary
Development of Antibodies to SARS-CoV-2
Number of patients that develop antibodies to SARS-CoV-2.
Time frame: Up to 28 days
Population: Data were not collected for this outcome measure.
Secondary
Drug Level on Day Five, One Hour After a Dose Taken on an Empty Stomach
Time frame: Day 5, 1 hour post dose
Population: Data were not collected for this outcome measure.
Secondary
Time Until Cessation of Shedding of SARS-CoV-2 Virus
This outcome is defined as the time in days from randomization to the first negative RT-PCR result of self-collected nasal swabs that is followed by only negative results (i.e. no later positive results are observed).
Time frame: Up to 28 days
Population: Patients with nasal swab data are included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Camostat Mesilate | Time Until Cessation of Shedding of SARS-CoV-2 Virus | 14 days |
| Placebo | Time Until Cessation of Shedding of SARS-CoV-2 Virus | 21 days |
p-value: 0.2495% CI: [0.7, 4.1]Cox proportional hazards model
Secondary
Time Until Resolution of Symptoms
This outcome is defined as absence of moderate or severe symptoms for at least 24 hours for those reporting moderate or severe symptoms at baseline.
Time frame: Up to 28 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Camostat Mesilate | Time Until Resolution of Symptoms | 11 days |
| Placebo | Time Until Resolution of Symptoms | 12 days |
p-value: 0.2495% CI: [0.32, 1.33]Cox proportional hazards model