Camostat Mesylate in COVID-19 Outpatients

• Sponsor: Yale University (Other)
• Overall Status: Completed
• CT.gov ID: NCT04353284
• Collaborator: (none)
• Enrollment: 70
• Location: 1
• Arms: 2
• Actual Duration (Months): 10.4
• Patients Per Site Per Month: 6.7

Study Details

Study Description

Brief Summary

The rationale of the present clinical trial is that an orally available drug given to outpatients that could reduce the viral burden in the upper respiratory tract could forestall complications of SARS-CoV-2 infection and reduce transmission from one infected individual to another.

Condition or Disease	Intervention/Treatment	Phase
COVID-19	Drug: Camostat Mesilate; Other: Placebo	Phase 2

Detailed Description

The study is designed as a double-blind randomized controlled clinical trial to test the hypothesis that camostat mesylate, a serine protease inhibitor shown to inhibit SARS-COV-2 replication in vitro, inhibits SARS-COV-2 replication in early stage, laboratory-confirmed, COVID-19 ambulatory patients.

Camostat mesylate, a serine protease inhibitor used primarily for treating postoperative reflux esophagitis and for acute exacerbations of chronic pancreatitis. This drug, with more than 15 years clinical experience in Japan with a very safe clinical track record, will be studied as a repurposed drug based on published in vitro virus inhibition data and in vivo protective effects in a mouse model of SARS.

The primary objective of this study is to determine whether camostat mesylate reduces SARS-COV-2 viral load in early COVID-19 disease.

Study Design

• Study Type: Interventional
• Actual Enrollment: 70 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: The Effect of Camostat Mesylate on COVID-19 Infection in Ambulatory Patients: An Investigator-Initiated Randomized, Placebo-Controlled, Phase IIa Trial
• Actual Study Start Date: Jun 9, 2020
• Actual Primary Completion Date: Mar 3, 2021
• Actual Study Completion Date: Apr 22, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Camostat mesylate Camostat mesylate 200mg taken 7 days.	Drug: Camostat Mesilate; Camostat mesilate 200mg taken orally, 4 times daily, for 7 days.; Other Names: Fiopan, Camostat Mesylate
Placebo Comparator: Placebo Placebo taken for 7 days.	Other: Placebo; Placebo taken orally, 4 times daily, for 7 days.

Outcome Measures

Primary Outcome Measures

1. Change in SARS-COV-2 Viral Load [5 days (day 0 to day 4)]

   To determine whether camostat mesylate reduces SARS-COV-2 viral load (N Gene) in early COVID-19 disease, change from day 0 to day 4 in respiratory (oropharyngeal swab RT-PCR) log10 viral load will be assessed.

Secondary Outcome Measures

1. Change in SARS-COV-2 Viral Load [3 days (day 0 to day 2)]

   To determine whether camostat mesylate reduces SARS-COV-2 viral load (N Gene) in early COVID-19 disease, change from day 0 to day 2 in respiratory (oropharyngeal swab RT-PCR) log10 viral load will be assessed.

2. Change in SARS-COV-2 Viral Load [7 days (day 0 to day 6)]

   To determine whether camostat mesylate reduces SARS-COV-2 viral load (N Gene) in early COVID-19 disease, change from day 0 to day 6 in respiratory (oropharyngeal swab RT-PCR) log10 viral load will be assessed.

3. Number of Participants With Change in Positive COVID-19 Status [7 days]

   Change in risk for a positive COVID-19 test at day 6 after enrollment (day 0) will be assessed by analyzing the proportion of positive cases in each study arm.

4. Number of Participants With Change in Positive COVID-19 Status [14 days]

   Change in risk for a positive COVID-19 test at day 13 after enrollment (day 0) will be assessed by analyzing the proportion of positive cases in each study arm.

5. Change in Positive COVID-19 Status [28 days]

   Number of Participants With Change in Positive COVID-19 Status

6. Change in COVID-19 Symptom Severity [Day 0 to Day 6]

   Change of COVID-19 symptom severity from day 0 to day 6 will be assessed with the COVID-19 daily self score tool. Adapted from the FLU-PRO instrument, it consists of 39 items that are answered daily. Items 1-33 are Likert scale questions (rated 0-4) where 0 = not at all and 4 = very much. These items are summed to score the severity of symptoms- where a total score of 132 would indicate the greatest severity of symptoms and a score of 0 would indicate no severity of symptoms. Items 34-38 are also Likert scale questions (rated 0-4) that measure the frequency of specific daily symptoms where 0 = 0 times and 4 = 4 times or more. These items are summed to score the frequency of symptoms- where the highest score for the frequency of symptoms (20) indicates the greatest burden of symptom frequency. The last question (39) asks patients for their highest temperature in Fahrenheit.

7. Change in COVID-19 Symptom Severity [Day 0 to Day 13]

   Change of COVID-19 symptom severity from day 0 to day 14 will be assessed with the COVID-19 daily self score tool. Adapted from the FLU-PRO instrument, it consists of 39 items that are answered daily. Items 1-33 are Likert scale questions (rated 0-4) where 0 = not at all and 4 = very much. These items are summed to score the severity of symptoms- where a total score of 132 would indicate the greatest severity of symptoms and a score of 0 would indicate no severity of symptoms. Items 34-38 are also Likert scale questions (rated 0-4) that measure the frequency of specific daily symptoms where 0 = 0 times and 4 = 4 times or more. These items are summed to score the frequency of symptoms- where the highest score for the frequency of symptoms (20) indicates the greatest burden of symptom frequency. The last question (39) asks patients for their highest temperature in Fahrenheit.

8. Change in COVID-19 Symptom Frequency [Day 0 to Day 6]

   Change of COVID-19 symptom frequency score from day 0 to day 6 will be assessed with the COVID-19 daily self score tool. Adapted from the FLU-PRO instrument, it consists of 39 items that are answered daily. Items 34-38 measure the frequency of specific daily symptoms and are also Likert scale questions (rated 0-4) that measure the frequency of specific daily symptoms where 0 = 0 times and 4 = 4 times or more. These items are summed to score the frequency of symptoms- where the highest score (20) indicates the greatest burden of symptom frequency, the lowest possible score (0) indicates no frequency of symptoms.

9. Change in COVID-19 Symptom Frequency [Day 0 to Day 13]

   Change of COVID-19 symptom frequency score from day 0 to day 6 will be assessed with the COVID-19 daily self score tool. Adapted from the FLU-PRO instrument, it consists of 39 items that are answered daily. Items 34-38 measure the frequency of specific daily symptoms and are also Likert scale questions (rated 0-4) that measure the frequency of specific daily symptoms where 0 = 0 times and 4 = 4 times or more. These items are summed to score the frequency of symptoms- where the highest score (20) indicates the greatest burden of symptom frequency, the lowest possible score (0) indicates no frequency of symptoms.

10. Change in Body Temperature [7 days (Day 0 to Day 6)]

    Change of COVID-19 symptom score from baseline to day 6 will be assessed with the COVID-19 daily self score tool. Adapted from the FLU-PRO instrument, it consists of 39 items that are answered daily. Items 1-33 are Likert scale questions (rated 0-4) where 0 = not at all and 4 = very much. These items are summed to score the severity of symptoms- where a total score of 132 would indicate the greatest severity of symptoms and a score of 0 would indicate no severity of symptoms. Items 34-38 are also Likert scale questions (rated 0-4) that measure the frequency of specific daily symptoms where 0 = 0 times and 4 = 4 times or more. These items are summed to score the frequency of symptoms- where the highest score for the frequency of symptoms (20) indicates the greatest burden of symptom frequency. The last question (39) asks patients for their highest temperature in Fahrenheit.

11. Change in Body Temperature [28 days]

    Change of COVID-19 symptom score from baseline to 28 days will be assessed with the COVID-19 daily self score tool. Adapted from the FLU-PRO instrument, it consists of 39 items that are answered daily. Items 1-33 are Likert scale questions (rated 0-4) where 0 = not at all and 4 = very much. These items are summed to score the severity of symptoms- where a total score of 132 would indicate the greatest severity of symptoms and a score of 0 would indicate no severity of symptoms. Items 34-38 are also Likert scale questions (rated 0-4) that measure the frequency of specific daily symptoms where 0 = 0 times and 4 = 4 times or more. These items are summed to score the frequency of symptoms- where the highest score for the frequency of symptoms (20) indicates the greatest burden of symptom frequency. The last question (39) asks patients for their highest temperature in Fahrenheit.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Be enrolled within 3 days of being notified of their first positive COVID-19 test result.

• Evidence of a recent active COVID-19 infection, as evidenced by the positive test results being associated with at least one COVID-19-compatible symptom such as fever, upper respiratory symptoms, cough, chills, loss of taste/smell, etc.(see COVID-19-PRO symptom score sheet), or a recent high-risk exposure to COVID-19

• Provision of informed consent.

• Stated willingness to comply with all study procedures and availability for the duration of the study.

• Diagnosed with COVID-19 within past 3 days and not exhibiting manifestations requiring hospitalization such as extreme shortness of breath or severe prostration. Nurses at the study site will assess such severe conditions requiring hospitalization, which would preclude enrollment.

• Ability to take oral medication and be willing to adhere to the camostat mesylate regimen.

• For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation and for an additional 4 weeks after the end of the camostat mesylate administration.

• For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner.

• Agreement to adhere to Lifestyle Considerations (see section 5.3) throughout study duration.

• English and Spanish speaking subjects as well as patients speaking any language for which we can find appropriate translators will be enrolled. A short form with interpretation will be used for anyone speaking a language for which a translated informed consent form is not currently available in accordance with local site IRB policies, including developing certified translations as necessary.

Exclusion Criteria:

• Presence of COVID-19 disease manifestations that would require referral for consideration of hospitalization.

• A previous positive COVID-19 test reported more than 7 days before, which would indicate likelihood of non-culturable, nonreplicating virus.

• A positive COVID-19 test without a known recent exposure that would indicate an active infection, hence an unknown chance of non-culturable, non-replicating virus being present (i.e., asymptomatic COVID-19 infection of unknown duration).

• Pregnancy or lactation.

• Known allergic reactions to components of camostat mesylate.

• With regard to inclusion or exclusion of women of child-bearing potential, women who report that they know they are pregnant are excluded. All women of child-bearing potential who test positive for pregnancy by urine test at first visit are excluded. A day 14 followup blood pregnancy test will be done on appropriate enrolled women (i.e. those who had a negative urine pregnancy test on day 0 for further safety assessment ).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Yale University	New Haven	Connecticut	United States	06511

Sponsors and Collaborators

• Yale University

Investigators

• Principal Investigator: Geoffrey Chupp, M.D., Director, Yale Center for Asthma and Airways Disease (YCAAD)
• Principal Investigator: Joseph Vinetz, M.D., Professor, Section of Infectious Diseases: Department of Internal Medicine

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Aug 18, 2020

More Information

Publications

None provided.

• Responsible Party: Yale University
• ClinicalTrials.gov Identifier: NCT04353284
• Other Study ID Numbers: 2000027971
• First Posted: Apr 20, 2020
• Last Update Posted: Mar 24, 2022
• Last Verified: Mar 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Additional relevant MeSH terms: COVID-19; Gabexate; Camostat

Study Results

Participant Flow

Arm/Group Title	Camostat Mesylate	Placebo
Arm/Group Description	Camostat mesylate 200mg taken 7 days. Camostat Mesilate: Camostat mesilate 200mg taken orally, 4 times daily, for 7 days.	Placebo taken for 7 days. Placebo: Placebo taken orally, 4 times daily, for 7 days.
Period Title: Overall Study
STARTED	35	35
COMPLETED	33	34
NOT COMPLETED	2	1

Baseline Characteristics

Arm/Group Title	Camostat Mesylate	Placebo	Total
Arm/Group Description	Camostat mesylate 200mg taken 7 days. Camostat Mesilate: Camostat mesilate 200mg taken orally, 4 times daily, for 7 days.	Placebo taken for 7 days. Placebo: Placebo taken orally, 4 times daily, for 7 days.	Total of all reporting groups
Overall Participants	35	35	70
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	44.1 (14.6)	44.1 (12.0)	44.1 (13.3)
Sex: Female, Male (Count of Participants)
Female	13 37.1%	15 42.9%	28 40%
Male	22 62.9%	20 57.1%	42 60%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	4 11.4%	3 8.6%	7 10%
Not Hispanic or Latino	30 85.7%	32 91.4%	62 88.6%
Unknown or Not Reported	1 2.9%	0 0%	1 1.4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	1 2.9%	0 0%	1 1.4%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 2.9%	4 11.4%	5 7.1%
White	28 80%	29 82.9%	57 81.4%
More than one race	2 5.7%	2 5.7%	4 5.7%
Unknown or Not Reported	3 8.6%	0 0%	3 4.3%
Region of Enrollment (participants) [Number]
United States	35 100%	35 100%	70 100%

Outcome Measures

1. Primary Outcome

Title	Change in SARS-COV-2 Viral Load
Description	To determine whether camostat mesylate reduces SARS-COV-2 viral load (N Gene) in early COVID-19 disease, change from day 0 to day 4 in respiratory (oropharyngeal swab RT-PCR) log10 viral load will be assessed.
Time Frame	5 days (day 0 to day 4)

Outcome Measure Data

Analysis Population Description

Intention to treat, baseline is pooled across treatment arms in the mixed models analysis as Day 0/Baseline data were collected prior to treatment.

Arm/Group Title	Camostat Mesylate	Placebo
Arm/Group Description	Camostat mesylate 200mg taken 7 days. Camostat Mesilate: Camostat mesilate 200mg taken orally, 4 times daily, for 7 days.	Placebo taken for 7 days. Placebo: Placebo taken orally, 4 times daily, for 7 days.
Measure Participants	35	35
Day 0	6.5	6.5
Day 4	4.4	3.7
Change (Day 4 - Day 0)	-2.0	-2.8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Camostat Mesylate, Placebo
	Comments	This analysis compares the change from baseline between treatment arms.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.06
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.74
	Confidence Interval	(2-Sided) 95%; -0.03 to 1.51
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Change in SARS-COV-2 Viral Load
Description	To determine whether camostat mesylate reduces SARS-COV-2 viral load (N Gene) in early COVID-19 disease, change from day 0 to day 2 in respiratory (oropharyngeal swab RT-PCR) log10 viral load will be assessed.
Time Frame	3 days (day 0 to day 2)

Outcome Measure Data

Analysis Population Description

Intention to treat, baseline is pooled across treatment arms in the mixed models analysis as Day 0/Baseline data were collected prior to treatment.

Arm/Group Title	Camostat Mesylate	Placebo
Arm/Group Description	Camostat mesylate 200mg taken 7 days. Camostat Mesilate: Camostat mesilate 200mg taken orally, 4 times daily, for 7 days.	Placebo taken for 7 days. Placebo: Placebo taken orally, 4 times daily, for 7 days.
Measure Participants	35	35
Least Squares Mean (95% Confidence Interval) [log10 copies/mL]	-1.2	-1.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Camostat Mesylate, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.87
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.06
	Confidence Interval	(2-Sided) 95%; -0.70 to 0.83
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Change in SARS-COV-2 Viral Load
Description	To determine whether camostat mesylate reduces SARS-COV-2 viral load (N Gene) in early COVID-19 disease, change from day 0 to day 6 in respiratory (oropharyngeal swab RT-PCR) log10 viral load will be assessed.
Time Frame	7 days (day 0 to day 6)

Outcome Measure Data

Analysis Population Description

Intention to treat, baseline is pooled across treatment arms in the mixed models analysis as Day 0/Baseline data were collected prior to treatment.

Arm/Group Title	Camostat Mesylate	Placebo
Arm/Group Description	Camostat mesylate 200mg taken 7 days. Camostat Mesilate: Camostat mesilate 200mg taken orally, 4 times daily, for 7 days.	Placebo taken for 7 days. Placebo: Placebo taken orally, 4 times daily, for 7 days.
Measure Participants	35	35
Least Squares Mean (95% Confidence Interval) [log10 copies/mL]	-3.6	-3.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Camostat Mesylate, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.69
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.23
	Confidence Interval	(2-Sided) 95%; -0.94 to 1.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Number of Participants With Change in Positive COVID-19 Status
Description	Change in risk for a positive COVID-19 test at day 6 after enrollment (day 0) will be assessed by analyzing the proportion of positive cases in each study arm.
Time Frame	7 days

Outcome Measure Data

Analysis Population Description

Intention to treat analysis using all participants with data at 7 days, 14 days and 28 days. The model excluded those with baseline data only (1 Camostat, 1 Placebo). Participants with valid data are presented at 7 days.

Arm/Group Title	Camostat Mesylate	Placebo
Arm/Group Description	Camostat mesylate 200mg taken 7 days. Camostat Mesilate: Camostat mesilate 200mg taken orally, 4 times daily, for 7 days.	Placebo taken for 7 days. Placebo: Placebo taken orally, 4 times daily, for 7 days.
Measure Participants	34	34
Positive	17 48.6%	18 51.4%
Negative	5 14.3%	7 20%
Positive	14 40%	21 60%
Negative	8 22.9%	4 11.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Camostat Mesylate, Placebo
	Comments	Nasopharyngeal Swab Samples analyzed.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.71
	Comments
	Method	GEE
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.30
	Confidence Interval	(2-Sided) 95%; 0.33 to 5.09
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Camostat Mesylate, Placebo
	Comments	Saliva RT-PCR samples analyzed.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.17
	Comments
	Method	GEE
	Comments	Within subject correlation is controlled by specifying a compound symmetry R-side structure in the model.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.40
	Confidence Interval	(2-Sided) 95%; 0.11 to 1.47
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Number of Participants With Change in Positive COVID-19 Status
Description	Change in risk for a positive COVID-19 test at day 13 after enrollment (day 0) will be assessed by analyzing the proportion of positive cases in each study arm.
Time Frame	14 days

Outcome Measure Data

Analysis Population Description

Intention to treat analysis using all participants with data at 7 days, 14 days and 28 days. The model excluded those with baseline data only (1 Camostat, 1 Placebo). Participants with valid data are presented at 14 days.

Arm/Group Title	Camostat Mesylate	Placebo
Arm/Group Description	Camostat mesylate 200mg taken 7 days. Camostat Mesilate: Camostat mesilate 200mg taken orally, 4 times daily, for 7 days.	Placebo taken for 7 days. Placebo: Placebo taken orally, 4 times daily, for 7 days.
Measure Participants	34	34
Positive	21 60%	12 34.3%
Negative	12 34.3%	21 60%
Positive	16 45.7%	14 40%
Negative	17 48.6%	18 51.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Camostat Mesylate, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.03
	Comments
	Method	GEE
	Comments	Within subject correlation is controlled by specifying a compound symmetry R-side structure in the model.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	3.05
	Confidence Interval	(2-Sided) 95%; 1.12 to 8.26
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Camostat Mesylate, Placebo
	Comments	Saliva RT-PCR samples analyzed.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.68
	Comments
	Method	GEE
	Comments	Within subject correlation is controlled by specifying a compound symmetry R-side structure in the model.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.23
	Confidence Interval	(2-Sided) 95%; 0.47 to 3.23
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Change in Positive COVID-19 Status
Description	Number of Participants With Change in Positive COVID-19 Status
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

Intention to treat analysis using all participants with data at 7 days, 14 days and 28 days. The model excluded those with baseline data only (1 Camostat, 1 Placebo). Participants with valid data are presented at 28 days.

Arm/Group Title	Camostat Mesylate	Placebo
Arm/Group Description	Camostat mesylate 200mg taken 7 days. Camostat Mesilate: Camostat mesilate 200mg taken orally, 4 times daily, for 7 days.	Placebo taken for 7 days. Placebo: Placebo taken orally, 4 times daily, for 7 days.
Measure Participants	34	34
Positive	5 14.3%	1 2.9%
Negative	27 77.1%	33 94.3%
Positive	5 14.3%	6 17.1%
Negative	27 77.1%	28 80%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Camostat Mesylate, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.10
	Comments
	Method	GEE
	Comments	Within subject correlation is controlled by specifying a compound symmetry R-side structure in the model.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	6.28
	Confidence Interval	(2-Sided) 95%; 0.70 to 56.60
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Camostat Mesylate, Placebo
	Comments	Saliva RT-PCR samples analyzed.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.87
	Comments
	Method	GEE
	Comments	Within subject correlation is controlled by specifying a compound symmetry R-side structure in the model.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.90
	Confidence Interval	(2-Sided) 95%; 0.25 to 3.23
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Change in COVID-19 Symptom Severity
Description	Change of COVID-19 symptom severity from day 0 to day 6 will be assessed with the COVID-19 daily self score tool. Adapted from the FLU-PRO instrument, it consists of 39 items that are answered daily. Items 1-33 are Likert scale questions (rated 0-4) where 0 = not at all and 4 = very much. These items are summed to score the severity of symptoms- where a total score of 132 would indicate the greatest severity of symptoms and a score of 0 would indicate no severity of symptoms. Items 34-38 are also Likert scale questions (rated 0-4) that measure the frequency of specific daily symptoms where 0 = 0 times and 4 = 4 times or more. These items are summed to score the frequency of symptoms- where the highest score for the frequency of symptoms (20) indicates the greatest burden of symptom frequency. The last question (39) asks patients for their highest temperature in Fahrenheit.
Time Frame	Day 0 to Day 6

Outcome Measure Data

Analysis Population Description

Intention to treat, baseline is pooled across treatment arms in the mixed models analysis as Day 0/Baseline data were collected prior to treatment.

Arm/Group Title	Camostat Mesylate	Placebo
Arm/Group Description	Camostat mesylate 200mg taken 7 days. Camostat Mesilate: Camostat mesilate 200mg taken orally, 4 times daily, for 7 days.	Placebo taken for 7 days. Placebo: Placebo taken orally, 4 times daily, for 7 days.
Measure Participants	35	35
Day 0	31.5	31.5
Day 6	12.4	19.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Camostat Mesylate, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.02
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-6.6
	Confidence Interval	(2-Sided) 95%; -12.1 to -1.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Change in COVID-19 Symptom Severity
Description	Change of COVID-19 symptom severity from day 0 to day 14 will be assessed with the COVID-19 daily self score tool. Adapted from the FLU-PRO instrument, it consists of 39 items that are answered daily. Items 1-33 are Likert scale questions (rated 0-4) where 0 = not at all and 4 = very much. These items are summed to score the severity of symptoms- where a total score of 132 would indicate the greatest severity of symptoms and a score of 0 would indicate no severity of symptoms. Items 34-38 are also Likert scale questions (rated 0-4) that measure the frequency of specific daily symptoms where 0 = 0 times and 4 = 4 times or more. These items are summed to score the frequency of symptoms- where the highest score for the frequency of symptoms (20) indicates the greatest burden of symptom frequency. The last question (39) asks patients for their highest temperature in Fahrenheit.
Time Frame	Day 0 to Day 13

Outcome Measure Data

Analysis Population Description

Intention to treat, baseline is pooled across treatment arms in the mixed models analysis as Day 0/Baseline data were collected prior to treatment.

Arm/Group Title	Camostat Mesylate	Placebo
Arm/Group Description	Camostat mesylate 200mg taken 7 days. Camostat Mesilate: Camostat mesilate 200mg taken orally, 4 times daily, for 7 days.	Placebo taken for 7 days. Placebo: Placebo taken orally, 4 times daily, for 7 days.
Measure Participants	35	35
Day 0	31.5	31.5
Day 13	7.8	9.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Camostat Mesylate, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.48
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-2.1
	Confidence Interval	(2-Sided) 95%; -7.9 to 3.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Change in COVID-19 Symptom Frequency
Description	Change of COVID-19 symptom frequency score from day 0 to day 6 will be assessed with the COVID-19 daily self score tool. Adapted from the FLU-PRO instrument, it consists of 39 items that are answered daily. Items 34-38 measure the frequency of specific daily symptoms and are also Likert scale questions (rated 0-4) that measure the frequency of specific daily symptoms where 0 = 0 times and 4 = 4 times or more. These items are summed to score the frequency of symptoms- where the highest score (20) indicates the greatest burden of symptom frequency, the lowest possible score (0) indicates no frequency of symptoms.
Time Frame	Day 0 to Day 6

Outcome Measure Data

Analysis Population Description

Intention to treat, baseline is pooled across treatment arms in the mixed models analysis as Day 0/Baseline data were collected prior to treatment.

Arm/Group Title	Camostat Mesylate	Placebo
Arm/Group Description	Camostat mesylate 200mg taken 7 days. Camostat Mesilate: Camostat mesilate 200mg taken orally, 4 times daily, for 7 days.	Placebo taken for 7 days. Placebo: Placebo taken orally, 4 times daily, for 7 days.
Measure Participants	35	35
Day 0	5.9	5.9
Day 6	5.0	4.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Camostat Mesylate, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.16
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.0
	Confidence Interval	(2-Sided) 95%; -0.4 to 2.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	Change in COVID-19 Symptom Frequency
Description	Change of COVID-19 symptom frequency score from day 0 to day 6 will be assessed with the COVID-19 daily self score tool. Adapted from the FLU-PRO instrument, it consists of 39 items that are answered daily. Items 34-38 measure the frequency of specific daily symptoms and are also Likert scale questions (rated 0-4) that measure the frequency of specific daily symptoms where 0 = 0 times and 4 = 4 times or more. These items are summed to score the frequency of symptoms- where the highest score (20) indicates the greatest burden of symptom frequency, the lowest possible score (0) indicates no frequency of symptoms.
Time Frame	Day 0 to Day 13

Outcome Measure Data

Analysis Population Description

Intention to treat, baseline is pooled across treatment arms in the mixed models analysis as Day 0/Baseline data were collected prior to treatment.

Arm/Group Title	Camostat Mesylate	Placebo
Arm/Group Description	Camostat mesylate 200mg taken 7 days. Camostat Mesilate: Camostat mesilate 200mg taken orally, 4 times daily, for 7 days.	Placebo taken for 7 days. Placebo: Placebo taken orally, 4 times daily, for 7 days.
Measure Participants	35	35
Day 0	5.9	5.9
Day 13	2.7	2.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Camostat Mesylate, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.34
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.7
	Confidence Interval	(2-Sided) 95%; -0.7 to 2.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

11. Secondary Outcome

Title	Change in Body Temperature
Description	Change of COVID-19 symptom score from baseline to day 6 will be assessed with the COVID-19 daily self score tool. Adapted from the FLU-PRO instrument, it consists of 39 items that are answered daily. Items 1-33 are Likert scale questions (rated 0-4) where 0 = not at all and 4 = very much. These items are summed to score the severity of symptoms- where a total score of 132 would indicate the greatest severity of symptoms and a score of 0 would indicate no severity of symptoms. Items 34-38 are also Likert scale questions (rated 0-4) that measure the frequency of specific daily symptoms where 0 = 0 times and 4 = 4 times or more. These items are summed to score the frequency of symptoms- where the highest score for the frequency of symptoms (20) indicates the greatest burden of symptom frequency. The last question (39) asks patients for their highest temperature in Fahrenheit.
Time Frame	7 days (Day 0 to Day 6)

Outcome Measure Data

Analysis Population Description

Data are presented for those with valid temperature data. Body temperature was not evenly collected at all visits as originally intended.

Arm/Group Title	Camostat Mesylate	Placebo
Arm/Group Description	Camostat mesylate 200mg taken 7 days. Camostat Mesilate: Camostat mesilate 200mg taken orally, 4 times daily, for 7 days.	Placebo taken for 7 days. Placebo: Placebo taken orally, 4 times daily, for 7 days.
Measure Participants	22	27
Day 0	98.5 (0.8)	98.3 (0.8)
Day 6	98.0 (1.0)	98.1 (0.7)

12. Secondary Outcome

Title	Change in Body Temperature
Description	Change of COVID-19 symptom score from baseline to 28 days will be assessed with the COVID-19 daily self score tool. Adapted from the FLU-PRO instrument, it consists of 39 items that are answered daily. Items 1-33 are Likert scale questions (rated 0-4) where 0 = not at all and 4 = very much. These items are summed to score the severity of symptoms- where a total score of 132 would indicate the greatest severity of symptoms and a score of 0 would indicate no severity of symptoms. Items 34-38 are also Likert scale questions (rated 0-4) that measure the frequency of specific daily symptoms where 0 = 0 times and 4 = 4 times or more. These items are summed to score the frequency of symptoms- where the highest score for the frequency of symptoms (20) indicates the greatest burden of symptom frequency. The last question (39) asks patients for their highest temperature in Fahrenheit.
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

Data are presented for those with valid temperature data. Body temperature was not evenly collected at all visits as originally intended.

Arm/Group Title	Camostat Mesylate	Placebo
Arm/Group Description	Camostat mesylate 200mg taken 7 days. Camostat Mesilate: Camostat mesilate 200mg taken orally, 4 times daily, for 7 days.	Placebo taken for 7 days. Placebo: Placebo taken orally, 4 times daily, for 7 days.
Measure Participants	22	27
Day 0	98.5 (0.8)	98.3 (0.8)
Day 27	97.8 (0.5)	97.7 (0.8)

Adverse Events

Time Frame	Up to 28 days
Arm/Group Title	Camostat Mesylate		Placebo
Arm/Group Description	Camostat mesylate 200mg taken 7 days. Camostat Mesilate: Camostat mesilate 200mg taken orally, 4 times daily, for 7 days.		Placebo taken for 7 days. Placebo: Placebo taken orally, 4 times daily, for 7 days.
All Cause Mortality
	Camostat Mesylate		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/35 (0%)		0/35 (0%)
Serious Adverse Events
	Camostat Mesylate		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/35 (5.7%)		0/35 (0%)
Respiratory, thoracic and mediastinal disorders
Shortness of Breath	1/35 (2.9%)	1	0/35 (0%)	0
Respiratory Infection	1/35 (2.9%)	1	0/35 (0%)	0
Other (Not Including Serious) Adverse Events
	Camostat Mesylate		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/35 (8.6%)		0/35 (0%)
Skin and subcutaneous tissue disorders
Pruritus	3/35 (8.6%)	3	0/35 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.