Camostat Mesylate in COVID-19 Outpatients

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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The Effect of Camostat Mesylate on COVID-19 Infection in Ambulatory Patients: An Investigator-Initiated Randomized, Placebo-Controlled, Phase IIa Trial

Conditions
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COVID-19

Intervention / Treatment
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* Drug: Camostat Mesilate
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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 ).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Camostat mesylate<br>Camostat mesylate 200mg taken 7 days. | Drug: Camostat Mesilate<br>* Camostat mesilate 200mg taken orally, 4 times daily, for 7 days.<br>* Other names: Fiopan, Camostat Mesylate;|
| Placebo Comparator: Placebo<br>Placebo taken for 7 days. | Other: Placebo<br>* Placebo taken orally, 4 times daily, for 7 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in SARS-COV-2 Viral Load | 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. | 5 days (day 0 to day 4) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in SARS-COV-2 Viral Load | 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. | 3 days (day 0 to day 2) | 
| Change in SARS-COV-2 Viral Load | 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. | 7 days (day 0 to day 6) | 
| Number of Participants With Change in Positive COVID-19 Status | 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. | 7 days | 
| Number of Participants With Change in Positive COVID-19 Status | 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. | 14 days | 
| Change in Positive COVID-19 Status | Number of Participants With Change in Positive COVID-19 Status | 28 days | 
| Change in COVID-19 Symptom Severity | 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. | Day 0 to Day 6 | 
| Change in COVID-19 Symptom Severity | 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. | Day 0 to Day 13 | 
| Change in COVID-19 Symptom Frequency | 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. | Day 0 to Day 6 | 
| Change in COVID-19 Symptom Frequency | 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. | Day 0 to Day 13 | 
| Change in Body Temperature | 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. | 7 days (Day 0 to Day 6) | 
| Change in Body Temperature | 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. | 28 days |