Camostat Mesylate in COVID-19 Outpatients

Sponsor
Yale University (Other)
Overall Status
Completed
CT.gov ID
NCT04353284
Collaborator
(none)
74
Enrollment
1
Location
2
Arms
10.4
Actual Duration (Months)
7.1
Patients Per Site Per Month

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 DiseaseIntervention/TreatmentPhase
  • 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 :
74 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

ArmIntervention/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]

      To determine whether camostat mesylate reduces SARS-COV-2 viral load 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]

      To determine whether camostat mesylate reduces SARS-COV-2 viral load 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]

      To determine whether camostat mesylate reduces SARS-COV-2 viral load 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. 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. 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]

      Change in risk for a positive COVID-19 test at day 27 after enrollment (day 0) will be assessed by analyzing the proportion of positive cases in each study arm.

    6. Change in COVID-19 symptom severity [7 days]

      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 [14 days]

      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 [7 days]

      Change of COVID-19 symptom 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 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.

    9. Change in COVID-19 symptom frequency [14 days]

      Change of COVID-19 symptom score 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.

    10. Change in body temperature [7 days]

      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 [14 days]

      Change of COVID-19 symptom score from baseline 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.

    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

    SiteCityStateCountryPostal Code
    1Yale UniversityNew HavenConnecticutUnited States06511

    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)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Geoffrey Chupp, Director, Yale Center for Asthma and Airways Disease (YCAAD), Yale University
    ClinicalTrials.gov Identifier:
    NCT04353284
    Other Study ID Numbers:
    • 2000027971
    First Posted:
    Apr 20, 2020
    Last Update Posted:
    Oct 8, 2021
    Last Verified:
    Oct 1, 2021
    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:

    Study Results

    No Results Posted as of Oct 8, 2021