Clinical trial NCT04353284: Camostat Mesylate in COVID-19 Outpatients
Official title: The Effect of Camostat Mesylate on COVID-19 Infection in Ambulatory Patients: An Investigator-Initiated Randomized, Placebo-Controlled, Phase IIa Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: COVID-19
Lead sponsor: Yale University
Sponsor class: OTHER
First posted: 2020-04-20
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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 ).

Primary outcomes:
measure: Change in SARS-COV-2 Viral Load
timeFrame: 5 days (day 0 to day 4)
Secondary outcomes:
measure: Change in SARS-COV-2 Viral Load
timeFrame: 3 days (day 0 to day 2)
measure: Change in SARS-COV-2 Viral Load
timeFrame: 7 days (day 0 to day 6)
measure: Number of Participants With Change in Positive COVID-19 Status
timeFrame: 7 days
measure: Number of Participants With Change in Positive COVID-19 Status
timeFrame: 14 days
measure: Change in Positive COVID-19 Status
timeFrame: 28 days
measure: Change in COVID-19 Symptom Severity
timeFrame: Day 0 to Day 6
measure: Change in COVID-19 Symptom Severity
timeFrame: Day 0 to Day 13
measure: Change in COVID-19 Symptom Frequency
timeFrame: Day 0 to Day 6
measure: Change in COVID-19 Symptom Frequency
timeFrame: Day 0 to Day 13
measure: Change in Body Temperature
timeFrame: 7 days (Day 0 to Day 6)
measure: Change in Body Temperature
timeFrame: 28 days
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale University
state: Connecticut
Study officials:
affiliation: Director, Yale Center for Asthma and Airways Disease (YCAAD)
name: Geoffrey Chupp, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Professor, Section of Infectious Diseases: Department of Internal Medicine
name: Joseph Vinetz, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kosinsky Y, Peskov K, Stanski DR, Wetmore D, Vinetz J. Semi-Mechanistic Pharmacokinetic-Pharmacodynamic Model of Camostat Mesylate-Predicted Efficacy against SARS-CoV-2 in COVID-19. Microbiol Spectr. 2022 Apr 27;10(2):e0216721. doi: 10.1128/spectrum.02167-21. Epub 2022 Apr 12.
citation: Chupp G, Spichler-Moffarah A, Sogaard OS, Esserman D, Dziura J, Danzig L, Chaurasia R, Patra KP, Salovey A, Nunez A, May J, Astorino L, Patel A, Halene S, Wang J, Hui P, Patel P, Lu J, Li F, Gan G, Parziale S, Katsovich L, Desir GV, Vinetz JM. A Phase 2 Randomized, Double-Blind, Placebo-controlled Trial of Oral Camostat Mesylate for Early Treatment of COVID-19 Outpatients Showed Shorter Illness Course and Attenuation of Loss of Smell and Taste. medRxiv [Preprint]. 2022 Jan 31:2022.01.28.22270035. doi: 10.1101/2022.01.28.22270035.