Camostat Mesylate in COVID-19 Outpatients

• ClinicalTrials.gov Identifier: NCT04353284
• Recruitment Status: Completed
• First Posted: April 20, 2020
• Results First Posted: March 24, 2022
• Last Update Posted: March 24, 2022
• Sponsor: Yale University
• Information provided by (Responsible Party): Yale University

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 (Clinical Trial)
• 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: June 9, 2020
• Actual Primary Completion Date: March 3, 2021
• Actual Study Completion Date: April 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 Name: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 28 days ]
   Number of Participants With Change in Positive COVID-19 Status
6. Change in COVID-19 Symptom Severity [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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 ).

Contacts and Locations

Locations

United States, Connecticut

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)

Documents provided by Yale University:

Study Protocol and Statistical Analysis Plan  [PDF] August 18, 2020

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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. 2022 Jan 31:2022.01.28.22270035. doi: 10.1101/2022.01.28.22270035. Preprint.

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

Individual Participant Data (IPD) Sharing Statement:

• 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; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Gabexate; Camostat; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Trypsin Inhibitors; Serine Proteinase Inhibitors; Anticoagulants