CamoCO-19: The Impact of Camostat Mesilate on COVID-19 Infection

Sponsor

University of Aarhus (Other)

Overall Status

Recruiting

CT.gov ID

NCT04321096

Collaborator

(none)

580

Enrollment

Locations

Arms

24.9

Anticipated Duration (Months)

52.7

Patients Per Site

2.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

SARS-CoV-2, one of a family of human coronaviruses, was initially identified in December 2019 in Wuhan city. This new coronavirus causes a disease presentation which has now been named COVID-19. The virus has subsequently spread throughout the world and was declared a pandemic by the World Health Organisation on 11th March 2020. As of 18 March 2020, there are 198,193 number of confirmed cases with an estimated case-fatality of 3%. There is no approved therapy for COVID-19 and the current standard of care is supportive treatment.

SARS-CoV-2 exploits the cell entry receptor protein angiotensin converting enzyme II (ACE-2) to access and infect human cells. The interaction between ACE2 and the spike protein is not in the active site. This process requires the serine protease TMPRSS2. Camostat Mesilate is a potent serine protease inhibitor. Utilizing research on severe acute respiratory syndrome coronavirus (SARS-CoV) and the closely related SARS-CoV-2 cell entry mechanism, it has been demonstrated that SARS-CoV-2 cellular entry can be blocked by camostat mesilate. In mice, camostat mesilate dosed at concentrations similar to the clinically achievable concentration in humans reduced mortality following SARS-CoV infection from 100% to 30-35%.

Condition or Disease	Intervention/Treatment	Phase
Corona Virus Infection	Drug: Camostat Mesilate Drug: Placebo oral tablet	Phase 1/Phase 2

Detailed Description

Cohort 1 - enrolment into the cohort of hospitalized patients has been completed (31 Dec 2020). Study results are publicly available at EClinicilMedicine, see link https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(21)00129-2/fulltext Cohort 2

outpatients - remains open for enrolment

Study Design

Study Type:

Interventional

Anticipated Enrollment :

580 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

There are 2 cohorts: Cohort 1 - hospitalized patients (n=180); Cohort 2 - outpatients (n=400). All participants in the two cohorts are randomized to one of two armsThere are 2 cohorts: Cohort 1 - hospitalized patients (n=180); Cohort 2 - outpatients (n=400). All participants in the two cohorts are randomized to one of two arms

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

Placebo-controlled

Primary Purpose:

Treatment

Official Title:

The Impact of Camostat Mesilate on COVID-19 Infection: An Investigator-initiated Randomized, Placebo-controlled, Phase IIa Trial

Actual Study Start Date :

Apr 4, 2020

Anticipated Primary Completion Date :

Jan 31, 2022

Anticipated Study Completion Date :

May 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo 2 pills 3 times daily for 5 days	Drug: Placebo oral tablet Placebo Other Names: Placebo
Experimental: Camostat Mesilate 2x100 mg pills 3 times daily for 5 days	Drug: Camostat Mesilate Serine protease inhibitor that blocks TMPRSS-2 mediated cell entry of SARS-CoV-2 Other Names: Foipan

Arm

Intervention/Treatment

Placebo Comparator: Placebo

2 pills 3 times daily for 5 days

Drug: Placebo oral tablet

Placebo

Other Names:

Placebo

Experimental: Camostat Mesilate

2x100 mg pills 3 times daily for 5 days

Drug: Camostat Mesilate

Serine protease inhibitor that blocks TMPRSS-2 mediated cell entry of SARS-CoV-2

Other Names:

Foipan

Outcome Measures

Primary Outcome Measures

Cohort 1: Days to clinical improvement from study enrolment [30 days]
Clinical improvement defined as live hospital discharge OR a 2 point improvement (from time of enrolment) in disease severity rating on the 7-point ordinal scale
Cohort 2: Days to clinical improvement from study enrolment [30 days]
Days to clinical improvement from study enrolment defined no fever for at least 48 hrs AND improvement in other symptoms (e.g. cough, expectoration, myalgia, fatigue, or head ache)

Secondary Outcome Measures

Safety evaluation, as measured by AEs, Adverse Reactions (ARs), SAEs, Serious ARs (SARs) [30 days]
Cohort 1: Clinical status as assessed by the 7-point ordinal scale at day 7, 14 and 30 [30 days]
The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen; 6) Not hospitalized, limitation on activities; 7) Not hospitalized, no limitations on activities.
Cohort 1: Day 30 mortality [30 days]
Mortality
Cohort 1: Change in NEW(2) score from baseline to day 30 [30 days]
NEWS2
Cohort 1: Admission to ICU [30 days]
ICU
Cohort 1: Use of invasive mechanical ventilation or ECMO [30 days]
invasive mechanical ventilation or ECMO
Cohort 1: Duration of supplemental oxygen (days) [30 days]
Nasal or high-flow oxygen
Cohort 1+2: Days to self-reported recovery (e.g. limitations in daily life activities) during telephone interviews conducted at day 30 [30 days]
Subjective clinical improvement
Cohort 2: Number participant-reported secondary infection of housemates [30 days]
No of new COVID-19 infections in the household
Cohort 2: Time to hospital admission related to COVID-19 infection [30 days]
Hospital admission

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 110 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Cohort 1)

Documented COVID-19 infection as evidenced by positive PCR (or comparable clinical assay) for SARS-CoV-2
Less than 48 hours since time of hospital admission OR if hospital-acquired COVID-19 is suspected, less than 48 hrs since onset of symptoms
Adolescents and adults age >=18 years
Subject or legally authorized representative able to give informed consent
Admitted to hospital

Cohort 2)

Documented COVID-19 infection as evidenced by positive PCR (or comparable clinical assay) for SARS-CoV-2
One or more of the following symptoms of COVID-19 infection: fever, cough, expectoration, shortness of breath, myalgia, fatigue, or head ache
No more than 5 days since the beginning of symptom onset
Adolescents and adults age >=18 years
Subject (or legally authorized representative, for Cohort 1 only) able to give informed consent
Do not require immediate hospitalization (newly diagnosed COVID-19 patients who are discharged within 24 hrs of hospital admission are eligible for enrollment)
Must be willing to fill out a daily symptom diary
Must be available for a daily phone call
Must be willing to take their own temperature at least once a day

Exclusion criteria

Any condition that, in the Investigator's opinion, will prevent adequate compliance with study therapy (e.g. the patient is considered to be moribund within the next 72 hrs or has uncontrolled substance abuse that prevents adherence to study medication). Patients needing ventilator treatment are eligible to be enrolled if they fulfill the other in/exclusion criteria.
The following laboratory values at baseline (Day 0):
Serum total bilirubin ≥3 ULN
Estimated glomerular filtration rate (eGFR) ≤30 mL/min (based on serum creatinine)
Known hypersensitivity to Camostat Mesilate
Women who are pregnant or breastfeeding, or with a positive pregnancy test as determined by a positive urine or blood beta- human chorionic gonadotropin test during screening or women of child bearing potential* who are unwilling or unable to use an acceptable method of contraception (combined estrogen and progestogen hormonal contraception (oral, intravaginal or transdermal), progesteron-only hormonal contraception (oral, injectable or implantable), intrauterine device or intrauterine hormone-releasing system) to avoid pregnancy during the study. Sexual abstinence will only be accepted in cases where this reflect the usual lifestyle.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Region Hospital North Jutland	Hjørring	Region Nord	Denmark
2	Department of Infectious Diseases	Aalborg		Denmark
3	Department for Infectious Diseases, Aarhus University Hospital	Aarhus N		Denmark	8200
4	Herning Regional Hospital	Herning		Denmark	7400
5	Northzealands hospital - Hillerød	Hillerød		Denmark	3400
6	Horsens Regional Hospital	Horsens		Denmark	8700
7	Bispebjerg hospital	København		Denmark	2400
8	Dept. of Infectious Diseases, Odense University Hospital	Odense		Denmark	5000
9	Randers Regional Hospital	Randers		Denmark	8900
10	Silkeborg Hospital	Silkeborg		Denmark	8600
11	Örebro Hsopital	Örebro	Örebrolan	Sweden