The Impact of Camostat Mesilate on COVID-19 Infection

Corona Virus Infection Clinical Trial

— CamoCO-19  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04321096
• Other study ID #: 2020-001200-42
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: April 4, 2020
• Est. completion date: May 1, 2022

Study information

• Verified date: April 2021
• Source: University of Aarhus
• Contact: Ole S Søgaard, MD PhD
• Phone: +45 2499 4962
• Email: olesoega[@]rm.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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%.

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 580
• Est. completion date: May 1, 2022
• Est. primary completion date: January 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 110 Years

Eligibility

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.

Related Conditions & MeSH terms

• Communicable Diseases
• Corona Virus Infection
• Coronavirus Infections
• Infection

Intervention

Drug:
• Camostat Mesilate
Serine protease inhibitor that blocks TMPRSS-2 mediated cell entry of SARS-CoV-2
• Placebo oral tablet
Placebo

Locations

Country	Name	City	State
Denmark	Department of Infectious Diseases	Aalborg
Denmark	Department for Infectious Diseases, Aarhus University Hospital	Aarhus N
Denmark	Herning Regional Hospital	Herning
Denmark	Northzealands hospital - Hillerød	Hillerød
Denmark	Region Hospital North Jutland	Hjørring	Region Nord
Denmark	Horsens Regional Hospital	Horsens
Denmark	Bispebjerg hospital	København
Denmark	Dept. of Infectious Diseases, Odense University Hospital	Odense
Denmark	Randers Regional Hospital	Randers
Denmark	Silkeborg Hospital	Silkeborg
Sweden	Örebro Hsopital	Örebro	Örebrolan

Sponsors (1)

Lead Sponsor	Collaborator
University of Aarhus

Countries where clinical trial is conducted

Denmark,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cohort 1: Days to clinical improvement from study enrolment	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	30 days
Primary	Cohort 2: Days to clinical improvement from study enrolment	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)	30 days
Secondary	Safety evaluation, as measured by AEs, Adverse Reactions (ARs), SAEs, Serious ARs (SARs)		30 days
Secondary	Cohort 1: Clinical status as assessed by the 7-point ordinal scale at day 7, 14 and 30	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.	30 days
Secondary	Cohort 1: Day 30 mortality	Mortality	30 days
Secondary	Cohort 1: Change in NEW(2) score from baseline to day 30	NEWS2	30 days
Secondary	Cohort 1: Admission to ICU	ICU	30 days
Secondary	Cohort 1: Use of invasive mechanical ventilation or ECMO	invasive mechanical ventilation or ECMO	30 days
Secondary	Cohort 1: Duration of supplemental oxygen (days)	Nasal or high-flow oxygen	30 days
Secondary	Cohort 1+2: Days to self-reported recovery (e.g. limitations in daily life activities) during telephone interviews conducted at day 30	Subjective clinical improvement	30 days
Secondary	Cohort 2: Number participant-reported secondary infection of housemates	No of new COVID-19 infections in the household	30 days
Secondary	Cohort 2: Time to hospital admission related to COVID-19 infection	Hospital admission	30 days