The Impact of Camostat Mesilate on COVID-19 Infection (CamoCO-19)

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

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%.

Study Overview

• Status: Completed
• Conditions: Corona Virus Infection
• Intervention / Treatment: Drug: Placebo oral tablet; Drug: Camostat Mesilate

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 Type: Interventional
• Enrollment (Actual): 206
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Denmark
  • Aalborg, Denmark
    • Department of Infectious Diseases
  • Aarhus N, Denmark, 8200
    • Department for Infectious Diseases, Aarhus University Hospital
  • Herning, Denmark, 7400
    • Herning Regional Hospital
  • Hillerød, Denmark, 3400
    • Northzealands hospital - Hillerød
  • Horsens, Denmark, 8700
    • Horsens Regional Hospital
  • København, Denmark, 2400
    • Bispebjerg Hospital
  • Odense, Denmark, 5000
    • Dept. of Infectious Diseases, Odense University Hospital
  • Randers, Denmark, 8900
    • Randers Regional Hospital
  • Silkeborg, Denmark, 8600
    • Silkeborg Hospital
  • Region Nord
    • Hjørring, Region Nord, Denmark
      • Region Hospital North Jutland
• Sweden
  • Örebrolan
    • Örebro, Örebrolan, Sweden
      • Örebro Hsopital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 106 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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
Cohort 1: Day 30 mortality	Mortality	30 days
Cohort 1: Change in NEW(2) score from baseline to day 30	NEWS2	30 days
Cohort 1: Admission to ICU	ICU	30 days
Cohort 1: Use of invasive mechanical ventilation or ECMO	invasive mechanical ventilation or ECMO	30 days
Cohort 1: Duration of supplemental oxygen (days)	Nasal or high-flow oxygen	30 days
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
Cohort 2: Number participant-reported secondary infection of housemates	No of new COVID-19 infections in the household	30 days
Cohort 2: Time to hospital admission related to COVID-19 infection	Hospital admission	30 days

Collaborators and Investigators

• Sponsor: University of Aarhus
• Investigators: Study Chair: Lars Østergaard, Professor, Head of Department

Publications and helpful links

General Publications

• Gunst JD, Staerke NB, Pahus MH, Kristensen LH, Bodilsen J, Lohse N, Dalgaard LS, Bronnum D, Frobert O, Honge B, Johansen IS, Monrad I, Erikstrup C, Rosendal R, Vilstrup E, Mariager T, Bove DG, Offersen R, Shakar S, Cajander S, Jorgensen NP, Sritharan SS, Breining P, Jespersen S, Mortensen KL, Jensen ML, Kolte L, Frattari GS, Larsen CS, Storgaard M, Nielsen LP, Tolstrup M, Saedder EA, Ostergaard LJ, Ngo HTT, Jensen MH, Hojen JF, Kjolby M, Sogaard OS. Efficacy of the TMPRSS2 inhibitor camostat mesilate in patients hospitalized with Covid-19-a double-blind randomized controlled trial. EClinicalMedicine. 2021 May;35:100849. doi: 10.1016/j.eclinm.2021.100849. Epub 2021 Apr 22.

Study record dates

Study Major Dates

• Study Start (Actual): April 4, 2020
• Primary Completion (Actual): January 31, 2022
• Study Completion (Actual): May 1, 2023

Study Registration Dates

• First Submitted: March 23, 2020
• First Submitted That Met QC Criteria: March 24, 2020
• First Posted (Actual): March 25, 2020

Study Record Updates

• Last Update Posted (Actual): April 18, 2025
• Last Update Submitted That Met QC Criteria: April 15, 2025
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: SARS-CoV-2; COVID-19
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Respiratory Tract Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Lung Diseases; Pneumonia, Viral; Pneumonia; Coronaviridae Infections; Nidovirales Infections; COVID-19; Infections; Communicable Diseases; Coronavirus Infections; Molecular Mechanisms of Pharmacological Action; Protease Inhibitors; Enzyme Inhibitors; Serine Proteinase Inhibitors; Trypsin Inhibitors; Camostat
• Other Study ID Numbers: 2020-001200-42

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data sharing plan: Individual deidentified participant data (including data dictionaries) will be shared following the publication of the primary and secondary endpoints as outlined in this protocol. Data to be shared includes deidentified data points in published, peer-reviewed articles. Additional, related documents will also be available (study protocol, informed consent form, statistical analysis plan). Data will become available following publication with no planned end date.
• IPD Sharing Access Criteria: Access to the data sharing will be given to researchers who provide a methodologically sound proposal for any type of analysis and requires IRB/Ethics committee approval (if applicable). Proposals should be addressed to olesoega@rm.dk.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No