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

• ClinicalTrials.gov Identifier: NCT04321096
• Recruitment Status: Unknown
• First Posted: March 25, 2020
• Last Update Posted: April 30, 2021
• Sponsor: University of Aarhus
• Information provided by (Responsible Party): University of Aarhus

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 (Clinical Trial)
• Estimated 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 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: April 4, 2020
• Estimated Primary Completion Date: January 31, 2022
• Estimated 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 Name: 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 Name: Foipan

Outcome Measures

Primary Outcome Measures :

1. Cohort 1: Days to clinical improvement from study enrolment [ Time Frame: 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
2. Cohort 2: Days to clinical improvement from study enrolment [ Time Frame: 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 :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 110 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts

Contact: Ole S Søgaard, MD PhD; +45 2499 4962; olesoega@rm.dk

Locations

Denmark

Region Hospital North Jutland; Recruiting

Hjørring, Region Nord, Denmark

Contact: Peter Leutscher p.leutscher@rn.dk

Department of Infectious Diseases; Recruiting

Aalborg, Denmark

Contact: Jacob Bodilsen

Department for Infectious Diseases, Aarhus University Hospital; Recruiting

Aarhus N, Denmark, 8200

Contact: Ole S Søgaard, MD, PhD +45 2499 4962 olesoega@rm.dk

Principal Investigator: Ole S Soegaard, MD, PhD

Herning Regional Hospital; Recruiting

Herning, Denmark, 7400

Contact: Lars S Dalgaard, MD

Northzealands hospital - Hillerød; Recruiting

Hillerød, Denmark, 3400

Contact: Nicolai L Lohse, MD

Horsens Regional Hospital; Recruiting

Horsens, Denmark, 8700

Contact: Ayfer Topcu, MD

Bispebjerg hospital; Recruiting

København, Denmark, 2400

Contact: Stine Johnsen, MD

Dept. of Infectious Diseases, Odense University Hospital; Recruiting

Odense, Denmark, 5000

Contact: Isik S. Johansen, MD

Randers Regional Hospital; Recruiting

Randers, Denmark, 8900

Contact: Bo Hønge, MD

Silkeborg Hospital; Recruiting

Silkeborg, Denmark, 8600

Contact: Britta Tarp, MD

Sweden

Örebro Hsopital; Recruiting

Örebro, Örebrolan, Sweden

Contact: Sara Cajandar, MD sara.cajander@regionorebrolan.se

Sponsors and Collaborators

University of Aarhus

Investigators

• Study Chair: Lars Østergaard, Professor; Head of Department

More Information

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

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.

• Responsible Party: University of Aarhus
• ClinicalTrials.gov Identifier: NCT04321096
• Other Study ID Numbers: 2020-001200-42
• First Posted: March 25, 2020
• Last Update Posted: April 30, 2021
• Last Verified: April 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• 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.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF)
• 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.

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University of Aarhus:

COVID-19; SARS-CoV-2

Additional relevant MeSH terms:

Infections; Communicable Diseases; COVID-19; Coronavirus Infections; Disease Attributes; Pathologic Processes; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Virus Diseases; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Camostat; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Trypsin Inhibitors; Serine Proteinase Inhibitors