Clinical trial NCT04321096: The Impact of Camostat Mesilate on COVID-19 Infection
Official title: The Impact of Camostat Mesilate on COVID-19 Infection: An Investigator-initiated Randomized, Placebo-controlled, Phase IIa Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Corona Virus Infection
Keywords: COVID-19
SARS-CoV-2
Lead sponsor: University of Aarhus
Sponsor class: OTHER
First posted: 2020-03-25
Enrollment: 206
Sex: ALL
Minimum age (years): 18
Maximum age (years): 110
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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
Primary purpose: TREATMENT

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%.

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

Eligibility 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.

Primary outcomes:
measure: Cohort 1: Days to clinical improvement from study enrolment
timeFrame: 30 days
measure: Cohort 2: Days to clinical improvement from study enrolment
timeFrame: 30 days
Secondary outcomes:
measure: Safety evaluation, as measured by AEs, Adverse Reactions (ARs), SAEs, Serious ARs (SARs)
timeFrame: 30 days
measure: Cohort 1: Clinical status as assessed by the 7-point ordinal scale at day 7, 14 and 30
timeFrame: 30 days
measure: Cohort 1: Day 30 mortality
timeFrame: 30 days
measure: Cohort 1: Change in NEW(2) score from baseline to day 30
timeFrame: 30 days
measure: Cohort 1: Admission to ICU
timeFrame: 30 days
measure: Cohort 1: Use of invasive mechanical ventilation or ECMO
timeFrame: 30 days
measure: Cohort 1: Duration of supplemental oxygen (days)
timeFrame: 30 days
measure: Cohort 1+2: Days to self-reported recovery (e.g. limitations in daily life activities) during telephone interviews conducted at day 30
timeFrame: 30 days
measure: Cohort 2: Number participant-reported secondary infection of housemates
timeFrame: 30 days
measure: Cohort 2: Time to hospital admission related to COVID-19 infection
timeFrame: 30 days
Other outcomes:
Locations:
city: Hjørring
country: Denmark
facility: Region Hospital North Jutland
state: Region Nord
city: Aalborg
country: Denmark
facility: Department of Infectious Diseases
city: Aarhus N
country: Denmark
facility: Department for Infectious Diseases, Aarhus University Hospital
city: Herning
country: Denmark
facility: Herning Regional Hospital
city: Hillerød
country: Denmark
facility: Northzealands hospital - Hillerød
city: Horsens
country: Denmark
facility: Horsens Regional Hospital
city: København
country: Denmark
facility: Bispebjerg hospital
city: Odense
country: Denmark
facility: Dept. of Infectious Diseases, Odense University Hospital
city: Randers
country: Denmark
facility: Randers Regional Hospital
city: Silkeborg
country: Denmark
facility: Silkeborg Hospital
city: Örebro
country: Sweden
facility: Örebro Hsopital
state: Örebrolan
Study officials:
affiliation: Head of Department
name: Lars Østergaard, Professor
role: STUDY_CHAIR
References:
citation: 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.