CAMOVID : Evaluation of Efficacy and Safety of Camostat Mesylate for the Treatment of SARS-CoV-2 Infection - COVID-19 in Ambulatory Adult Patients

Phase 3TerminatedNCT04608266

Assistance Publique - Hôpitaux de Paris70 enrolled

Overview

The overall objective of the study is to determine the therapeutic effect and tolerance of Camostat mesylate, compared to placebo in adult patients with ambulatory COVID-19 disease, presenting with risk factors of severe COVID-19. Camostat mesylate is a serine protease TMPRSS2 (Transmembrane Serine Protease 2) inhibitor which has been successfully and safely used to treat pancreatitis-associated pain and post-operative reflux oesophagitis in Japan. More recently, it has been shown to inhibit SARS-CoV-2 viral entry and reduce infection of human primary pneumocytes and lung cell lines. Camostat mesylate or placebo will be administered to consenting adult patients with virologically confirmed COVID-19, not requiring initial hospitalization. All patients will receive standard of care along with randomized treatments. Outcomes of included patients will be compared between the 2 groups.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Covid19

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Patients ≥ 18 years old * Patients with an increased risk of severe COVID-19 belonging to one or more of the following groups : * Age ≥ 50 years * Body Mass Index ≥ 30 kg/m² * Diabetes * Hypertension * Chronic renal failure (eGFR \<60 mL/min) * Chronic heart disease * Asthma/Chronic Obstructive Pumonary Disease/Cystic fibrosis * Chronic liver disease * Chronic neurological disease * Solid organ transplant * Bone marrow transplant * Sickle cell anemia/ Major thalassemias * Active or currently treated or \<1 year diagnosed cancer * Active or currently treated or \<1 year diagnosed malignant blood disease * Immunosuppressive treatment observed for more than 1 month * Laboratory confirmed SARS-CoV2 infection with mild COVID-19, fulfilling all the following criteria: * Positive SARS-CoV-2 RT-PCR nasal swab samples AND * Clinical symptoms and signs consistent with SARS-CoV2 infection including but not limited to, fever, upper respiratory tract infection signs, digestive signs, muscle pain, anosmia, dysgueusia…(1) * Informed consent to participate to the trial * Patients must be able and willing to comply with study visits and procedures Exclusion Criteria: * Initial need for hospitalization for COVID-19 management * Pregnancy and breastfeeding * Participation to another interventional drug trial * Subject protected by law under guardianship or curatorship * Absence of health insurance * Known hypersensitivity to camostat mesylate * Known person sharing the same household already included in the study * Participation to another COVID-19 ambulatory interventional study * Patients having completed a full SARS-CoV2 vaccine immunization procedure less than 4 weeks prior to COVID-19 diagnosis (last vaccine injection performed less than 4 weeks prior to COVID-19 diagnosis)

Locations (6)

Centre Hospitalier Victor Dupouy

Argenteuil, France

AP-HP Hôpital Henri Mondor

Créteil, France

Centre Hospitalier Sud Ile de France - Melun

Melun, France

AP-HP Hôpital Bichat

Paris, France

APHP - Saint Louis

Paris, France

Centre de Santé Richerand

Paris, France

Outcomes

Primary Outcomes

Hospitalization for COVID-19 deterioration or death without hospitalization

Proportion of patients hospitalized for COVID-19 deterioration or who died without hospitalization

Time frame: Day 21

Secondary Outcomes

Adverse events

Number of patients with at least one adverse event

Time frame: Day 21

Serious adverse events

Number of patients with at least one serious adverse event

Time frame: Day 21

Investigational medication discontinuation

Number of patients who discontinued the investigational medication

Time frame: Day 21

Hospitalization for COVID-19 deterioration or death without hospitalization, evaluated by independent adjudication comittee

Proportion of patients hospitalized for COVID-19 deterioration (reviewed by independent adjudication comitter) or who died without hospitalization

Time frame: Day 21

Clinical improvement using the Word Health Organization (WHO) COVID-19 scale

WHO clinical scale: Uninfected - No clinical or virological evidence of infection: 0; Ambulatory - No limitation of activities: 1; Ambulatory - limitation of activities: 2; Hospitalized - no oxygen therapy: 3; Hospitalized - oxygen by mask or nasal prongs: 4; Hospitalized; oxygen by non invasive ventilation or High flow: 5; Intubation and Mechanical ventilation: 6; Mechanical ventilation + additional organ support (pressors, Renal replacement therapy, ECMO):7; Dead: 8

Time frame: Day 7, 14, 21

Need for intensive care

Proportion of patients admitted to an intensive care unit

Time frame: Day 21

Duration of hospitalization

Number of days alive without hospitalization up to day 21

Time frame: Day 21

Need for invasive mechanical ventilation for severe COVID-19

Proportion of patients with initiation of invasive mechanical ventilation

Time frame: Day 21

Need for oxygen therapy for COVID-19

Proportion of patients with initiation of oxygen therapy

Time frame: Day 21

Overall survival

Proportion of patients alive at day 90

Time frame: Day 90

Duration of symptoms

Number of days alive without symptoms at day 21

Time frame: Day 21

SARS-CoV-2 virological assessment

By Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) on nasal swab and droplet quantification of SARS-CoV2 ribonucleic acid-emia (RNAemia)

Time frame: Day 7, 14, 21

SARS-CoV-2 serological assessment

SARS-CoV2 antibodies quantification in blood

Time frame: Day 7, 14, 21 and 90

Peripheral blood lymphocyte phenotyping

Peripheral blood lymphocyte phenotyping with telomere length measurement

Time frame: Day 1, 14, 90

Acute kidney failure

Acute kidney failure defined as at least serum creatinine increase of 0.3mg/dl or 1.5-1.9 times baseline and/or oliguria \< 0.5ml/kg/h

Time frame: Day 21

Renal function

estimated glomerular filtration rate

Time frame: Day 7, 14 and 21

Concentration of urea in blood

Uricemia in mmol/L or mg/dL

Time frame: Day 7, 14 and 21

Concentration of potassium in blood

Kaliemia in mmol/L

Time frame: Day 7, 14 and 21

Liver function

Liver transaminases dosage on blood sample

Time frame: Day 7, 14 and 21

Liver function (2)

Gamma-glutamyl transferase (gamma-GT) dosage on blood sample

Time frame: Day 7, 14 and 21