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

Study Overview
=================
Brief Summary
-----------------
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.

Official Title
-----------------
A Multicenter Randomized Trial to Evaluate the Efficacy and Safety of Camostat Mesylate for the Treatment of SARS-CoV-2 Infection - COVID-19 in Ambulatory Adult Patients (CAMOVID)

Conditions
-----------------
Covid19

Intervention / Treatment
-----------------
* Drug: Camostat Mesylate
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
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)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Camostat mesylate<br>Camostat mesylate, oral administration 600mg/day | Drug: Camostat Mesylate<br>* Camostat mesylate, oral administration 600mg/day (2 x 100mg tablets every 8 hours) for 14 days<br>|
| Placebo Comparator: Placebo<br>Placebo tablets, oral administration | Drug: Placebo<br>* Placebo tablets, oral administration 2 tablets every 8 hours for 14 days<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hospitalization for COVID-19 deterioration or death without hospitalization | Proportion of patients hospitalized for COVID-19 deterioration or who died without hospitalization | Day 21 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events | Number of patients with at least one adverse event | Day 21 | 
| Serious adverse events | Number of patients with at least one serious adverse event | Day 21 | 
| Investigational medication discontinuation | Number of patients who discontinued the investigational medication | 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 | 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 | Day 7, 14, 21 | 
| Need for intensive care | Proportion of patients admitted to an intensive care unit | Day 21 | 
| Duration of hospitalization | Number of days alive without hospitalization up to day 21 | Day 21 | 
| Need for invasive mechanical ventilation for severe COVID-19 | Proportion of patients with initiation of invasive mechanical ventilation | Day 21 | 
| Need for oxygen therapy for COVID-19 | Proportion of patients with initiation of oxygen therapy | Day 21 | 
| Overall survival | Proportion of patients alive at day 90 | Day 90 | 
| Duration of symptoms | Number of days alive without symptoms at day 21 | 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) | Day 7, 14, 21 | 
| SARS-CoV-2 serological assessment | SARS-CoV2 antibodies quantification in blood | Day 7, 14, 21 and 90 | 
| Peripheral blood lymphocyte phenotyping | Peripheral blood lymphocyte phenotyping with telomere length measurement | 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 | Day 21 | 
| Renal function | estimated glomerular filtration rate | Day 7, 14 and 21 | 
| Concentration of urea in blood | Uricemia in mmol/L or mg/dL | Day 7, 14 and 21 | 
| Concentration of potassium in blood | Kaliemia in mmol/L | Day 7, 14 and 21 | 
| Liver function | Liver transaminases dosage on blood sample | Day 7, 14 and 21 | 
| Liver function (2) | Gamma-glutamyl transferase (gamma-GT) dosage on blood sample | Day 7, 14 and 21 |