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

• ClinicalTrials.gov Identifier: NCT04608266
• Recruitment Status: Terminated
• First Posted: October 29, 2020
• Last Update Posted: February 10, 2022
• Sponsor: Assistance Publique - Hôpitaux de Paris
• Information provided by (Responsible Party): Assistance Publique - Hôpitaux de Paris

Tracking Information

• First Submitted Date: October 28, 2020
• First Posted Date: October 29, 2020
• Last Update Posted Date: February 10, 2022
• Actual Study Start Date: December 3, 2020
• Actual Primary Completion Date: September 27, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 28, 2020)

Hospitalization for COVID-19 deterioration or death without hospitalization [ Time Frame: Day 21 ]

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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 2, 2020)

• Adverse events [ Time Frame: Day 21 ]
  Number of patients with at least one adverse event
• Serious adverse events [ Time Frame: Day 21 ]
  Number of patients with at least one serious adverse event
• Investigational medication discontinuation [ Time Frame: Day 21 ]
  Number of patients who discontinued the investigational medication
• Hospitalization for COVID-19 deterioration or death without hospitalization, evaluated by independent adjudication comittee [ Time Frame: Day 21 ]
  Proportion of patients hospitalized for COVID-19 deterioration (reviewed by independent adjudication comitter) or who died without hospitalization
• Clinical improvement using the Word Health Organization (WHO) COVID-19 scale [ Time Frame: Day 7, 14, 21 ]
  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
• Need for intensive care [ Time Frame: Day 21 ]
  Proportion of patients admitted to an intensive care unit
• Duration of hospitalization [ Time Frame: Day 21 ]
  Number of days alive without hospitalization up to day 21
• Need for invasive mechanical ventilation for severe COVID-19 [ Time Frame: Day 21 ]
  Proportion of patients with initiation of invasive mechanical ventilation
• Need for oxygen therapy for COVID-19 [ Time Frame: Day 21 ]
  Proportion of patients with initiation of oxygen therapy
• Overall survival [ Time Frame: Day 90 ]
  Proportion of patients alive at day 90
• Duration of symptoms [ Time Frame: Day 21 ]
  Number of days alive without symptoms at day 21
• SARS-CoV-2 virological assessment [ Time Frame: Day 7, 14, 21 ]
  By Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) on nasal swab and droplet quantification of SARS-CoV2 ribonucleic acid-emia (RNAemia)
• SARS-CoV-2 serological assessment [ Time Frame: Day 7, 14, 21 and 90 ]
  SARS-CoV2 antibodies quantification in blood
• Peripheral blood lymphocyte phenotyping [ Time Frame: Day 1, 14, 90 ]
  Peripheral blood lymphocyte phenotyping with telomere length measurement
• Acute kidney failure [ Time Frame: Day 21 ]
  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
• Renal function [ Time Frame: Day 7, 14 and 21 ]
  estimated glomerular filtration rate
• Concentration of urea in blood [ Time Frame: Day 7, 14 and 21 ]
  Uricemia in mmol/L or mg/dL
• Concentration of potassium in blood [ Time Frame: Day 7, 14 and 21 ]
  Kaliemia in mmol/L
• Liver function [ Time Frame: Day 7, 14 and 21 ]
  Liver transaminases dosage on blood sample
• Liver function (2) [ Time Frame: Day 7, 14 and 21 ]
  Gamma-glutamyl transferase (gamma-GT) dosage on blood sample

Original Secondary Outcome Measures (submitted: October 28, 2020)

• Adverse events [ Time Frame: Day 21 ]
  Number of patients with at least one adverse event
• Serious adverse events [ Time Frame: Day 21 ]
  Number of patients with at least one serious adverse event
• Investigational medication discontinuation [ Time Frame: Day 21 ]
  Number of patients who discontinued the investigational medication
• Hospitalization for COVID-19 deterioration or death without hospitalization, evaluated by independent adjudication comittee [ Time Frame: Day 21 ]
  Proportion of patients hospitalized for COVID-19 deterioration (reviewed by independent adjudication comitter) or who died without hospitalization
• Clinical improvement using the Word Health Organization (WHO) COVID-19 scale [ Time Frame: Day 7, 14, 21 ]
  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
• Need for intensive care [ Time Frame: Day 21 ]
  Proportion of patients admitted to an intensive care unit
• Duration of hospitalization [ Time Frame: Day 21 ]
  Number of days alive without hospitalization up to day 21
• Need for invasive mechanical ventilation for severe COVID-19 [ Time Frame: Day 21 ]
  Proportion of patients with initiation of invasive mechanical ventilation
• Need for oxygen therapy for COVID-19 [ Time Frame: Day 21 ]
  Proportion of patients with initiation of oxygen therapy
• Overall survival [ Time Frame: Day 90 ]
  Proportion of patients alive at day 90
• Duration of symptoms [ Time Frame: Day 21 ]
  Number of days alive without symptoms at day 21
• SARS-CoV-2 virological assessment [ Time Frame: Day 7, 14, 21 ]
  By Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) on nasal swab and droplet quantification of SARS-CoV2 ribonucleic acid-emia (RNAemia)
• SARS-CoV-2 serological assessment [ Time Frame: Day 7, 14, 21 and 90 ]
  SARS-CoV2 antibodies quantification in blood
• Peripheral blood lymphocyte phenotyping [ Time Frame: Day 1, 14, 90 ]
  Peripheral blood lymphocyte phenotyping with telomere length measurement
• Acute kidney failure [ Time Frame: Day 21 ]
  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
• Renal function [ Time Frame: Day 7, 14 and 21 ]
  estimated glomerular filtration rate
• Uricemia [ Time Frame: Day 7, 14 and 21 ]
  Uricemia
• Kaliemia [ Time Frame: Day 7, 14 and 21 ]
  Kaliemia
• Liver function [ Time Frame: Day 7, 14 and 21 ]
  Liver transaminases dosage on blood sample
• Liver function (2) [ Time Frame: Day 7, 14 and 21 ]
  Gamma-glutamyl transferase (gamma-GT) dosage on blood sample

Current Other Pre-specified Outcome Measures (submitted: October 28, 2020)

Biobanking for biomarker assessment [ Time Frame: Day 1, 7, 14, 21, 90 ]

Biobanking of blood samples for predictive biomarker assessment

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

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

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Covid19

Intervention

• Drug: Camostat Mesylate
  Camostat mesylate, oral administration 600mg/day (2 x 100mg tablets every 8 hours) for 14 days
• Drug: Placebo
  Placebo tablets, oral administration 2 tablets every 8 hours for 14 days

Study Arms

• Experimental: Camostat mesylate
  Camostat mesylate, oral administration 600mg/day
  Intervention: Drug: Camostat Mesylate
• Placebo Comparator: Placebo
  Placebo tablets, oral administration
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: January 27, 2022): 70
• Original Estimated Enrollment (submitted: October 28, 2020): 596
• Actual Study Completion Date: December 2, 2021
• Actual Primary Completion Date: September 27, 2021 (Final data collection date for primary outcome measure)

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)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France

Administrative Information

• NCT Number: NCT04608266
• Other Study ID Numbers: APHP200702
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Current Responsible Party: Assistance Publique - Hôpitaux de Paris
• Original Responsible Party: Same as current
• Current Study Sponsor: Assistance Publique - Hôpitaux de Paris
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Assistance Publique - Hôpitaux de Paris
• Verification Date: October 2020