Combination Therapy With Camostat Mesilate + Hydroxychloroquine for COVID-19

NCT ID: NCT04338906

Last Updated: 2020-12-21

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE4
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-05-31
• Study Completion Date: 2021-12-31

Brief Summary

Evaluation of the efficacy and safety of hydroxychloroquine - camostat combination therapy in hospitalized patients with moderate COVID-19 infection, CLOCC-Trial Primary Objectives: The primary objective of this study is to demonstrate, that a combination therapy of hydroxychloroquine and camostat (Foipan®) is superior to hydroxychloroquine + placebo in participants with moderate COVID-19.

Detailed Description

The ongoing pandemic with the novel coronavirus (SARS-CoV-2) poses a massive threat to public health. SARS-CoV-2 is highly contagious and may lead to severe acute respiratory distress syndrome in affected individuals. No therapeutic intervention has yet been approved for COVID-19, and initial interventional studies with single agents showed only minimal improvement in outcome or were not convincing in design. Therefore, the CLOCC trial will evaluate the efficacy and safety of a combination therapy consisting of hydroxychloroquine, which was used already as single agent with some effect, together with camostat mesylate in hospitalized patients with moderate COVID-19 infection. The rationale for this combination therapy stems from the observation that hydroxychloroquine interferes with viral entry and replication through several mechanisms including changes in endosomal pH and in glycosylation of the ACE2 receptor, which serves as entry receptor for SARS-CoV-2. Camostat acts as inhibitor of the host cell serine protease TMPRSS2, which is needed to prime the viral S protein for cell entry. Participants will be recruited in a total of 6 German centers, and the trial will be randomized (1:1) and enrolled in either the hydroxychloroquine + placebo or the hydroxychloroquine + camostat arm (7-day treatment). The trial will be carried out in a double-blinded fashion. The primary efficacy outcome is the number of patients discharged by day 14 (status 1 and 2 of a 7-point ordinal clinical status scale). Several secondary outcomes regarding efficacy but also safety will be evaluated. Exploratory endpoints include analysis of viral titers and the emergence of viral resistance in response to therapy.

Conditions

COVID

Keywords

Camostat; Hydroxychloroquine; Moderate COVID-10

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Camostat + Hydroxychloroquine

Subjects will receive Camostat (400 mg tid) + hydroxychloroquine (400 mg bid day1, 200 mg bid d2-d7)

Group Type: EXPERIMENTAL

Camostat Mesilate

Intervention Type: DRUG

400 mg tid, d1-d7

Hydroxychloroquine

Intervention Type: DRUG

400 mg bid on day 1, 200 mg bid d2-d7

Placebo + Hydroxychloroquine

Subjects will receive placebo (tid) + hydroxychloroquine (400 mg bid day1, 200 mg bid d2-d7)

Group Type: ACTIVE_COMPARATOR

Placebo

Intervention Type: DRUG

Instead of Camostat Mesilate, tid, d1-d7

Hydroxychloroquine

Intervention Type: DRUG

400 mg bid on day 1, 200 mg bid d2-d7

Interventions

Camostat Mesilate

400 mg tid, d1-d7

Intervention Type: DRUG

Placebo

Instead of Camostat Mesilate, tid, d1-d7

Intervention Type: DRUG

Hydroxychloroquine

400 mg bid on day 1, 200 mg bid d2-d7

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Participants ≥18 years of age with SARS-CoV-2 infection confirmed by PCR before randomization
• Willing and able to provide written informed consent
• Hospitalized and requiring medical care for COVID-19, (status 3 or 4 of 7-point ordinal clinical status scale)
• SpO2 ≥93% on room air
• Evidence of pulmonary infiltrate on chest X ray/and or CT scan

Exclusion Criteria

• Age <18 years old
• Pregnant or breast feeding
• Inability to take oral medication
• Inability to provide informed written consent
• Known hypersensitivity towards 4-aminoquinolines, e.g. hydroxychloroquine and/or camostat
• Use of hydroxychloroquine, chloroquine and or camostat within 6 months prior to baseline
• Patients with known retinopathy or macular degeneration Patients with known glucose-6-phosphate dehydrogenase (G6PD) deficiency
• Prolonged QTc-interval in baseline ECG (>500 ms)
• Concomitant medication associated with QTc-interval prolongation, which cannot be withdrawn prior to study drug administration
• Major comorbidities, possibly leading to increased unwanted side effects of study drugs:

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Universitätsklinikum Hamburg-Eppendorf

OTHER

Sponsor Role: collaborator

Goethe University

OTHER

Sponsor Role: collaborator

St. Georg Hospital Leipzig, Germany

UNKNOWN

Sponsor Role: collaborator

Hospital Schwabing Munich, Germany

UNKNOWN

Sponsor Role: collaborator

Missioklinik, Wuerzburg, Germany

UNKNOWN

Sponsor Role: collaborator

Heinrich-Heine University, Duesseldorf

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Other Identifiers

CLOCC-2020

Identifier Type: -

Identifier Source: org_study_id