Combination Therapy With Camostat Mesilate + Hydroxychloroquine for COVID-19 (CLOCC)

Evaluation of the Efficacy and Safety of Camostat Mesilate + Hydroxychloroquine Combination Therapy in Hospitalized Patients With Moderate COVID-19 Infection

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.

Study Overview

• Status: Withdrawn
• Conditions: COVID
• Intervention / Treatment: Drug: Camostat Mesilate; Drug: Hydroxychloroquine; Drug: Placebo

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.

• Study Type: Interventional
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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:

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Camostat + Hydroxychloroquine; Subjects will receive Camostat (400 mg tid) + hydroxychloroquine (400 mg bid day1, 200 mg bid d2-d7)	Drug: Camostat Mesilate; 400 mg tid, d1-d7; Drug: Hydroxychloroquine; 400 mg bid on day 1, 200 mg bid d2-d7
Active Comparator: Placebo + Hydroxychloroquine; Subjects will receive placebo (tid) + hydroxychloroquine (400 mg bid day1, 200 mg bid d2-d7)	Drug: Hydroxychloroquine; 400 mg bid on day 1, 200 mg bid d2-d7; Drug: Placebo; Instead of Camostat Mesilate, tid, d1-d7

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Not hospitalized	day 14 from baseline

Secondary Outcome Measures

Outcome Measure	Time Frame
Time to improvement of 2 categories from admission on a 7-point ordinal scale	day 14
Proportion of participants in each group with normalization of fever	day 7 and day 14
Proportion of participants in each group with oxygen saturation > 94% on room air for >24h	day 7 and day 14
Time to fever normalization (if febrile at baseline)	within 14 days
Time to first negative SARS-CoV-2 PCR in NP swap (if pos. at baseline)	within 14 days
Time to first negative SARS-CoV-2 PCR in lower respiratory tract specimens (sputum, bronchoalveolar lavage, tracheal aspirate) (if positive at baseline)	within 14 days
Duration of oxygen therapy	within 28 days
Proportion of participants in each group with need for mechanical ventilation	within 28 days
Duration of hospitalization	within 28 days
All cause mortality	day 28

Collaborators and Investigators

• Sponsor: Heinrich-Heine University, Duesseldorf
• Collaborators: Universitätsklinikum Hamburg-Eppendorf; University Hospital Frankfurt; St. Georg Hospital Leipzig, Germany; Hospital Schwabing Munich, Germany; Missioklinik, Wuerzburg, Germany

Study record dates

Study Major Dates

• Study Start (Anticipated): May 1, 2020
• Primary Completion (Anticipated): December 1, 2021
• Study Completion (Anticipated): December 1, 2021

Study Registration Dates

• First Submitted: April 3, 2020
• First Submitted That Met QC Criteria: April 6, 2020
• First Posted (Actual): April 8, 2020

Study Record Updates

• Last Update Posted (Actual): December 21, 2020
• Last Update Submitted That Met QC Criteria: December 17, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: Hydroxychloroquine; Camostat; Moderate COVID-10
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Protease Inhibitors; Serine Proteinase Inhibitors; Antiprotozoal Agents; Antiparasitic Agents; Trypsin Inhibitors; Antimalarials; Hydroxychloroquine; Camostat
• Other Study ID Numbers: CLOCC-2020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Sharing Time Frame: 3 Months after publication
• IPD Sharing Access Criteria: Open
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No