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

• ClinicalTrials.gov Identifier: NCT04338906
• Recruitment Status: Withdrawn
• First Posted: April 8, 2020
• Last Update Posted: December 21, 2020
• Sponsor: Heinrich-Heine University, Duesseldorf
• Collaborators: Universitätsklinikum Hamburg-Eppendorf; Goethe University; St. Georg Hospital Leipzig, Germany; Hospital Schwabing Munich, Germany; Missioklinik, Wuerzburg, Germany
• Information provided by (Responsible Party): Heinrich-Heine University, Duesseldorf

Study Description

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.

Condition or disease	Intervention/treatment	Phase
COVID	Drug: Camostat Mesilate; Drug: Placebo; Drug: Hydroxychloroquine	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 0 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Evaluation of the efficacy and safety of hydroxychloroquine + camostat combination therapy in comparison to hydroxychloroquine + placebo in hospitalized patients with moderate COVID-19 infection, CLOCC-Trial
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Evaluation of the Efficacy and Safety of Camostat Mesilate + Hydroxychloroquine Combination Therapy in Hospitalized Patients With Moderate COVID-19 Infection
• Estimated Study Start Date: May 2020
• Estimated Primary Completion Date: December 2021
• Estimated Study Completion Date: December 2021

Arms and Interventions

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: Placebo; Instead of Camostat Mesilate, tid, d1-d7; Drug: Hydroxychloroquine; 400 mg bid on day 1, 200 mg bid d2-d7

Outcome Measures

Primary Outcome Measures :

1. Not hospitalized [ Time Frame: day 14 from baseline ]

Secondary Outcome Measures :

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

Eligibility Criteria

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

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:

Contacts and Locations

No Contacts or Locations Provided

More Information

• Responsible Party: Heinrich-Heine University, Duesseldorf
• ClinicalTrials.gov Identifier: NCT04338906
• Other Study ID Numbers: CLOCC-2020
• First Posted: April 8, 2020
• Last Update Posted: December 21, 2020
• Last Verified: December 2020

Individual Participant Data (IPD) Sharing Statement:

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

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

Keywords provided by Heinrich-Heine University, Duesseldorf:

Camostat; Hydroxychloroquine; Moderate COVID-10

Additional relevant MeSH terms:

Hydroxychloroquine; Camostat; Antimalarials; Antiprotozoal Agents; Antiparasitic Agents; Anti-Infective Agents; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Protease Inhibitors; Trypsin Inhibitors; Serine Proteinase Inhibitors