Combination Therapy With Camostat Mesilate + Hydroxychloroquine for COVID-19

COVID Clinical Trial

— CLOCC  

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04338906
• Other study ID #: CLOCC-2020
• Status: Withdrawn
• Phase: Phase 4
• Start date: May 2020
• Est. completion date: December 2021

Study information

• Verified date: December 2020
• Source: Heinrich-Heine University, Duesseldorf
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: December 2021
• Est. primary completion date: December 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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:

Related Conditions & MeSH terms

• COVID

Intervention

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

Locations

Country	Name	City	State
n/a

Sponsors (6)

Lead Sponsor	Collaborator
Heinrich-Heine University, Duesseldorf	Hospital Schwabing Munich, Germany, Missioklinik, Wuerzburg, Germany, St. Georg Hospital Leipzig, Germany, Universitätsklinikum Hamburg-Eppendorf, University Hospital, Frankfurt

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Not hospitalized		day 14 from baseline
Secondary	Time to improvement of 2 categories from admission on a 7-point ordinal scale		day 14
Secondary	Proportion of participants in each group with normalization of fever		day 7 and day 14
Secondary	Proportion of participants in each group with oxygen saturation > 94% on room air for >24h		day 7 and day 14
Secondary	Time to fever normalization (if febrile at baseline)		within 14 days
Secondary	Time to first negative SARS-CoV-2 PCR in NP swap (if pos. at baseline)		within 14 days
Secondary	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
Secondary	Duration of oxygen therapy		within 28 days
Secondary	Proportion of participants in each group with need for mechanical ventilation		within 28 days
Secondary	Duration of hospitalization		within 28 days
Secondary	All cause mortality		day 28