Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04338906
Recruitment Status : Not yet recruiting
First Posted : April 8, 2020
Last Update Posted : April 8, 2020
Sponsor:
Collaborators:
Universitätsklinikum Hamburg-Eppendorf
University Hospital, Frankfurt
St. Georg Hospital Leipzig, Germany
Hospital Schwabing Munich, Germany
Missioklinik, Wuerzburg, Germany
Information provided by (Responsible Party):
Heinrich-Heine University, Duesseldorf

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 334 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 : June 1, 2020
Estimated Primary Completion Date : June 1, 2021
Estimated Study Completion Date : December 31, 2021

Resource links provided by the National Library of Medicine


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




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 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
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:
Layout table for additonal information
Responsible Party: Heinrich-Heine University, Duesseldorf
ClinicalTrials.gov Identifier: NCT04338906    
Other Study ID Numbers: CLOCC-2020
First Posted: April 8, 2020    Key Record Dates
Last Update Posted: April 8, 2020
Last Verified: April 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

Layout table for additional information
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:
Layout table for MeSH terms
Camostat
Hydroxychloroquine
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antirheumatic Agents
Protease Inhibitors
Trypsin Inhibitors
Serine Proteinase Inhibitors