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