E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute coronavirus disease 2019 |
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E.1.1.1 | Medical condition in easily understood language |
Acute coronavirus disease 2019 |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10053983 |
E.1.2 | Term | Corona virus infection |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Primary objective: Effect of HCQ on in vivo viral clearance. |
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E.2.2 | Secondary objectives of the trial |
Exploratory objectives are to assess the effect of infection and HCQ treatment on clinical outcome, cardiac function, mucosal, humoral and cellular immune response including single cell phenotype and RNA expression, effect on anti-viral defense, assessment of chronic symptoms and quality of life. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Written informed consent • Age above 18 years • Women of childbearing age only: Must agree to practice continuous effective contraception for the duration of the study (a method which results in a failure rate less than 1% per year) • Disease severe enough to require hospitalisation • QTc interval lower than 450 msec
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E.4 | Principal exclusion criteria |
• Respiratory rate >24/min • Pregnancy or lactation • Weight <50 kg • Hemodynamic/rhythm instability • Acute myocardial infarction Type 1 • Use of concomitant medications that prolong the QT/QTc interval. • Any regular concomitant medication which is contraindicated in the use together with HCQ • Hypersensitivity to Hydroxychloroquine, Chloroquine or other 4-Aminoquinolines • Pre-existing retinopathy or maculopathy • Known Glucose-6-phosphate dehydrogenase deficiency (haemolytic anaemia, Favism) • Haematopoietic systems diseases • Myasthenia gravis • Any other significant disease, disorder or finding which, in the opinion of the investigator, may significantly increase the risk to the volunteer because of participation in the study, affect the ability of the volunteer to participate in the study or impair interpretation of the study data
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary efficacy endpoint: Viral clearance defined as time to sustained SARS-CoV-2-specific RNA copy number ≤100, measured by real time reverse-transcription polymerase chain reaction in throat swabs
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
One interim analysis for evaluating the primary efficacy endpoint is planned for this study. The interim analysis will be done when 40% of events have accrued. In case the interim analysis shows a HR > 1.93 (nominal p < 0.0018), efficacy is shown and the trial may be stopped. Final analysis upon completion of the trial and final database lock. |
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E.5.2 | Secondary end point(s) |
Exploratory endpoints: ● In-hospital mortality within 60 days ● All-cause mortality within 60 days ● Proportion requiring non-invasive ventilation ● Proportion requiring invasive ventilation ● Proportion admitted to ICU ● Duration of hospitalization ● Reduction in viral RNA load in upper respiratory tract specimen as assessed by area under viral load curve ● Reduction in viral RNA load in upper respiratory tract specimen defined as decline of RNA load by 2 log-levels or to below detection level |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
After interim and final data base lock |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |