E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute coronavirus disease 2019 |
|
E.1.1.1 | Medical condition in easily understood language |
Acute coronavirus disease 2019 |
|
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 | 23.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10053983 |
E.1.2 | Term | Corona virus infection |
E.1.2 | System Organ Class | 100000004862 |
|
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 |
Difference in time to resolution of clinical signs and symptoms of mild COVID-19 treated with hydroxychloroquine or placebo as assessed by daily self-assessment |
|
E.2.2 | Secondary objectives of the trial |
Difference between hydroxychloroquine- and placebo-treated patients on an ordinal outcome scale until Day 28 (death, admission to intensive care, hospitalization, continuing disease, recovered)
All-cause mortality within 28 days
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Must be ≥18 years at the time of signing the informed consent • Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures • Able to adhere to the study visit schedule and other protocol requirements • Mild COVID-19 with outpatient management as decided by the treating physician • Early warning score for 2019-nCoV infected patients ≤ 4 • Females of childbearing potential (FCBP) must agree: o to practice continuous effective contraception for at least 28 days before starting study drug, while participating in the study (including dose interruptions), and for at least 28 days after study treatment discontinuation and must agree to regular pregnancy testing during this timeframe (a method which results in a failure rate less than 1% per year) o to abstain from breastfeeding during study participation and 28 days after study drug discontinuation • All subjects must agree to refrain from donating blood while on study drug and for 28 days after discontinuation from this study treatment • All subjects must agree not to share medication
|
|
E.4 | Principal exclusion criteria |
• Requirement for supplemental oxygen • Shortness of breath in resting position • Early warning score of 3 in one of the categories: o Respiratory rate (≤8 or ≥25 breaths/min) o Systolic blood pressure (≤90 mmHg or ≥220 mmHg) o Heart rate (≤40 or ≥ 130 beats/min) • Known or suspected renal insufficiency • Known glucose-6-phosphate-dehydrogenase deficiency (favism) • Known Myasthenia gravis • Ongoing disorders of the hemopoietic system • Known hypersensitivity against 4-amino-quinolines • Women during pregnancy and lactation • Current participation in other clinical interventional trials • Elevated Tisdale score for QTc prolongation (score between 7-21) • History or current evidence of clinically significant cardiac arrhythmia except atrial fibrillation or paroxysmal supraventricular tachycardia • Active or clinically significant cardiac disease including congestive heart failure (New York Heart Association Class III or higher) • Epilepsy • Physician decision that involvement in the study is not in the patient´s best interest |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint will be the difference in duration from the initiation of treatment until resolution of the clinical signs and symptoms assessed by daily self-assessment in hydroxychloroquine- versus placebo-treated patients. |
|
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. A one-sided Hwang-Shih-DeCani spending function with gamma = -4 (alpha-spending) was considered in the sample size calculation to account for multiplicity repeated tests. In case the interim analysis shows a HR > 1.21 (nominal p < 0.0018), efficacy is shown and the trial may be stopped. Final analysis upon completion of the trial and final database lock |
|
E.5.2 | Secondary end point(s) |
Difference between hydroxychloroquine- and placebo-treated patients on an ordinal outcome scale until Day 28 (death, requiring intensive care, requiring hospitalization, outpatient but ill, healthy)
All-cause mortality within 28 days
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
After interim and final database lock |
|
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 | No |
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
|
|
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 | |
E.8.9.1 | In the Member State concerned days | |