E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
The novel coronavirus designated SARS CoV-2, and the disease caused by this virus designated COVID-19. No treatment is available for early disease stages and non-hospitalized patients to date. This trial focusses on SARS-CoV-2 positive patients with pre-existing risk factors for a moderate or severe COVID-19 disease course. |
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E.1.1.1 | Medical condition in easily understood language |
SARS-CoV-2 infected patients to be treated at an early stage after positive testing and of high risk to develop moderate to severe and potentially life-threatening pneumonia. |
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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 | 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 |
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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 | 10084272 |
E.1.2 | Term | SARS-CoV-2 infection |
E.1.2 | System Organ Class | 100000004862 |
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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 | 10084442 |
E.1.2 | Term | SARS-CoV-2 PCR test positive |
E.1.2 | System Organ Class | 100000004848 |
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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 | 10084270 |
E.1.2 | Term | SARS-CoV-2 acute respiratory disease |
E.1.2 | System Organ Class | 100000004862 |
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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 |
The working hypothesis to be tested in the RES-Q HR study is that the early use of camostat mesylate reduces the likelihood of disease progression to modified WHO stages 4-8 in SARS-CoV-2 positive adult patients at high risk of moderate or severe COVID-19 progression. The primary endpoint of the study is the cumulative number of individuals who progressed to or beyond category 4 on the modified WHO COVID-19 ordinal scale within 28 days after randomization. |
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E.2.2 | Secondary objectives of the trial |
% of patients with at least 1 COVID-19-related medically visit (incl. telemedicine/phone) through day 28; Cumulative no. in the SoC+treatment arm vs. SoC+placebo in WHO categories 4-8 by day 8,14,56 & 90; Cumulative no. in the SoC+treatment arm vs. SoC+placebo in WHO categories 3 by day 8,14,28,56 & 90; "Event-free” survival at day 90 & evaluation of all-cause mortality at day 90 using Kaplan-Meier; The proportion of patients with remdesivir therapy & WHO status at initiation of remdesivir; The proportion of patients on dexamethasone therapy & WHO status at baseline dexamethasone; % of patients with novel COVID-19- associated symptoms, Time to resolution of COVID-19 related symptoms; Time to first negative SARS-CoV-2-PCR ; Duration of oxygen therapy (days); % of participants in each group with need for mechanical ventilation (& ventilation days); Duration of hospital stay (days), duration in intensive care (days); All-cause mortality at day 28 SARS-CoV-2 genetic variants |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Individuals (female, male diverse) ≥ 18 years with SARS-CoV-2 infection, confirmed by PCR before study enrollment 2.SARS-CoV-2 positive PCR ≤ 3 days old (date of NP swab) 3.Ability to provide written informed consent 4.Potassium values between 3.5-4.9 mmol/l 5.Platelets on full blood count must be ≥ 50.000/µl 6.Presence of at least one of the following criteria: - Patients ≥ 55 years - BMI ≥ 35 kg/m2, - coronary artery disease (CAD), - chronic kidney disease (CKD) with GFR <60 ml/min but ≥ 30 ml/min, - diabetes mellitus, - active tumor disease -Patients with chronic pulmonary disease, e.g. obstructive pulmonary disease (COPD), pulmonary fibrosis |
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E.4 | Principal exclusion criteria |
1.Age <18 years 2.Unable to give informed consent 3.Pregnant women or breast-feeding mothers 4.Known hypersensitivity to camostat mesylate and/or severe pancreatitis 5.Life expectancy < 6 months 6.Duration SARS-CoV-2 typical symptoms > 3 days 7.SARS-CoV-2 PCR detection older than 3 days 8.SARS-CoV-2 associated clinical condition ≥ WHO stage 3 (patients hospitalized for other reasons than mAB treatment, pAB-treatment, CP-treatment, social reasons and COVID-19 may be included if they fulfill all inclusion and none of the exclusion criteria) 9.Previously or currently hospitalized due to SARS-CoV-2 10.Previous antiviral therapy for SARS-CoV-2 11.ALT or AST > 5 x ULN at screening 12.Liver cirrhosis > Child A (patients with Child B/C cirrhosis are excluded from the trial) 13.Chronic kidney disease with GFR < 30 ml/min 14.Concurrent or planned anticancer treatment during trial period 15.Accommodation in an institution due to legal orders (§40(4) AMG). 16.Any psycho-social condition hampering compliance with the study protocol. 17.Evidence of current drug or alcohol abuse. 18.Use of other investigational treatment within 5 half-lives of enrollment is prohibited 19.Concomitant proven influenza A infection 20.Patients with organ or bone marrow transplant in the three months prior to Screening Visit |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of the study is the number of individuals whose clinical status is on the COVID-19 modified WHO ordinal scale ≥ 4 up to and including day 28. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Cumulative number of persons in the SoC+treatment arm versus SoC+placebo in WHO category 3 by day 28 |
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E.5.2 | Secondary end point(s) |
• Percentage of patients with at least one COVID-19-related medically attended visit through day 28. These include telemedicine/phone visits, in-person physician-visits, emergency department visits, and hospitalization. • Cumulative number of persons in the SoC+treatment arm versus SoC+placebo in WHO categories 4-8 by day 8, day 14, day 56 and day 90 • Cumulative number of persons in the SoC+treatment arm versus SoC+placebo in WHO category 3 by day 8, day 14, day 28, day 56 and day 90 • "Event-free” (not hospitalized, no COVID-19 associated long-term effects such secondary sclerosing cholangitis, pulmonary disease, no reinfection) survival at day 90 and evaluation of all-cause mortality at day 90 using Kaplan-Meier • The proportion of patients with remdesivir therapy and WHO status at initiation of remdesivir • The proportion of patients on dexamethasone therapy and WHO status at baseline dexamethasone • Percentage of patients with novel COVID-19-associated symptoms after enrolment • Time to resolution of COVID-19-related symptoms (e.g. fever) • Time to first negative SARS-CoV-2-PCR • Duration of oxygen therapy (in days) • Frequency of occurrence of COVID-19 pneumonia • Percentage of participants in each group with need for mechanical ventilation (and ventilation days) • Duration of hospital stay (in days), duration in intensive care/IMC (in days) • All-cause mortality at day 28 • Cumulative incidence of SAEs per group within 90 days follow up • Cumulative incidence of grade 3/4 AEs per group • SARS-CoV-2 antibody concentrations (IgA, IgG, NT) in serum on baseline, day 8, day 14, day 90 • SARS-CoV-2 genetic variants (at baseline) and accumulation of variants of concern (VOC) during treatment period (at last positive PCR test) • Change of Quality of life from baseline to day 28, day 90 (VAS, SF-12) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Results of study visits day 8, day 14, day 28, day 56 and day 90 after inclusion into the study. |
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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 | Yes |
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 | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
2-arm, multicenter, randomized, double-blind, controlled trial |
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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 | 10 |
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 | |