E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Post-COVID-19 syndrome without (PCS) or with (PCS/CFS) fulfillment of myalgic encephalomyelitis/chronic fatique syndrome (ME/CFS) criteria |
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E.1.1.1 | Medical condition in easily understood language |
Post-COVID-19 syndrome with or without fulfillment of myalgic encephalomyelitis/chronic fatique syndrome criteria is commonly referred to as long-covid syndrome with severe fatigue as a key symptom. |
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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 | 24.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10085867 |
E.1.2 | Term | Post-COVID-19 syndrome |
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 |
To show improvementin SF-36-PFfrom baseline to week 10 when comparing Vericiguat with placebo based on mean differences. |
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E.2.2 | Secondary objectives of the trial |
Main secondary objective(s)are to show differences in: 1)The occurrenceof SF-36-PF responder(10-point increase); 2)Improvement in other SF-36 sub-domains from baseline to week 10 when comparing Vericiguat with placebo; 3)An improvement in fatigue severity scalefrom baseline to week 10 when comparing Vericiguat with placebo; 4)An improvement in muscle fatigue assessedby repetitive hand grip strength (HGS) test from screening to week 10 when comparing Vericiguat with placebo ;5)Assessmentof investigational medical product (IMP) safety and side/adverse effects during the IMP intake and titration regimen. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Main inclusion criteria: - Male or female adult who is 18-50 years old - Confirmed (PCRor serology),non-hospitalized, mild to moderate acute COVID-19 cases according to WHO criteria with proven chronic ED and either: ME/CFS CCC criteriawithpost exertional malaise(PEM)2 -14 hours = PCS orME/CFS CCC criteria with PEM > 14 hours = PCS/CFS - Ongoing symptoms of PCSor PCS/CFSfor≥ 6 months - Bell Score: 30-60 - Evidence for ED [as indicated byreactive hyperemia index(RHI)<1.8 and/or ET-1 level > 90 percentile of healthy age-and gender matched controls or muscle fatigue (below cut-off values of AUC reference values for age-matched healthy controls and/or pathological optical coherence tomography angiography(OCTA))] - For female subjects: Confirmed post-menopausal state (defined as amenorrhea for at least 12 months) or for women of childbearing potential: Negative highly sensitive urine or serum pregnancy test before inclusion/randomisationandPracticing a highly effective birth control method (failure rate of less than 1%) |
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E.4 | Principal exclusion criteria |
Main exclusion criteria: - COVID-19 vaccination within the last 4 weeks before inclusion - Pre-COVID history of chronic fatigue syndrome or other fatigue syndromes that are due to associated diseases (e.g.,cancer, autoimmune diseases [patients with a preexcisting Hashimoto thyroiditis and/orfibromyalgiawithout fatigue syndromes can be included]) - Concomitant use of Vericiguat due to other diseases - Contraindications against IMP - Concurrent or anticipated concomitant use of PDE-5 inhibitors such as vardenafil, tadalafil, and sildenafil, nitrates,or sGC-stimulators - Use of other sGC stimulators, e.g.,riociguat - Hypersensitivity to the active substance or any of the other ingredients - Systolic blood pressure: < 100mmHg at screening Known SARS-CoV-2 infection-related organ damage/comorbiditySevere renal or hepatic insufficiency - Pregnancy or breastfeeding |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary endpoint: Primary outcome is toshowintra-patient change in SF-36-PF from baseline to week 10 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Main secondary endpointswilldemonstrate: 1) Occurrenceof responders. Responders aredefined as an intra-patient 10-point increase in SF-36-PF from baseline to week 10; 2) Intra-patient change in other SF-36 subdomains from baseline to week 10; 3) Intra-patient change in fatigue severity scale from baseline to week 10;4)Intra-patient change inhand grip force(maximum, mean), fatigue ratio,and recovery rate from screening to week 10; 5) Occurrence of IMP side and adverse effects, assessed with AE, SAE and SUSAR reports. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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 | No |
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 | |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | |