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A study to investigate improvement in physical function in SF-36 with Vericiguat compared with Placebo in participants with post-COVID-19 syndrome (PCS and PCS/CFS)

Phase 2
Recruiting
Conditions
Post-COVID-19 syndrome without (PCS) or with (PCS/CFS) fulfillment of myalgic encephalomyelitis/chronic fatique syndrome (ME/CFS) criteria
Registration Number
2024-517713-33-00
Lead Sponsor
Charite Universitaetsmedizin Berlin KöR
Brief Summary

To show improvement in SF-36-PF from baseline to week 10 when comparing Vericiguat with placebo based on mean differences.

Detailed Description

Not available

Recruitment & Eligibility

Status
Ongoing, recruiting
Sex
Not specified
Target Recruitment
104
Inclusion Criteria

Male or female adult who is 18-55 years old. Female study participants older than 50 years of age must either havea sustained menstrual cycle (as reported by the patient) or a FSH value < 20 IU/l)

Confirmed (PCR or serology), non-hospitalized, mild to moderate acute COVID-19 cases according to WHO criteria with proven chronic ED and either: ME/CFS CCC criteria with post exertional malaise (PEM) 2 - 14 hours = PCS or ME/CFS CCC criteria with PEM > 14 hours = PCS/CFS

Ongoing symptoms of PCS or PCS/CFS for ≥ 6 months

Bell Score: 30-60

Evidence for endothelial dysfunction (as indicated by RHI < 1.8 and/or Endothelin-1 level > 90 percentile of healthy age- and sex matched controls or muscle fatigue (below cut-off values of AUC reference values for age-matched healthy controls (Jaekel et al., 2021) and/or pathological OCTA)

Normal thyroid function

Subject is willing, understanding, and able to provide informed consent

Signed informed consent prior to initiation of any trial related measure

For female subjects: Confirmed post-menopausal state (defined as amenorrhea for at least 12 months) or For women of childbearing potential (WOCBP): Negative highly sensitive urine or serum pregnancy test before inclusion/randomisation and Practicing a highly effective birth control method (failure rate of less than 1%): a) combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral/intravaginal/ transdermal), or b) progestogen-only hormonal contraception associated with inhibition of ovulation (oral/injectable/implantable), or c) intrauterine device, or d) intrauterine hormone-releasing system, or e) bilateral tubal occlusion, or f) vasectomised partner, or g) heterosexual abstinence.

Exclusion Criteria

COVID-19 vaccination within the last 4 weeks before inclusion

Systolic blood pressure: < 100 mmHg at screening

Contraindication against MRI investigation (e.g., stents, metal clips)

Severe hepatic insufficiency such as with hepatic encephalopathy or hepatic laboratory abnormalities (ALT or AST ≥3 × ULN or total bilirubin ≥2 × ULN) at screening.

BMI: > 32 kg/m2 at screening (provided that the patient's BMI was ≤ 30 kg/m2 in the medical history (according to the patient's information) before the COVID-19 infection that resulted in the post-COVID syndrome)

Subject is pregnant or breastfeeding at screening

Subject is institutionalized by order of court or public authority

Any medical condition that, in the opinion of the Investigator, might interfere with the patient’s participation in the trial, poses any added risk for the patient, or confounds the assessment of the patient

Subject who might be dependent on the sponsor, the investigator, or the trial site

Participation in another clinical trial with an investigational medical product within 3 months or 5 half-lives, whichever is longer, before screening visit

Known SARS-CoV-2 infection-related organ damage/comorbidity

Renal impairment with an estimated glomerular filtration rate <15 mL/min/1.73 m2 or on dialysis at screening

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 preexisting Hashimoto thyroiditis and/or fibromyalgia without fatigue syndromes can be included])

Concomitant or previous use of Vericiguat

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

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Primary outcome is to show intra-patient change in SF-36-PF from baseline to week 10

Primary outcome is to show intra-patient change in SF-36-PF from baseline to week 10

Secondary Outcome Measures
NameTimeMethod
Occurrence of responders. Responders are defined as an intra-patient 10-point increase in SF-36-PF from baseline to week 10;

Occurrence of responders. Responders are defined as an intra-patient 10-point increase in SF-36-PF from baseline to week 10;

Intra-patient change in other SF-36 subdomains from baseline to week 10;

Intra-patient change in other SF-36 subdomains from baseline to week 10;

Intra-patient change in fatigue severity scale from baseline to week 10;

Intra-patient change in fatigue severity scale from baseline to week 10;

Intra-patient change in hand grip force (maximum, mean), fatigue ratio, and recovery rate from screening to week 10;

Intra-patient change in hand grip force (maximum, mean), fatigue ratio, and recovery rate from screening to week 10;

Occurrence of IMP side and adverse effects, assessed with AE, SAE and SUSAR reports.

Occurrence of IMP side and adverse effects, assessed with AE, SAE and SUSAR reports.

Trial Locations

Locations (1)

Charite Universitaetsmedizin Berlin KöR

🇩🇪

Berlin, Germany

Charite Universitaetsmedizin Berlin KöR
🇩🇪Berlin, Germany
Judith Bellmann-Strobl
Site contact
+4930450540660
judith.bellmann-strobl@charite.de

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