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)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Charite Universitaetsmedizin Berlin KöR

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Virus Diseases [C02]

Trial duration

31 May 2023 → 7 May 2026

Decision date (initial)

2024-11-13

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-517713-33-00

EudraCT number

2021-005494-11

WHO UTN

U1111-1313-0253

ClinicalTrials.gov

NCT05697640

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Pharmacokinetic, Safety, Efficacy

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

Secondary objectives 5

1. The occurrence of 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 scale from baseline to week 10 when comparing Vericiguat with placebo;
4. An improvement in muscle fatigue assessed by repetitive hand grip strength (HGS) test from screening to week 10 when comparing Vericiguat with placebo;
5. Assessment of investigational medical product (IMP) safety and side/adverse effects during the IMP intake and titration regimen.

Conditions and MedDRA coding

Post-COVID-19 syndrome without (PCS) or with (PCS/CFS) fulfillment of myalgic encephalomyelitis/chronic fatique syndrome (ME/CFS) criteria

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. 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)
2. 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
3. Ongoing symptoms of PCS or PCS/CFS for ≥ 6 months
4. Bell Score: 30-60
5. 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)
6. Normal thyroid function
7. Subject is willing, understanding, and able to provide informed consent
8. Signed informed consent prior to initiation of any trial related measure
9. 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 18

1. COVID-19 vaccination within the last 4 weeks before inclusion
2. Known SARS-CoV-2 infection-related organ damage/comorbidity
3. Renal impairment with an estimated glomerular filtration rate <15 mL/min/1.73 m2 or on dialysis at screening
4. 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])
5. Concomitant or previous use of Vericiguat
6. Contraindications against IMP
7. Concurrent or anticipated concomitant use of PDE-5 inhibitors such as vardenafil, tadalafil, and sildenafil, nitrates, or sGC-stimulators
8. Use of other sGC stimulators, e.g., riociguat
9. Hypersensitivity to the active substance or any of the other ingredients
10. Systolic blood pressure: < 100 mmHg at screening
11. Contraindication against MRI investigation (e.g., stents, metal clips)
12. Severe hepatic insufficiency such as with hepatic encephalopathy or hepatic laboratory abnormalities (ALT or AST ≥3 × ULN or total bilirubin ≥2 × ULN) at screening.
13. 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)
14. Subject is pregnant or breastfeeding at screening
15. Subject is institutionalized by order of court or public authority
16. 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
17. Subject who might be dependent on the sponsor, the investigator, or the trial site
18. Participation in another clinical trial with an investigational medical product within 3 months or 5 half-lives, whichever is longer, before screening visit

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

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

Secondary endpoints 5

1. Occurrence of responders. Responders are defined 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 in hand 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.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Placebo 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Charite Universitaetsmedizin Berlin KöR

Sponsor organisation

Charite Universitaetsmedizin Berlin KöR

Address

Augustenburger Platz 1, Wedding Wedding

City

Berlin

Postcode

13353

Country

Germany

Scientific contact point

Organisation

Charite Universitaetsmedizin Berlin KöR

Contact name

Neuroimmunology Team, Clinical Research Unit, ECRC

Public contact point

Organisation

Charite Universitaetsmedizin Berlin KöR

Contact name

Neuroimmunology Team, Clinical Research Unit, ECRC

Third parties 3

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 8 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications