Sonlicromanol in post-COVID: A randomized, double-blind, placebo-controlled, phase II trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Amsterdam UMC Stichting

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18], Diseases [C] - Virus Diseases [C02]

Trial duration

12 Dec 2025 → ongoing

Decision date (initial)

2025-12-02

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

ZonMW · Khondrion

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy

Reduction of post-COVID related fatigue measured with the FAS on week 13

Secondary objectives 1

1. Secondary endpoints include improvement in various disease domains within long COVID on week 4, 8 and 13 using the SF-36 and the PROMIS cognitive function 8a score. In addition, physical improvement will be measured using the Repeated Handgrip Strength and the Amsterdam Cognition Scan on baseline and week 4, 8 and 13.

Conditions and MedDRA coding

long COVID

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. • Any gender aged ≥18 ≤ 65 years. • A confirmed post-COVID as diagnosed by two experienced clinicians: o history of SARS-CoV-2 infection o symptoms consistent with post-COVID beginning after the index infection and continuing more than 6 months • Presence of post exertional malaise, according to the DSQ-PEM questionnaire. • Healthy (i.e. no symptoms present) prior to NAAT or serology-proven SARS-CoV-2 infection as determined by medical history). • Bell’s functionality score between from 20-70% • None of the included participants were admitted to the hospital during acute SARS-CoV-2. • Able and willing to provide written Informed Consent prior to screening evaluations and to attend study appointments within the specified time windows. • In the investigator's opinion, likely to comply with the protocol and able to adhere to the study requirements for the length of the study. • Stable exercise regimen for at least 4 weeks prior to randomization and must stay on a stable regimen for the duration of the study period (for participants who participate in a regular exercise regimen). • Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective/adequate methods of contraception during study treatment. Highly effective contraception methods include: • Total sexual abstinence: if defined as refraining from heterosexual intercourse during the entire period of risk associated with study treatment. Reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject. • Combined oral, intravaginal, transdermal, implanted, injected (estrogen and progestogen containing) hormonal contraception or progesterone only hormonal contraception associated with inhibition of ovulation. • Placement of an intrauterine device (IUD) or intrauterine hormone-releasing system (IUS) • Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment. • Vasectomy of the partner; vasectomized partner is considered a highly effective birth control method provided that partner is the sole sexual partner of the subject and that the vasectomized partner has received medical assessment of the surgical success.

Exclusion criteria 1

1. Treatment with an IMP for PMD within 3 months prior to screening or plans to use an IMP during the study. Surgery of gastrointestinal tract that might interfere with drug absorption. Or severe GI dysmotility which will impair appropriate IMP absorption in the opinion of the investigator. Participant has clinically significant respiratory disease and/or cardiac disease in the opinion of the investigator, or prior interventional cardiac procedure within 3 months prior to randomization. QTcF > 450 msec (men) or QTcF > 470 msec (women). Structural heart disease based on Echocardiography and/or abnormal conduction (QRS and/or PR > 120 msec), and/or repolarization, myocardial function (LVEF <52% in men and < 54% in women), symptomatic ischemic heart disease, and/or pathologic hypertrophy, that is not well controlled under current specialized care. Subjects with congestive heart failure class II and above should also be excluded. Family history of unexplained syncope or congenital long and short QT syndrome or sudden death. ECG evidence of acute ischemia, atrial fibrillation or active conduction system abnormalities. History of acute heart failure (within the last 3 months), (family) history of unexplained syncope or congenital long and short QT syndrome or sudden death. Higher degree of AV-blocks (II° or III°) in the absence of a pacemaker or ICD. In case QTcFridericia is >450ms (men) and >470ms (women) and a simultaneous bundle-branch-block is not present at screening then QTcF will be calculated using regular QT interval. In case LBBB or RBBB is present the modified QT interval should be calculated. Patient is excluded if ECG shows active acute coronary syndrome criteria as described by the American Heart Association and that are clearly a deviation from the subject’s baseline ECG. Participants with pacemaker or AICD. Recent history of unstable disease, inadequately controlled neurological manifestations or not recovered from stroke-like episodes including but not limited to stroke-like episodes within the last 6 months, hospitalized for status epilepticus within the last 6 months. Blood pressure >160/90 mmHg at screening or baseline confirmed by re-testing. ≥1 clinical laboratory test value outside the reference range, based on the blood and urine samples taken at the screening visit, that are of potential risk to the patient's safety. See protocol for specifications. Medical history of drug abuse as defined in the protocol. Within 4 weeks prior to screening, the use of certain medication and supplements (see protocol). Patient has psychiatric conditions such as schizophrenia, bipolar disorder or major depressive disorder that has not been under control within 3 months prior to screening. Patient has severe behavioral or cognitive problems that preclude participation in the study. Patient has undergone an inpatient hospitalization that precludes participation in the study, within the 30 days prior to the randomization. Patient has a planned hospitalization or a surgical procedure during the study, which may affect the study assessments. Patient has clinically significant and unstable respiratory disease and/or cardiac disease, or prior interventional cardiac procedure within 3 months prior to randomization. Patient requires any ventilator support, including CPAP or BiPAP at night. Patient has severe vision impairment that may interfere with their ability to complete all study requirements. Active malignancy or any other cancer from which the patient has been disease-free for <5 years, except for curative treated localized non-melanoma skin cancer. Patient has a solid organ transplant and/or is currently receiving treatment with therapy for immunosuppression. History of active human immunodeficiency virus, hepatitis B or hepatitis C infection. Patient has BMI below 18.5 kg/m2 or above 35 kg/m2 at screening. Any active infection at the time of randomization. Pregnancy or breast feeding.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Fatigue symptoms measured at week 13 by the FAS

Secondary endpoints 1

1. Secondary endpoints include improvement in various disease domains within long COVID on week 4, 8 and 13 using the SF-36 and the PROMIS cognitive function 8a score. In addition, physical improvement will be measured using the Repeated Handgrip Strength and the Amsterdam Cognition Scan on baseline and week 4, 8 and 13.

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Amsterdam UMC Stichting

Sponsor organisation

Amsterdam UMC Stichting

Address

De Boelelaan 1117

City

Amsterdam

Postcode

1081 HV

Country

Netherlands

Scientific contact point

Organisation

Amsterdam UMC Stichting

Contact name

post COVID research information

Public contact point

Organisation

Amsterdam UMC Stichting

Contact name

post COVID research information

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 5 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