Open Sonlicromanol in Post-COVID: A Randomized, Double-blind, Placebo-controlled, Phase II Trial (SON4PEM) [Netherlands, not yet recruiting]

[forestglip]

SON4PEM Study: Sonlicromanol in Post-COVID: A Randomized, Double-blind, Placebo-controlled, Phase II Trial

Brief Summary
The aim of this randomized, doube-blind, placebo-controlled, phase II trial, is to study the effect of sonlicromanol on fatigue in patiënt with post-COVID who experience post-exertional malaise (PEM).

Inclusion Criteria

• Post COVID according to WHO criteria and verified by post COVID physician
• Post-exertional malaise (PEM) according to DSQ-PEM questionnaire
• Bell's disability score 20-70%
• Mild initial SARS-CoV-2 infection (no hospitalisation)
• WHO performance score of 0 before initial SARS-CoV-2 infection

Spoiler: Exclusion Criteria

• Patiënts at risk for cardiac conduction disorders
• History of clinical significant gastro-intestinal surgery or dysmotility that impairs the adsorption of the IMP
• Clinical significant respiratory or cardiovascular disease,
• Instable neurological disease
• Clinical significant active psychiatric disorder that requires treatment
• History of substance abuse
• Active malignancy within the past 5 years
• History of solid organ transplantation
• Active HIV, hepatitis B or C infection
• BMI < 18.5 or > 35
• Pregnancy or breast feeding
• Clinicaly relevant laboratory test value outside the reference range
• Use of the following medication, unless stable for at least one month before study and remaining stable throughout the study: (multi)vitamins, co-enzyme Q10, Vitamin E, riboflavin, amino acids, antioxidant supplements and any medicatin negatively influencing mitochondrial functioning (including but not limited to valproic acid, glitazones, statins, anti-virals, amiodarone and NSAID's)
• Use of the following medication: any moderate or strong Cytochrome P450 (CYP)3A4 inhibitors (all 'conazoles-anti-fungals', HIV antivirals, grapefruit), strong CYP3A4 inducers ((including HIV antivirals, carbamazepine, phenobarbital, phenytoin, rifampicin, St. John's wort, pioglitazone, troglitazone) or any medication metabolized by CYP3A4 with a narrow therapeutic index, medication known to be substrate of Organic Cation Transporter 1 (OCT1) and organic cation transporter 2 (OCT2) or strong P-glycoprotein inhibitors (including amiodarone, azithromycin, captopril, clarithromycin, cyclosporine, piperine, quercetin, quinidine, quinine, reserpine, ritonavir, tariquidar, and verapamil).
• Use of any medication known to affect cardiac repolarization unless QTc interval at screening is normal during stable treatment for a period of two weeks, or 5 half-lives

Intervention

• Sonlicromanol 90mg bid for 13 weeks
• Placebo bid for 13 weeks

Enrollment (Estimated)
80

Study Completion (Estimated)
2027-03

Primary Outcome

• Post-COVID related fatigue measured with the Fatigue Assessment Scale

Secondary Outcomes

• Muscle strength measured with the Repeated Handgrip Strength of the dominant hand
• Post-COVID related cognitive function measured with the PROMIS cognitive function SF 8a
• Health related quality of life measured with the SF-36 questionnaire

Sponsor
Michele van Vugt

Collaborators

• ZonMw: The Netherlands Organisation for Health Research and Development
• Khondrion BV

 

[forestglip]

Thread for this drug in a different condition:

Phase 2b program with sonlicromanol in patients with mitochondrial disease due to m.3243A>G mutation, 2025, Smeitink et al.

 

[forestglip]

From the above thread:

The reason for posting this is that the Dutch government research funder ZonMw has funded a stud on this drug (sonlicromanol) for Long Covid patients. It's led by Michele van Vugt at Amsterdam University.

Honorering van projecten biomedische en klinische rondes post-COV

22 onderzoeken op het gebied van biomedisch en klinisch onderzoek post-COVID gaan nog dit jaar van start. Van de ingediende aanvragen binnen de biomedische en k

www.zonmw.nl

They refer to the trial above as a justification but the study had only 27 participants and the primary outcome was not significant.

Here's the justification for this trial, from that website, auto-translated, with line breaks added:

Patients with post-COVID (pC) report as main complaints persistent fatigue and post-exertional malaise (PEM), for which there is no treatment.

In pC patients, the research group has found a different construction and function of the power plants (mitochondria) of the cell as is also seen in mitochondrial diseases. This provides clues for testing new drugs such as sonlicromanol.

The recently completed phase 2b trial (RCT plus 52 week extension) with sonlicromanol showed improved quality of life in mitochondrial patients at 52 weeks with a statistically and clinically relevant decrease in fatigue complaints and muscle weakness.

Patients taking sonlicromanol for more than a total of 21.5 years (“named patient” program) indicate that the improvement in complaints persist and further improve. The safety profile of sonlicromanol is good.

The research group wants to investigate whether with sonlicromanol also in pC patients the fatigue and PEM reduce.