Sonlicromanol in Post-COVID (SON4PEM)

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

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

Study Overview

• Status: Recruiting
• Conditions: Post COVID Condition
• Intervention / Treatment: Drug: Sonlicromanol; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 2

Contacts and Locations

Study Locations

• Netherlands
  • North Holland
    • Amsterdam, North Holland, Netherlands, 1105 AZ
      • Recruiting
      • Amsterdam University Medical Center, Location Academic Medical Center (AMC)
      • Contact: Bastienne De Jonghe, MD; Phone Number: 020 566 9111; Email: postcovidtrials@amsterdamumc.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Exclusion Criteria:

• Patients at risk for cardiac conduction disorders
• History of clinical significant gastro-intestinal surgery or dysmotility that impairs the adsorption of the IMP
• Clinically significant respiratory or cardiovascular disease
• Unstable neurological disease
• Clinically 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 breastfeeding
• Clinically 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 medication negatively influencing mitochondrial functioning (including but not limited to valproic acid, glitazones, statins, antivirals, amiodarone and NSAIDs)
• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention group	Drug: Sonlicromanol; Sonlicromanol 90mg twice daily for 13 weeks
Placebo Comparator: Placebo group	Drug: Placebo; Placebo twice daily for 13 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fatigue	Post-COVID related fatigue measured with the Fatigue Assessment Scale (FAS), a 10-item questionnaire measuring physical/mental fatigue (ranging from 10-50), with scores <22 indicating no fatigue, 22-34 mild-to-moderate, and ≥35 severe fatigue	Between group differences at week 13

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Muscle strength	Muscle strength measured with the Repeated Handgrip Strength of the dominant hand	Between group differences at week 13
Cognitive function	Post-COVID related cognitive function measured with the PROMIS cognitive function SF 8a, measures self-perceived cognitive abilities, with scores converted to a T-score (mean 50, SD 10), where higher scores indicate better functioning	Between group differences at week 13
Health related quality of life	Health related quality of life measured with the SF-36 questionnaire with scores ranging from 0-100, where higher scores indicate better quality of life	Between group differences at week 13
Fatigue	Post-COVID related fatigue measured with the NeuroQoL SF Fatigue, resulting in a T-score (mean 50, SD 10) where higher scores mean more fatigue	Between group differences at week 13

Collaborators and Investigators

• Sponsor: Michele van Vugt
• Collaborators: ZonMw: The Netherlands Organisation for Health Research and Development; Khondrion BV

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): March 1, 2027

Study Registration Dates

• First Submitted: December 11, 2025
• First Submitted That Met QC Criteria: December 11, 2025
• First Posted (Actual): December 22, 2025

Study Record Updates

• Last Update Posted (Actual): April 13, 2026
• Last Update Submitted That Met QC Criteria: April 7, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Post-Infectious Disorders; COVID-19; Pathologic Processes; Chronic Disease; Disease Attributes; Respiratory Tract Infections; Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Lung Diseases; Pneumonia, Viral; Pneumonia; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; Pathological Conditions, Signs and Symptoms; Post-Acute COVID-19 Syndrome
• Other Study ID Numbers: 2025-521866-92-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No