A Phase 3 interventional study of Sonlicromanol and Placebo in Mitochondrial Diseases, Maternally Inherited Diabetes and Deafness (MIDD) and Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke-like Episodes (MELAS), sponsored by Khondrion BV. Recruiting at 10 sites in 7 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-06-29.
Sponsored by Khondrion BV · Phase 3, Interventional, and Treatment
The KHENERFIN study aims to determine whether the study medicine, sonlicromanol, is able to reduce symptoms of fatigue and the impact of fatigue on daily life, and whether sonlicromanol is able to improve physical abilities of people like balance control and lower limb skeletal muscle strength in people with mitochondrial disease.
In this study, the effects of sonlicromanol are compared against a placebo, a tablet identical in appearance and taste but without the active drug. Participants take either sonlicromanol or placebo twice daily for a treatment duration of 52 weeks.
In addition to these primary objectives, the study evaluates the efficacy of sonlicromanol on secondary and exploratory outcomes, as well as its safety and tolerability after one year of treatment.
The KHENERFIN study is investigating the medicine sonlicromanol. The study aims to see if sonlicromanol can reduce symptoms of fatigue and reduce the impact of fatigue on daily life. The study also investigates if sonlicromanol improves physical abilities like balance control and lower limb skeletal muscle strength in people with mitochondrial disease. In addition to these primary objectives, the study evaluates the efficacy of sonlicromanol on selected secondary and exploratory outcomes. It also assesses the safety and tolerability of sonlicromanol.
This study is a placebo controlled, double blind study; the effects of sonlicromanol will be compared with a placebo (study medication that looks like the actual study medicine but contains no active medicine). Neither the participants nor the study team know who is receiving the study medicine or placebo. Participants cannot change their assigned rreatment.
During the screening period, which lasts a maximum of 4 weeks, it is assessed whether the potential participant meets all requirements to participate in the study. Patients who complete the screening phase and are enrolled in the study are randomly (by chance) assigned to receive either the study medicine sonlicromanol or placebo (no active medication). Participants have an equal chance of receiving either sonlicromanol or a placebo. A final follow-up visit is scheduled 2 weeks after taking the last dose of study medication. Total study duration is approximately 60 weeks.
Sonlicromanol will be supplied in tablet form, containing 90 mg of sonlicromanol (equivalent to 100 mg of sonlicromanol.HCl), with the tablets embossed accordingly or provided as a placebo. The study medication must be taken twice daily during the treatment period of 52 weeks. Up to 220 subjects with a confirmed mitochondrial DNA tRNALeu(UUR) 3243A>G mutation will be randomly assigned in a 1:1 ratio to receive either sonlicromanol or placebo.
182 studies on the registry are indexed under Mitochondrial Diseases; 54 are open to participants now.
This study's planned enrollment of 220 is above the median of 30 across 100 interventional studies indexed under Mitochondrial Diseases.
Browse Mitochondrial Diseases studies →Khondrion BV is the lead sponsor of 6 studies on the registry; 1 is open to participants now.
Counted across the registry records on this site, refreshed daily.
Presence of chronic fatigue (not attributable to other etiologies than PMD):
5xSST at Screening and Baseline should be ≥ 11 seconds and participant must demonstrate the ability to complete the test at baseline (i.e., complete the test within 30 seconds).
6. Other Inclusion criteria per protocol.
Exclusion criteria
Family history of unexplained/uninvestigated syncope or congenital long and short QT syndrome or sudden death (under the age of 60). ECG evidence of acute or recent ischemia, acute or Recent Myocardial Infraction, atrial fibrillation, high grade AV Blocks (Second Degree AV Block Type II or Third-degree AV Block), complete Heart Block or active conduction system abnormalities with the exception of any of the following:
Administration of 90 mg sonlicromanol (equivalent to 100 mg sonlicromanol.HCl) twice daily
Drug: Sonlicromanol
Administration of 100 mg matching placebo twice daily
Drug: Placebo
Administration of 90 mg sonlicromanol (100 mg sonlicromanol.HCl) twice daily during 52 weeks
Administration of 100 mg placebo twice daily during 52 weeks
Neuro-QoL Fatigue Short Form v1
Change from baseline compared to placebo at week 52 and at other relevant study visits of the Quality of Life in Neurological Disorders Fatigue Short Form version 1 (Neuro-QoL Fatigue - SF v1): The Neuro-QoL Fatigue SF v1 is an 8-item self-assessment questionnaire evaluating the perception of fatigue and its impact in daily life activities. Each question is scored as following: 1=Never, 2=Rarely, 3=Sometimes, 4=Often, and 5=Always. Total raw scores range from 8-40. T-scores are calculated from the short form scoring table provided in the instruments´ manual. T-score distributions rescale raw scores into standardized scores with a mean of 50 and a standard deviation (SD) of 10. Change from baseline: Negative numbers mean less fatigue, better outcome, positive score means more fatigue, worse outcome.
Time frame: Screening, Baseline (Day 1), Weeks 13, 26, 39, 52 (End of Trial Visit)
Five Times Sit-To-Stand Test (5XSST)
Change from Baseline compared to placebo at week 52 and at other relevant study visits of the 5xSST in total time (in seconds) to complete the 5xSTS. The 5xSST scoring is based on the amount of time (to the nearest decimal in seconds a subject is able to transfer from a seated to a standing position and back to sitting five times. Inability to complete five repetitions without assistance or use of upper extremity support indicates 'failure to perform of test, any modifications should be documented. Participant is directed to stand up straight as quickly as possible 5 times, without stopping in between, keeping arms folded across the chest. When 5xSST is not reached within 30.0 seconds the test is stopped and the actual number of sit to stands reached within those 30 seconds is recorded. Faster times (in sec) denotes better performance.
Time frame: Screening, Baseline (Day 1), Weeks 13, 26, 39, 52 (End of Trial Visit)
36-Item Short Form Survey (SF-36)
Change from Baseline at week 52 and at other relevant study visits of the 36-item Short Form Survey Instrument (SF-36). SF36 is a 36-item multidimensional self-report health related quality of life (HRQoL) questionnaire, containing 36 items measuring eight dimensions of HRQoL: physical functioning, bodily pain, role limitations due to physical health problems, role limitations due to personal or emotional problems, emotional well-being, social functioning, energy/fatigue, and general health perceptions. It also includes a single item that provides an indication of perceived change in health. To score the SF-36, scales are standardized with a scoring algorithm to obtain a score ranging from 0 to 100. Standard scoring algorithms yield two distinct, higher-order summary scores: Physical Component Summary (PCS) and Mental Component Summary (MCS). Higher scores on all subscales represent better health and functioning.
Time frame: Baseline (Day 1), Weeks 13, 26, 39, 52 (End of Trial Visit)
The PROMIS Fatigue Primary Mitochondrial Disease Short Form (PROMIS) Fatigue PMD SF)
Change from baseline at week 52 and at other relevant study visits of the Patient-Reported Outcomes Measurement Information System (PROMIS®) Fatigue Primary Mitochondrial Disease Short Form (PROMIS Fatigue PMD SF). The PROMIS Fatigue Primary Mitochondrial Disease Short Form is a nine-item self-report inventory to assess fatigue symptoms and impacts on daily living measured in PMD. The PROMIS Fatigue PMD SF asks the respondent to rate the experience and impact of fatigue symptoms by asking how often they feel or experienced specific fatigue symptoms in the past seven days on a 5-point rating scale scored as: "never" (1), "rarely" (2), "sometimes" (3), "often" (4), "always" (5). Higher scores indicate greater fatigue severity.
Time frame: Screening, Baseline (Day 1), Weeks 13, 26, 39, 52 (End of Trial Visit)
Beck Depression Inventory-2 (BDI-2)
Change from Baseline compared to placebo at week 52 and at other relevant study visits of the Beck Depression Inventory (BDI). The Beck Depression Inventory (BDI) is a 21-question multiple-choice self-report inventory, for measuring the severity of depression. It is composed of items relating to symptoms of depression such as hopelessness and irritability, cognitions such as guilt or feelings of being punished, as well as physical symptoms such as fatigue, weight loss, and lack of interest in sex. Each answer is scored on a scale value of 0 to 3; higher scores indicate more severe depressive symptoms.
Time frame: Screening, Baseline (Day 1), Weeks 13, 26, 39, 52 (End of Trial Visit)
Patient-scored Global Impression of Severity scale (PGI-S)
Change from Baseline compared to placebo at week 52 and at other relevant study visits of the Patient Global Impression of Severity (PGI-S).The Patient scored Global Impression - Severity questionnaire assesses patient's impression of disease severity. The PGI-S item asks the respondent to rate the severity of their PMD symptoms at the time of assessment ("Please choose the response that best describes the severity of your Primary Mitochondrial Disease (PMD) symptoms today") on a 7-point scale scored as: "none" (1), "very mild" (2), "mild" (3), "moderate" (4), "moderately severe" (5), "severe", (6), or "extremely severe" (7). Higher scores indicate a higher level of severity.
Time frame: Baseline (Day 1), Weeks 13, 26, 39, 52 (End of Trial Visit)
Clinician-scored Global Impression of Severity (CGI-S)
Change from Baseline compared to placebo at week 52 and at other relevant study visits of the Clinician Global Impression of Severity (CGI-S). The Clinician scored Global Impression - Severity (CGI-S) scale is a 7-point scale that requires the clinician to rate the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. The CGI-S asks the clinician one question: "Considering your total clinical experience with this particular population, how ill is the patient at this time?" which is rated on the following seven-point scale: "normal, not at all ill" (1), "borderline" (2), "mild" (3), "moderate" (4), or "marked" (5), "severe" (6), and "among the most extremely affected patients" (7). This rating is based upon observed and reported symptoms, behaviour, and function at the time of the assessment.Higher scores indicate a higher level of severity.
Time frame: Baseline (Day 1), Weeks 13, 26, 39, 52 (End of Trial Visit)
Newcastle Mitochondrial Disease Adult Scale (NMDAS)
Change from Baseline compared to placebo at week 52 and at other relevant study visits of the Newcastle Mitochondrial Disease Scale for Adults (NMDAS). The NMDAS is a semi-quantitative clinical rating scale designed specifically for all forms of mitochondrial disease. The rating scale encompasses all aspects of mitochondrial disease by exploring several domains: current function, system specific involvement, and current clinical assessment. Each question/item in the NMDAS has a possible score from 0-5. Each of the three section scores are calculated by simply summing the scores obtained for each question in that section, with the higher the score the more severe the disease. Thus, scores can range from 0 to 50 for Sections I and III, and from 0 to 45 for Section II, and from 0 to 145 for Sections I through III. Higher scores indicate a higher level of disease severity.
Time frame: Baseline (Day 1), Weeks 26, 52 (End of Trial Visit)
Brief Pain Inventory Short Form (BPI-SF)
Change from Baseline compared to placebo at week 52 and at other relevant study visits of the Brief Pain Inventory-Short Form (BPI-SF). The BPI-SF is a validated (33) self-administered questionnaire to assess the severity of pain and the impact of pain on the patient's daily functions. BPI-SF evaluates pain severity at its worst, least, and average during the last 24 hours, as well as current pain level, with 0 representing no pain and 10 the worst pain imaginable. Seven items measuring interference with daily functioning (general activity, walking, work, mood, relations with others, sleep, and enjoyment of life) are also assessed on an 11-point scale, where 0 represents no interference and 10 complete interferences. The scores can be averaged to the two components of the BPI SF score, the Pain Severity Index and the Pain Interference Index. Higher scores indicate a higher level of severity and impact of pain.
Time frame: Baseline (Day 1), Weeks 13, 26, 39, 52 (End of Trial Visit)
Health Economics and Outcomes Research (HEOR) Assessments: EQ-5D-5L
Change from Baseline compared to placebo at week 52 and at other relevant study visits of the EQ-5Dimension-5 Level (EQ-5D-5L). The EQ-5D-5L is a self-report health-related quality of life (HRQoL) instrument consisting a descriptive system and a visual analogue scale (EQ-VAS). The descriptive system that defines health in five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 response categories (levels): no problems, slight problems, moderate problems, severe problems and extreme problems. The EQ-VAS records the respondent's self-rated health on a vertical VAS. The respondents can report their perceived health status with a grade ranging from 0 ('the worst health you can imagine') to 100 ('the best health you can imagine'). A higher score denotes a worse health state.
Time frame: Screening, Baseline (Day 1), Weeks 13, 26, 39, 52 (End of Trial Visit) and at week 54 (Follow-up)
Columbia-Suicide Severity Rating Scale (C-SSRS)
Change from Baseline compared to placebo at week 52 and at other relevant study visits of the Columbia-Suicide Severity Rating Scale (C-SSRS). The instrument assesses severity of suicidal ideation ("severity subscale"), rated on a 5-point ordinal scale, the intensity of ideation subscale ("intensity subscale"), comprising 5 items, rated on a 5-point ordinal scale: frequency, duration, controllability, deterrents, and reason for ideation, resulting in 0-25 score range summed from five items, with higher scores indicating more severe suicidal ideation. A score of 0 indicates that no suicide ideation is present. The behaviour subscale is a nominal scale including actual, aborted, and interrupted attempts; preparatory behaviour; and self-injurious behaviour. The lethality subscale assesses actual attempts; actual lethality rated on a 6-point ordinal scale. Higher scores indicate a higher level of severity.
Time frame: Screening, Baseline (Day 1), Weeks 13, 26, 39, 52 (End of Trial Visit)
Gastro-Intestinal symptoms.
Change from Baseline compared to placebo on the number of gastro-intestinal complaints, intensity and duration. The number of gastro-intestinal complaints/month will be captured, starting at screening until (and including) the week 52 visit. For this purpose the Gastro-Intestinal symptoms questionnaire will be used.
Time frame: Through week 52
Seizure episodes
Change from Baseline compared to placebo on the number of seizures, intensity and duration and on the use of medication. Seizure data (e.g., occurrence, duration, intensity severity; and any use of migraine medication) are captured daily through a daily headache-diary.
Time frame: Through week 52
Safety and tolerability assessed by nature, frequency and severity of treatment emergent adverse events (TEAEs)
Safety and tolerability assessed by nature, frequency and severity of treatment emergent adverse events (TEAEs) Treatment emergent adverse events will be coded using medical dictionary for regulatory activities (MedDRA). A TEAE is defined as an adverse event (AE) observed after starting administration of the investigational product (IP) to 14 days after last dose of IP. An AE is any untoward medical occurrence in a participant, temporally associated with the use of IP, whether or not considered related to the IP. An AE can therefore be any unfavourable and unintended, symptom, or disease (new or exacerbated) temporally associated with the use of IP.
Time frame: Through Week 52
Safety: 12 lead ECG parameters: QRS duration (milliseconds)
12 lead ECG parameter data QRS duration (milliseconds) will be summarised.
Time frame: Baseline (Day 1), Weeks 13, 26, 39, 52 (End of Trial Visit)
Safety: 12 lead ECG parameters: QRS morphology (peak, axis)
12 lead ECG parameter data QRS morphology (peak, axis) will be summarised.
Time frame: Baseline (Day 1), Weeks 13, 26, 39, 52 (End of Trial Visit)
Safety: 12 lead ECG parameters: QTcF (Fridericia)
12 lead ECG parameter data QTcF (Fridericia) will be summarised.
Time frame: Screening, Baseline (Day 1), Day 6, Weeks 4, 8, 13, 26, 39, 52 (End of Trial Visit), 54 (Safety FU)
Safety: 12 lead ECG parameters: PQ interval: milliseconds (ms))
12 lead ECG parameter data PQ intervals (milliseconds) will be summarised.
Time frame: Screening, Baseline (Day 1), Day 6, Weeks 4, 8, 13, 26, 39, 52 (End of Trial Visit), 54 (Safety FU)
Safety: 12 lead ECG parameters: Heart rate: beats per minute (bpm)
12 lead ECG parameter data Heart rate (beats per minute (bpm) be summarised.
Time frame: Screening, Baseline (Day 1), Day 6, Weeks 4, 8, 13, 26, 39, 52 (End of Trial Visit), 54 (Safety FU)
Safety: 12 lead ECG parameters: Tpeak-Tend interval
12 lead ECG parameter data (Tpeak-Tend interval) will be summarised.
Time frame: Screening, Baseline (Day 1), Day 6, Weeks 4, 8, 13, 26, 39, 52 (End of Trial Visit), 54 (Safety FU)
Safety: 12 lead ECG parameters: T wave morphology (peak, symmetry)
12 lead ECG parameter data T-wave morphology (symmetry) will be summarised.
Time frame: Screening, Baseline (Day 1), Day 6, Weeks 4, 8, 13, 26, 39, 52 (End of Trial Visit), 54 (Safety FU)
Safety: Incidence of laboratory abnormalities, based on haematology, clinical chemistry, and urinalysis test results
Incidence of laboratory abnormalities outside the clinical reference ranges based on haematology, serum biochemistry, and urinalysis test
Time frame: Screening, Baseline (Day 1), Weeks 4, 8, 13, 26, 39, 52 (End of Trial Visit)
Safety: Vital signs abnormalities and/or AEs
Incidence of clinically significant vital sign values.
Time frame: Screening, Baseline (Day 1), Weeks 26, 52 (End of Trial Visit),54 (Safety FU)
Pharmacokinetics: Tmax (hours)
Tmax: Time to reach maximum (peak) plasma concentration following drug administration (hours)
Time frame: Week 39: pre-dose, and at 1, 2, 4, 6, 8 hours post dosing.
Pharmacokinetics: Cmax (ng/mL)
Maximum (peak) plasma drug concentration in ng/mL
Time frame: Week 39: pre-dose, and at 1, 2, 4, 6, 8 hours post dosing.
Pharmacokinetics: Ctrough (ng/mL)
Plasma concentration (measured concentration at the end of a dosing interval at steady state in ng/mL
Time frame: Week 39: pre-dose, and at 1, 2, 4, 6, 8 hours post dosing.
Pharmacokinetics: AUCinf (h*ng/mL)
Area under the plasma concentration time curve from time zero to infinity in h\*ng/mL
Time frame: Week 39: pre-dose, and at 1, 2, 4, 6, 8 hours post dosing.
Pharmacokinetics: AUCtau (h*ng/mL)
Area under the plasma concentration time curve in h\*ng/mL
Time frame: Week 39: pre-dose, and at 1, 2, 4, 6, 8 hours post dosing.
Pharmacokinetics: T1/2 (hours)
Terminal Elimination Half-life
Time frame: Week 39: pre-dose, and at 1, 2, 4, 6, 8 hours post dosing.
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