Mitochondrial DiseasesPhase 3KH176-301NCT06451757
KHENERFIN Study: A Trial to Evaluate the Efficacy and Safety of Sonlicromanol in Primary Mitochondrial Diseases
A Phase 3 study testing Sonlicromanol in people with Mitochondrial Diseases and Maternally Inherited Diabetes and Deafness (MIDD), run by Khondrion BV at 10 sites in 7 countries.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Mitochondrial Diseases, Maternally Inherited Diabetes and Deafness (MIDD), Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke-like Episodes (MELAS)
- What is being tested?
- Sonlicromanol
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 220 participants
- Where
- 10 sitesin 7 countries
- Study dates
- 14 Apr 2026to Sep 2029
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed Informed Consent
- Males and females aged ≥18 years with a multi-system primary mitochondrial disease.
- A confirmed mitochondrial DNA tRNALeu(UUR) m.3243A>G mutation (m.3243A>G PMD) plus an age adjusted heteroplasmy percentage ≥ 20% in white blood cells [=blood heteroplasmy/0.977(age+12)]. Or in urine (urinary epithelial cells), or buccal smear or skeletal muscle (results (obtained per local guidance) ≥ 20% must be available prior to the subject being randomized).
- Presence of chronic fatigue (not attributable to other etiologies than PMD):
- Patient self-reported chronic fatigue for at least 3 months prior to the Screening Visit and recorded in the clinical patient files; AND
- Presence of fatigue (raw total score >22), assessed by Neuro-QoL SFv1-F at Screening.
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- Presence of mitochondrial myopathy defined as:
- 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.
Who cannot join
- Treatment with any IMP within 3 months (or 5 times the half-life of the IMP, whichever is longer) prior to screening or plans to use an IMP (other than the study intervention) during the study.
- Bone deformities, motor abnormalities or chronic ulcers that in the opinion of the PI may interfere with and/or confound the interpretation of the subject's performance during the 5 times sit to stand test (5XSST).
- Surgery of gastrointestinal tract that might interfere with drug absorption. Or severe GI dysmotility, chronic vomiting, diarrhea, bouts of pseudo-obstruction which will impair appropriate IMP absorption in the opinion of the investigator.
- Clinically significant respiratory disease and/or cardiac disease (medical history or current clinical findings) in the opinion of the investigator.
- Prior interventional cardiac procedure (e.g., cardiac catheterization, angioplasty/percutaneous coronary intervention, balloon valvuloplasty, etc.) within 3 months prior to screening.
- Structural heart disease based on cardiac MRI or Echocardiography (e.g., clinically significant valve disease; i.e., aortic or mitral valve stenosis or regurgitation) and / or Left ventricular dysfunction (LVEF <52% in men and < 54% in women) and / or congestive cardiac failure (more severe than grade II) and / or Maximum left-ventricular septal or posterior wall thickness > 15 mm and / or Evidence of active myocardial ischaemia, ECG evidence and / or recent history of myocardial infarction (< 6-months) and / or coronary angioplasty / coronary bypass surgery (< 12 months).
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- Family history of unexplained/uninvestigated syncope or congenital long and short QT syndrome or sudden death (under the age of 60) and / or Abnormal QTcF interval [QTcF > 450 msec (men) or QTcF > 470 msec (women) = abnormally long QTcF or QTcF < QT < 320ms = abnormally short QtcF] and / or Intermittent or persistent WPW (pre-excitation) syndrome on ECG [ie: abnormally wide QRS > 120ms with slurred up-stroke ('delta' wave) and PR-interval < 120ms] and / or ECG evidence of atrial fibrillation (permanent, persistent or paroxysmal) and / or
- High grade AV Block [2nd-degree AV block Type II (ie: 2:1) or complete AV block (3rd degree) or intermittent conduction system abnormalities with the exception of any of the following:
- 1st degree atrioventricular (AV)-block
- 2nd degree AV-block Type 1 (Mobitz Type 1 / Wenckebach type)
- Right bundle branch block.
- History of acute heart failure (within the last 3 months).
- Higher degree of AV-blocks (AVB II° or III°).
- Other exclusion criteria per protocol
Trial locations and contacts
10 sites in 7 countries. Contact the study team or a site near you to ask about taking part.
10 sites in 7 countries
United States3 sites, 3 recruiting
- Not yet recruiting
Massachusetts General Hospital
Boston, Massachusetts, 02114
Erica Kelly, 617-724-7726, elkelly@mgh.harvard.edu
Amel Karaa, Dr.
- Not yet recruiting
Cleveland Clinic Neurological Institute Mellen Center
Cleveland, Ohio, 44195
Jamie Jobson, jobsonj@ccf.org
Sumit Parikh, Dr.
- Recruiting
The University of Texas Health Science Center at Houston
Houston, Texas, 77030
Lindsey Miller, 713-500-7143, lindsey.b.miller@uth.tmc.edu
Antoinette Bernal Tent, (713) 500-6991, antoinette.w.bernaltent@uth.tmc.edu
France2 sites, 2 recruiting
- Not yet recruiting
CHU de Bordeaux - Hôpital Pellegrin Service Gynecologie Obstetrique
Bordeaux, Gironde, 33000
Ndeye Fatou Ngom, +33557820348, ndeye-fatou.ngom@chu-bordeaux.fr
Samira Madi Radjabou, +33540451129 x51129, samira.madi-radjabou@chu-bordeaux.fr
- Recruiting
Groupe Hospitalier Pitie-Salpetriere - Charles-Foix Clinical Investigation Center Paris-Est
Paris, Paris, 75013
Sarah Taieb Tamacha, +33473750750, sarah.taieb-tamacha@icm-institute.org
Fanny Mochel, Dr.
Denmark1 site, 1 recruiting
- Recruiting
Rigshospitalet, University of Copenhagen
Kopenhagen, Region Sjælland, DK2100
Emma Roerbaek Larsen, +4535453545, emma.roerbaek.larsen.01@regionh.dk
Pia Hynne, +4535457357, pia.hynne.02@regionh.dk
Germany1 site, 1 recruiting
- Recruiting
Klinikum der Universität München Friedrich-Baur-Institut
München, 80336
Natalie Adriana Villalobos Trigueros, +49 89/4400-57402, natalie.villalobos@med.uni-muenchen.de
Thomas Klopstock, Prof. Dr.
Italy1 site, 1 recruiting
- Recruiting
Fondazione IRCCS Istituto Neurologico Carlo Besta
Milan, 20133
Roberta Piazza, +39223942113, roberta.piazza@istituto-besta.it
Costanza Lamperti, Dr.
Netherlands1 site, 1 recruiting
- Recruiting
Radboud University Medical Center
Nijmegen, Gelderland, 6525
Evertine Abbink, MD, PhD, +31 24 3618819, evertine.abbink@radboudumc.nl
evertine.abbink@radboudumc.nl
United Kingdom1 site, 1 recruiting
- Recruiting
University College London Hospitals NHS Foundation Trust National Hospital for Neurology and Neurosurgery
London, Greater London, WC1N 3BG
Laura Berg, laura.berg1@nhs.net
Robbert Pitceathly, Dr.
About this study
Official title: A Phase III, Randomised, Double-blind, Placebo-controlled, Parallel-group, Pivotal Trial to Assess the Efficacy and Safety of Sonlicromanol in Adult Subjects With a Genetically Confirmed Mitochondrial DNA tRNALeu(UUR) m.3243A>G Variant
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.
Read the detailed description
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.
- Conditions
- Mitochondrial Diseases, Maternally Inherited Diabetes and Deafness (MIDD), Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke-like Episodes (MELAS), Mitochondrial DNA tRNALeu(UUR) m.3243A<G Mutation
- Being tested
- Sonlicromanol, Placebo
- Keywords
- Mitochondrial Diseases, Oxidative Phosphorylation (OXPHOS), Maternally Inherited Diabetes and Deafness (MIDD), Mitochondrial DNA tRNALeu(UUR) m.3243A<G Mutation, Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke-like episodes (MELAS), Sonlicromanol
- Medical subject headings
- Mitochondrial Diseases, Noninsulin-dependent diabetes mellitus with deafness, MELAS Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SonlicromanolDrug
Administration of 90 mg sonlicromanol (100 mg sonlicromanol.HCl) twice daily during 52 weeks
PlaceboDrug
Administration of 100 mg placebo twice daily during 52 weeks
| Study group | Role | What they receive |
|---|---|---|
| Sonlicromanol (KH176) | Experimental | Administration of 90 mg sonlicromanol (equivalent to 100 mg sonlicromanol.HCl) twice daily Receives: Drug: Sonlicromanol |
| Matching Placebo | Placebo comparator | Administration of 100 mg matching placebo twice daily Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Screening, Baseline (Day 1), Weeks 13, 26, 39, 52 (End of Trial Visit)
Secondary outcomes (5)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline (Day 1), Weeks 13, 26, 39, 52 (End of Trial Visit)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jun 2024
- Study start14 Apr 2026
- Primary completionSep 2029 (estimated)
- Study completionSep 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Mitochondrial DiseasesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- The study will be a double-blind, randomised, placebo-controlled, multi-centre, parallel-group study. 220 subjects, with a confirmed mitochondrial DNA tRNALeu(UUR) 3243A\>G mutation will be randomised in a 1:1 ratio to receive oral administration of 90 mg sonlicromanol (100 mg sonlicromanol.HCl) or placebo twice daily.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 220 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Khondrion BV
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06451757
- Sponsor's protocol ID
- Khondrion B.V.
- Acronym
- KH176-301
- Status last verified
- Oct 2026
- First submitted
- 29 May 2024
- Last updated
- 14 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
- Expanded access
- Available
Study at a glance
From the registry record, last updated by the sponsor on 14 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III, Randomised, Double-blind, Placebo-controlled, Parallel-group, Pivotal Trial to Assess the Efficacy and Safety of Sonlicromanol in Adult Subjects With a Genetically Confirmed Mitochondrial DNA tRNALeu(UUR) m.3243A>G Variant
- ClinicalTrials.gov ID
- NCT06451757
- Acronym / sponsor ID
- KH176-301 / Khondrion B.V.
- Conditions
- Mitochondrial Diseases, Maternally Inherited Diabetes and Deafness (MIDD), Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke-like Episodes (MELAS), Mitochondrial DNA tRNALeu(UUR) m.3243A<G Mutation
- Keywords
- Mitochondrial Diseases, Oxidative Phosphorylation (OXPHOS), Maternally Inherited Diabetes and Deafness (MIDD), Mitochondrial DNA tRNALeu(UUR) m.3243A<G Mutation, Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke-like episodes (MELAS), Sonlicromanol
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 220 participants (estimated)
- Lead sponsor
- Khondrion BVIndustry (pharma, biotech, devices)
- Study start
- 14 Apr 2026 (actual)
- Primary completion
- Sep 2029 (estimated)
- Study completion
- Sep 2029 (estimated)
- First posted
- 11 Jun 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- The study will be a double-blind, randomised, placebo-controlled, multi-centre, parallel-group study. 220 subjects, with a confirmed mitochondrial DNA tRNALeu(UUR) 3243A>G mutation will be randomised in a 1:1 ratio to receive oral administration of 90 mg sonlicromanol (100 mg sonlicromanol.HCl) or placebo twice daily.
| Arm | Type | Receives |
|---|---|---|
| Sonlicromanol (KH176) | Experimental | Drug: SonlicromanolAdministration of 90 mg sonlicromanol (equivalent to 100 mg sonlicromanol.HCl) twice daily |
| Matching Placebo | Placebo comparator | Drug: PlaceboAdministration of 100 mg matching placebo twice daily |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Signed Informed Consent
- Males and females aged ≥18 years with a multi-system primary mitochondrial disease.
- A confirmed mitochondrial DNA tRNALeu(UUR) m.3243A>G mutation (m.3243A>G PMD) plus an age adjusted heteroplasmy percentage ≥ 20% in white blood cells [=blood heteroplasmy/0.977(age+12)]. Or in urine (urinary epithelial cells), or buccal smear or skeletal muscle (results (obtained per local guidance) ≥ 20% must be available prior to the subject being randomized).
- Presence of chronic fatigue (not attributable to other etiologies than PMD):
- Presence of mitochondrial myopathy defined as:
Key exclusion criteria (14 listed)
- Treatment with any IMP within 3 months (or 5 times the half-life of the IMP, whichever is longer) prior to screening or plans to use an IMP (other than the study intervention) during the study.
- Bone deformities, motor abnormalities or chronic ulcers that in the opinion of the PI may interfere with and/or confound the interpretation of the subject's performance during the 5 times sit to stand test (5XSST).
- Surgery of gastrointestinal tract that might interfere with drug absorption. Or severe GI dysmotility, chronic vomiting, diarrhea, bouts of pseudo-obstruction which will impair appropriate IMP absorption in the opinion of the investigator.
- Clinically significant respiratory disease and/or cardiac disease (medical history or current clinical findings) in the opinion of the investigator.
- Prior interventional cardiac procedure (e.g., cardiac catheterization, angioplasty/percutaneous coronary intervention, balloon valvuloplasty, etc.) within 3 months prior to screening.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SonlicromanolAdministration of 90 mg sonlicromanol (100 mg sonlicromanol.HCl) twice daily during 52 weeks | Drug | Sonlicromanol (KH176) |
| PlaceboAdministration of 100 mg placebo twice daily during 52 weeks | Drug | Matching Placebo |
Primary outcome
Neuro-QoL Fatigue Short Form v1
Time frame: Screening, Baseline (Day 1), Weeks 13, 26, 39, 52 (End of Trial Visit)
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.
Five Times Sit-To-Stand Test (5XSST)
Time frame: Screening, Baseline (Day 1), Weeks 13, 26, 39, 52 (End of Trial Visit)
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.
5 secondary outcomes
36-Item Short Form Survey (SF-36)
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)
Time frame: Screening, Baseline (Day 1), Weeks 13, 26, 39, 52 (End of Trial Visit)
Beck Depression Inventory-2 (BDI-2)
Time frame: Screening, Baseline (Day 1), Weeks 13, 26, 39, 52 (End of Trial Visit)
Patient-scored Global Impression of Severity scale (PGI-S)
Time frame: Baseline (Day 1), Weeks 13, 26, 39, 52 (End of Trial Visit)
Clinician-scored Global Impression of Severity (CGI-S)
Time frame: Baseline (Day 1), Weeks 13, 26, 39, 52 (End of Trial Visit)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Oct 2026.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
10 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Sonlicromanol in people with Mitochondrial Diseases and Maternally Inherited Diabetes and Deafness (MIDD), run by Khondrion BV at 10 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 14 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States, France, Denmark, Germany, Italy and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jasper Levink, MSc. (+31 24 7635000, Khenerfin@khondrion.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Neuro-QoL Fatigue Short Form v1 (time frame: Screening, Baseline (Day 1), Weeks 13, 26, 39, 52 (End of Trial Visit)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Oct 2026.