New drug aims to ease fatigue in mitochondrial disease

NCT ID NCT05650229

Symptom relief Sponsor: Pharming Technologies B.V. Source: ClinicalTrials.gov ↗

First seen Jun 27, 2026 · Last updated Jun 27, 2026

Summary

This Phase 2 trial tests whether KL1333 can reduce fatigue and improve leg strength in adults with primary mitochondrial disease, a genetic condition that affects energy production. About 180 participants will receive either KL1333 or a placebo twice daily for 48 weeks. The study measures changes in fatigue symptoms and physical function.

What this could mean

Our plain-language read of the trial. This is informational only, not medical advice or a prediction.

Active substance: KL1333
What this could lead to: If it works, this could point toward a treatment that reduces fatigue and improves daily function for people with primary mitochondrial disease.
What could go wrong: This is an early Phase 2 trial with only 180 participants, so results may not apply to everyone. It is also a placebo-controlled study, meaning some may not receive the active drug.

This is an AI summary of the original study and may miss details. Read our disclaimer.

Study facts

What this study's own registry entry says, in plain language.

Phase

Phase 2

Tests whether the treatment actually works, and watches for side effects, in a larger group.

Participants

About 180 people

The number the study aims to enrol. It can still change while the study runs.

Started

Dec 2022

Expected to finish

Nov 2027

An estimate. End dates often move.

Lead sponsor

A company

The lead sponsor is a pharmaceutical, biotech, or medical-device company.

Who can take part

This study's own entry requirements. Only the study team can say for certain whether you qualify.

Ages

18 years and older

Sex

Anyone

Healthy volunteers

Not accepted

This study is not open to healthy volunteers. The entry requirements below say who it is open to.

Show the full entry requirements

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: * Age 18 years or older. * A confirmed PMD diagnosis caused by a known pathogenic gene mutation or deletion of the mitochondrial genome (category 6 of the International Classification of Inborn Metabolic Disorders \[ICIMD\])12 according to American College of Medical Genetics (ACMG)/Association of Molecular Pathology (AMP) criteria1, with multisystemic disease expressions, including: 1. m.3243A\>G associated MELAS-MIDD spectrum disorders, 2. single large scale mtDNA deletion associated KSS-CPEO spectrum disorders, 3. other multisystemic mtDNA-related disease (including MERRF). * Presence of chronic mitochondrial fatigue: * History of mitochondrial fatigue for at least 3 months prior to the Screening Visit AND * Presence of at least moderate level of fatigue, assessed by PROMIS® Fatigue PMD Short form raw score ≥ 27 at Screening and Baseline * Presence of mitochondrial myopathy defined as: * Myopathy (proximal muscle weakness), NMDAS Section III Clinical Assessment, item 5 score ≥ 1, which reads: "minimal reduction in hip flexion and/or shoulder abduction only (e.g. MRC 4+/5)". For the inclusion only hip flexion, but not shoulder abduction, should be taken into account. AND / OR * Exercise Tolerance: NMDAS Section I, item 9 score ≥ 1, which reads: "unlimited on flat - symptomatic on inclines or stairs". * Patients must be able to perform at least 2 repetitions and the maximal capacity must not exceed 17 repetitions in males or 16 repetitions in females in a 30s STS test at screening. * Clinically stable, apart from symptoms associated with the diagnosis of mitochondrial disease, at Screening and Baseline, as determined by medical history, physical examination, 12-lead ECG, vital signs measurements, and clinical laboratory evaluations at Screening, as assessed by the investigator. * The patient is willing and able to attend study appointments within the specified time windows. * Willingness and ability to complete electronic PROs. * Willingness to maintain a stable diet during the Screening and study periods. * Patients who take any mitochondrial disease-focused vitamins or supplemental therapies, including coenzyme Q10 (CoQ10), niacin/nicotinamide (vitamin B3), and L-arginine, has been on a stable dose regimen of these for 3 months prior to randomisation and intends to stay on a stable dose for the duration of the study period. * Willingness to suspend treatment with idebenone during the study. * Female patient is not pregnant and at least one of the following conditions apply: 1. Not a woman of childbearing potential (WOCBP) 2. WOCBP must agree not to try and become pregnant and use a highly effective method of contraception from the time of informed consent through at least 36 days (\~5 half-lives of KL1333 plus 30 days) after the last dose of investigational medicinal product (IMP) administration. * Male patients with female partner(s) of childbearing potential must agree to use a male condom in addition to using highly effective contraception throughout the treatment period and for 96 days after the last dose of IMP administration. The requirement to use a male condom also applies to male patients with a pregnant or breastfeeding partner. * Female patients must agree not to breastfeed starting at Screening and throughout the study period and for 36 days after the last dose of IMP administration. * Female patients must agree to not donate ova throughout the study period and for 36 days after the last dose of IMP administration, and male patients must agree to not donate sperm throughout the study period and for 96 days after the last dose of IMP administration. Exclusion Criteria: * Primary mitochondrial disease with predominant neurodegenerative phenotypes, such as, but not limited to, Leigh syndrome, Leber hereditary optic neuropathy (LHON) and Neuropathy ataxia-retinitis pigmentosa syndrome (NARP). * Primary mitochondrial disease nuclear DNA mutations or mutations causing mtDNA destabilisation. Genetic mtDNA variants of uncertain significance, likely pathogenic, or pathogenic mutations with degrees of heteroplasmy below what can be considered to definitely cause PMD. * General fatigue or muscle weakness due to causes other than mitochondrial disease, in the opinion of the investigator. * Significant cardiovascular disease (e.g., sustained or symptomatic arrhythmia; dilated heart chambers or reduced function; Mobitz II atrioventricular block or greater) OR abnormal ECG that is clinically significant, as determined by the investigator. Any QTcF \> 450 msec for male patients and \> 470 msec for female patients is exclusionary. In the case of an exclusionary QTcF, the ECG can be repeated twice and the average of 3 QTcF intervals should be used to determine the QTcF eligibility. * Recent history of unstable disease, inadequately controlled neurological manifestations or not recovered from stroke-like episodes including but not limited to: 1. stroke-like episodes within the last 6 months 2. more than 1 seizure/month within the last 6 months 3. hospitalised for Status Epilepticus within the last 6 months 4. more than 4 days of migraine episodes/month within the last 6 months * History of inflammatory bowel disease, gastric erosions, peptic ulcer disease, or gastrointestinal bleeding episodes. Gastroesophageal reflux disease diagnosed by objective endoscopic or radiographic means, and clinically symptomatic at any point over the last 6 months. * The patient has one or more clinical laboratory test values 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, or the patient has, at the Screening Visit: * estimated glomerular filtration rate (eGFR) calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation \<30 mL/min/1.73 m2 * a serum total bilirubin value \> 1.5 times the upper limit of the reference range unless elevation is related to Gilbert's syndrome and the investigator can rule out any underlying liver dysfunction based on other tests, the patient has a Child-Pugh score ≤6, and after discussing the case with the medical monitor * a serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) value \> 2 times the upper limit of the reference range. Values between 2 and 3 times the upper limit of the reference range may be allowed if concomitant to elevation in creatine kinase as long as the investigator can rule out any underlying liver dysfunction based on other tests, the patient has a Child-Pugh score ≤6, and after discussing the case with the medical monitor * The patient has, in the investigator's opinion, severe ataxia, neuropathy, balance problems or other medical condition that would interfere the evaluation of the 30s STS test. * Untreated or undertreated sleep apnoea, in the opinion of the investigator. * Use of idebenone within 14 days prior to the first dose. * Patients have a history of unstable or severe pulmonary, immunological, oncological, hepatic disease, renal disease, or another medically significant illness other than PMD or takes medication that could, in the investigator's opinion, interfere with the assessments of safety, tolerability, or efficacy, or interfere with the conduct or interpretation of the study. * The patient is, in the investigator's opinion, unlikely to comply with the protocol e.g. due to cognitive impairment or is unsuitable for any reason. * The patient has an immediate family member (defined as family members residing at the same address) who participates in the study. * Female patients with a positive pregnancy result at Screening or at Baseline. * A patient cannot participate if they received an investigational drug 30 days or 5 half-lives prior to the Screening Visit (whichever is longer), or plans to use an investigational drug (other than the study intervention) during the study * Hypersensitivity to the active substance or to any of the excipients or placebo.

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Conditions

The condition(s) this trial relates to.

diabetes mellitus mitochondrial disease muscle tissue disorder Muscle Weakness

As listed by the trial registrant

The condition terms exactly as the trial's registrant entered them.

Primary mitochondrial disease

How to take part

Only the study team decides who joins. These are the ways to reach them.

The study's own enquiry address

This study publishes an address for enquiries. See it below .
The places running it

54 sites in 11 countries. The list below names each one and where it is.
The official record

ClinicalTrials.gov lists the study team's own contact details, including names and phone numbers. We don't republish those.

Open the record ↗
A doctor treating you

A doctor who knows your case can contact a study site on your behalf, and can tell you whether this study is worth pursuing at all.

Contacts and locations

Show contact details

Study contacts

Contact

Email: •••••@•••••

Locations

Akron Children's Hospital
RECRUITING

Akron, Ohio, 44307, United States
Azienda Ospedaliera Universitaria Gaetano Martino Messina
RECRUITING

Messina, 98125, Italy
Azienda Ospedaliero Universitaria Pisana
RECRUITING

Pisa, 56126, Italy
Baylor College of Medicine (BCM)
RECRUITING

Houston, Texas, 77030, United States
CHU de NICE - Hôpital Archet 2
RECRUITING

Nice, France
CIBERER- IDIBAPS, Faculty of Medicine, University of Barcelona
RECRUITING

Barcelona, Spain
Centre Hospitalier Universitaire (CHU) de Bordeaux - Groupe Hospitalier Pellegrin
RECRUITING

Bordeaux, France
Centre Hospitalier Universitaire d'Angers
RECRUITING

Angers, 49933, France
Centre Hospitalier Universitaire de Nantes
NOT_YET_RECRUITING

Nantes, 44093, France
Centre Hospitalier Universitaire de Nice, Hopital Pasteur 2
RECRUITING

Nice, France
Charite - Universitaetsmedizin Berlin
RECRUITING

Berlin, 10117, Germany
Charles University and General University Hospital
NOT_YET_RECRUITING

Prague, 128 08, Czechia
Children's Hospital Colorado - Center for Cancer and Blood Disorders (CCBD) - Anschutz Medical Campus Location
RECRUITING

Aurora, Colorado, 80045, United States
Columbia University Irving Medical Center
NOT_YET_RECRUITING

New York, New York, 100032, United States
Copenhagen Neuromuscular Center, Rigshospitalet
RECRUITING

Copenhagen, Denmark
Department of Clinical Neurosciences, Addenbrooke's Hospital
RECRUITING

Cambridge, United Kingdom
Fondazione IRCCS Istituto Neurologico Carlo Besta
RECRUITING

Milan, 20133, Italy
Fondazione Policlinico Universitario Agostino Gemelli IRCCS - Universita Cattolica del Sacro Cuore
RECRUITING

Roma, 00168, Italy
Groupe Hospitalier Pitie-Salpetriere
RECRUITING

Paris, France
Hopital Roger Salengro, CHRU de Lille
RECRUITING

Lille, France
Hopital Universitaire Necker Enfants Malades
NOT_YET_RECRUITING

Paris, 75015, France
Hopital Universitaire de Bruxelles (H.U.B)/ Academisch Ziekenhuis Brussel
RECRUITING

Brussels, Belgium
Hopitaux Universitaires de Strasbourg
RECRUITING

Strasbourg, 67091, France
Hospital General Universitario de Catalunya
RECRUITING

Barcelona, Spain
Hospital Universitario 12 de Octubre
RECRUITING

Madrid, Spain
Hospital Universitario Vall d'Hebron
RECRUITING

Barcelona, 08035, Spain
Hospital de la Santa Creu i Sant Pau
COMPLETED

Barcelona, Spain
IRCCS Institute of Neurological Sciences of Bologna- Universita di Bologna
RECRUITING

Bologna, 40139, Italy
IU Health University Hospital
NOT_YET_RECRUITING

Indianapolis, Indiana, 46202, United States
Icahn School of Medicine at Mount Sinai
NOT_YET_RECRUITING

New York, New York, 10029-6574, United States
Johns Hopkins University School of Medicine
NOT_YET_RECRUITING

Baltimore, Maryland, 21205, United States
Mayo Clinic
RECRUITING

Rochester, Minnesota, 55905, United States
Neurology and Neuromuscular Care Center-Neurology Rare Disease Center
NOT_YET_RECRUITING

Flower Mound, Texas, 75028, United States
Neuroscience Research Australia
NOT_YET_RECRUITING

Randwick, New South Wales, 2031, Australia
Novel Clinical Research Center, LLC
RECRUITING

Miami, Florida, 33186, United States
Perron Institute
NOT_YET_RECRUITING

Nedlands, Western Australia, 6009, Australia
Radboud University Medical Center
RECRUITING

Nijmegen, 6525, Netherlands
Rare Disease Research, LLC
RECRUITING

Atlanta, Georgia, 303129, United States
Royal Melbourne Hospital
NOT_YET_RECRUITING

Parkville, Victoria, 3050, Australia
Royal North Shore Hospital
NOT_YET_RECRUITING

Saint Leonards, New South Wales, 2065, Australia
Royal Victoria Infirmary - The Newcastle Upon Tyne Hospitals NHS Foundation Trust
RECRUITING

Newcastle, United Kingdom
Tekton Marlboro Neurology
RECRUITING

Marlboro, New Jersey, 07746, United States
The Children's Hospital of Philadelphia
NOT_YET_RECRUITING

Philadelphia, Pennsylvania, 19104, United States
The Regents of the University of California - San Diego
RECRUITING

San Diego, California, 292093, United States
The University of Texas Health Science Center at Houston
RECRUITING

Houston, Texas, 77030, United States
UCSF Movement Disorders Clinic
NOT_YET_RECRUITING

San Francisco, California, 94158, United States
UPMC Children's Hospital of Pittsburgh
RECRUITING

Pittsburgh, Pennsylvania, 15224, United States
Universitaetsklinikum Halle
RECRUITING

Halle, 6120, Germany
Universitair Ziekenhuis Gent
RECRUITING

Ghent, Belgium
Universitair Ziekenhuis Leuven Gasthuisberg Campus
RECRUITING

Leuven, Belgium
Universitat de Valencia
NOT_YET_RECRUITING

Valencia, 46026, Spain
University College London Hospitals Nhs Foundation Trust
RECRUITING

London, United Kingdom
University of California, Irvine - ALS & Neuromuscular Center
RECRUITING

Orange, California, 92868, United States
Washington University School of Medicine - Center for Advanced Medicine (CAM) - Neuroscience Center
NOT_YET_RECRUITING

St Louis, Missouri, 63110, United States
Yale University School of Medicine
NOT_YET_RECRUITING

New Haven, Connecticut, 06519, United States

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