Efficacy of KL1333 in Adult Patients With Primary Mitochondrial Disease (FALCON)

April 10, 2026 updated by: Abliva AB

An Interventional, Randomised, Double-blind, Parallel-group, Placebo-controlled, Flexible-dose, Adaptive Study of the Efficacy of KL1333 in Adult Patients With Primary Mitochondrial Disease

The primary objective of the FALCON study is to evaluate the efficacy of KL1333 on selected disease manifestations of primary mitochondrial disease (PMD) following 48 weeks of treatment. This objective involves evaluating the efficacy of KL1333 versus placebo on fatigue symptoms and impacts on daily living as well as on functional lower extremity strength and endurance. Additionally, the study evaluates the safety and tolerability of KL1333.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The FALCON study is investigating whether the study medicine, KL1333, improves fatigue levels and physical abilities of people living with mitochondrial disease. The investigators are also evaluating the tolerability of the study medicine. For this study, the effects of KL1333 are compared with those from a placebo (a pill that looks like the study medicine but contains no active medicine). The study medicine (or placebo) is a tablet that is taken twice daily during the treatment period of 48 weeks.

Participation in the FALCON study is divided into 3 parts:

  • Screening and baseline: 8-12 weeks
  • Treatment: 48 weeks
  • Safety follow-up: 5 weeks Total duration: 61 - 65 weeks

Patients who complete the screening phase and are enrolled in the study are randomly assigned to receive either the study medicine (KL1333) or placebo (no active medication). Patients are more likely to receive the study medication than placebo (for every five people who take part, three receive KL1333 and two receive placebo). Neither the participants nor the study team know who is receiving the study medicine or placebo and participants are not able to change which treatment they are assigned.

Study Type

Interventional

Enrollment (Estimated)

180

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Belgium
      • Brussels, Belgium
      • Ghent, Belgium
      • Leuven, Belgium
        • Recruiting
        • Universitair Ziekenhuis Leuven Gasthuisberg Campus
        • Principal Investigator:
          • Kristl Claeys, MD
        • Contact:
  • Denmark
      • Copenhagen, Denmark
        • Recruiting
        • Copenhagen Neuromuscular Center, Rigshospitalet
        • Principal Investigator:
          • Nicolai Preisler, MD
        • Contact:
  • France
      • Bordeaux, France
        • Recruiting
        • Centre Hospitalier Universitaire (CHU) de Bordeaux - Groupe Hospitalier Pellegrin
        • Principal Investigator:
          • Aurelien Trimouille, MD
        • Contact:
      • Lille, France
        • Recruiting
        • Hôpital Roger Salengro, CHRU de Lille
        • Principal Investigator:
          • Celine Tard, MD
        • Contact:
      • Nice, France
        • Recruiting
        • CHU de Nice - Hôpital Archet 2
        • Principal Investigator:
          • Véronique Paquis-Flucklinger, MD
      • Nice, France
        • Recruiting
        • Centre Hospitalier Universitaire de Nice, Hopital Pasteur 2
        • Principal Investigator:
          • Sabrina Sacconi, MD
        • Contact:
      • Paris, France
        • Recruiting
        • Groupe Hospitalier Pitie-Salpetriere
        • Principal Investigator:
          • Anthony Behin, MD
        • Contact:
  • Germany
      • Berlin, Germany, 10117
        • Recruiting
        • Charite - Universitaetsmedizin Berlin
        • Contact:
      • Halle, Germany, 6120
  • Italy
  • Netherlands
      • Nijmegen, Netherlands, 6525
        • Recruiting
        • Radboud University Medical Center
        • Contact:
  • Spain
      • Barcelona, Spain
        • Completed
        • Hospital De La Santa Creu I Sant Pau
      • Barcelona, Spain
        • Recruiting
        • CIBERER- IDIBAPS, Faculty of Medicine, University of Barcelona
        • Contact:
        • Principal Investigator:
          • Gloria Garrabou, MD
      • Barcelona, Spain
        • Recruiting
        • Hospital General Universitario de Catalunya
        • Contact:
        • Principal Investigator:
          • Josep Gamez Carbonell, MD
      • Madrid, Spain
  • United Kingdom
      • Cambridge, United Kingdom
        • Recruiting
        • Department of Clinical Neurosciences, Addenbrooke's Hospital
        • Contact:
        • Principal Investigator:
          • Rita Horvath, MD
      • London, United Kingdom
        • Recruiting
        • University College London Hospitals NHS Foundation Trust
        • Principal Investigator:
          • Robert Pitceathly, MD
        • Contact:
      • Newcastle, United Kingdom
        • Recruiting
        • Royal Victoria Infirmary - the Newcastle Upon Tyne Hospitals Nhs Foundation Trust
        • Contact:
        • Principal Investigator:
          • Grainne Gorman, MD
  • United States
    • California
      • Orange, California, United States, 92868
        • Recruiting
        • University of California, Irvine - ALS & Neuromuscular Center
        • Contact:
          • Mozaffar Tahseen, MD Professor
          • Phone Number: 714-456-2332
          • Email: mozaffar@uci.edu
      • San Diego, California, United States, 292093
        • Recruiting
        • The Regents of the University of California - San Diego
        • Contact:
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Recruiting
        • Children's Hospital Colorado - Center for Cancer and Blood Disorders (CCBD) - Anschutz Medical Campus Location
        • Contact:
    • Georgia
      • Atlanta, Georgia, United States, 303129
    • Minnesota
      • Rochester, Minnesota, United States, 55905
    • Missouri
      • St Louis, Missouri, United States, 63110
        • Not yet recruiting
        • Washington University School of Medicine - Center for Advanced Medicine (CAM) - Neuroscience Center
        • Contact:
    • New York
      • New York, New York, United States, 100032
        • Not yet recruiting
        • Columbia University Irving Medical Center
        • Contact:
    • Ohio
      • Akron, Ohio, United States, 44307
        • Recruiting
        • Akron Children's Hospital
        • Principal Investigator:
          • Bruce Cohen, MD
        • Contact:
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15224
    • Texas
      • Houston, Texas, United States, 77030
        • Recruiting
        • The University of Texas Health Science Center at Houston
        • Principal Investigator:
          • Mary Kay Koenig, MD
        • Contact:
      • Houston, Texas, United States, 77030
        • Recruiting
        • Baylor College of Medicine (BCM)
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: KL1333
Twice daily
Drug: KL1333
Twice daily
Placebo Comparator: Matching Placebo
Twice daily
Drug: Placebo
Twice daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in 30 Second Site-to-Stand Test.
Time Frame: Baseline and 48 Weeks
Change in number of stands
Baseline and 48 Weeks
Change in-patient-reported fatigue symptoms and impacts on daily living measured by Patient-Reported Outcomes Measurement Information System (PROMIS®) Fatigue PMD Short Form
Time Frame: Baseline and 48 Weeks
Change in t-score. Higher scores indicate greater fatigue severity.
Baseline and 48 Weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Individual Activity Assessments - Interference
Time Frame: Baseline and 48 Weeks
Assessing how much Primary Mitochondrial Disease symptoms get in the way of the ability to perform individually selected activities. A 5 point scale ranging from "No interference" to "Completely interferes"
Baseline and 48 Weeks
Individual Activity Assessment - Change
Time Frame: 48 weeks
Assessing the ability to perform individually selected activities compared to baseline. A 5 point scale ranging from "Much worse" to "Much better"
48 weeks
Change in Patient Global Impression of Severity
Time Frame: Baseline and 48 weeks
Scale ranging from 1 (none) to 4 (severe).
Baseline and 48 weeks
Score on Patient Global Impression of Change
Time Frame: 48 weeks
Scale ranging from 2 (much better) to -2 (much worse).
48 weeks
Change in Clinician Global Impression of Severity
Time Frame: Baseline and 48 weeks
Scale ranging from 1 (none) to 4 (severe).
Baseline and 48 weeks
Score on Clinician Global Impression of Change
Time Frame: 48 weeks
Scale ranging from 2 (much better) to -2 (much worse).
48 weeks
Change in Newcastle Mitochondrial Disease Adult Scale (NMDAS) - subscales I-III
Time Frame: Baseline and 48 weeks
Measured on a 6-point rating scale from 0 to 5. Total score across all 3 subscales ranges from 0 to 140. Higher scores indicate more extensive and severe system involvements.
Baseline and 48 weeks
Change from baseline in Glycated haemoglobin (HbA1c) for subjects with diabetes
Time Frame: Baseline and 48 weeks
mmol/mol
Baseline and 48 weeks
Change in Quality of Life in Neurological Disorders (Neuro-QoL) Lower Extremity Function (Mobility) Short Form
Time Frame: Baseline and 48 weeks
Change in t-score. Higher scores indicate greater functional ability.
Baseline and 48 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Abliva AB

Investigators

  • Principal Investigator: Amel Karaa, MD, Massachusetts General Hospital
  • Principal Investigator: Grainne Gorman, MD, PhD, Wellcome Centre for Mitochondrial Research, Newcastle University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 13, 2022

Primary Completion (Estimated)

October 1, 2027

Study Completion (Estimated)

November 1, 2027

Study Registration Dates

First Submitted

December 6, 2022

First Submitted That Met QC Criteria

December 6, 2022

First Posted (Actual)

December 14, 2022

Study Record Updates

Last Update Posted (Actual)

April 15, 2026

Last Update Submitted That Met QC Criteria

April 10, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • KL1333 2020-104A

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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