Efficacy of KL1333 in Adult Patients With Primary Mitochondrial Disease

NCT05650229 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: KL1333 2020-104A
• Study Type: interventional
• Target: 180
• Locations: 9 countries
• Sites: 35

Brief Summary

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.

Conditions

Primary Mitochondrial Disease

Keywords

Chronic fatigue; Myopathy; Muscle weakness; Exercise intolerance; Diabetes

Outcome Measures

Primary Outcomes (2)

• Change in-patient-reported fatigue symptoms and impacts on daily living measured by Patient-Reported Outcomes Measurement Information System (PROMIS®) Fatigue PMD Short Form

  Change in t-score. Higher scores indicate greater fatigue severity.

  Baseline and 48 Weeks

• Change in 30 Second Site-to-Stand Test.

  Change in number of stands

  Baseline and 48 Weeks

Secondary Outcomes (9)

• Change in Quality of Life in Neurological Disorders (Neuro-QoL) Lower Extremity Function (Mobility) Short Form

  Baseline and 48 weeks

• Change in Individual Activity Assessments - Interference

  Baseline and 48 Weeks

• Individual Activity Assessment - Change

  48 weeks

• Change in Patient Global Impression of Severity

  Baseline and 48 weeks

• Score on Patient Global Impression of Change

  48 weeks

Study Arms (2)

KL1333

EXPERIMENTAL

Twice daily

Drug: KL1333

Matching Placebo

PLACEBO COMPARATOR

Twice daily

Drug: Placebo

Interventions

KL1333 DRUG

Twice daily

KL1333

Placebo DRUG

Twice daily

Matching Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• m.3243A\>G associated MELAS-MIDD spectrum disorders,
• single large scale mtDNA deletion associated KSS-CPEO spectrum disorders,
• 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:
• 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.

You may not qualify if:

• 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.
• Recent history of unstable disease, inadequately controlled neurological manifestations or not recovered from stroke-like episodes including but not limited to:
• stroke-like episodes within the last 6 months
• more than 1 seizure/month within the last 6 months
• hospitalised for Status Epilepticus within the last 6 months
• 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.

Sponsors & Collaborators

• Abliva AB: lead

Study Sites (35)

University of California, Irvine - ALS & Neuromuscular Center

Orange, California, 92868, United States

RECRUITING

The Regents of the University of California - San Diego

San Diego, California, 292093, United States

RECRUITING

Children's Hospital Colorado - Center for Cancer and Blood Disorders (CCBD) - Anschutz Medical Campus Location

Aurora, Colorado, 80045, United States

RECRUITING

Rare Disease Research, LLC

Atlanta, Georgia, 303129, United States

RECRUITING

Mayo Clinic

Rochester, Minnesota, 55905, United States

RECRUITING

Washington University School of Medicine - Center for Advanced Medicine (CAM) - Neuroscience Center

St Louis, Missouri, 63110, United States

NOT YET RECRUITING

Columbia University Irving Medical Center

New York, New York, 100032, United States

NOT YET RECRUITING

Akron Children's Hospital

Akron, Ohio, 44307, United States

RECRUITING

UPMC Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15224, United States

NOT YET RECRUITING

Baylor College of Medicine (BCM)

Houston, Texas, 77030, United States

RECRUITING

The University of Texas Health Science Center at Houston

Houston, Texas, 77030, United States

RECRUITING

Hopital Universitaire de Bruxelles (H.U.B)/ Academisch Ziekenhuis Brussel

Brussels, Belgium

RECRUITING

Universitair Ziekenhuis Gent

Ghent, Belgium

RECRUITING

Universitair Ziekenhuis Leuven Gasthuisberg Campus

Leuven, Belgium

RECRUITING

Copenhagen Neuromuscular Center, Rigshospitalet

Copenhagen, Denmark

RECRUITING

Centre Hospitalier Universitaire (CHU) de Bordeaux - Groupe Hospitalier Pellegrin

Bordeaux, France

RECRUITING

Hopital Roger Salengro, CHRU de Lille

Lille, France

RECRUITING

Centre Hospitalier Universitaire de Nice, Hopital Pasteur 2

Nice, France

RECRUITING

CHU de NICE - Hôpital Archet 2

Nice, France

RECRUITING

Groupe Hospitalier Pitie-Salpetriere

Paris, France

RECRUITING

Charite - Universitaetsmedizin Berlin

Berlin, 10117, Germany

RECRUITING

Universitaetsklinikum Halle

Halle, 6120, Germany

RECRUITING

IRCCS Institute of Neurological Sciences of Bologna- Universita di Bologna

Bologna, 40139, Italy

RECRUITING

Azienda Ospedaliera Universitaria Gaetano Martino Messina

Messina, 98125, Italy

RECRUITING

Fondazione IRCCS Istituto Neurologico Carlo Besta

Milan, 20133, Italy

RECRUITING

Azienda Ospedaliero Universitaria Pisana

Pisa, 56126, Italy

RECRUITING

Fondazione Policlinico Universitario Agostino Gemelli IRCCS - Universita Cattolica del Sacro Cuore

Roma, 00168, Italy

RECRUITING

Radboud University Medical Center

Nijmegen, 6525, Netherlands

RECRUITING

CIBERER- IDIBAPS, Faculty of Medicine, University of Barcelona

Barcelona, Spain

RECRUITING

Hospital de la Santa Creu i Sant Pau

Barcelona, Spain

COMPLETED

Hospital General Universitario de Catalunya

Barcelona, Spain

RECRUITING

Hospital Universitario 12 de Octubre

Madrid, Spain

RECRUITING

Department of Clinical Neurosciences, Addenbrooke's Hospital

Cambridge, United Kingdom

RECRUITING

University College London Hospitals Nhs Foundation Trust

London, United Kingdom

RECRUITING

Royal Victoria Infirmary - The Newcastle Upon Tyne Hospitals NHS Foundation Trust

Newcastle, United Kingdom

RECRUITING

MeSH Terms

Conditions

Muscular Diseases; Muscle Weakness; Diabetes Mellitus

Condition Hierarchy (Ancestors)

Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Neuromuscular Manifestations; Neurologic Manifestations; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Amel Karaa, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

• Grainne Gorman, MD, PhD

  Wellcome Centre for Mitochondrial Research, Newcastle University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Communication Manager

CONTACT

+46462756220; clinicaltrialinfo@abliva.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 6, 2022
• First Posted: December 14, 2022
• Study Start: December 13, 2022
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): November 1, 2027
• Last Updated: April 15, 2026

Record last verified: 2026-04

Locations

US (11); DK (1); ES (4); FR (5); BE (3); IT (5); GB (3); NL (1); DE (2)