Open Label Extension to Assess Long Term Safety and Efficacy of KL1333 in Patients With Primary Mitochondrial Disease

NCT07514338 | Recruiting Phase 2 FDA Drug

• 3 other identifiers: KL1333 2025-104B2025-524367-20-002025
• Study Type: interventional
• Target: 140
• Locations: 9 countries
• Sites: 23

Brief Summary

The purpose of this study is to investigate if the study medicine, KL1333, is safe, well-tolerated and effective long-term in improving the symptoms of fatigue and impacts on daily living and functional capacity (physical abilities) in people with PMD.

Conditions

Mitochondrial Diseases

Outcome Measures

Primary Outcomes (9)

• Adverse events

  Number of adverse events will be monitored throughout the study for all subjects

  Through study at least for 48 weeks

• Physical examination

  The following parameters and body systems will be examined and any abnormalities described: height and weight; general appearance; skin; head, ears, eyes, nose, and throat; lungs; heart; lower extremity examination; abdomen; neurologic and lymph nodes. Any clinically significant changes from baseline should be recorded as AEs.

  At Baseline Week 0, Week 4, Week 24 and Week 48

• Vital signs

  Body temperature, systolic and diastolic cuff blood pressure, pulse rate and pulse oximetry will be measured and any clinically significant changes from baseline should be recorded as AEs.

  At Baseline Week 0, Week 4, Week 24 and Week 48

• Electrocardiogram

  Changes from baseline of ECG parameters will be evaluated.

  At Baseline Week 0, Week 4, Week 24 and Week 48

• Safety laboratory - blood chemistry

  Monitoring of the clinically significant laboratory results for sodium, potassium, chloride, bicarbonate/carbon dioxide;, blood urea nitrogen, serum creatinine, glucose, albumin, total protein, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, total bilirubin, direct bilirubin, indirect bilirubin, calcium, gamma-glutamyl transferase, creatine kinase

  At Baseline Week 0, Week 4, Week 24 and Week 48

• Safety laboratory - urinalysis

  Monitoring of the clinically significant laboratory results for specific gravity, pH, semi-quantitative "dipstick" evaluation of glucose, protein, bilirubin, ketones, leukocytes, blood microscopy and/or culture to be performed if clinically indicated or if urinalysis results positive.

  At Baseline Week 0, Week 4, Week 24 and Week 48

• Safety laboratory - hematology

  Monitoring of the clinically significant laboratory results for Hemoglobin, hematocrit, white blood cell with differentials (monocytes, eosinophils, basophils, neutrophils, lymphocytes) as an absolute value, red blood cell count, platelet count, C-reactive protein

  At Baseline Week 0, Week 4, Week 24 and Week 48

• Occurence of metabolic decompensation and lactic acidosis or image-verified stroke-like episodes consequent to GI AE and AESIs

  These events will be monitored throughout the study.

  Through study at least for 48 weeks

• Columbia Suicide Severity Rating Scale (C-SSRS)

  C-SSRS assesses suicidal ideation and behavior risk through a series of questions to assess for suicidal ideation and behavior, the severity and immediacy of the risk, and the level of support the subject may need. C-SSRS Severity of Ideation scores of 4 or 5 are considered SAEs.

  At Baseline Week 0

Secondary Outcomes (8)

• Patient-reported mitochondrial fatigue

  Through study at least for 48 weeks

• Functional outcome

  At Baseline Week 0, Week 4, Week 24 and Week 48

• Patient-reported lower extremity function

  At Baseline Week 0, Week 4, Week 12, Week 24, Week 36 and Week 48

• Other patient-reported outcome - Patient Global Impression (multiple)

  At Baseline Week 0, Week 4, Week 12, Week 24, Week 36 and Week 48

• Other patient-reported outcomes - 5-level EuroQol-5 Dimension

  At Baseline Week 0, Week 4, Week 12, Week 24, Week 36 and Week 48

Study Arms (1)

Open label extension

EXPERIMENTAL

Subjects will receive medication twice a day for 48 weeks minimum

Drug: Napazimone

Interventions

Napazimone DRUG

Product: KL1333 (international nonproprietary name: napazimone) Dose: Each subject will be up-titrated to his/her maximum well tolerated dose. The starting dose will be 25 mg KL1333 twice daily (BID; total daily dose of 50 mg). If KL1333 is considered to be well tolerated after 4 weeks of treatment, the dose will be increased to 50 mg KL1333 BID (total daily dose of 100 mg). The dose may be lowered from 50 mg BID to 25 mg BID at the investigator's discretion throughout the study in case of tolerability issues. Frequency: Twice daily Route: Oral

Also known as: KL1333

Open label extension

Eligibility Criteria

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

You may qualify if:

• Completed the FALCON study (age 18 years or older), and in the opinion of the investigator and sponsor has been compliant with the study requirements
• Willingness and ability to attend study appointments within the specified time windows
• Willingness and ability to complete electronic patient-reported outcomes
• Concomitant medications likely to remain stable throughout participation in the study where clinically possible
• Willingness to suspend treatment with idebenone during the study

You may not qualify if:

• The subject is, in the investigator's opinion, unlikely to comply with the protocol, e.g., due to cognitive impairment, or is unsuitable for any reason.
• Any medical, psychiatric, laboratory or other condition that may negatively affect the benefit-risk considerations of study participation or interfere with the interpretation of study results and, in the judgment of the investigator and/or the medical monitor, would make the subject inappropriate for entry into this study.
• General fatigue or muscle weakness due to causes other than mitochondrial disease, in the opinion of the investigator.

Sponsors & Collaborators

• Pharming Technologies B.V.: lead
• ICON plc: collaborator

Study Sites (23)

Akron Children's Hospital

Akron, Ohio, 44308, United States

RECRUITING

Hospital Erasme

Brussels, 1070, Belgium

RECRUITING

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

Brussels, Belgium

RECRUITING

University Hospital

Ghent, 9000, Belgium

RECRUITING

Universitair Ziekenhuis Gent

Ghent, Belgium

RECRUITING

University Hospital

Leuven, 3000, Belgium

RECRUITING

Universitair Ziekenhuis Leuven Gasthuisberg Campus

Leuven, Belgium

RECRUITING

Charles University and General University Hospital

Prague, 128 08, Czechia

RECRUITING

Copenhagen Neuromuscular Center, Rigshospitalet

Copenhagen, Denmark

RECRUITING

Centre Hospitalier Universitaire d'Angers

Angers, 49933, France

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 Nantes

Nantes, 44093, France

RECRUITING

Centre Hospitalier Universitaire de Nice, Hopital Pasteur 2

Nice, France

RECRUITING

CHU de NICE - Hôpital Archet 2

Nice, France

RECRUITING

Hopitaux Universitaires de Strasbourg

Strasbourg, 67091, France

RECRUITING

Universitaetsklinikum Halle

Halle, 6120, Germany

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

Radboud University Medical Center

Nijmegen, 6525, Netherlands

RECRUITING

Hospital General Universitario de Catalunya

Barcelona, Spain

RECRUITING

Hospital Universitario 12 de Octubre

Madrid, Spain

RECRUITING

MeSH Terms

Conditions

Mitochondrial Diseases

Condition Hierarchy (Ancestors)

Metabolic Diseases; Nutritional and Metabolic Diseases

Central Study Contacts

Audrey Simon, Sr. CPM

CONTACT

+31 71 524 7448; a.simon@pharming.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Open-label Extension

Study Record Dates

• First Submitted: February 24, 2026
• First Posted: April 7, 2026
• Study Start: June 12, 2026
• Primary Completion (Estimated): March 31, 2029
• Study Completion (Estimated): March 31, 2029
• Last Updated: September 16, 2026

Record last verified: 2026-07

Locations

CZ (1); BE (6); ES (2); IT (3); DK (1); DE (1); US (1); FR (7); NL (1)