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

Official title

An Open-label, Single-arm Extension Study to Evaluate the Long-term Safety, Tolerability, and Efficacy of KL1333 (Napazimone) in Patients With Primary Mitochondrial Disease

Overview

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.

Detailed description

This is a 12-month open-label extension (OLE) study to evaluate the safety, tolerability, and efficacy of KL1333 in subjects previously treated with KL1333 or placebo in Study KL1333-2020-104A (hereafter referred to as FALCON).

Subjects can be enrolled in this extension study either directly at the FALCON study completion visit (FALCON Week 48) or the safety follow-up visit (FALCON Week 53) or later in time. Subjects who previously received KL1333 in FALCON will receive retreatment whereas subjects previously treated with placebo will be treatment naïve to KL1333.

The study consists of a screening visit (if the subject rolls over directly from the FALCON study completion visit \[FALCON Week 48\] or the safety follow up visit \[FALCON Week 53\], the screening visit is coincident with the visit), a 48-week treatment course with KL1333 up to 100 mg/day, a completion visit (end of treatment; EoT) and approximately 5 weeks of follow up, including the end of study (EoS) visit. The treatment period may extend beyond 48 weeks until the study drug is commercially or otherwise available, in which case the EoT visit will occur later than Week 48. Periodic safety monitoring visits (phone visits every 4 weeks after Week 48 and clinic visits every 24 weeks after Week 48) will continue for subjects who receive KL1333 in the optional extended treatment period until the study drug is commercially or otherwise available.

Interventions

• Drug Napazimone
  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 toler

Primary outcome measures

• Adverse events [Time frame: Through study at least for 48 weeks]
• Physical examination [Time frame: At Baseline Week 0, Week 4, Week 24 and Week 48]
• Vital signs [Time frame: At Baseline Week 0, Week 4, Week 24 and Week 48]
• Electrocardiogram [Time frame: At Baseline Week 0, Week 4, Week 24 and Week 48]
• Safety laboratory - blood chemistry [Time frame: At Baseline Week 0, Week 4, Week 24 and Week 48]
• Safety laboratory - urinalysis [Time frame: At Baseline Week 0, Week 4, Week 24 and Week 48]
• Safety laboratory - hematology [Time frame: 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 [Time frame: Through study at least for 48 weeks]
• Columbia Suicide Severity Rating Scale (C-SSRS) [Time frame: At Baseline Week 0]

Secondary outcome measures (8)

• Patient-reported mitochondrial fatigue [Time frame: Through study at least for 48 weeks]
• Functional outcome [Time frame: At Baseline Week 0, Week 4, Week 24 and Week 48]
• Patient-reported lower extremity function [Time frame: At Baseline Week 0, Week 4, Week 12, Week 24, Week 36 and Week 48]
• Other patient-reported outcome - Patient Global Impression (multiple) [Time frame: At Baseline Week 0, Week 4, Week 12, Week 24, Week 36 and Week 48]
• Other patient-reported outcomes - 5-level EuroQol-5 Dimension [Time frame: At Baseline Week 0, Week 4, Week 12, Week 24, Week 36 and Week 48]
• Global impression of severity of PMD disease expression [Time frame: At Baseline Week 0, Week 24 and Week 48]
• Assessments of mitochondrial disease progression [Time frame: At Baseline Week 0, Week 24 and Week 48]
• Mitochondrial diabetes, subgroup analysis [Time frame: At Baseline Week 0, Week 24 and Week 48]

Eligibility criteria

Inclusion criteria

• 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

Exclusion criteria

• 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.

Subjects not enrolling directly at the FALCON study completion visit (FALCON Week 48) or the safety follow-up visit (FALCON Week 53) study will be required to fulfill the additional exclusion criteria below during the screening visit:

• General fatigue or muscle weakness due to causes other than mitochondrial disease, in the opinion of the investigator.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07514338 · KL1333 2025-104B · 2025-524367-20-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗