A Phase III, Randomised, Double-blind, Placebo-controlled, Parallel-group, Pivotal Trial to Assess the Efficacy and Safety of Sonlicromanol in Adult Subjects With a Genetically Confirmed Mitochondrial DNA tRNALeu(UUR) m.3243A>G Variant
The KHENERFIN study aims to determine whether the study medicine, sonlicromanol, is able to reduce symptoms of fatigue and the impact of fatigue on daily life, and whether sonlicromanol is able to improve physical abilities of people like balance control and lower limb skeletal muscle strength in people with mitochondrial disease. In this study, the effects of sonlicromanol are compared against a placebo, a tablet identical in appearance and taste but without the active drug. Participants take either sonlicromanol or placebo twice daily for a treatment duration of 52 weeks. In addition to these primary objectives, the study evaluates the efficacy of sonlicromanol on secondary and exploratory outcomes, as well as its safety and tolerability after one year of treatment.
• Signed Informed Consent
• Males and females aged ≥18 years with a multi-system primary mitochondrial disease.
• A confirmed mitochondrial DNA tRNALeu(UUR) m.3243A\>G mutation (m.3243A\>G PMD) plus an age adjusted heteroplasmy percentage ≥ 20% in white blood cells \[=blood heteroplasmy/0.977(age+12)\]. Or in urine (urinary epithelial cells), or buccal smear or skeletal muscle (results (obtained per local guidance) ≥ 20% must be available prior to the subject being randomized).
• Presence of chronic fatigue (not attributable to other etiologies than PMD):
‣ Patient self-reported chronic fatigue for at least 3 months prior to the Screening Visit and recorded in the clinical patient files; AND
⁃ Presence of fatigue (raw total score \>22), assessed by Neuro-QoL SFv1-F at Screening.
• Presence of mitochondrial myopathy defined as:
∙ 5xSST at Screening and Baseline should be ≥ 11 seconds and participant must demonstrate the ability to complete the test at baseline (i.e., complete the test within 30 seconds).
∙ 6\. Other Inclusion criteria per protocol.