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EU mitochondrial myopathy

Mitochondrial myopathy trials: leading sites, investigators and clinical assessments

Updated 19 September 2026

European mitochondrial myopathy programs concentrate at a small group of specialist neuromuscular and mitochondrial centres. Fatigue and objective motor or muscle function are the most consistently used efficacy domains.

Sites

Five centres recur across late-stage mitochondrial disease programs

Repeated participation is concentrated in France and Italy, with the same institutions appearing across the sonlicromanol Phase III and KL1333 extension programs.

Sites appearing across both late-stage programs
AP-HP · France2
Gaetano Martino Messina · Italy2
AOU Pisana · Italy2
Gemelli IRCCS · Italy2
Carlo Besta · Italy2

Investigators

Five recurrent investigators in the late-stage programs

These investigators are repeatedly named across the sonlicromanol Phase III and KL1333 extension programs.

Selected recurrent investigators across the two late-stage programs
Aurélien Trimouille · Bordeaux, France2
Costanza Lamperti · Milan, Italy2
Guido Alessandro Primiano · Rome, Italy2
Michelangelo Mancuso · Pisa, Italy2
Olimpia Musumeci · Messina, Italy2

Trial participation reflects recorded study experience, not current capacity, patient access or recruitment performance.

Assessments

Fatigue and motor function are the most consistent efficacy domains

The protocols repeatedly combine patient-reported symptoms with direct measures of physical function, while broader disease severity and biomarker measures usually support the main efficacy readout.

Assessment domains represented across mitochondrial myopathy programs
Fatigue5
Motor / muscle function5
Quality of life / daily function4
Disease / metabolic biomarkers4
Global disease severity3

Previous trial findings

Findings from previous sonlicromanol trials

The sonlicromanol development history shows how endpoint choice evolved before the current Phase III study.

Ceiling effects limited early physical measures

KHENERGY reported no significant improvement in gait, 6-minute walk, grip strength, 30-second sit-to-stand or NMDAS. The protocol notes that many participants were mildly affected and had normal baseline functional scores.

More affected patients showed stronger signals

In KHENERGYZE, the primary attention analysis was not significant overall. Post-hoc analyses found stronger effects in participants with poorer baseline performance, including a significant attention-domain result at 50 mg twice daily.

Long-term signals extended beyond cognition

KHENEREXT reported improvements from baseline in physical health, lower-limb strength, balance, pain and fatigue. Improvements observed at Week 52 persisted through Week 78 in participants who continued treatment.

The current Phase III focuses on fatigue and sit-to-stand

KHENERFIN uses Neuro-QoL Fatigue and Five Times Sit-to-Stand as co-primary endpoints in adults with symptomatic m.3243A>G primary mitochondrial disease and measurable myopathy.

Source: CTIS trial records, protocols and filed results, reviewed 19 September 2026.

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