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Randomized Phase 2 Study of ACE-083 in Patients With Charcot-Marie-Tooth Disease
Journal article   Open access   Peer reviewed

Randomized Phase 2 Study of ACE-083 in Patients With Charcot-Marie-Tooth Disease

Florian P Thomas, Thomas H Brannagan, Russell J Butterfield, Urvi Desai, Ali A Habib, David N Herrmann, Katy J Eichinger, Nicholas E Johnson, Chafic Karam, Alan Pestronk, …
Neurology, Vol.98(23), pp.e2356-e2367
05/01/2022
DOI: 10.1212/WNL.0000000000200325
PMCID: PMC9202530
PMID: 35545446
url
https://www.ncbi.nlm.nih.gov/pmc/articles/9202530View
Open Access

Abstract

ObjectiveTo determine whether locally acting ACE-083 is safe, well tolerated, and increases muscle volume, motor function, and quality of life (QoL) in adults with Charcot-Marie-Tooth disease (CMT) type 1.MethodsThis phase 2 study enrolled adults with CMT1 or CMTX (N=63). Part 1 was open-label and evaluated safety and tolerability of different dose levels of ACE-083 for use in Part 2. Part 2 was a randomized, placebo-controlled, 6-month study of 240 mg/muscle ACE-083 injected bilaterally in the tibialis anterior muscle, followed by a 6-month, open-label extension in which all patients received ACE-083. Pharmacodynamic endpoints included total muscle volume (TMV; primary endpoint), contractile muscle volume (CMV), and fat fraction. Additional secondary endpoints included 6-minute walk test, 10-meter walk/run, muscle strength, and QoL. Safety was assessed with treatment-emergent adverse events (TEAEs) and clinical laboratory tests.ResultsIn Part 1 (n=18), ACE-083 was generally safe and well tolerated at all dose levels, with no serious AEs, TEAEs ≥Grade 3, or death reported. In Part 2 (n=45 enrolled, n=44 treated), there was significantly greater change in TMV with ACE-083 compared with placebo (LS mean difference: 13.5%; p = 0.0096). There was significant difference between ACE-083 and placebo for CMV and change in ankle dorsiflexion strength. Fat fraction and all other functional outcomes were not significantly improved by ACE-083. Moderate-to-mild injection-site reactions were the most common TEAEs.ConclusionsDespite significantly increased TMV and CMV, patients with CMT receiving ACE-083 in tibialis anterior muscles did not demonstrate greater functional improvement compared with those receiving placebo.Classification of evidenceThis study provides Class II evidence that intramuscular ACE-083 is safe, well tolerated, and increases total muscle volume after 6 months of treatment in adults with CMT1 or CMTX.
 6.1 Pharmaceuticals Charcot-Marie-Tooth Disease Clinical Research Clinical Sciences Clinical Trials and Supportive Activities Cognitive Sciences Evaluation of treatments and therapeutic interventions Neurology & Neurosurgery Neurosciences Rare Diseases

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