Clinical Trial: Study of ACE-083 in Patients With Charcot-Marie-Tooth Disease

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study of ACE-083 in Patients With Charcot-Marie-Tooth Disease Types 1 and X

Brief Summary: This is a multicenter, phase 2 study to evaluate the safety, tolerability, pharmacodynamics (PD), efficacy, and pharmacokinetics (PK) of ACE-083 in patients with CMT1 and CMTX, to be conducted in two parts. Part 1 is non-randomized, open-label, dose-escalation and Part 2 is randomized, double-blind, and placebo-controlled.

Detailed Summary:

Part 1 (non-randomized, open-label, dose-escalation) Part 1 will consist of up to 3 cohorts of 6 patients each and will evaluate multiple ascending dose levels of ACE-083 administered bilaterally once every 3 weeks for up to 5 doses in the tibialis anterior (TA) muscle. Patients in each cohort will be enrolled in a 4-week screening period before beginning treatment.

Part 2 (randomized, double-blind, placebo-controlled) Prior to the initiation of Part 2, a review of safety and efficacy data from Part 1 will be conducted by the Safety Review Team (SRT) to determine the recommended dose level (maximum 250 mg/muscle). A total of up to 24 new patients may be enrolled and randomized (2:1 randomization) to receive either ACE-083 (n=16) or placebo (n=8) bilaterally by injection into both TA muscles once every 3 weeks for up to 5 doses.

Study duration for Parts 1 and 2 for each patient will be approximately 24 weeks, including a 4-week screening period, a 12-week treatment period, and an 8-week follow-up period after the last dose.

Sponsor: Acceleron Pharma, Inc.

Current Primary Outcome:

• Part 1: Frequency of adverse events [ Time Frame: From initiation of treatment (Study Day 1) to end of follow-up period (Study Day 141). ]
  Number of subjects with adverse events related to treatment intervention
• Part 2: Change in muscle volume [ Time Frame: From initiation of treatment (Study Day 1) to end of follow-up period (Study Day 141). ]
  Percent change from baseline in volume of injected muscle, by MRI

Original Primary Outcome: Same as current

Current Secondary Outcome:

• Change in amount of intramuscular fat tissue [ Time Frame: From initiation of treatment (Study Day 1) to end of follow-up period (Study Day 141). ]
  Percent change from baseline in intramuscular fat fraction of the injected muscle, by MRI
• Change in muscle strength [ Time Frame: From initiation of treatment (Study Day 1) to end of follow-up period (Study Day 141). ]
  Percent change from baseline in strength of the injected muscle, by Quantitative Muscle Testing (QMT)
• Change in muscle function - walk/run time [ Time Frame: From initiation of treatment (Study Day 1) to end of follow-up period (Study Day 141). ]
  Percent change from baseline in functional assessments, as measured by 10-meter walk/run time
• Change in muscle function - walk distance [ Time Frame: From initiation of treatment (Study Day 1) to end of follow-up period (Study Day 141). ]
  Percent change from baseline in functional assessments, as measured by 6-minute walk distance
• Change in balance and fall risk [ Time Frame: From initiation of treatment (Study Day 1) to end of follow-up period (Study Day 141). ]
  Percent change from baseline in static and dynamic balance, as measured by the Berg Balance Scale, a 14-item scoring system to assess balance and fall risk in adults
• Change in clinical examination score [ Time Frame: From initiation of treatment (Study Day 1) to end of follow-up period (Study Day 141). ]
  Percent change from baseline in the CMT Examination Score (CMTES2), a composite acoring system to assess sensory and motor impairment in subjects with CMT
• Change in patient-reported quality of life [ Time Frame: From initiation of treatment (Study Day 1) to end of follow-up period (Study Day 141). ]
  Percent change from baseline in CMT-HI, a disease-specific, patient-reported health index score

Original Secondary Outcome: Same as current

Information By: Acceleron Pharma, Inc.

Dates:
Date Received: April 12, 2017
Date Started: June 2017
Date Completion: July 2019
Last Updated: April 25, 2017
Last Verified: April 2017