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NCT03124459

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

Terminated Phase 2 Results posted Last updated 26 September 2022
What this trial tests

Phase 2 trial testing ACE-083 in Charcot-Marie-Tooth Disease in 63 participants. Terminated before completion.

Timeline
31 July 2017
Primary endpoint
11 March 2020
11 March 2020

Quick facts

Lead sponsorAcceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA
PhasePhase 2
StatusTerminated
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment63
Start date31 July 2017
Primary completion11 March 2020
Estimated completion11 March 2020
Sites16 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA — full company profile →

Who can join

18 and older, any sex, with Charcot-Marie-Tooth Disease. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Part 1: Frequency of Adverse Events Primary · From initiation of treatment (Study Day 1) to end of follow-up period for Part 1 (Study Day 141).

Number of subjects with at least one adverse event related to treatment intervention from Part 1 of this study. Since this outcome measure was only pre-specified for Part 1, only data from the Part 1 participants is reported.

GroupValue95% CI
Part 1 Cohort 1 (150 mg)6
Part 1 Cohort 2 (200 mg)5
Part 1 Cohort 3 (240 mg)6
Part 2: Percent Change in Muscle Volume to the End of the Double-blind Placebo-controlled Portion of the Study. Primary · From initiation of treatment (Study Day 1) to end of follow-up period of the double-blind placebo-controlled portion of the study (Study Day 190).

The percent change from baseline in volume of injected muscle, by MRI compared to the Day 190 Assessment is reported. The pre-specified timepoint for this outcome was only for data collected from participants to the end of the double-blind placebo controlled portion of the study, therefore data for the open-label arm of the study is not reported.

GroupValue95% CI
Part 2 (Double-blind Placebo Controlled) Placebo Arm2.2± 4.1
Part 2 (Double-blind Placebo Controlled) ACE-083 Arm15.8± 4.3
Part 2: Absolute Change in Amount of Intramuscular Fat Tissue to the End of the Double-blind Placebo-controlled Portion of the Study Secondary · From initiation of treatment (Study Day 1) to end of follow-up period of the double-blind placebo-controlled portion of the study (Study Day 190).

The absolute change from baseline in intramuscular fat fraction of the injected muscle, by MRI compared to Day 190 Assessment is reported. The pre-specified timepoint for this outcome was only for data collected from participants to the end of the double-blind placebo controlled portion of the study, therefore data for the open-label arm of the study is not reported.

GroupValue95% CI
Part 2 (Double-blind Placebo Controlled) Placebo Arm1± 1.8
Part 2 (Double-blind Placebo Controlled) ACE-083 Arm-2.1± 1.9
Part 2: Percent Change in Muscle Strength to the End of the Double-blind Placebo-controlled Portion of the Study Secondary · From initiation of treatment (Study Day 1) to end of follow-up period of the double-blind placebo-controlled portion of the study (Study Day 190).

Percent change from baseline in strength of the injected muscle, by Quantitative Muscle Testing (QMT) compared to Day 190 Assessment is reported. The pre-specified timepoint for this outcome was only for data collected from participants to the end of the double-blind placebo controlled portion of the study, therefore data for the open-label arm of the study is not reported.

GroupValue95% CI
Part 2 (Double-blind Placebo Controlled) Placebo Arm-3.4± 19.8
Part 2 (Double-blind Placebo Controlled) ACE-083 Arm32.0± 19.8
Part 2: Percent Change in Muscle Function - Walk/Run Time to the End of the Double-blind Placebo-controlled Portion of the Study Secondary · From initiation of treatment (Study Day 1) to end of follow-up period of the double-blind placebo-controlled portion of the study (Study Day 190).

The percent change from baseline in functional assessments, as measured by 10-meter walk/run time when compared to Day 190 Assessment is reported. The pre-specified timepoint for this outcome was only for data collected from participants to the end of the double-blind placebo controlled portion of the study, therefore data for the open-label arm of the study is not reported.

GroupValue95% CI
Part 2 (Double-blind Placebo Controlled) Placebo Arm-10.1± 4.7
Part 2 (Double-blind Placebo Controlled) ACE-083 Arm-8.2± 4.7
Part 2: Percent Change in Muscle Function - Walk Distance Assessed at the End of the Double-blind Placebo-controlled Portion of the Study Secondary · From initiation of treatment (Study Day 1) to end of follow-up period for the double-blind placebo-controlled portion of the study (Study Day 190).

Percent change from baseline in functional assessments, as measured by 6-minute walk distance when compared to Day 190 Assessment, is reported. The pre-specified timepoint for this outcome was only for data collected from participants to the end of the double-blind placebo controlled portion of the study, therefore data for the open-label arm of the study is not reported.

GroupValue95% CI
Part 2 (Double-blind Placebo Controlled) Placebo Arm6± 4
Part 2 (Double-blind Placebo Controlled) ACE-083 Arm9.1± 3.8
Part 2: Change in Balance and Fall Risk at the End of the Double-blind Placebo-controlled Portion of the Study. Secondary · From initiation of treatment (Study Day 1) to end of follow-up period of the double-blind placebo-controlled portion of the study (Study Day 190).

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. The Berg balance scale is used to objectively determine a patient's ability (or inability) to safely balance during a series of predetermined tasks. It is a 14 item list with each item consisting of a five-point ordinal scale ranging from 0 to 4, with 0 indicating the lowest level of function and 4 the highest level of function. Total scores are used for reporting, with a range of 0-56, with higher scores mean a better demonstration of f

Baseline
GroupValue95% CI
Part 2 (Double-blind Placebo Controlled) Placebo Arm52.8± 1.99
Part 2 (Double-blind Placebo Controlled) ACE-083 Arm50.8± 5.58
Day 190
GroupValue95% CI
Part 2 (Double-blind Placebo Controlled) Placebo Arm53± 2.77
Part 2 (Double-blind Placebo Controlled) ACE-083 Arm51.4± 5.6
Part 2: Percent Change in Balance and Fall Risk From Baseline to the End of the Double-blind Placebo-controlled Portion of the Study Secondary · From initiation of treatment (Study Day 1) to end of follow-up period of the double-blind placebo-controlled portion of the study (Study Day 190).

Percent change was calculated for the difference from baseline and Day 190 Assessment scores on the Berg Balance Scale. The Berg Balance Scale, is a 14-item scoring system to assess balance and fall risk in adults. The Berg balance scale is used to objectively determine a patient's ability (or inability) to safely balance during a series of predetermined tasks. It is a 14 item list with each item consisting of a five-point ordinal scale ranging from 0 to 4, with 0 indicating the lowest level of function and 4 the highest level of function. Total scores are used for reporting, with a range of 0

GroupValue95% CI
Part 2 (Double-blind Placebo Controlled) Placebo Arm0.4± 3.59
Part 2 (Double-blind Placebo Controlled) ACE-083 Arm1.3± 3.13
Part 2: Change in Clinical Examination Score From Baseline to End of the Double-blind Placebo-controlled Portion of the Study Secondary · From initiation of treatment (Study Day 1) to end of follow-up period of the double-blind placebo-controlled portion of the study (Study Day 190).

Change from baseline in the Charcot-Marie-Tooth (CMT) Examination Score, version 2 (CMTES2), a composite scoring system to assess sensory and motor impairment in subjects with CMT. The total score is a subset of the following items from the CMT neuropathy score instrument: Sensory symptoms, Motor symptoms (legs), Motor symptoms (arms), Pinprick Sensibility, Vibration, Strength (legs), and Strength (arms). Each individual item is assessed using a rating from 0 to 4 inclusive. The range of CMTES2 scores is from 0 to 28 inclusive. A higher score means a greater degree of symptom severity. The Bas

Baseline
GroupValue95% CI
Part 2 (Double-blind Placebo Controlled) Placebo Arm10.1± 3.4
Part 2 (Double-blind Placebo Controlled) ACE-083 Arm10.9± 3.67
Day 190
GroupValue95% CI
Part 2 (Double-blind Placebo Controlled) Placebo Arm9.5± 3.02
Part 2 (Double-blind Placebo Controlled) ACE-083 Arm11.2± 4.77
Part 2: Percent Change in Clinical Examination Score in Baseline to End of the Double-blind Placebo-controlled Portion of the Study Secondary · From initiation of treatment (Study Day 1) to end of follow-up period of the double-blind placebo-controlled portion of the study (Study Day 190).

Percent change was calculated for the difference in the Charcot-Marie-Tooth (CMT) Examination Score (CMTES2) from baseline and Day 190 Assessment scores. The pre-specified timepoints for reporting are baseline Berg scale score and Day 190 score, therefore data for the open-label arm of the study is not reported.

GroupValue95% CI
Part 2 (Double-blind Placebo Controlled) Placebo Arm-0.2± 34.63
Part 2 (Double-blind Placebo Controlled) ACE-083 Arm2.4± 24.26
Part 2: Change in Patient-reported Quality of Life From Baseline to the End of the Double-blind Placebo-controlled Portion of the Study Secondary · From initiation of treatment (Study Day 1) to end of follow-up period of the double-blind placebo-controlled portion of the study (Study Day 190).

The absolute change from baseline in Charcot-Marie-Tooth Health Index (CMT-HI), a disease-specific, patient-reported health index score from baseline and Day 190 Assessment scores. The pre-specified timepoints for reporting are baseline Berg scale score and Day 190 score, therefore data for the open-label arm of the study is not reported.

GroupValue95% CI
Part 2 (Double-blind Placebo Controlled) Placebo Arm-0.2± 3.3
Part 2 (Double-blind Placebo Controlled) ACE-083 Arm-2.2± 3.1

Adverse events — posted to ClinicalTrials.gov

Time frame: Part 1 adverse events (AEs) were collected from baseline through Day 141. For Part 2, AEs were collected from on or after the first double-blind study drug administration up to the end of the double-blind period (Day 190). For the open-label period, adverse events are defined as AEs that started or worsened in intensity on or after the first open-label study drug administration up to the end of the study(Day 393/end-of-study).. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Part 1 Cohort 1(150mg)
Serious: 0/6 (0%)
Deaths: 0/6
Part 1 Cohort 2 (200mg)
Serious: 0/6 (0%)
Deaths: 0/6
Part 1 Cohort 3 (250mg)
Serious: 1/6 (17%)
Deaths: 0/6
Part 2 (Double-blind Placebo Controlled) Placebo Arm
Serious: 1/21 (5%)
Deaths: 0/21
Part 2 (Double-blind Placebo Controlled) ACE-083 Arm
Serious: 0/23 (0%)
Deaths: 0/23
Part 2 (Open Label)
Serious: 1/40 (3%)
Deaths: 0/40

Serious adverse events (3 terms)

ReactionSystemPart 1 Cohort 1(150mg)Part 1 Cohort 2 (200mg)Part 1 Cohort 3 (250mg)Part 2 (Double-blind Place…Part 2 (Double-blind Place…Part 2 (Open Label)
HypokalaemiaMetabolism and nutrition disorders
Suicide attemptPsychiatric disorders
CellulitisInfections and infestations
Other adverse events (158 terms — click to expand)

ReactionSystemPart 1 Cohort 1(150mg)Part 1 Cohort 2 (200mg)Part 1 Cohort 3 (250mg)Part 2 (Double-blind Place…Part 2 (Double-blind Place…Part 2 (Open Label)
fallInjury, poisoning and procedural complications
injection site erythemaGeneral disorders
pain in extremityMusculoskeletal and connective tissue disorders
injection site swellingGeneral disorders
myalgiaMusculoskeletal and connective tissue disorders
injection site warmthGeneral disorders
contusionInjury, poisoning and procedural complications
arthralgiaMusculoskeletal and connective tissue disorders
injection site bruisingGeneral disorders
injection site painGeneral disorders
injection site pruritusGeneral disorders
injection site discomfortGeneral disorders
nasopharyngitisInfections and infestations
urine analysis abnormalInvestigations
musculoskeletal stiffnessMusculoskeletal and connective tissue disorders
peripheral swellingGeneral disorders
injection site indurationGeneral disorders
oedema peripheralGeneral disorders
sinusitisInfections and infestations
headacheNervous system disorders
paraesthesiaNervous system disorders
erythemaSkin and subcutaneous tissue disorders
coughRespiratory, thoracic and mediastinal disorders
dyspnoeaRespiratory, thoracic and mediastinal disorders
flushingVascular disorders
muscle spasmMusculoskeletal and connective tissue disorders
joint stiffnessMusculoskeletal and connective tissue disorders
back painMusculoskeletal and connective tissue disorders
muscular weaknessMusculoskeletal and connective tissue disorders
musculoskeletal discomfortMusculoskeletal and connective tissue disorders
neck painMusculoskeletal and connective tissue disorders
injection site discolorationGeneral disorders
fatigueGeneral disorders
pyrexiaGeneral disorders
injection site haematomaGeneral disorders
influenzaInfections and infestations
upper respiratory tract infectionInfections and infestations
localised infectionInfections and infestations
urinary tract infectionInfections and infestations
fungal skin infectionInfections and infestations

Most-reported serious reactions: Hypokalaemia, Suicide attempt, Cellulitis.

Data from ClinicalTrials.gov NCT03124459 adverse events section.

Sponsor's own description

This is a multicenter, phase 2 study to evaluate the safety, tolerability, pharmacodynamics (PD), efficacy, and pharmacokinetics (PK) of ACE-083 in patients with Charcot-Marie-Tooth Disease Type 1 and Type X (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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Charcot-Marie-Tooth: From Molecules to Therapy.
    Morena J, Gupta A, Hoyle JC. · · 2019 · cited 128× · PMID 31336816 · DOI 10.3390/ijms20143419
  2. Treating pediatric neuromuscular disorders: The future is now.
    Dowling JJ, D Gonorazky H, Cohn RD, Campbell C. · · 2018 · cited 83× · PMID 28889642 · DOI 10.1002/ajmg.a.38418
  3. Myostatin/Activin Receptor Ligands in Muscle and the Development Status of Attenuating Drugs.
    Rodgers BD, Ward CW. · · 2022 · cited 68× · PMID 34520530 · DOI 10.1210/endrev/bnab030
  4. Emerging Therapies for Charcot-Marie-Tooth Inherited Neuropathies.
    Stavrou M, Sargiannidou I, Georgiou E, Kagiava A, et al · · 2021 · cited 52× · PMID 34205075 · DOI 10.3390/ijms22116048
  5. Locally acting ACE-083 increases muscle volume in healthy volunteers.
    Glasser CE, Gartner MR, Wilson D, Miller B, et al · · 2018 · cited 43× · PMID 29486514 · DOI 10.1002/mus.26113
  6. Advances in research on pharmacotherapy of sarcopenia.
    Feike Y, Zhijie L, Wei C. · · 2021 · cited 41× · PMID 34553120 · DOI 10.1002/agm2.12168
  7. Therapeutic applications and challenges in myostatin inhibition for enhanced skeletal muscle mass and functions.
    Wetzlich B, Nyakundi BB, Yang J. · · 2025 · cited 37× · PMID 39340593 · DOI 10.1007/s11010-024-05120-y
  8. Challenges in Treating Charcot-Marie-Tooth Disease and Related Neuropathies: Current Management and Future Perspectives.
    Pisciotta C, Saveri P, Pareyson D. · · 2021 · cited 35× · PMID 34827446 · DOI 10.3390/brainsci11111447

Verify or expand the search:

Other trials of ACE-083

Trials testing the same drug.

Other recruiting trials for Charcot-Marie-Tooth Disease

Currently open trials in the same condition.

Other Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA trials

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT03124459.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing