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Trial record 1 of 1 for:    NCT03124459
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Study of ACE-083 in Patients With Charcot-Marie-Tooth Disease

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ClinicalTrials.gov Identifier: NCT03124459
Recruitment Status : Terminated ((Investigation of ACE-083 for use in patients with CMT is being discontinued as it did not achieve functional secondary endpoints in the A083-03 trial.)
First Posted : April 21, 2017
Results First Posted : July 28, 2021
Last Update Posted : July 28, 2021
Sponsor:
Information provided by (Responsible Party):
Acceleron Pharma Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Charcot-Marie-Tooth Disease
Interventions Drug: ACE-083
Drug: Placebo
Enrollment 63
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Part 1 Cohort 1 (150 mg) Part 1 Cohort 2 (200 mg) Part 1 Cohort 3 (240 mg) Part 2 (Double-blind Placebo Controlled) Placebo Arm Part 2 (Double-blind Placebo Controlled) ACE-083 Arm Part 2 (Open-label) ACE-083 Arm
Hide Arm/Group Description

ACE-083 150 mg intramuscular (IM; tibialis anterior muscle), once every 3 weeks for up to 5 doses.

ACE-083: Part 1 - Recombinant fusion protein.

ACE-083 200 mg IM, (tibialis anterior muscle), once every 3 weeks for up to 5 doses.

ACE-083: Part 1 - Recombinant fusion protein.

ACE-083 240 mg IM (tibialis anterior muscle), once every 3 weeks for up to 5 doses.

ACE-083: Part 1 - Recombinant fusion protein.

Placebo once every 3 weeks for up to 9 doses

ACE-083: Part 2 -buffer solution

ACE-083 240 mg IM (tibialis anterior muscle) once every 3 weeks for up to 9 doses

ACE-083: Part 2 - Recombinant fusion protein

ACE-083 240 mg IM (tibialis anterior muscle) once every 3 weeks for up to 8 doses

ACE-083: Part 2 - Recombinant fusion protein

Period Title: Part 1-Open Label Dose Escalation
Started [1] 6 6 6 0 [2] 0 [2] 0 [3]
Completed 6 6 6 0 [2] 0 [2] 0 [3]
Not Completed 0 0 0 0 0 0
[1]
Participants in the Part 2 double-blind placebo controlled portion of the study were not the same participants that participated in the Part 1 Open-Label Dose escalation portion of the study.
[2]
Patients in the double-blind placebo controlled study were not the same participants that participated in the Part 1 Open-Label Dose escalation portion of the study.
[3]
Patients in the double-blind placebo controlled study were not the same participants that participated in the Part 1 Open-Label Dose escalation portion of the study. Participants that completed the double-blind portion of the study then moved into this Part 2 open-label portion of the study.
Period Title: Phase 2- Randomized Doubled-blind
Started [1] 0 [1] 0 [1] 0 [1] 21 [2] 24 [2] 0 [3]
Completed 0 0 0 9 5 0
Not Completed 0 0 0 12 19 0
Reason Not Completed
Adverse Event             0             0             0             0             2             0
Lost to Follow-up             0             0             0             0             1             0
Study terminated by Sponsor             0             0             0             11             12             0
Withdrawal by Subject             0             0             0             1             4             0
[1]
Participants in Part 1 Open-Label Dose escalation portion of the study were not the same participants that participated in the double-blind placebo controlled study.
[2]
Participants in the double-blind placebo controlled study were not the same participants that participated in the Part 1 Open-Label Dose escalation portion of the study.
[3]
Participants in the double-blind placebo controlled study were not the same participants that participated in the Part 1 Open-Label Dose escalation portion of the study. Participants that completed the double-blind portion of the study then moved into this Part 2 open-label portion of the study.
Period Title: Part 2- Open Label ACE-083
Started [1] 0 0 0 0 [2] 0 [2] 40 [3]
Completed 0 0 0 0 0 17
Not Completed 0 0 0 0 0 23
Reason Not Completed
Study terminated by Sponsor             0             0             0             0             0             22
Withdrawal by Subject             0             0             0             0             0             1
[1]
Participants in Part 1 Open-Label Dose escalation portion of the study were not the same participants that participated in the double-blind placebo controlled study. Participants that completed the Part 2 double-blind placebo controlled portion of the study were able to move into the open-label portion of the study.
[2]
Participants in the double-blind placebo controlled study were not the same participants that participated in the Part 1 Open-Label Dose escalation portion of the study. Participants that completed the double-blind placebo controlled portion of Part 2, moved into the open-label portion part 2 study.
[3]
The open-label portion of Part 2 are the participants that were enrolled in and completed the double-blind placebo-controlled portion of Part 2.
Arm/Group Title Part 1 Cohort 1 Part 1 Cohort 2 Part 1 Cohort 3 Part 2 (Double-blind Placebo Controlled) Placebo Part 2 (Double-blind Placebo Controlled) ACE-083 Part 2 (Open-label) ACE 083-03 Arm Total
Hide Arm/Group Description

ACE-083 150 mg IM (tibialis anterior muscle), once every 3 weeks for up to 5 doses.

ACE-083: Part 1 - Recombinant fusion protein.

ACE-083 200 mg IM, (tibialis anterior muscle), once every 3 weeks for up to 5 doses.

ACE-083: Part 1 - Recombinant fusion protein.

ACE-083 240 mg IM (tibialis anterior muscle), once every 3 weeks for up to 5 doses.

ACE-083: Part 1 - Recombinant fusion protein.

Placebo once every 3 weeks for up to 9 doses

ACE-083: Part 2 - buffer solution.

ACE-083 up to 250 mg IM (tibialis anterior muscle) once every 3 weeks for up to 9 doses

ACE-083 Part 2 - Recombinant fusion protein

ACE-083 up to 250 mg IM (tibialis anterior muscle) once every 3 weeks for up to 8 doses

ACE-083 Part 2 - Recombinant fusion protein

Total of all reporting groups
Overall Number of Baseline Participants 6 6 6 21 24 40 103
Hide Baseline Analysis Population Description
The Full Analysis Set includes all randomized patients who have received at least 1 dose of study drug (includes placebo). Additionally, the participants in the Open-Label portion of Part 2 are a sub-set of the participants that enrolled and then subsequently completed the double-blind placebo controlled portion of Part 2. The open-label baseline measures are captured separately.
Age, Categorical   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 6 participants 6 participants 21 participants 24 participants 0 participants 63 participants
<=18 years
0
   0.0%
1
  16.7%
0
   0.0%
1
   4.8%
0
   0.0%
2
   3.2%
Between 18 and 65 years
6
 100.0%
5
  83.3%
6
 100.0%
17
  81.0%
23
  95.8%
57
  90.5%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
3
  14.3%
1
   4.2%
4
   6.3%
[1]
Measure Analysis Population Description: The participants in the Open-Label portion of Part 2 are a sub-set of the participants that enrolled and then subsequently completed the double-blind placebo controlled portion of Part 2. The open-label baseline measures are captured separately.
Age, Categorical   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 0 participants 0 participants 0 participants 0 participants 0 participants 40 participants 40 participants
<=18 years
0
   0.0%
0
   0.0%
Between 18 and 65 years
36
  90.0%
36
  90.0%
>=65 years
4
  10.0%
4
  10.0%
[1]
Measure Analysis Population Description: The participants in the Open-Label portion of Part 2 are a sub-set of the participants that enrolled and then subsequently completed the double-blind placebo controlled portion of Part 2.
Age, Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 6 participants 6 participants 6 participants 21 participants 23 participants 0 participants 62 participants
40  (18.1) 39  (17.8) 49  (9.7) 47.1  (15.3) 45.8  (11.2) 45.3  (13.6)
[1]
Measure Analysis Population Description: One patient in the Phase 2 randomized portion of the study was randomized (to the ACE-083 arm) but not dosed.
Age, Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 0 participants 0 participants 0 participants 0 participants 0 participants 40 participants 40 participants
47.3  (12.9) 47.3  (12.9)
[1]
Measure Analysis Population Description: The participants in the Open-Label portion of Part 2 are a sub-set of the participants that enrolled and then subsequently completed the double-blind placebo controlled portion of Part 2.
Sex: Female, Male   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 6 participants 6 participants 21 participants 23 participants 0 participants 62 participants
Female
3
  50.0%
3
  50.0%
4
  66.7%
13
  61.9%
17
  73.9%
40
  64.5%
Male
3
  50.0%
3
  50.0%
2
  33.3%
8
  38.1%
6
  26.1%
22
  35.5%
[1]
Measure Analysis Population Description: One patient in the Phase 2 randomized portion of the study was randomized (to the ACE-083 arm) but not dosed.
Sex: Female, Male   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 0 participants 0 participants 0 participants 0 participants 0 participants 40 participants 40 participants
Female
28
  70.0%
28
  70.0%
Male
12
  30.0%
12
  30.0%
[1]
Measure Analysis Population Description: The participants in the Open-Label portion of Part 2 are a sub-set of the participants that enrolled and then subsequently completed the double-blind placebo controlled portion of Part 2.
Ethnicity (NIH/OMB)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 6 participants 6 participants 21 participants 23 participants 0 participants 62 participants
Hispanic or Latino
0
   0.0%
0
   0.0%
0
   0.0%
2
   9.5%
1
   4.3%
3
   4.8%
Not Hispanic or Latino
6
 100.0%
6
 100.0%
5
  83.3%
19
  90.5%
22
  95.7%
58
  93.5%
Unknown or Not Reported
0
   0.0%
0
   0.0%
1
  16.7%
0
   0.0%
0
   0.0%
1
   1.6%
[1]
Measure Analysis Population Description: One patient in the Phase 2 randomized portion of the study was randomized (to the ACE-083 arm) but not dosed.
Ethnicity (NIH/OMB)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 0 participants 0 participants 0 participants 0 participants 0 participants 40 participants 40 participants
Hispanic or Latino
3
   7.5%
3
   7.5%
Not Hispanic or Latino
37
  92.5%
37
  92.5%
Unknown or Not Reported
0
   0.0%
0
   0.0%
[1]
Measure Analysis Population Description: The participants in the Open-Label portion of Part 2 are a sub-set of the participants that enrolled and then subsequently completed the double-blind placebo controlled portion of Part 2.
Race (NIH/OMB)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 6 participants 6 participants 21 participants 23 participants 0 participants 62 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
1
  16.7%
0
   0.0%
0
   0.0%
0
   0.0%
2
   8.7%
3
   4.8%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
White
5
  83.3%
6
 100.0%
6
 100.0%
21
 100.0%
20
  87.0%
58
  93.5%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   4.3%
1
   1.6%
[1]
Measure Analysis Population Description: One patient in the Phase 2 randomized portion of the study was randomized (to the ACE-083 arm) but not dosed.
Race (NIH/OMB)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 0 participants 0 participants 0 participants 0 participants 0 participants 40 participants 40 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
Asian
1
   2.5%
1
   2.5%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
White
38
  95.0%
38
  95.0%
More than one race
1
   2.5%
1
   2.5%
Unknown or Not Reported
0
   0.0%
0
   0.0%
[1]
Measure Analysis Population Description: The participants in the Open-Label portion of Part 2 are a sub-set of the participants that enrolled and then subsequently completed the double-blind placebo controlled portion of Part 2.
Region of Enrollment   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 6 participants 6 participants 6 participants 21 participants 24 participants 0 participants 63 participants
6
 100.0%
6
 100.0%
6
 100.0%
21
 100.0%
24
 100.0%
63
 100.0%
[1]
Measure Analysis Population Description: The participants in the Open-Label portion of Part 2 are a sub-set of the participants that enrolled and then subsequently completed the double-blind placebo controlled portion of Part 2. The open-label baseline measures are captured separately.
Region of Enrollment   [1] 
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 0 participants 0 participants 0 participants 0 participants 0 participants 40 participants 40 participants
40 40
[1]
Measure Analysis Population Description: The participants in the Open-Label portion of Part 2 are a sub-set of the participants that enrolled and then subsequently completed the double-blind placebo controlled portion of Part 2.
1.Primary Outcome
Title Part 1: Frequency of Adverse Events
Hide Description 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.
Time Frame From initiation of treatment (Study Day 1) to end of follow-up period for Part 1 (Study Day 141).
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety Set consists of all patients enrolled in the study who have received at least 1 dose of study drug.
Arm/Group Title Part 1 Cohort 1 (150 mg) Part 1 Cohort 2 (200 mg) Part 1 Cohort 3 (240 mg)
Hide Arm/Group Description:

ACE-083 150 mg IM (tibialis anterior muscle), once every 3 weeks for up to 5 doses.

ACE-083: Part 1 - Recombinant fusion protein.

ACE-083 200 mg IM, (tibialis anterior muscle), once every 3 weeks for up to 5 doses.

ACE-083: Part 1 - Recombinant fusion protein.

ACE-083 240 mg IM (tibialis anterior muscle), once every 3 weeks for up to 5 doses.

ACE-083: Part 1 - Recombinant fusion protein.

Overall Number of Participants Analyzed 6 6 6
Measure Type: Count of Participants
Unit of Measure: Participants
6
 100.0%
5
  83.3%
6
 100.0%
2.Primary Outcome
Title Part 2: Percent Change in Muscle Volume to the End of the Double-blind Placebo-controlled Portion of the Study.
Hide Description 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.
Time Frame 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).
Hide Outcome Measure Data
Hide Analysis Population Description
Per Protocol Set: All participants enrolled/randomized in the study who received at least 1 dose of the study drug (includes placebo) with no major protocol violations
Arm/Group Title Part 2 (Double-blind Placebo Controlled) Placebo Arm Part 2 (Double-blind Placebo Controlled) ACE-083 Arm
Hide Arm/Group Description:

Placebo once every 3 weeks for up to 9 doses

ACE-083: Part 2 -buffer solution

ACE-083 240 mg IM (tibialis anterior muscle) once every 3 weeks for up to 9 doses

ACE-083: Part 2 - Recombinant fusion protein

Overall Number of Participants Analyzed 20 19
Least Squares Mean (Standard Error)
Unit of Measure: percent change
2.2  (4.1) 15.8  (4.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 2 (Double-blind Placebo Controlled) Placebo Arm, Part 2 (Double-blind Placebo Controlled) ACE-083 Arm
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.01
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 13.5
Confidence Interval (2-Sided) 90%
4.9 to 22.1
Parameter Dispersion
Type: Standard Error of the Mean
Value: 5.2
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Part 2: Absolute Change in Amount of Intramuscular Fat Tissue to the End of the Double-blind Placebo-controlled Portion of the Study
Hide Description 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.
Time Frame 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).
Hide Outcome Measure Data
Hide Analysis Population Description
Per Protocol Set: All participants enrolled/randomized in the study who received at least 1 dose of the study drug (includes placebo) with no major protocol violations
Arm/Group Title Part 2 (Double-blind Placebo Controlled) Placebo Arm Part 2 (Double-blind Placebo Controlled) ACE-083 Arm
Hide Arm/Group Description:

Placebo once every 3 weeks for up to 9 doses

ACE-083: Part 2 -buffer solution

ACE-083 240 mg IM (tibialis anterior muscle) once every 3 weeks for up to 9 doses

ACE-083: Part 2 - Recombinant fusion protein

Overall Number of Participants Analyzed 20 19
Least Squares Mean (Standard Error)
Unit of Measure: mm3
1  (1.8) -2.1  (1.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 2 (Double-blind Placebo Controlled) Placebo Arm, Part 2 (Double-blind Placebo Controlled) ACE-083 Arm
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.16
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -3.1
Confidence Interval (2-Sided) 90%
-6.8 to 0.6
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.2
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Part 2: Percent Change in Muscle Strength to the End of the Double-blind Placebo-controlled Portion of the Study
Hide Description 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.
Time Frame 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).
Hide Outcome Measure Data
Hide Analysis Population Description
Per Protocol Set: All participants enrolled/randomized in the study who received at least 1 dose of the study drug (includes placebo) with no major protocol violations
Arm/Group Title Part 2 (Double-blind Placebo Controlled) Placebo Arm Part 2 (Double-blind Placebo Controlled) ACE-083 Arm
Hide Arm/Group Description:

Placebo once every 3 weeks for up to 9 doses

ACE-083: Part 2 -buffer solution

ACE-083 240 mg IM (tibialis anterior muscle) once every 3 weeks for up to 9 doses

ACE-083: Part 2 - Recombinant fusion protein

Overall Number of Participants Analyzed 19 17
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-3.4  (19.8) 32.0  (19.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 2 (Double-blind Placebo Controlled) Placebo Arm, Part 2 (Double-blind Placebo Controlled) ACE-083 Arm
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.13
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 35.4
Confidence Interval (2-Sided) 90%
-3.2 to 74
Parameter Dispersion
Type: Standard Error of the Mean
Value: 23.5
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Part 2: Percent Change in Muscle Function - Walk/Run Time to the End of the Double-blind Placebo-controlled Portion of the Study
Hide Description 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.
Time Frame 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).
Hide Outcome Measure Data
Hide Analysis Population Description
Per Protocol Set: All participants enrolled/randomized in the study who received at least 1 dose of the study drug (includes placebo) with no major protocol violations
Arm/Group Title Part 2 (Double-blind Placebo Controlled) Placebo Arm Part 2 (Double-blind Placebo Controlled) ACE-083 Arm
Hide Arm/Group Description:

Placebo once every 3 weeks for up to 9 doses

ACE-083: Part 2 -buffer solution

ACE-083 240 mg IM (tibialis anterior muscle) once every 3 weeks for up to 9 doses

ACE-083: Part 2 - Recombinant fusion protein

Overall Number of Participants Analyzed 20 19
Least Squares Mean (Standard Error)
Unit of Measure: Percent change
-10.1  (4.7) -8.2  (4.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 2 (Double-blind Placebo Controlled) Placebo Arm, Part 2 (Double-blind Placebo Controlled) ACE-083 Arm
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.73
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.9
Confidence Interval (2-Sided) 90%
-7.1 to 10.9
Parameter Dispersion
Type: Standard Error of the Mean
Value: 5.5
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Part 2: Percent Change in Muscle Function - Walk Distance Assessed at the End of the Double-blind Placebo-controlled Portion of the Study
Hide Description 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.
Time Frame 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).
Hide Outcome Measure Data
Hide Analysis Population Description
Per Protocol Set: All participants enrolled/randomized in the study who received at least 1 dose of the study drug (includes placebo) with no major protocol violations
Arm/Group Title Part 2 (Double-blind Placebo Controlled) Placebo Arm Part 2 (Double-blind Placebo Controlled) ACE-083 Arm
Hide Arm/Group Description:

Placebo once every 3 weeks for up to 9 doses

ACE-083: Part 2 -buffer solution

ACE-083 240 mg IM (tibialis anterior muscle) once every 3 weeks for up to 9 doses

ACE-083: Part 2 - Recombinant fusion protein

Overall Number of Participants Analyzed 20 19
Least Squares Mean (Standard Error)
Unit of Measure: Percent change
6  (4) 9.1  (3.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 2 (Double-blind Placebo Controlled) Placebo Arm, Part 2 (Double-blind Placebo Controlled) ACE-083 Arm
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.51
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 3.1
Confidence Interval (2-Sided) 90%
-4.6 to 10.9
Parameter Dispersion
Type: Standard Error of the Mean
Value: 4.7
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Part 2: Change in Balance and Fall Risk at the End of the Double-blind Placebo-controlled Portion of the Study.
Hide Description 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 function. A score of 56 indicates functional balance. A score of < 45 indicates individuals may be at greater risk of falling. 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.
Time Frame 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).
Hide Outcome Measure Data
Hide Analysis Population Description
Per Protocol Set: All participants enrolled/randomized in the study who received at least 1 dose of the study drug (includes placebo) with no major protocol violations
Arm/Group Title Part 2 (Double-blind Placebo Controlled) Placebo Arm Part 2 (Double-blind Placebo Controlled) ACE-083 Arm
Hide Arm/Group Description:

Placebo once every 3 weeks for up to 9 doses

ACE-083: Part 2 -buffer solution

ACE-083 240 mg IM (tibialis anterior muscle) once every 3 weeks for up to 9 doses

ACE-083: Part 2 - Recombinant fusion protein

Overall Number of Participants Analyzed 20 20
Mean (Standard Deviation)
Unit of Measure: score on scale
Baseline 52.8  (1.99) 50.8  (5.58)
Day 190 53  (2.77) 51.4  (5.6)
8.Secondary Outcome
Title Part 2: Percent Change in Balance and Fall Risk From Baseline to the End of the Double-blind Placebo-controlled Portion of the Study
Hide Description 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 0-56, with higher scores mean a better demonstration of function. A score of 56 indicates functional balance. A score of < 45 indicates individuals may be at greater risk of falling. 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.
Time Frame 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).
Hide Outcome Measure Data
Hide Analysis Population Description
Per Protocol Set: All participants enrolled/randomized in the study who received at least 1 dose of the study drug (includes placebo) with no major protocol violations
Arm/Group Title Part 2 (Double-blind Placebo Controlled) Placebo Arm Part 2 (Double-blind Placebo Controlled) ACE-083 Arm
Hide Arm/Group Description:

Placebo once every 3 weeks for up to 9 doses

ACE-083: Part 2 -buffer solution

ACE-083 240 mg IM (tibialis anterior muscle) once every 3 weeks for up to 9 doses

ACE-083: Part 2 - Recombinant fusion protein

Overall Number of Participants Analyzed 20 20
Mean (Standard Deviation)
Unit of Measure: percent change in score on scale
0.4  (3.59) 1.3  (3.13)
9.Secondary Outcome
Title Part 2: Change in Clinical Examination Score From Baseline to End of the Double-blind Placebo-controlled Portion of the Study
Hide Description 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 Baseline score and score on the Day 190 Assessment are reported. 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.
Time Frame 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).
Hide Outcome Measure Data
Hide Analysis Population Description
Per Protocol Set: All participants enrolled/randomized in the study who received at least 1 dose of the study drug (includes placebo) with no major protocol violations
Arm/Group Title Part 2 (Double-blind Placebo Controlled) Placebo Arm Part 2 (Double-blind Placebo Controlled) ACE-083 Arm
Hide Arm/Group Description:

Placebo once every 3 weeks for up to 9 doses

ACE-083: Part 2 -buffer solution

ACE-083 240 mg IM (tibialis anterior muscle) once every 3 weeks for up to 9 doses

ACE-083: Part 2 - Recombinant fusion protein

Overall Number of Participants Analyzed 20 20
Mean (Standard Deviation)
Unit of Measure: score on scale
Baseline 10.1  (3.4) 10.9  (3.67)
Day 190 9.5  (3.02) 11.2  (4.77)
10.Secondary Outcome
Title Part 2: Percent Change in Clinical Examination Score in Baseline to End of the Double-blind Placebo-controlled Portion of the Study
Hide Description 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.
Time Frame 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).
Hide Outcome Measure Data
Hide Analysis Population Description
Per Protocol Set: All participants enrolled/randomized in the study who received at least 1 dose of the study drug (includes placebo) with no major protocol violations.
Arm/Group Title Part 2 (Double-blind Placebo Controlled) Placebo Arm Part 2 (Double-blind Placebo Controlled) ACE-083 Arm
Hide Arm/Group Description:

Placebo once every 3 weeks for up to 9 doses

ACE-083: Part 2 -buffer solution

ACE-083 240 mg IM (tibialis anterior muscle) once every 3 weeks for up to 9 doses

ACE-083: Part 2 - Recombinant fusion protein

Overall Number of Participants Analyzed 20 20
Mean (Standard Deviation)
Unit of Measure: percent change in score on scale
-0.2  (34.63) 2.4  (24.26)
11.Secondary Outcome
Title Part 2: Change in Patient-reported Quality of Life From Baseline to the End of the Double-blind Placebo-controlled Portion of the Study
Hide Description 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.
Time Frame 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).
Hide Outcome Measure Data
Hide Analysis Population Description
Per Protocol Set: All participants enrolled/randomized in the study who received at least 1 dose of the study drug (includes placebo) with no major protocol violations
Arm/Group Title Part 2 (Double-blind Placebo Controlled) Placebo Arm Part 2 (Double-blind Placebo Controlled) ACE-083 Arm
Hide Arm/Group Description:

Placebo once every 3 weeks for up to 9 doses

ACE-083: Part 2 -buffer solution

ACE-083 240 mg IM (tibialis anterior muscle) once every 3 weeks for up to 9 doses

ACE-083: Part 2 - Recombinant fusion protein

Overall Number of Participants Analyzed 19 18
Least Squares Mean (Standard Deviation)
Unit of Measure: absolute change in score on a scale
-0.2  (3.3) -2.2  (3.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 2 (Double-blind Placebo Controlled) Placebo Arm, Part 2 (Double-blind Placebo Controlled) ACE-083 Arm
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.63
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.9
Confidence Interval (2-Sided) 90%
-8.4 to 4.6
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.9
Estimation Comments [Not Specified]
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).
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Part 1 Cohort 1(150mg) Part 1 Cohort 2 (200mg) Part 1 Cohort 3 (250mg) Part 2 (Double-blind Placebo Controlled) Placebo Arm Part 2 (Double-blind Placebo Controlled) ACE-083 Arm Part 2 (Open Label)
Hide Arm/Group Description

ACE-083 150 mg IM (tibialis anterior muscle), once every 3 weeks for up to 5 doses.

ACE-083: Part 1 - Recombinant fusion protein.

ACE-083 200 mg IM, (tibialis anterior muscle), once every 3 weeks for up to 5 doses.

ACE-083: Part 1 - Recombinant fusion protein.

ACE-083 up to 250 mg IM (tibialis anterior muscle), once every 3 weeks for up to 5 doses.

ACE-083: Part 1 - Recombinant fusion protein.

Placebo, once every 3 weeks for up to 9 doses

ACE-083:

Part 2 - Placebo: buffer solution

ACE-083 up to 250 mg IM (tibialis anterior muscle) once every 3 weeks for up to 9 doses

ACE-083:

Part 2 - Recombinant fusion protein

ACE-083 up to 250 mg IM (tibialis anterior muscle), once every 3 weeks for up to 8 doses

ACE-083: Part 1 - Recombinant fusion protein. Part 2 - Recombinant fusion protein or buffer solution.

All-Cause Mortality
Part 1 Cohort 1(150mg) Part 1 Cohort 2 (200mg) Part 1 Cohort 3 (250mg) Part 2 (Double-blind Placebo Controlled) Placebo Arm Part 2 (Double-blind Placebo Controlled) ACE-083 Arm Part 2 (Open Label)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/6 (0.00%)   0/6 (0.00%)   0/6 (0.00%)   0/21 (0.00%)   0/23 (0.00%)   0/40 (0.00%) 
Hide Serious Adverse Events
Part 1 Cohort 1(150mg) Part 1 Cohort 2 (200mg) Part 1 Cohort 3 (250mg) Part 2 (Double-blind Placebo Controlled) Placebo Arm Part 2 (Double-blind Placebo Controlled) ACE-083 Arm Part 2 (Open Label)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/6 (0.00%)   0/6 (0.00%)   1/6 (16.67%)   1/21 (4.76%)   0/23 (0.00%)   1/40 (2.50%) 
Infections and infestations             
Cellulitis  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  0/23 (0.00%)  1/40 (2.50%) 
Metabolism and nutrition disorders             
Hypokalaemia  1  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/21 (0.00%)  0/23 (0.00%)  0/40 (0.00%) 
Psychiatric disorders             
Suicide attempt  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/21 (4.76%)  0/23 (0.00%)  0/40 (0.00%) 
1
Term from vocabulary, MEdDRA 19.1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Part 1 Cohort 1(150mg) Part 1 Cohort 2 (200mg) Part 1 Cohort 3 (250mg) Part 2 (Double-blind Placebo Controlled) Placebo Arm Part 2 (Double-blind Placebo Controlled) ACE-083 Arm Part 2 (Open Label)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   6/6 (100.00%)   6/6 (100.00%)   6/6 (100.00%)   19/21 (90.48%)   20/23 (86.96%)   36/40 (90.00%) 
Cardiac disorders             
palpitations  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  0/23 (0.00%)  1/40 (2.50%) 
tachycardia  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  0/23 (0.00%)  1/40 (2.50%) 
Endocrine disorders             
goitre  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/21 (4.76%)  0/23 (0.00%)  0/40 (0.00%) 
Eye disorders             
inflammation of lacrimal passage  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  0/23 (0.00%)  1/40 (2.50%) 
vitreous haemorrhage  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  0/23 (0.00%)  1/40 (2.50%) 
Gastrointestinal disorders             
diarrhoea  1  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  1/21 (4.76%)  1/23 (4.35%)  0/40 (0.00%) 
gingival swelling  1  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  0/23 (0.00%)  0/40 (0.00%) 
vomiting  1  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  1/23 (4.35%)  0/40 (0.00%) 
nausea  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  2/23 (8.70%)  1/40 (2.50%) 
gingival pain  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  1/23 (4.35%)  0/40 (0.00%) 
lip swelling  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/21 (4.76%)  0/23 (0.00%)  0/40 (0.00%) 
oral pain  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  1/23 (4.35%)  0/40 (0.00%) 
toothache  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  1/23 (4.35%)  0/40 (0.00%) 
abdominal pain upper  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  0/23 (0.00%)  1/40 (2.50%) 
dysphagia  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  0/23 (0.00%)  1/40 (2.50%) 
gastrointestinal disorders  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  0/23 (0.00%)  2/40 (5.00%) 
General disorders             
injection site discomfort  1  3/6 (50.00%)  2/6 (33.33%)  3/6 (50.00%)  4/21 (19.05%)  4/23 (17.39%)  4/40 (10.00%) 
injection site bruising  1  2/6 (33.33%)  2/6 (33.33%)  2/6 (33.33%)  1/21 (4.76%)  6/23 (26.09%)  6/40 (15.00%) 
injection site erythema  1  2/6 (33.33%)  1/6 (16.67%)  1/6 (16.67%)  1/21 (4.76%)  7/23 (30.43%)  10/40 (25.00%) 
injection site pain  1  1/6 (16.67%)  1/6 (16.67%)  1/6 (16.67%)  2/21 (9.52%)  6/23 (26.09%)  6/40 (15.00%) 
injection site swelling  1  1/6 (16.67%)  1/6 (16.67%)  1/6 (16.67%)  2/21 (9.52%)  6/23 (26.09%)  8/40 (20.00%) 
injection site pruritus  1  1/6 (16.67%)  0/6 (0.00%)  1/6 (16.67%)  0/21 (0.00%)  5/23 (21.74%)  6/40 (15.00%) 
injection site discoloration  1  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  1/21 (4.76%)  1/23 (4.35%)  2/40 (5.00%) 
injection site macule  1  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/21 (0.00%)  0/23 (0.00%)  1/40 (2.50%) 
injection site reaction  1  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  0/23 (0.00%)  0/40 (0.00%) 
injection site warmth  1  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  2/21 (9.52%)  4/23 (17.39%)  7/40 (17.50%) 
peripheral swelling  1  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/21 (0.00%)  2/23 (8.70%)  3/40 (7.50%) 
fatigue  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  2/23 (8.70%)  0/40 (0.00%) 
vessel puncture site bruise  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/21 (4.76%)  1/23 (4.35%)  1/40 (2.50%) 
chest discomfort  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/21 (4.76%)  0/23 (0.00%)  0/40 (0.00%) 
injection site dysaethesia  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  1/23 (4.35%)  1/40 (2.50%) 
injection site induration  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  1/23 (4.35%)  3/40 (7.50%) 
injection site papule  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  1/23 (4.35%)  0/40 (0.00%) 
injection site paraesthesia  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  1/23 (4.35%)  1/40 (2.50%) 
local swelling  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/21 (4.76%)  0/23 (0.00%)  0/40 (0.00%) 
malaise  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  1/23 (4.35%)  1/40 (2.50%) 
medical device site pain  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  1/23 (4.35%)  0/40 (0.00%) 
pyrexia  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  1/23 (4.35%)  2/40 (5.00%) 
influenza like illness  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  0/23 (0.00%)  1/40 (2.50%) 
injection site haematoma  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  0/23 (0.00%)  2/40 (5.00%) 
oedema peripheral  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  0/23 (0.00%)  3/40 (7.50%) 
tenderness  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  0/23 (0.00%)  1/40 (2.50%) 
Hepatobiliary disorders             
hepatic cyst  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  0/23 (0.00%)  1/40 (2.50%) 
Infections and infestations             
influenza  1  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/21 (0.00%)  0/23 (0.00%)  2/40 (5.00%) 
nasopharyngitis  1  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  2/21 (9.52%)  3/23 (13.04%)  4/40 (10.00%) 
upper respiratory tract infection  1  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/21 (0.00%)  2/23 (8.70%)  1/40 (2.50%) 
viral infection  1  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  1/23 (4.35%)  0/40 (0.00%) 
viral upper respiratory tract infection  1  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/21 (0.00%)  1/23 (4.35%)  1/40 (2.50%) 
localised infection  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  2/21 (9.52%)  0/23 (0.00%)  0/40 (0.00%) 
urinary tract infection  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  2/23 (8.70%)  0/40 (0.00%) 
cellulitis  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  1/23 (4.35%)  1/40 (2.50%) 
gingivitis  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  1/23 (4.35%)  0/40 (0.00%) 
onychomycosis  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  1/23 (4.35%)  0/40 (0.00%) 
pharyngitis streptococcal  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/21 (4.76%)  0/23 (0.00%)  1/40 (2.50%) 
pneunomia  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  1/23 (4.35%)  0/40 (0.00%) 
respiratory tract infection  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  1/23 (4.35%)  0/40 (0.00%) 
sinobronchitis  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  1/23 (4.35%)  0/40 (0.00%) 
sinusitis  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  1/23 (4.35%)  3/40 (7.50%) 
conjunctivitis  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  0/23 (0.00%)  1/40 (2.50%) 
ear infection  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  0/23 (0.00%)  1/40 (2.50%) 
fungal skin infection  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  0/23 (0.00%)  2/40 (5.00%) 
labyrinthitis  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  0/23 (0.00%)  1/40 (2.50%) 
laryngitis  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  0/23 (0.00%)  1/40 (2.50%) 
lyme disease  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  0/23 (0.00%)  1/40 (2.50%) 
Injury, poisoning and procedural complications             
fall  1  1/6 (16.67%)  2/6 (33.33%)  0/6 (0.00%)  5/21 (23.81%)  5/23 (21.74%)  11/40 (27.50%) 
ligament sprain  1  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/21 (0.00%)  0/23 (0.00%)  2/40 (5.00%) 
thermal burn  1  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  0/23 (0.00%)  0/40 (0.00%) 
tibia fracture  1  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/21 (0.00%)  0/23 (0.00%)  0/40 (0.00%) 
contusion  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  5/21 (23.81%)  3/23 (13.04%)  7/40 (17.50%) 
skin abrasion  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/21 (4.76%)  1/23 (4.35%)  1/40 (2.50%) 
arthropod bite  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/21 (4.76%)  0/23 (0.00%)  0/40 (0.00%) 
arthropod sting  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  1/23 (4.35%)  0/40 (0.00%) 
bone contusion  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/21 (4.76%)  0/23 (0.00%)  0/40 (0.00%) 
muscle strain  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/21 (4.76%)  0/23 (0.00%)  1/40 (2.50%) 
post-traumatic pain  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  1/23 (4.35%)  1/40 (2.50%) 
exposure to communicable disease  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  0/23 (0.00%)  1/40 (2.50%) 
joint dislocation  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  0/23 (0.00%)  2/40 (5.00%) 
limb injury  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  0/23 (0.00%)  1/40 (2.50%) 
procedural pain  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  0/23 (0.00%)  1/40 (2.50%) 
Investigations             
blood creatine phosphokinase increased  1  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  1/23 (4.35%)  1/40 (2.50%) 
crystal urine present  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/21 (4.76%)  0/23 (0.00%)  0/40 (0.00%) 
myoglobin blood increased  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  1/23 (4.35%)  1/40 (2.50%) 
thyroxine free increased  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/21 (4.76%)  0/23 (0.00%)  0/40 (0.00%) 
urine analysis abnormal  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  1/23 (4.35%)  4/40 (10.00%) 
bacterial test positive  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  0/23 (0.00%)  1/40 (2.50%) 
gamma-glutamyltransferase increased  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  0/23 (0.00%)  1/40 (2.50%) 
platelet count increased  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  0/23 (0.00%)  1/40 (2.50%) 
Metabolism and nutrition disorders             
hypokalaemia  1  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/21 (0.00%)  0/23 (0.00%)  1/40 (2.50%) 
hypercholesterolaemia  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/21 (4.76%)  0/23 (0.00%)  0/40 (0.00%) 
decreased appetitie  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  0/23 (0.00%)  1/40 (2.50%) 
iron deficiency  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  0/23 (0.00%)  1/40 (2.50%) 
Musculoskeletal and connective tissue disorders             
pain in extremity  1  3/6 (50.00%)  0/6 (0.00%)  2/6 (33.33%)  4/21 (19.05%)  6/23 (26.09%)  8/40 (20.00%) 
muscle spasm  1  1/6 (16.67%)  2/6 (33.33%)  1/6 (16.67%)  1/21 (4.76%)  2/23 (8.70%)  1/40 (2.50%) 
myalgia  1  1/6 (16.67%)  1/6 (16.67%)  1/6 (16.67%)  2/21 (9.52%)  7/23 (30.43%)  6/40 (15.00%) 
joint stiffness  1  1/6 (16.67%)  0/6 (0.00%)  1/6 (16.67%)  0/21 (0.00%)  2/23 (8.70%)  1/40 (2.50%) 
muscle tightness  1  1/6 (16.67%)  0/6 (0.00%)  1/6 (16.67%)  1/21 (4.76%)  1/23 (4.35%)  1/40 (2.50%) 
arthralgia  1  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  3/21 (14.29%)  6/23 (26.09%)  6/40 (15.00%) 
back pain  1  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  2/21 (9.52%)  1/23 (4.35%)  1/40 (2.50%) 
limb discomfort  1  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  1/23 (4.35%)  1/40 (2.50%) 
muscle twitching  1  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/21 (0.00%)  0/23 (0.00%)  1/40 (2.50%) 
muscular weakness  1  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  2/23 (8.70%)  0/40 (0.00%) 
musculoskeletal stiffness  1  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  3/23 (13.04%)  0/40 (0.00%) 
osteoarthritis  1  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/21 (0.00%)  0/23 (0.00%)  0/40 (0.00%) 
musculoskeletal discomfort  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  2/21 (9.52%)  0/23 (0.00%)  0/40 (0.00%) 
neck pain  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  1/23 (4.35%)  2/40 (5.00%) 
arthritis  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  0/23 (0.00%)  1/40 (2.50%) 
flank pain  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  0/23 (0.00%)  1/40 (2.50%) 
haemarthrosis  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  0/23 (0.00%)  1/40 (2.50%) 
joint instability  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  0/23 (0.00%)  1/40 (2.50%) 
systemic lupus erythematosus  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  0/23 (0.00%)  1/40 (2.50%) 
Nervous system disorders             
headache  1  1/6 (16.67%)  0/6 (0.00%)  1/6 (16.67%)  0/21 (0.00%)  1/23 (4.35%)  3/40 (7.50%) 
memory impairment  1  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/21 (0.00%)  0/23 (0.00%)  0/40 (0.00%) 
paraesthesia  1  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/21 (0.00%)  3/23 (13.04%)  2/40 (5.00%) 
restless legs syndrome  1  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  2/21 (9.52%)  0/23 (0.00%)  0/40 (0.00%) 
burning sensation  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  2/23 (8.70%)  1/40 (2.50%) 
dizziness  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  1/23 (4.35%)  0/40 (0.00%) 
migraine  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  1/23 (4.35%)  0/40 (0.00%) 
sensory loss  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  1/23 (4.35%)  0/40 (0.00%) 
disturbance in attention  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  0/23 (0.00%)  1/40 (2.50%) 
hypoaesthesia  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  0/23 (0.00%)  1/40 (2.50%) 
presyncope  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  0/23 (0.00%)  2/40 (5.00%) 
syncope  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  0/23 (0.00%)  1/40 (2.50%) 
Psychiatric disorders             
anxiety  1  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/21 (0.00%)  0/23 (0.00%)  2/40 (5.00%) 
attention deficit/hyperactivity disorder  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/21 (4.76%)  0/23 (0.00%)  0/40 (0.00%) 
confusional state  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  0/23 (0.00%)  1/40 (2.50%) 
Renal and urinary disorders             
chromaturia  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  1/23 (4.35%)  0/40 (0.00%) 
urine odour abnormal  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  1/23 (4.35%)  0/40 (0.00%) 
calculus urinary  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  0/23 (0.00%)  1/40 (2.50%) 
nephrolithiasis  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  0/23 (0.00%)  1/40 (2.50%) 
Reproductive system and breast disorders             
pelvic pain  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  1/23 (4.35%)  0/40 (0.00%) 
menorrhagia  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  0/23 (0.00%)  1/40 (2.50%) 
Respiratory, thoracic and mediastinal disorders             
cough  1  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  1/23 (4.35%)  3/40 (7.50%) 
dyspnoea  1  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  0/23 (0.00%)  3/40 (7.50%) 
dyspnoea exertional  1  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  0/23 (0.00%)  0/40 (0.00%) 
epistaxis  1  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/21 (0.00%)  0/23 (0.00%)  0/40 (0.00%) 
oropharyngeal pain  1  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  1/23 (4.35%)  0/40 (0.00%) 
rhinorrheoea  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  1/23 (4.35%)  0/40 (0.00%) 
upper respiratory tract congestion  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  1/23 (4.35%)  2/40 (5.00%) 
paranasal sinus discomfort  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  0/23 (0.00%)  1/40 (2.50%) 
snoring  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  0/23 (0.00%)  1/40 (2.50%) 
Skin and subcutaneous tissue disorders             
dermatitis contact  1  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/21 (0.00%)  0/23 (0.00%)  0/40 (0.00%) 
erythema  1  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/21 (0.00%)  2/23 (8.70%)  3/40 (7.50%) 
nail discolouration  1  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  0/23 (0.00%)  0/40 (0.00%) 
pruritus  1  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/21 (0.00%)  2/23 (8.70%)  1/40 (2.50%) 
skin warm  1  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/21 (0.00%)  0/23 (0.00%)  0/40 (0.00%) 
dermatosis  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/21 (4.76%)  0/23 (0.00%)  0/40 (0.00%) 
eczema  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/21 (4.76%)  0/23 (0.00%)  0/40 (0.00%) 
mechanical urticaria  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  1/23 (4.35%)  0/40 (0.00%) 
onychoclasis  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  1/23 (4.35%)  0/40 (0.00%) 
pseudofolliculitis barbae  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  1/23 (4.35%)  0/40 (0.00%) 
rash  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/21 (4.76%)  0/23 (0.00%)  1/40 (2.50%) 
skin burning sensation  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  1/23 (4.35%)  0/40 (0.00%) 
skin discolouration  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  1/23 (4.35%)  0/40 (0.00%) 
Surgical and medical procedures             
tooth extraction  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/21 (4.76%)  0/23 (0.00%)  0/40 (0.00%) 
Vascular disorders             
flushing  1  0/6 (0.00%)  2/6 (33.33%)  0/6 (0.00%)  0/21 (0.00%)  0/23 (0.00%)  3/40 (7.50%) 
Behcet's syndrome  1  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  0/23 (0.00%)  0/40 (0.00%) 
hypertension  1  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/21 (0.00%)  0/23 (0.00%)  0/40 (0.00%) 
haematoma  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/21 (0.00%)  0/23 (0.00%)  1/40 (2.50%) 
1
Term from vocabulary, MedDRA (19.1)
Indicates events were collected by systematic assessment
The study was terminated because the statistically significant increase in total muscle volume (TMV) failed to translate to statistically significant improvements in functional or disease-related quality of life secondary endpoints in the study.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: SVP Regulatory Affairs
Organization: Acceleron Pharma Inc.
Phone: 617-649-9200
EMail: jdesiderio@acceleronpharma.com
Layout table for additonal information
Responsible Party: Acceleron Pharma Inc.
ClinicalTrials.gov Identifier: NCT03124459    
Other Study ID Numbers: A083-03
ACE-083 ( Other Identifier: Acceleron Pharma Inc. )
First Submitted: April 12, 2017
First Posted: April 21, 2017
Results First Submitted: March 11, 2021
Results First Posted: July 28, 2021
Last Update Posted: July 28, 2021