Trial Outcomes & Findings for Extension Study to Evaluate the Long-Term Effects of ACE-083 in Patients With Facioscapulohumeral Muscular Dystrophy (FSHD) and Charcot-Marie Tooth (CMT) Disease Types 1 and X (CMT1 and CMTX) (NCT NCT03943290)

Last Updated: 2022-09-26

Results Overview

The number of participants that had a least one Treatment Emergent Adverse Event during the Part 2 of the study. The pre-specified analysis for this outcome measure was for those participants in the part 2 cohorts of this study therefore, only data of part 2 portion of the study are reported.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

62 participants

Primary outcome timeframe

From baseline to end of participation of the Part 2 portion of the study

Results posted on

2022-09-26

Participant Flow

Participant milestones

Participant milestones
Measure	Part 1 Cohort 1a ACE-083 240 mg/muscle administered bilaterally by injection into the TA muscle every 4 weeks for up to 6 doses for FSHD patients ACE-083: Recombinant fusion protein	Part 1 Cohort 1b ACE-083 240 mg/muscle administered bilaterally by injection into the BB muscle every 4 weeks for up to 6 doses for FSHD patients ACE-083: Recombinant fusion protein	Part 1 Cohort 1c ACE-083 240 mg/muscle administered bilaterally by injection into the TA muscle every 4 weeks for up to 6 doses for CMT patients ACE-083: Recombinant fusion protein	Part 2 Cohort 2a ACE-083 Administered into the TA muscle q4w for up to 24 months (24 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 2b ACE-083 Administered into the BB muscle q4w for up to 24 months (24 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 2c ACE-083 Administered into the TA muscle q4w for up to 24 months (24 doses) for CMT patients ACE-083: Recombinant fusion protein	Part 2 Cohort 3a ACE-083 Administered into the TA muscle q8w for up to 24 months (12 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 3b ACE-083 Administered into the BB muscle q8w for up to 24 months (12 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 3c ACE-083 Administered into the TA muscle q8w for up to 24 months (12 doses) for CMT patients ACE-083: Recombinant fusion protein
Overall Study STARTED	7	1	13	6	7	6	6	8	8
Overall Study COMPLETED	0	0	0	0	0	0	0	0	0
Overall Study NOT COMPLETED	7	1	13	6	7	6	6	8	8

Reasons for withdrawal

Reasons for withdrawal
Measure	Part 1 Cohort 1a ACE-083 240 mg/muscle administered bilaterally by injection into the TA muscle every 4 weeks for up to 6 doses for FSHD patients ACE-083: Recombinant fusion protein	Part 1 Cohort 1b ACE-083 240 mg/muscle administered bilaterally by injection into the BB muscle every 4 weeks for up to 6 doses for FSHD patients ACE-083: Recombinant fusion protein	Part 1 Cohort 1c ACE-083 240 mg/muscle administered bilaterally by injection into the TA muscle every 4 weeks for up to 6 doses for CMT patients ACE-083: Recombinant fusion protein	Part 2 Cohort 2a ACE-083 Administered into the TA muscle q4w for up to 24 months (24 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 2b ACE-083 Administered into the BB muscle q4w for up to 24 months (24 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 2c ACE-083 Administered into the TA muscle q4w for up to 24 months (24 doses) for CMT patients ACE-083: Recombinant fusion protein	Part 2 Cohort 3a ACE-083 Administered into the TA muscle q8w for up to 24 months (12 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 3b ACE-083 Administered into the BB muscle q8w for up to 24 months (12 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 3c ACE-083 Administered into the TA muscle q8w for up to 24 months (12 doses) for CMT patients ACE-083: Recombinant fusion protein
Overall Study Sponsor Terminated Study	6	1	11	6	7	6	6	7	8
Overall Study Lost to Follow-up	1	0	1	0	0	0	0	1	0
Overall Study Withdrawal by Subject	0	0	1	0	0	0	0	0	0

Baseline Characteristics

Extension Study to Evaluate the Long-Term Effects of ACE-083 in Patients With Facioscapulohumeral Muscular Dystrophy (FSHD) and Charcot-Marie Tooth (CMT) Disease Types 1 and X (CMT1 and CMTX)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part 1 Cohort 1a n=7 Participants ACE-083 240 mg/muscle administered bilaterally by injection into the TA muscle every 4 weeks for up to 6 doses for FSHD patients ACE-083: Recombinant fusion protein	Part 1 Cohort 1b n=1 Participants ACE-083 240 mg/muscle administered bilaterally by injection into the BB muscle every 4 weeks for up to 6 doses for FSHD patients ACE-083: Recombinant fusion protein	Part 1 Cohort 1c n=13 Participants ACE-083 240 mg/muscle administered bilaterally by injection into the TA muscle every 4 weeks for up to 6 doses for CMT patients ACE-083: Recombinant fusion protein	Part 2 Cohort 2a n=6 Participants ACE-083 Administered into the TA muscle q4w for up to 24 months (24 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 2b n=7 Participants ACE-083 Administered into the BB muscle q4w for up to 24 months (24 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 2c n=6 Participants ACE-083 Administered into the TA muscle q4w for up to 24 months (24 doses) for CMT patients ACE-083: Recombinant fusion protein	Part 2 Cohort 3a n=6 Participants ACE-083 Administered into the TA muscle q8w for up to 24 months (12 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 3b n=8 Participants ACE-083 Administered into the BB muscle q8w for up to 24 months (12 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 3c n=8 Participants ACE-083 Administered into the TA muscle q8w for up to 24 months (12 doses) for CMT patients ACE-083: Recombinant fusion protein	Total n=62 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants
Age, Categorical Between 18 and 65 years	7 Participants n=5 Participants	1 Participants n=7 Participants	13 Participants n=5 Participants	5 Participants n=4 Participants	6 Participants n=21 Participants	5 Participants n=8 Participants	6 Participants n=8 Participants	8 Participants n=24 Participants	8 Participants n=42 Participants	59 Participants n=42 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants	1 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	3 Participants n=42 Participants
Age, Continuous	47 years STANDARD_DEVIATION 13.3 • n=5 Participants	56 years n=7 Participants	45.2 years STANDARD_DEVIATION 15.5 • n=5 Participants	51.7 years STANDARD_DEVIATION 14.8 • n=4 Participants	49.7 years STANDARD_DEVIATION 14.6 • n=21 Participants	55 years STANDARD_DEVIATION 9.3 • n=8 Participants	40.2 years STANDARD_DEVIATION 14.3 • n=8 Participants	40.4 years STANDARD_DEVIATION 11.2 • n=24 Participants	45.4 years STANDARD_DEVIATION 10.7 • n=42 Participants	46.6 years STANDARD_DEVIATION 13.3 • n=42 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	1 Participants n=7 Participants	7 Participants n=5 Participants	4 Participants n=4 Participants	2 Participants n=21 Participants	3 Participants n=8 Participants	5 Participants n=8 Participants	2 Participants n=24 Participants	5 Participants n=42 Participants	32 Participants n=42 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	0 Participants n=7 Participants	6 Participants n=5 Participants	2 Participants n=4 Participants	5 Participants n=21 Participants	3 Participants n=8 Participants	1 Participants n=8 Participants	6 Participants n=24 Participants	3 Participants n=42 Participants	30 Participants n=42 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	1 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	1 Participants n=42 Participants	3 Participants n=42 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	6 Participants n=5 Participants	1 Participants n=7 Participants	13 Participants n=5 Participants	6 Participants n=4 Participants	7 Participants n=21 Participants	5 Participants n=8 Participants	6 Participants n=8 Participants	7 Participants n=24 Participants	7 Participants n=42 Participants	58 Participants n=42 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	1 Participants n=24 Participants	0 Participants n=42 Participants	1 Participants n=42 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	1 Participants n=42 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	1 Participants n=24 Participants	0 Participants n=42 Participants	1 Participants n=42 Participants
Race (NIH/OMB) White	7 Participants n=5 Participants	1 Participants n=7 Participants	13 Participants n=5 Participants	5 Participants n=4 Participants	6 Participants n=21 Participants	6 Participants n=8 Participants	6 Participants n=8 Participants	7 Participants n=24 Participants	8 Participants n=42 Participants	59 Participants n=42 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	1 Participants n=42 Participants
Region of Enrollment Canada	2 participants n=5 Participants	1 participants n=7 Participants	0 participants n=5 Participants	1 participants n=4 Participants	4 participants n=21 Participants	0 participants n=8 Participants	1 participants n=8 Participants	4 participants n=24 Participants	0 participants n=42 Participants	13 participants n=42 Participants
Region of Enrollment United States	5 participants n=5 Participants	0 participants n=7 Participants	13 participants n=5 Participants	3 participants n=4 Participants	2 participants n=21 Participants	6 participants n=8 Participants	3 participants n=8 Participants	2 participants n=24 Participants	8 participants n=42 Participants	42 participants n=42 Participants
Region of Enrollment Spain	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	2 participants n=4 Participants	1 participants n=21 Participants	0 participants n=8 Participants	2 participants n=8 Participants	2 participants n=24 Participants	0 participants n=42 Participants	7 participants n=42 Participants

PRIMARY outcome

Timeframe: From baseline to end of participation of the Part 2 portion of the study

Population: The Safety Population consisted of all participants enrolled/randomized in the study who received at least 1 dose of study drug.

Outcome measures

Outcome measures
Measure	Part 2 Cohort 2a n=6 Participants ACE-083 Administered into the TA muscle q4w for up to 24 months (24 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 2b n=7 Participants ACE-083 Administered into the BB muscle q4w for up to 24 months (24 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 2c n=6 Participants ACE-083 Administered into the TA muscle q4w for up to 24 months (24 doses) for CMT patients ACE-083: Recombinant fusion protein	Part 2 Cohort 3a n=6 Participants ACE-083 Administered into the TA muscle q8w for up to 24 months (12 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 3b n=8 Participants ACE-083 Administered into the BB muscle q8w for up to 24 months (12 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 3c n=8 Participants ACE-083 Administered into the TA muscle q8w for up to 24 months (12 doses) for CMT patients ACE-083: Recombinant fusion protein
Part 2- Frequency of Adverse Events - Presence and Nature of Adverse Events (AE) During Part 2	3 Participants	4 Participants	5 Participants	3 Participants	4 Participants	4 Participants

PRIMARY outcome

Timeframe: From baseline to the end of the part 2 portion of the study

Population: The Safety Population consisted of all participants enrolled/randomized in the study who received at least 1 dose of study drug.

The number of participants that had a least one grade 3 or higher Treatment Emergent Adverse Event during Part 2 of the study. The pre-specified analysis for this outcome measure was for those participants in the double-blind, placebo-controlled Part 2 of the study therefore, only data from the part 2 portion of the study are reported.

Outcome measures

Outcome measures
Measure	Part 2 Cohort 2a n=6 Participants ACE-083 Administered into the TA muscle q4w for up to 24 months (24 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 2b n=7 Participants ACE-083 Administered into the BB muscle q4w for up to 24 months (24 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 2c n=6 Participants ACE-083 Administered into the TA muscle q4w for up to 24 months (24 doses) for CMT patients ACE-083: Recombinant fusion protein	Part 2 Cohort 3a n=6 Participants ACE-083 Administered into the TA muscle q8w for up to 24 months (12 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 3b n=8 Participants ACE-083 Administered into the BB muscle q8w for up to 24 months (12 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 3c n=8 Participants ACE-083 Administered into the TA muscle q8w for up to 24 months (12 doses) for CMT patients ACE-083: Recombinant fusion protein
Part 2: Frequency of Adverse Events - Presence and Nature of Grade 3 or Higher Adverse Events (AE) During the Part 2 of the Study.	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: During the Part 2 portion of the study: Baseline to Day 113

Population: Per Protocol Set (PPS) consisted of all participants enrolled/randomized in the study, who received at least 1 dose of study drug with no clinical study report-reportable protocol violations and at least 1 post-baseline MRI evaluation.

The primary pharmacodynamic variable was the difference in mean percent change in total muscle volume (average of left and right side) at the first 6 months of the maintenance phase (Day 169; q4w or q8w) from the total muscle volume (average of left and right sides) at the start of the maintenance phase (or equivalently the end of the loading phase). Due to the early termination of this trial, percent change is only able to be reported as percent change from baseline to Day 113. The pre-specified analysis for this outcome measure was for those participants in the part 2 portion in cohorts with data to Day 113. Therefore, only data from these part 2 arms- 2b, 2c, 3b and 3c of the study are reported.

Outcome measures

Outcome measures
Measure	Part 2 Cohort 2a n=2 Participants ACE-083 Administered into the TA muscle q4w for up to 24 months (24 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 2b n=3 Participants ACE-083 Administered into the BB muscle q4w for up to 24 months (24 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 2c n=1 Participants ACE-083 Administered into the TA muscle q4w for up to 24 months (24 doses) for CMT patients ACE-083: Recombinant fusion protein	Part 2 Cohort 3a n=3 Participants ACE-083 Administered into the TA muscle q8w for up to 24 months (12 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 3b ACE-083 Administered into the BB muscle q8w for up to 24 months (12 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 3c ACE-083 Administered into the TA muscle q8w for up to 24 months (12 doses) for CMT patients ACE-083: Recombinant fusion protein
Part 2: Change in Total Muscle Volume - Percent Change From Baseline to Day 113 in Total Muscle Volume of Injected Muscle by Magnetic Resonance Imaging (MRI) During the Part 2 Portion	6.49 percent change Standard Error 8.63	19.36 percent change Standard Error 13.78	-12.14 percent change	12.72 percent change Standard Error 1.18	—	—

SECONDARY outcome

Timeframe: Baseline and End of Treatment visit for Part 2 of the study

Population: Per Protocol Set: All patients enrolled/randomized in the study who have received at least one dose of study drug (includes placebo) with no major protocol violations.

Timing (in seconds) participants took to complete a 10-meter walk/run distance. Baseline and end of treatment visit values were used to report absolute change from baseline in functional assessment due to early termination of the trial. The pre-specified analysis for this outcome measure was for those participants with data available at baseline and at the end of treatment in part 2 of this study therefore, only data from the part 2 cohorts 2a, 2c and 3a of the study are reported.

Outcome measures

Outcome measures
Measure	Part 2 Cohort 2a n=5 Participants ACE-083 Administered into the TA muscle q4w for up to 24 months (24 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 2b n=1 Participants ACE-083 Administered into the BB muscle q4w for up to 24 months (24 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 2c n=6 Participants ACE-083 Administered into the TA muscle q4w for up to 24 months (24 doses) for CMT patients ACE-083: Recombinant fusion protein	Part 2 Cohort 3a ACE-083 Administered into the TA muscle q8w for up to 24 months (12 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 3b ACE-083 Administered into the BB muscle q8w for up to 24 months (12 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 3c ACE-083 Administered into the TA muscle q8w for up to 24 months (12 doses) for CMT patients ACE-083: Recombinant fusion protein
Part 2: Change in Muscle Function. Absolute Change From Baseline in Functional Assessment for Tibialis Anterior (TA) Muscle:10-meter Walk/Run During Part 2 of the Study	0.5 seconds Standard Error 0.38	-0.4 seconds	0.3 seconds Standard Error 0.51	—	—	—

SECONDARY outcome

Timeframe: Baseline and End of Treatment visit for Part 2 of the study

Population: Per Protocol Set: All patients enrolled/randomized in the study who have received at least one dose of study drug (includes placebo) with no major protocol violations.

Outcome measures

Outcome measures
Measure	Part 2 Cohort 2a n=5 Participants ACE-083 Administered into the TA muscle q4w for up to 24 months (24 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 2b n=1 Participants ACE-083 Administered into the BB muscle q4w for up to 24 months (24 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 2c n=6 Participants ACE-083 Administered into the TA muscle q4w for up to 24 months (24 doses) for CMT patients ACE-083: Recombinant fusion protein	Part 2 Cohort 3a ACE-083 Administered into the TA muscle q8w for up to 24 months (12 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 3b ACE-083 Administered into the BB muscle q8w for up to 24 months (12 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 3c ACE-083 Administered into the TA muscle q8w for up to 24 months (12 doses) for CMT patients ACE-083: Recombinant fusion protein
Part 2: Change in Muscle Function. Percent Change From Baseline in Functional Assessment for Tibialis Anterior (TA) Muscle:10-meter Walk/Run During Part 2 of the Study	5.29 percent change Standard Error 4.05	-5.06 percent change	2.55 percent change Standard Error 5.45	—	—	—

SECONDARY outcome

Timeframe: Baseline and End of Treatment Visit during Part 2 of the study

During Part 2: for the 6-minute walk test, participants walked at normal pace for six minutes and the distance was measured in meters. Absolute change from baseline to end of treatment in phase 2 were reported since this trial was terminated early. Further, only part 2 cohorts 2a, 2c, and 3a had data to report for this analysis.

Outcome measures

Outcome measures
Measure	Part 2 Cohort 2a n=4 Participants ACE-083 Administered into the TA muscle q4w for up to 24 months (24 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 2b n=1 Participants ACE-083 Administered into the BB muscle q4w for up to 24 months (24 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 2c n=5 Participants ACE-083 Administered into the TA muscle q4w for up to 24 months (24 doses) for CMT patients ACE-083: Recombinant fusion protein	Part 2 Cohort 3a ACE-083 Administered into the TA muscle q8w for up to 24 months (12 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 3b ACE-083 Administered into the BB muscle q8w for up to 24 months (12 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 3c ACE-083 Administered into the TA muscle q8w for up to 24 months (12 doses) for CMT patients ACE-083: Recombinant fusion protein
Part 2: Change in Muscle Function. Absolute Change From Baseline in Functional Assessment for Tibialis Anterior (TA) Muscle: 6-minute Walk Test	12.25 meters Standard Error 17.3	14 meters	0 meters Standard Error 7.44	—	—	—

SECONDARY outcome

Timeframe: Baseline and End of Treatment visit during Part 2 of the study

Outcome measures

Outcome measures
Measure	Part 2 Cohort 2a n=4 Participants ACE-083 Administered into the TA muscle q4w for up to 24 months (24 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 2b n=1 Participants ACE-083 Administered into the BB muscle q4w for up to 24 months (24 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 2c n=5 Participants ACE-083 Administered into the TA muscle q4w for up to 24 months (24 doses) for CMT patients ACE-083: Recombinant fusion protein	Part 2 Cohort 3a ACE-083 Administered into the TA muscle q8w for up to 24 months (12 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 3b ACE-083 Administered into the BB muscle q8w for up to 24 months (12 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 3c ACE-083 Administered into the TA muscle q8w for up to 24 months (12 doses) for CMT patients ACE-083: Recombinant fusion protein
Part 2: Change in Muscle Function - Percent Change From Baseline in Functional Assessment for Tibialis Anterior (TA) Muscle in 6-minute Walk Test	4.46 percent change Standard Error 4.27	3.82 percent change	-0.39 percent change Standard Error 2.23	—	—	—

SECONDARY outcome

Timeframe: Baseline, End of Treatment visit during Part 2

During Part 2 in FSHD participants only: This is a measure (in seconds) of participants going up 4 standard stairs. Absolute Change is compared from baseline to the end of treatment visit as this trial was terminated early. As this analysis was pre-specified for FSHD patients only, data is only reported for participants with FSHD (cohorts 2a and 3a).

Outcome measures

Outcome measures
Measure	Part 2 Cohort 2a n=5 Participants ACE-083 Administered into the TA muscle q4w for up to 24 months (24 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 2b n=6 Participants ACE-083 Administered into the BB muscle q4w for up to 24 months (24 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 2c ACE-083 Administered into the TA muscle q4w for up to 24 months (24 doses) for CMT patients ACE-083: Recombinant fusion protein	Part 2 Cohort 3a ACE-083 Administered into the TA muscle q8w for up to 24 months (12 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 3b ACE-083 Administered into the BB muscle q8w for up to 24 months (12 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 3c ACE-083 Administered into the TA muscle q8w for up to 24 months (12 doses) for CMT patients ACE-083: Recombinant fusion protein
Part 2: Change in Muscle Function. Absolute Change From Baseline in Functional Assessment for Tibialis Anterior (TA) Muscle: 4-stair Climb Up (in Participants With FSHD Only)	-0.16 seconds Standard Error 0.38	-0.5 seconds Standard Error 0.34	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, End of Treatment visit during Part 2

During Part 2 in FSHD participants only: This is a measure (in seconds) of participants going up 4 standard stairs. Percent Change is compared from baseline to the end of treatment visit as this trial was terminated early. As this analysis was pre-specified for FSHD patients only, data is only reported for participants with FSHD (cohorts 2a and 3a).

Outcome measures

Outcome measures
Measure	Part 2 Cohort 2a n=5 Participants ACE-083 Administered into the TA muscle q4w for up to 24 months (24 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 2b n=6 Participants ACE-083 Administered into the BB muscle q4w for up to 24 months (24 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 2c ACE-083 Administered into the TA muscle q4w for up to 24 months (24 doses) for CMT patients ACE-083: Recombinant fusion protein	Part 2 Cohort 3a ACE-083 Administered into the TA muscle q8w for up to 24 months (12 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 3b ACE-083 Administered into the BB muscle q8w for up to 24 months (12 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 3c ACE-083 Administered into the TA muscle q8w for up to 24 months (12 doses) for CMT patients ACE-083: Recombinant fusion protein
Part 2: Change in Muscle Function - Percent Change From Baseline in Functional Assessment for Tibialis Anterior (TA) Muscle in 4-stair Climb Up (in Participants With FSHD Only)	2.78 percent change Standard Error 9.10	-7.58 percent change Standard Error 4.51	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, End of Treatment visit during Part 2

During Part 2 (in FSHD participants only)This is a measure (in seconds) of participants going down 4 standard stairs. Absolute Change is compared from baseline to the end of treatment visit as this trial was terminated early. As this analysis was pre-specified for FSHD patients only, data is only reported for participants with FSHD (cohorts 2a and 3a).

Outcome measures

Outcome measures
Measure	Part 2 Cohort 2a n=5 Participants ACE-083 Administered into the TA muscle q4w for up to 24 months (24 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 2b n=6 Participants ACE-083 Administered into the BB muscle q4w for up to 24 months (24 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 2c ACE-083 Administered into the TA muscle q4w for up to 24 months (24 doses) for CMT patients ACE-083: Recombinant fusion protein	Part 2 Cohort 3a ACE-083 Administered into the TA muscle q8w for up to 24 months (12 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 3b ACE-083 Administered into the BB muscle q8w for up to 24 months (12 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 3c ACE-083 Administered into the TA muscle q8w for up to 24 months (12 doses) for CMT patients ACE-083: Recombinant fusion protein
Part 2: Change in Muscle Function. Absolute Change From Baseline in Functional Assessment for Tibialis Anterior (TA) Muscle: 4-stair Climb Down (in Participants With FSHD Only)	0.74 seconds Standard Error 0.77	-0.18 seconds Standard Error 0.22	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, End of Treatment visit during Part 2

During Part 2 (in FSHD participants only)This is a measure (in seconds) of participants going down 4 standard stairs. Percent Change is compared from baseline to the end of treatment visit as this trial was terminated early. As this analysis was pre-specified for FSHD patients only, data is only reported for participants with FSHD (cohorts 2a and 3a).

Outcome measures

Outcome measures
Measure	Part 2 Cohort 2a n=5 Participants ACE-083 Administered into the TA muscle q4w for up to 24 months (24 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 2b n=6 Participants ACE-083 Administered into the BB muscle q4w for up to 24 months (24 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 2c ACE-083 Administered into the TA muscle q4w for up to 24 months (24 doses) for CMT patients ACE-083: Recombinant fusion protein	Part 2 Cohort 3a ACE-083 Administered into the TA muscle q8w for up to 24 months (12 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 3b ACE-083 Administered into the BB muscle q8w for up to 24 months (12 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 3c ACE-083 Administered into the TA muscle q8w for up to 24 months (12 doses) for CMT patients ACE-083: Recombinant fusion protein
Part 2: Change in Muscle Function. Percent Change From Baseline in Functional Assessment for Tibialis Anterior (TA) Muscle: 4-stair Climb Down (in Patients With FSHD Only)	6.81 percent change Standard Error 7.72	-6.89 percent change Standard Error 5.19	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, End of Treatment visit for Part 2 of the study

During Part 2 this measure is the timing (in seconds) to complete 100-meter walk test. Percent Change is reported from baseline to the end of treatment visit as this trial was terminated early. As this analysis was pre-specified for part 2 only, data is only reported for participants with FSHD and CMT in part 2 with data for both timepoints (cohorts 2a, 2c and 3a).

Outcome measures

Outcome measures
Measure	Part 2 Cohort 2a n=5 Participants ACE-083 Administered into the TA muscle q4w for up to 24 months (24 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 2b n=1 Participants ACE-083 Administered into the BB muscle q4w for up to 24 months (24 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 2c n=6 Participants ACE-083 Administered into the TA muscle q4w for up to 24 months (24 doses) for CMT patients ACE-083: Recombinant fusion protein	Part 2 Cohort 3a ACE-083 Administered into the TA muscle q8w for up to 24 months (12 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 3b ACE-083 Administered into the BB muscle q8w for up to 24 months (12 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 3c ACE-083 Administered into the TA muscle q8w for up to 24 months (12 doses) for CMT patients ACE-083: Recombinant fusion protein
Part 2: Change in Muscle Function. Absolute Change From Baseline in Functional Assessment for Tibialis Anterior (TA) Muscle: 100-meter Timed Test	6.8 seconds Standard Error 3.64	10 seconds	8.8 seconds Standard Error 5.78	—	—	—

SECONDARY outcome

Timeframe: Baseline, End of Treatment visit, Part 2

Outcome measures

Outcome measures
Measure	Part 2 Cohort 2a n=5 Participants ACE-083 Administered into the TA muscle q4w for up to 24 months (24 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 2b n=1 Participants ACE-083 Administered into the BB muscle q4w for up to 24 months (24 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 2c n=6 Participants ACE-083 Administered into the TA muscle q4w for up to 24 months (24 doses) for CMT patients ACE-083: Recombinant fusion protein	Part 2 Cohort 3a ACE-083 Administered into the TA muscle q8w for up to 24 months (12 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 3b ACE-083 Administered into the BB muscle q8w for up to 24 months (12 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 3c ACE-083 Administered into the TA muscle q8w for up to 24 months (12 doses) for CMT patients ACE-083: Recombinant fusion protein
Part 2: Change in Muscle Function - Percent Change From Baseline for Tibialis Anterior (TA) Muscle in 100-meter Timed Test	8.49 percent change Standard Error 3.68	13.51 percent change	14.82 percent change Standard Error 12.41	—	—	—

SECONDARY outcome

Timeframe: Baseline, End of Treatment visit during Part 2

Part 2: Performance of upper limb (PUL) - Middle level elbow dimension score- Sum of the 9 items for this particular dimension (Minimum=0, Maximum = 34, with higher scores indicating increased functionality). These include: "Hand(s) to Mouth", "Hand(s) to table from lap", "Move weight on table", "Lifting light cans", "Lifting heavy cans", "Stacking light cans", "Stacking heavy cans", "Remove lid from container", and "Tearing paper". Pre-specified analysis was for absolute change in BB cohorts for FSHD participants only with Baseline and End of Treatment visit data (cohorts 2b and 3b) due to the early termination of the study. Thus, data is only reported for these two cohorts.

Outcome measures

Outcome measures
Measure	Part 2 Cohort 2a n=6 Participants ACE-083 Administered into the TA muscle q4w for up to 24 months (24 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 2b n=7 Participants ACE-083 Administered into the BB muscle q4w for up to 24 months (24 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 2c ACE-083 Administered into the TA muscle q4w for up to 24 months (24 doses) for CMT patients ACE-083: Recombinant fusion protein	Part 2 Cohort 3a ACE-083 Administered into the TA muscle q8w for up to 24 months (12 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 3b ACE-083 Administered into the BB muscle q8w for up to 24 months (12 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 3c ACE-083 Administered into the TA muscle q8w for up to 24 months (12 doses) for CMT patients ACE-083: Recombinant fusion protein
Part 2: Change in Muscle Function. Absolute Change From Baseline in Functional Assessment for Biceps Brachii (BB) Muscle: Mid-level Performance of the Upper Limb (PUL) Test.	0.5 units on a scale Standard Error 0.34	0 units on a scale Standard Error 0	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, End of Treatment

Part 2: Performance of upper limb (PUL) - Middle level elbow dimension score- Sum of the 9 items for this particular dimension (Minimum=0, Maximum = 34, with higher scores indicating increased functionality). These include: "Hand(s) to Mouth", "Hand(s) to table from lap", "Move weight on table", "Lifting light cans", "Lifting heavy cans", "Stacking light cans", "Stacking heavy cans", "Remove lid from container", and "Tearing paper". Pre-specified analysis was for percent change in BB cohorts for FSHD participants only with Baseline and End of Treatment visit data (cohorts 2b and 3b) due to the early termination of the study. Thus, data is only reported for these two cohorts.

Outcome measures

Outcome measures
Measure	Part 2 Cohort 2a n=6 Participants ACE-083 Administered into the TA muscle q4w for up to 24 months (24 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 2b n=7 Participants ACE-083 Administered into the BB muscle q4w for up to 24 months (24 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 2c ACE-083 Administered into the TA muscle q4w for up to 24 months (24 doses) for CMT patients ACE-083: Recombinant fusion protein	Part 2 Cohort 3a ACE-083 Administered into the TA muscle q8w for up to 24 months (12 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 3b ACE-083 Administered into the BB muscle q8w for up to 24 months (12 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 3c ACE-083 Administered into the TA muscle q8w for up to 24 months (12 doses) for CMT patients ACE-083: Recombinant fusion protein
Part 2: Change in Muscle Function - Percent Change From Baseline for Biceps Brachii (BB) Muscle in Mid-level Performance of the Upper Limb (PUL) Test	1.55 percent change in units on scale Standard Error 1.06	0 percent change in units on scale Standard Error 0	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, End of Treatment visit during part 2 of the study

Performance of upper limb (PUL) -PUL upper level/shoulder dimension- Shoulder domain score which represents the sum of the following 4 items that the patient is asked to do on the preferred side \[either right or left side identified by patient to be done on the same side for all scheduled times\]: a. Largest weight patient can use to perform shoulder abduction to shoulder height (elbow to shoulder level) b. Largest weight patient can use to perform shoulder abduction above shoulder height (elbow to eye level) c. Largest weight patient can use to perform shoulder flexion to shoulder height (elbow to shoulder level) d. Largest weight patient can use to perform shoulder flexion above shoulder height (elbow to eye level) Each of the 4 components above is scored depending on the highest weight performed where scores are: 0 = Unable; 1 = Able no weights; 2 = 200 g; 3 = 500 g; 4 = 1000 g. The maximum score is 16, with 16 being highest functionality. Reportable data is for Cohort 3b only.

Outcome measures

Outcome measures
Measure	Part 2 Cohort 2a n=4 Participants ACE-083 Administered into the TA muscle q4w for up to 24 months (24 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 2b ACE-083 Administered into the BB muscle q4w for up to 24 months (24 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 2c ACE-083 Administered into the TA muscle q4w for up to 24 months (24 doses) for CMT patients ACE-083: Recombinant fusion protein	Part 2 Cohort 3a ACE-083 Administered into the TA muscle q8w for up to 24 months (12 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 3b ACE-083 Administered into the BB muscle q8w for up to 24 months (12 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 3c ACE-083 Administered into the TA muscle q8w for up to 24 months (12 doses) for CMT patients ACE-083: Recombinant fusion protein
Part 2: Change in Muscle Function. Absolute Change From Baseline in Functional Assessment for Biceps Brachii (BB) Muscle: Upper Level Performance of the Upper Limb (PUL) Test.	3.75 units on a scale Standard Error 3.75	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, End of Treatment visit during Part 2

Outcome measures

Outcome measures
Measure	Part 2 Cohort 2a n=4 Participants ACE-083 Administered into the TA muscle q4w for up to 24 months (24 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 2b ACE-083 Administered into the BB muscle q4w for up to 24 months (24 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 2c ACE-083 Administered into the TA muscle q4w for up to 24 months (24 doses) for CMT patients ACE-083: Recombinant fusion protein	Part 2 Cohort 3a ACE-083 Administered into the TA muscle q8w for up to 24 months (12 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 3b ACE-083 Administered into the BB muscle q8w for up to 24 months (12 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 3c ACE-083 Administered into the TA muscle q8w for up to 24 months (12 doses) for CMT patients ACE-083: Recombinant fusion protein
Part 2: Change in Muscle Function. Percent Change From Baseline in Functional Assessment for Biceps Brachii (BB) Muscle: Upper Level Performance of the Upper Limb (PUL) Test.	375 percent change units on a scale Standard Error 375	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, End of Treatment visit during part 2

The FSHD Health Index (FSHD-HI) is a disease-specific patient reported outcome questionnaire that uses direct patient input to measure disease burden. For this index, the total score is scored from 0 to 100 with 0 representing no disease burden and 100 representing the maximum amount of disease burden in the particular domain. Pre-specified analysis was for FSHD cohorts only with absolute change in total score reported as this trial was terminated early.

Outcome measures

Outcome measures
Measure	Part 2 Cohort 2a n=1 Participants ACE-083 Administered into the TA muscle q4w for up to 24 months (24 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 2b n=6 Participants ACE-083 Administered into the BB muscle q4w for up to 24 months (24 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 2c n=4 Participants ACE-083 Administered into the TA muscle q4w for up to 24 months (24 doses) for CMT patients ACE-083: Recombinant fusion protein	Part 2 Cohort 3a n=3 Participants ACE-083 Administered into the TA muscle q8w for up to 24 months (12 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 3b ACE-083 Administered into the BB muscle q8w for up to 24 months (12 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 3c ACE-083 Administered into the TA muscle q8w for up to 24 months (12 doses) for CMT patients ACE-083: Recombinant fusion protein
Part 2: Change in Patient-reported Quality of Life. Absolute Change From Baseline in FSHD-health Index Total Score (FSHD-HI, in Patients With FSHD Only)	-0.39 units on a scale	-1.14 units on a scale Standard Error 2.53	-2.63 units on a scale Standard Error 1.74	0.80 units on a scale Standard Error 4.19	—	—

SECONDARY outcome

Timeframe: Baseline, Day 113 during Part 2

Part 2: The CMT-Health Index (CMT-HI) is a disease-specific patient reported outcome measure designed to measure patient reported disease burden during clinical trials in patients with Charcot-Marie-Tooth Disease. For this index, the total score is scored from 0 to 100 with 0 representing no disease burden and 100 representing the maximum amount of disease burden. Pre-specified analysis was for cohorts of CMT participants only and due to the early termination of this trial, the absolute change is reported for the change from Baseline to Day 113.

Outcome measures

Outcome measures
Measure	Part 2 Cohort 2a n=3 Participants ACE-083 Administered into the TA muscle q4w for up to 24 months (24 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 2b n=2 Participants ACE-083 Administered into the BB muscle q4w for up to 24 months (24 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 2c ACE-083 Administered into the TA muscle q4w for up to 24 months (24 doses) for CMT patients ACE-083: Recombinant fusion protein	Part 2 Cohort 3a ACE-083 Administered into the TA muscle q8w for up to 24 months (12 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 3b ACE-083 Administered into the BB muscle q8w for up to 24 months (12 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 3c ACE-083 Administered into the TA muscle q8w for up to 24 months (12 doses) for CMT patients ACE-083: Recombinant fusion protein
Part2: Change in Patient-reported Quality of Life. Absolute Change From Baseline in CMT Health Index Total Score (CMT-HI, in Patients With CMT Only)	9.72 units on a scale Standard Error 7.60	-14.55 units on a scale Standard Error 9.99	—	—	—	—

SECONDARY outcome

Timeframe: day 1, 24 -hours post-dose in Part 1

Population: The PK Population consisted of all participants who received at least 1 dose of study drug and had sufficient PK samples collected and assayed for PK analysis.

Part1: ACE-083 serum concentration samples were taken on day 1, 24-hours post-dose. PK parameters of ACE-083 were not determined due to limited quantifiable concentration data. Pre-specified analysis was for part 1 cohorts only, therefore, available data is only reported for part 1 cohorts (1a, 1b and 1c). Mean and standard deviation descriptive statistics are being reported for the Day 1, 24-hour post-dose timepoint only, due to early termination of this trial.

Outcome measures

Outcome measures
Measure	Part 2 Cohort 2a n=7 Participants ACE-083 Administered into the TA muscle q4w for up to 24 months (24 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 2b n=1 Participants ACE-083 Administered into the BB muscle q4w for up to 24 months (24 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 2c n=13 Participants ACE-083 Administered into the TA muscle q4w for up to 24 months (24 doses) for CMT patients ACE-083: Recombinant fusion protein	Part 2 Cohort 3a ACE-083 Administered into the TA muscle q8w for up to 24 months (12 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 3b ACE-083 Administered into the BB muscle q8w for up to 24 months (12 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 3c ACE-083 Administered into the TA muscle q8w for up to 24 months (12 doses) for CMT patients ACE-083: Recombinant fusion protein
Part 1: ACE-083 Serum Concentration Samples Part 1-Day1, 24-hour Post-dose	38.3 ng/mL Standard Deviation 13.8	76.4 ng/mL	41.10 ng/mL Standard Deviation 12.6	—	—	—

SECONDARY outcome

Timeframe: day 85, 24 -hours post-dose in Part 1

Population: The PK Population consisted of all participants who received at least 1 dose of study drug and had sufficient PK samples collected and assayed for PK analysis.

Part1: ACE-083 serum concentration samples were taken on day 85, 24-hours post-dose. PK parameters of ACE-083 were not determined due to limited quantifiable concentration data. Pre-specified analysis was for part 1 cohorts only, therefore, available data is only reported for part 1 cohorts (1a, 1b and 1c). Mean and standard deviation descriptive statistics are being reported for the Day 85, 24-hour post-dose timepoint only, due to early termination of this trial.

Outcome measures

Outcome measures
Measure	Part 2 Cohort 2a n=7 Participants ACE-083 Administered into the TA muscle q4w for up to 24 months (24 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 2b n=1 Participants ACE-083 Administered into the BB muscle q4w for up to 24 months (24 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 2c n=13 Participants ACE-083 Administered into the TA muscle q4w for up to 24 months (24 doses) for CMT patients ACE-083: Recombinant fusion protein	Part 2 Cohort 3a ACE-083 Administered into the TA muscle q8w for up to 24 months (12 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 3b ACE-083 Administered into the BB muscle q8w for up to 24 months (12 doses) for FSHD patients ACE-083: Recombinant fusion protein	Part 2 Cohort 3c ACE-083 Administered into the TA muscle q8w for up to 24 months (12 doses) for CMT patients ACE-083: Recombinant fusion protein
Part1: ACE-083 Serum Concentration Samples Part 1-Day 85, 24-hour Post-dose	23.1 ng/mL Standard Deviation 2.26	53 ng/mL	39.34 ng/mL Standard Deviation 18.2	—	—	—

SECONDARY outcome

Timeframe: From baseline to End of Treatment in Part 1

Population: The PK Population consisted of all participants who received at least 1 dose of study drug and had sufficient PK samples collected and assayed for PK analysis.

Part 1: ACE-083 concentrations ranged from 20.1 to 238.6 μg/L across FSHD and CMT cohorts with the majority of serum concentrations were below the lower limit of quantification (LLOQ) or just above LLOQ. Further, given the early termination of this trial, there were not enough samples per cohort collected at the pre-specified timeline points to be able to determine Tmax.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From baseline to End of Treatment in Part 1

Population: The PK Population consisted of all participants who received at least 1 dose of study drug and had sufficient PK samples collected and assayed for PK analysis.