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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)

Primary Purpose

Facioscapulohumeral Muscular Dystrophy, Charcot-Marie-Tooth Disease

Status

Terminated

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

ACE-083

About this trial

This is an interventional treatment trial for Facioscapulohumeral Muscular Dystrophy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Key Inclusion Criteria:

Completion of treatment with study drug per protocol and completion of the end of treatment (ET) visit in Study A083-02 or Study A083-03.
Females of childbearing potential (defined as sexually mature women who have not undergone hysterectomy or bilateral oophorectomy or are not naturally postmenopausal ≥ 24 consecutive months) must have negative urine pregnancy test prior to enrollment and use highly effective birth control methods (abstinence, oral contraceptives, barrier method with spermicide, or surgical sterilization) during study participation and for 8 weeks following the last dose of ACE-083. Hormonal birth control use must be stable for at least 14 days prior to Day 1. Males must agree to use a condom during any sexual contact with females of childbearing potential while participating in the study and for 8 weeks following the last dose of ACE-083, even if they have undergone a vasectomy. Subjects must be counseled about contraception prior to the first dose of ACE-083 and every three months thereafter during the study.
Ability to adhere to the study visit schedule/procedures and to understand and comply with protocol requirements
Signed written informed consent

Key Exclusion Criteria:

Current/active malignancy (e.g., remission less than 5 years' duration), with the exception of fully excised or treated basal cell carcinoma, cervical carcinoma in-situ, or ≤ 2 squamous cell carcinomas of the skin
Co-morbidities, including symptomatic cardiopulmonary disease, significant orthopedic or neuropathic pain, or other conditions that, in the opinion of the investigator, would limit a subject's ability to complete strength and/or functional assessments
Type 1 or type 2 diabetes mellitus
Thyroid disorder unless condition is stable with no change in treatment for at least 4 weeks before the first dose and no expected change for duration of study
Renal impairment (serum creatinine ≥ 2 times the upper limit of normal [ULN])
Aspartate transaminase (AST) and/or alanine transaminase (ALT) ≥ 3 times ULN
Increased risk of bleeding (i.e., due to hemophilia, platelet disorders, or use of any anticoagulation/platelet modifying therapies up to 2 weeks prior to Study Day 1 and for duration of study; single agent low dose aspirin [≤ 100 mg daily] is permitted)
Severe deformity or ankle fixation that would sufficiently limit passive range of motion to affect functional assessments (TA patients only)
Major surgery within 4 weeks prior to Study Day 1
Chronic pharmacologic doses of systemic corticosteroids (≥ 2 weeks) within 4 weeks before Study Day 1 and for duration of study; intra-articular/topical/inhaled/intranasal physiologic doses of systemic corticosteroids are permitted
Androgens, growth hormone, insulin or oral hormone replacement therapy within 6 months before Study Day 1 and for duration of study; topical physiologic androgen replacement is permitted. Chronic insulin therapy is permitted for diabetic FSHD patients. Oral HRT is permitted if started at least 3 months prior to receiving study drug
Any change in medications potentially affecting muscle strength or function within 4 weeks of Study Day 1 and for duration of study (e.g., creatinine, CoQ10, systemic beta-adrenergic agonists)
Previous exposure to any other investigational agent (not including ACE-083) potentially affecting muscle volume, muscle strength, or muscle or nerve function within 5 half-lives of last dose plus an additional 8-week washout period (or 12 weeks prior to Study Day 1 if half-life is unknown)
Significant change in physical activity or exercise (e.g., significant increase or decrease in intensity or frequency) within 8 weeks before Study Day 1 or inability to maintain the baseline level of physical activity throughout the study
Any condition that would prevent MRI scanning or compromise the ability to obtain a clear and interpretable scan of the treated muscles (e.g., knee/hip replacement metallic implants)
Known active substance abuse, including alcohol
History of sensitivity to protein pharmaceuticals
Female that is pregnant or lactating/breast-feeding

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm Type

Experimental

Arm Label

Part 1 Cohort 1a

Part 1 Cohort 1b

Part 1 Cohort 1c

Part 2 Cohort 2a

Part 2 Cohort 2b

Part 2 Cohort 2c

Part 2 Cohort 3a

Part 2 Cohort 3b

Part 2 Cohort 3c

Arm Description

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-083 240 mg/muscle administered bilaterally by injection into the BB muscle every 4 weeks for up to 6 doses for FSHD patients

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 Administered into the TA muscle q4w for up to 24 months (24 doses) for FSHD patients

ACE-083 Administered into the BB muscle q4w for up to 24 months (24 doses) for FSHD patients

ACE-083 Administered into the TA muscle q4w for up to 24 months (24 doses) for CMT patients

ACE-083 Administered into the TA muscle q8w for up to 24 months (12 doses) for FSHD patients

ACE-083 Administered into the BB muscle q8w for up to 24 months (12 doses) for FSHD patients

ACE-083 Administered into the TA muscle q8w for up to 24 months (12 doses) for CMT patients

Outcomes

Primary Outcome Measures

Part 2- Frequency of Adverse Events - Presence and Nature of Adverse Events (AE) During Part 2

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.

Part 2: Frequency of Adverse Events - Presence and Nature of Grade 3 or Higher Adverse Events (AE) During the Part 2 of the Study.

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.

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

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.

Secondary Outcome Measures

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

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.

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

Part 2: Change in Muscle Function. Absolute Change From Baseline in Functional Assessment for Tibialis Anterior (TA) Muscle: 6-minute Walk Test

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.

Part 2: Change in Muscle Function - Percent Change From Baseline in Functional Assessment for Tibialis Anterior (TA) Muscle in 6-minute Walk Test

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)

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).

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)

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).

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)

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).

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)

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).

Part 2: Change in Muscle Function. Absolute Change From Baseline in Functional Assessment for Tibialis Anterior (TA) Muscle: 100-meter Timed Test

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).

Part 2: Change in Muscle Function - Percent Change From Baseline for Tibialis Anterior (TA) Muscle in 100-meter Timed Test

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.

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.

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

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.

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.

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.

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.

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)

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.

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)

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.

Part 1: ACE-083 Serum Concentration Samples Part 1-Day1, 24-hour Post-dose

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.

Part1: ACE-083 Serum Concentration Samples Part 1-Day 85, 24-hour Post-dose

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.

Part1: Pharmacokinetics Parameter of Time to Maximum Serum Concentration Following Administration (Tmax)

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.

Part1: Pharmacokinetics Parameter of Area Under the Plasma Concentration Versus Time Curve (AUC)

Full Information

NCT ID

NCT03943290

First Posted

April 17, 2019

Last Updated

September 13, 2022

Sponsor

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

1. Study Identification

Unique Protocol Identification Number

NCT03943290

Brief Title

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)

Official Title

An Open-Label Extension Study to Evaluate the Long-Term Effects of ACE-083 in Patients With Facioscapulohumeral Muscular Dystrophy (FSHD) Previously Enrolled in Study A083-02 and in Patients With Charcot-Marie Tooth (CMT) Disease Types 1 and X Previously Enrolled in Study A083-03

Study Type

Interventional

2. Study Status

Record Verification Date

September 2022

Overall Recruitment Status

Terminated

Why Stopped

Investigation of ACE-083 for use in patients with CMT and FSHD is being discontinued in this extension study as functional secondary endpoints were not achieved in the A083-023 or A083-03 trial (the parent trials).

Study Start Date

May 10, 2019 (Actual)

Primary Completion Date

March 11, 2020 (Actual)

Study Completion Date

March 11, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

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

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

5. Study Description

Brief Summary

This is an open-label, multicenter, phase 2 extension study to evaluate the safety, tolerability, PK, PD, and efficacy of ACE-083 in subjects with FSHD previously enrolled in Study A083-02 and subjects with CMT1 and CMTX previously enrolled in Study A083-03. This study will be conducted in two Parts: Part 1, which is a loading phase of 6 months' duration, and Part 2, the maintenance phase, which will last up to 24 months.

Detailed Description

Part 1 (6-month, non-randomized, open-label, loading phase for subjects from A083-02 Part 1 and A083-03 Part 1) Part 1 will consist of 3 cohorts of up to 18 subjects each. Subjects enrolled in Cohorts 1a and 1b will have completed Part 1 of Study A083-02; subjects enrolled in Cohort 1c will have completed Part 1 of Study A083-03. In this loading phase, 240 mg/muscle ACE-083 will be administered bilaterally every 4 weeks (q4w) for 6 doses (6 months) into either the tibialis anterior (TA) muscle or the biceps brachii (BB) muscle, depending on the muscle injected in the previous study; subjects may not switch muscle cohort upon enrollment in this study. Subjects will participate in a screening period of up to 4 weeks before receiving the first dose of ACE-083. Part 2 (24-month, randomized, open-label rollover maintenance phase for subjects from A083-02 Part 2, A083-03 Part 2, and A083-04 Part 1) Subjects who complete Part 1 of this study (the loading phase), Part 2 of A083-02, or Part 2 of A083-03 will enroll directly into the Part 2 open-label maintenance phase of treatment with ACE-083 and will consist of 6 cohorts of up to 23 FSHD or 29 CMT subjects each. These subjects will be randomized (1:1) to receive ACE-083, 240 mg/muscle bilaterally, either q4w or q8w. Thus, subjects enrolled in Cohorts 2a, 2b, and 2c will be FSHD TA, FSHD BB, and CMT TA treated q4w, and subjects enrolled in Cohorts 3a, 3b, and 3c will be FSHD TA, FSHD BB, and CMT TA treated q8w. Study duration for a subject initially enrolled in Part 1 and then extended to Part 2 will be approximately 33 months, including a 1-month screening period, 6-month Part 1 loading phase, 24-month Part 2 maintenance phase, and 2-month follow-up period. For subjects who enrolled directly into Part 2 of this study from Part 2 of Studies A083-02 and A083-03, the duration of the study will be approximately 26 months, including a 24-month maintenance phase and a 2-month follow-up period.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Facioscapulohumeral Muscular Dystrophy, Charcot-Marie-Tooth Disease

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

62 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Part 1 Cohort 1a

Arm Type

Experimental

Arm Description

ACE-083 240 mg/muscle administered bilaterally by injection into the TA muscle every 4 weeks for up to 6 doses for FSHD patients

Arm Title

Part 1 Cohort 1b

Arm Type

Experimental

Arm Description

ACE-083 240 mg/muscle administered bilaterally by injection into the BB muscle every 4 weeks for up to 6 doses for FSHD patients

Arm Title

Part 1 Cohort 1c

Arm Type

Experimental

Arm Description

ACE-083 240 mg/muscle administered bilaterally by injection into the TA muscle every 4 weeks for up to 6 doses for CMT patients

Arm Title

Part 2 Cohort 2a

Arm Type

Experimental

Arm Description

ACE-083 Administered into the TA muscle q4w for up to 24 months (24 doses) for FSHD patients

Arm Title

Part 2 Cohort 2b

Arm Type

Experimental

Arm Description

ACE-083 Administered into the BB muscle q4w for up to 24 months (24 doses) for FSHD patients

Arm Title

Part 2 Cohort 2c

Arm Type

Experimental

Arm Description

ACE-083 Administered into the TA muscle q4w for up to 24 months (24 doses) for CMT patients

Arm Title

Part 2 Cohort 3a

Arm Type

Experimental

Arm Description

ACE-083 Administered into the TA muscle q8w for up to 24 months (12 doses) for FSHD patients

Arm Title

Part 2 Cohort 3b

Arm Type

Experimental

Arm Description

ACE-083 Administered into the BB muscle q8w for up to 24 months (12 doses) for FSHD patients

Arm Title

Part 2 Cohort 3c

Arm Type

Experimental

Arm Description

ACE-083 Administered into the TA muscle q8w for up to 24 months (12 doses) for CMT patients

Intervention Type

Drug

Intervention Name(s)

ACE-083

Intervention Description

Recombinant fusion protein

Primary Outcome Measure Information:

Title

Part 2- Frequency of Adverse Events - Presence and Nature of Adverse Events (AE) During Part 2

Description

Time Frame

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

Title

Part 2: Frequency of Adverse Events - Presence and Nature of Grade 3 or Higher Adverse Events (AE) During the Part 2 of the Study.

Description

Time Frame

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

Title

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

Description

Time Frame

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

Secondary Outcome Measure Information:

Title

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

Description

Time Frame

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

Title

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

Description

Time Frame

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

Title

Part 2: Change in Muscle Function. Absolute Change From Baseline in Functional Assessment for Tibialis Anterior (TA) Muscle: 6-minute Walk Test

Description

Time Frame

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

Title

Part 2: Change in Muscle Function - Percent Change From Baseline in Functional Assessment for Tibialis Anterior (TA) Muscle in 6-minute Walk Test

Description

Time Frame

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

Title

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)

Description

Time Frame

Baseline, End of Treatment visit during Part 2

Title

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)

Description

Time Frame

Baseline, End of Treatment visit during Part 2

Title

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)

Description

Time Frame

Baseline, End of Treatment visit during Part 2

Title

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)

Description

Time Frame

Baseline, End of Treatment visit during Part 2

Title

Part 2: Change in Muscle Function. Absolute Change From Baseline in Functional Assessment for Tibialis Anterior (TA) Muscle: 100-meter Timed Test

Description

Time Frame

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

Title

Part 2: Change in Muscle Function - Percent Change From Baseline for Tibialis Anterior (TA) Muscle in 100-meter Timed Test

Description

Time Frame

Baseline, End of Treatment visit, Part 2

Title

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.

Description

Time Frame

Baseline, End of Treatment visit during Part 2

Title

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

Description

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.

Time Frame

Baseline, End of Treatment

Title

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.

Description

Time Frame

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

Title

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.

Description

Time Frame

Baseline, End of Treatment visit during Part 2

Title

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)

Description

Time Frame

Baseline, End of Treatment visit during part 2

Title

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)

Description

Time Frame

Baseline, Day 113 during Part 2

Title

Part 1: ACE-083 Serum Concentration Samples Part 1-Day1, 24-hour Post-dose

Description

Time Frame

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

Title

Part1: ACE-083 Serum Concentration Samples Part 1-Day 85, 24-hour Post-dose

Description

Time Frame

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

Title

Part1: Pharmacokinetics Parameter of Time to Maximum Serum Concentration Following Administration (Tmax)

Description

Time Frame

From baseline to End of Treatment in Part 1

Title

Part1: Pharmacokinetics Parameter of Area Under the Plasma Concentration Versus Time Curve (AUC)

Description

Time Frame

From baseline to End of Treatment in Part 1

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Key Inclusion Criteria: Completion of treatment with study drug per protocol and completion of the end of treatment (ET) visit in Study A083-02 or Study A083-03. Females of childbearing potential (defined as sexually mature women who have not undergone hysterectomy or bilateral oophorectomy or are not naturally postmenopausal ≥ 24 consecutive months) must have negative urine pregnancy test prior to enrollment and use highly effective birth control methods (abstinence, oral contraceptives, barrier method with spermicide, or surgical sterilization) during study participation and for 8 weeks following the last dose of ACE-083. Hormonal birth control use must be stable for at least 14 days prior to Day 1. Males must agree to use a condom during any sexual contact with females of childbearing potential while participating in the study and for 8 weeks following the last dose of ACE-083, even if they have undergone a vasectomy. Subjects must be counseled about contraception prior to the first dose of ACE-083 and every three months thereafter during the study. Ability to adhere to the study visit schedule/procedures and to understand and comply with protocol requirements Signed written informed consent Key Exclusion Criteria: Current/active malignancy (e.g., remission less than 5 years' duration), with the exception of fully excised or treated basal cell carcinoma, cervical carcinoma in-situ, or ≤ 2 squamous cell carcinomas of the skin Co-morbidities, including symptomatic cardiopulmonary disease, significant orthopedic or neuropathic pain, or other conditions that, in the opinion of the investigator, would limit a subject's ability to complete strength and/or functional assessments Type 1 or type 2 diabetes mellitus Thyroid disorder unless condition is stable with no change in treatment for at least 4 weeks before the first dose and no expected change for duration of study Renal impairment (serum creatinine ≥ 2 times the upper limit of normal [ULN]) Aspartate transaminase (AST) and/or alanine transaminase (ALT) ≥ 3 times ULN Increased risk of bleeding (i.e., due to hemophilia, platelet disorders, or use of any anticoagulation/platelet modifying therapies up to 2 weeks prior to Study Day 1 and for duration of study; single agent low dose aspirin [≤ 100 mg daily] is permitted) Severe deformity or ankle fixation that would sufficiently limit passive range of motion to affect functional assessments (TA patients only) Major surgery within 4 weeks prior to Study Day 1 Chronic pharmacologic doses of systemic corticosteroids (≥ 2 weeks) within 4 weeks before Study Day 1 and for duration of study; intra-articular/topical/inhaled/intranasal physiologic doses of systemic corticosteroids are permitted Androgens, growth hormone, insulin or oral hormone replacement therapy within 6 months before Study Day 1 and for duration of study; topical physiologic androgen replacement is permitted. Chronic insulin therapy is permitted for diabetic FSHD patients. Oral HRT is permitted if started at least 3 months prior to receiving study drug Any change in medications potentially affecting muscle strength or function within 4 weeks of Study Day 1 and for duration of study (e.g., creatinine, CoQ10, systemic beta-adrenergic agonists) Previous exposure to any other investigational agent (not including ACE-083) potentially affecting muscle volume, muscle strength, or muscle or nerve function within 5 half-lives of last dose plus an additional 8-week washout period (or 12 weeks prior to Study Day 1 if half-life is unknown) Significant change in physical activity or exercise (e.g., significant increase or decrease in intensity or frequency) within 8 weeks before Study Day 1 or inability to maintain the baseline level of physical activity throughout the study Any condition that would prevent MRI scanning or compromise the ability to obtain a clear and interpretable scan of the treated muscles (e.g., knee/hip replacement metallic implants) Known active substance abuse, including alcohol History of sensitivity to protein pharmaceuticals Female that is pregnant or lactating/breast-feeding

Facility Information:

Facility Name

University of California-Irvine

City

Orange

State/Province

California

ZIP/Postal Code

92697

Country

United States

Facility Name

University of California Davis Medical Center

City

Sacramento

State/Province

California

ZIP/Postal Code

95817

Country

United States

Facility Name

University of Colorado

City

Aurora

State/Province

Colorado

ZIP/Postal Code

80045

Country

United States

Facility Name

University of Florida

City

Gainesville

State/Province

Florida

ZIP/Postal Code

32611

Country

United States

Facility Name

Indiana University

City

Indianapolis

State/Province

Indiana

ZIP/Postal Code

46202

Country

United States

Facility Name

University of Iowa

City

Iowa City

State/Province

Iowa

ZIP/Postal Code

52242

Country

United States

Facility Name

University of Kansas Medical Center

City

Kansas City

State/Province

Kansas

ZIP/Postal Code

66160

Country

United States

Facility Name

Brigham & Women's Hospital

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02115

Country

United States

Facility Name

University of Minnesota

City

Minneapolis

State/Province

Minnesota

ZIP/Postal Code

55455

Country

United States

Facility Name

Washington University School of Medicine

City

Saint Louis

State/Province

Missouri

ZIP/Postal Code

63110

Country

United States

Facility Name

Hackensack University Medical Center

City

Hackensack

State/Province

New Jersey

ZIP/Postal Code

07601

Country

United States

Facility Name

Columbia University

City

New York

State/Province

New York

ZIP/Postal Code

10027

Country

United States

Facility Name

University of Rochester School of Medicine

City

Rochester

State/Province

New York

ZIP/Postal Code

14642

Country

United States

Facility Name

Carolinas Healthcare System Neurosciences Institute

City

Charlotte

State/Province

North Carolina

ZIP/Postal Code

28207

Country

United States

Facility Name

Duke University Medical Center

City

Durham

State/Province

North Carolina

ZIP/Postal Code

27710

Country

United States

Facility Name

Oregon Health & Science University

City

Portland

State/Province

Oregon

ZIP/Postal Code

97239

Country

United States

Facility Name

University of Pennsylvania

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19104

Country

United States

Facility Name

University of Utah

City

Salt Lake City

State/Province

Utah

ZIP/Postal Code

84112

Country

United States

Facility Name

Virginia Commonwealth University

City

Richmond

State/Province

Virginia

ZIP/Postal Code

23284

Country

United States

Facility Name

University of Calgary

City

Calgary

State/Province

Alberta

Country

Canada

Facility Name

London Health Sciences Centre

City

London

State/Province

Ontario

Country

Canada

Facility Name

Montreal Neurological Institute & Hospital

City

Montréal

State/Province

Quebec

Country

Canada

Facility Name

Hospital de la Santa Creu i Sant Pau

City

Barcelona

Country

Spain

Facility Name

Hospital Universitario Vall d'Hebrón

City

Barcelona

Country

Spain

12. IPD Sharing Statement

Learn more about this trial

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)

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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)

Facioscapulohumeral Muscular Dystrophy, Charcot-Marie-Tooth Disease

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial