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)

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT03943290
• Date of registration: 17/04/2019
• Prospective Registration: Yes
• Primary sponsor: Acceleron Pharma, Inc.
• Public 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)
• Scientific 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
• Date of first enrolment: May 10, 2019
• Target sample size: 62
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT03943290
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

Canada, Spain, United States

Key inclusion & exclusion criteria

Key Inclusion Criteria:

1. 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.

2. 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.

3. Ability to adhere to the study visit schedule/procedures and to understand and comply
with protocol requirements

4. Signed written informed consent

Key Exclusion Criteria:

1. 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

2. 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

3. Type 1 or type 2 diabetes mellitus

4. 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

5. Renal impairment (serum creatinine = 2 times the upper limit of normal [ULN])

6. Aspartate transaminase (AST) and/or alanine transaminase (ALT) = 3 times ULN

7. 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)

8. Severe deformity or ankle fixation that would sufficiently limit passive range of
motion to affect functional assessments (TA patients only)

9. Major surgery within 4 weeks prior to Study Day 1

10. 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

11. 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

12. 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)

13. 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)

14. 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

15. 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)

16. Known active substance abuse, including alcohol

17. History of sensitivity to protein pharmaceuticals

18. Female that is pregnant or lactating/breast-feeding



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Facioscapulohumeral Muscular Dystrophy

Charcot-Marie-Tooth Disease

Intervention(s)

Drug: ACE-083

Primary Outcome(s)

Frequency of adverse events - Presence and nature of adverse events (AE) [Time Frame: From baseline to Month 23 in Part 2]

Change in muscle volume - Percent change from baseline in muscle volume of injected muscle by magnetic resonance imaging (MRI) [Time Frame: From baseline to Month 23 in Part 2]

Secondary Outcome(s)

Change in muscle function. Percent and absolute change from baseline in functional assessment for biceps brachii (BB) muscle: mid-level and high level performance of the upper limb (PUL) test [Time Frame: From baseline to Month 23 in Part 2]

Change in muscle function - percent change from baseline for biceps brachii (BB) muscle in mid-level an high level performance of the upper limb (PUL) test [Time Frame: From baseline to Month 23 in Part 2]

Change in muscle function - percent change from baseline for tibialis anterior (TA) muscle in 10-meter walk/run [Time Frame: From baseline to Month 23 in Part 2]

Change in muscle function. Percent and absolute change from baseline in functional assessment for tibialis anterior (TA) muscle:10-meter walk/run [Time Frame: From baseline to Month 23 in Part 2]

Change in muscle function - percent change from baseline for tibialis anterior (TA) muscle in 100-meter timed test [Time Frame: From baseline to Month 23 in Part 2]

Change in patient-reported quality of life. Absolute change from baseline in CMT health index score (CMT-HI, subjects from A083-03) [Time Frame: From baseline to Month 23 in Part 2]

Change in muscle function. Percent and absolute change from baseline in functional assessment for tibialis anterior (TA) muscle: 4-stair climb (subjects from A083-02 only) [Time Frame: From baseline to Month 23 in Part 2]

Pharmacokinetics parameter of area under the plasma concentration versus time curve (AUC) [Time Frame: From baseline to Month 5 in Part 1]

Pharmacokinetics parameter of time to maximum serum concentration following administration (Tmax) [Time Frame: From baseline to Month 5 in Part 1]

Change in patient-reported quality of life. Absolute change from baseline in FSHD-health index score (FSHD-HI, subjects from A083-02) [Time Frame: From baseline to Month 23 in Part 2]

Change in muscle function - percent change from baseline for tibialis anterior (TA) muscle in 6-minute walk test [Time Frame: From baseline to Month 23 in Part 2]

Change in muscle function. Percent and absolute change from baseline in functional assessment for tibialis anterior (TA) muscle: 6-minute walk test [Time Frame: From baseline to Month 23 in Part 2]

Change in muscle function - percent change from baseline for tibialis anterior (TA) muscle in 4-stair climb (subjects from A083-02 only) [Time Frame: From baseline to Month 23 in Part 2]

Change in muscle function. Percent and absolute change from baseline in functional assessment for tibialis anterior (TA) muscle: 100-meter timed test [Time Frame: From baseline to Month 23 in Part 2]

Pharmacokinetics parameter of peak plasma concentration (Cmax) [Time Frame: From baseline to Month 5 in Part 1]

Secondary ID(s)

ACE-083

A083-04

Source(s) of Monetary Support

Please refer to primary and secondary sponsors