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)
Condition: Facioscapulohumeral Muscular Dystrophy; Charcot-Marie-Tooth Disease
MeSH terms: Muscular Dystrophies; Muscular Dystrophy, Facioscapulohumeral; Tooth Diseases; Charcot-Marie-Tooth Disease; Nerve Compression Syndromes; Hereditary Sensory and Motor Neuropathy
Intervention: ACE-083
Intervention description: Recombinant fusion protein
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 62.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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.
    

Eligibility 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. Chronic insulin therapy is permitted for diabetic FSHD patients. Oral
             HRT is permitted if started at least 3 months prior to receiving study drug

         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