Study of ACE-083 in Patients With Charcot-Marie-Tooth Disease

Exclusion Criteria

• •1. History of active malignancy, with the exception of fully excised or treated basal cell carcinoma, cervical carcinoma in-situ, or ≤ 2 squamous cell carcinomas of the skin
• •2. Symptomatic cardiopulmonary disease, significant functional impairment, significant orthopedic or neuropathic pain, or other co morbidities that in the opinion of the investigator would limit a patient's ability to complete strength and/or functional assessments on study
• •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; low dose aspirin \[≤ 100 mg daily\] is permitted)
• •8. Severe deformity or ankle fixation that would sufficiently limit passive range of motion to affect assessment of dorsiflexion strength
• •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 investigational agent 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. Any previous or current exposure to ACE-083
• •15. 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
• •16. Any condition that would prevent MRI scanning or compromise the ability to obtain a clear and interpretable scan of the lower leg, as applicable (e.g., knee/hip replacement metallic implants)
• •17. Known active substance abuse, including alcohol
• •18. History of sensitivity to protein pharmaceuticals
• •19. Female that is lactating/breast-feeding