Study of ACE-083 in Patients With Facioscapulohumeral Muscular Dystrophy (FSHD)

Key Inclusion Criteria:

1. Age ≥ 18 years
2. Genetically-confirmed FSHD1 or FSHD2 (or a first-degree relative with genetically confirmed FSHD1 or FSHD2) and clinical findings meeting FSHD criteria

3. For tibialis anterior (TA) cohorts:

   1. Able to walk independently for at least 10 meters, without a brace
   2. Mild to moderate weakness in left and/or right ankle dorsiflexion

   Note: Opposite side must not be severely affected.

   For biceps brachii (BB) cohorts: mild to moderate weakness in left and/or right elbow flexion.

4. Females of childbearing potential must have negative urine pregnancy test prior to enrollment and use highly effective birth control methods during study participation. Males must agree to use a condom during any sexual contact with females of childbearing potential while participating in the study even if he has undergone a successful vasectomy.
5. Ability to adhere to the study visit schedule/procedures, and to understand and comply with protocol requirements
6. Signed written informed consent

Key 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, 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. Renal impairment (serum creatinine ≥ 2 times the upper limit of normal [ULN])
4. Aspartate transaminase (AST) and/or alanine transaminase (ALT) ≥ 3 times ULN
5. 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; low dose aspirin [≤ 100 mg daily] is permitted)
6. Major surgery within 4 weeks prior to Study Day 1
7. Systemic corticosteroids within 2 weeks before Study Day 1 and for duration of study; inhaled therapeutic or physiologic doses of corticosteroids are permitted
8. Any change in medications potentially affecting muscle function within 4 weeks of Study Day 1 and for duration of study
9. Previous exposure to any marketed or investigational agent potentially affecting muscle volume, strength, or function within 5 half-lives of last dose or 4 weeks of Study Day 1 if half-life is unknown, or any prior exposure to ACE-083
10. 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
11. Any condition that would prevent MRI scanning or compromise the ability to obtain a clear and interpretable scan of the TA or BB muscles, as applicable (e.g., pacemaker, knee/hip replacement, or metallic implants)
12. Known active substance abuse, including alcohol
13. History of sensitivity to protein pharmaceuticals
14. Female that is lactating/breast-feeding