Study of ACE-083 in Patients With Facioscapulohumeral Muscular Dystrophy (FSHD)
Condition: Facioscapulohumeral Muscular Dystrophy
MeSH terms: Muscular Dystrophies; Muscular Dystrophy, Facioscapulohumeral
Intervention: ACE-083; ACE-083 or placebo
Intervention description: Recombinant fusion protein.; Recombinant fusion protein or normal saline.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 95.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: FSHD

Summary:

      Study A083-02 is a multi-center, Phase 2 study to evaluate the safety, tolerability,
      pharmacodynamics (PD), efficacy, and pharmacokinetics (PK) of locally-acting ACE-083 in
      patients with Facioscapulohumeral muscular dystrophy (FSHD) to be conducted in two parts.
      Part 1 is open-label, dose-escalation and Part 2 is randomized, double-blind, and
      placebo-controlled.
    

Eligibility criteria:

        Key Inclusion Criteria:

          1. Age ≥ 18 years

          2. Genetically confirmed Facioscapulohumeral muscular dystrophy type 1 (FSHD1) or FSHD2
             (or a first-degree relative with genetically confirmed FSHD1 or FSHD2) and clinical
             findings meeting FSHD criteria

          3. Part 1 TA cohorts:

               1. 6-minute walk distance (6MWD) ≥ 150 meters (without a brace)

               2. Mild to moderate weakness in left and/or right ankle dorsiflexion

             Part 1 BB cohorts:

             a. Mild to moderate weakness in left and/or right elbow flexion

             Part 2 TA cohorts:

               1. 6MWD ≥ 150 and ≤ 500 meters (without a brace)

               2. Mild to moderate weakness in left and right ankle dorsiflexion

             Part 2 BB cohorts:

             a. 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.
             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 even if he has undergone a successful
             vasectomy.

        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. 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
             anti-coagulation/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. Chronic systemic corticosteroids (≥ 2 weeks) within 4 weeks before Study Day 1 and for
             duration of study; intra-articular/topical/inhaled therapeutic or physiologic doses of
             corticosteroids are permitted

          8. Androgens or growth hormone within 6 months before Study Day 1 and for duration of
             study; topical physiologic androgen replacement is permitted

          9. 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)