Facioscapulohumeral Muscular Dystrophy MedDRA version: 20.0 Level: PT Classification code 10064087 Term: Facioscapulohumeral muscular dystrophy System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Name: ACE-083
Product Code: ACE-083
Pharmaceutical Form: Lyophilisate for solution for injection
INN or Proposed INN: pending
CA
Sponsors
Acceleron Pharma Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
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 a 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 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 150 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
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 subjects 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 the use of MRI or compromise the ability to obtain a clear and interpretable image 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): • Presence and nature of adverse events (AE), including injection site reactions and changes in clinical laboratory parameters • Percent change from baseline in muscle volume of injected muscle by magnetic resonance imaging (MRI) ;Main Objective: To evaluate the long-term safety and pharmacodynamic (PD) 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 (CMT1 and CMTX) previously enrolled in Study A083-03.; Secondary Objective: •To evaluate the safety and PD effects of every 4 week (q4w) dosing in the loading phase, and of q4w and q8w dosing in the maintenance phase. •To evaluate changes in strength, motor function, and quality of life (patient-reported outcomes) during the maintenance and loading phases of treatment. •To evaluate the pharmacokinetics (PK) of ACE-083 when administered as a local muscle injection during the maintenance and loading phases of treatment. ; Timepoint(s) of evaluation of this end point: • Safety assessments from Day 1 through Day 701/EOS include monitoring of adverse events (AEs), injection site reactions, concomitant medications, clinical laboratory assessments (including hematology, chemistry, and ADA), urinalysis, vital signs, and physical examination findings. • MRI: - Loading phase: Day 1, 85 - Maintenance and Follow up Phase: Day 1, 113, 169, 337, 505, 673 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Percent and absolute change from baseline in the intramuscular fat fraction of injected muscle by MRI • Percent change from baseline in strength measurements • Percent and absolute change from baseline in functional assessments: For tibialis anterior (TA) muscle: 10-meter walk/run, 6-minute walk test, 4-stair climb (subjects from A083-02 only), and 100-meter timed test; for biceps brachii (BB) muscle: mid-level and high level performance of the upper limb (PUL) test • Absolute change from baseline in FSHD-health index (FSHD-HI, subjects from A083-02) or CMT health index (CMT-HI, subjects from A083-03) total score and subscale scores • PK parameters of ACE-083 serum concentrations over time ; Timepoint(s) of evaluation of this end point: • MRI: - Loading phase: Day 1, 85 - Maintenance and Follow up Phase: Day 1, 113, 169, 337, 505, 673 • evaluate changes in strength, motor function, and quality of life (patient-reported outcomes) during the maintenance and loading phases of treatment. • Percent and absolute change from baseline in functional assessments: - Loading Phase: Screening, Day 1, Day 85 (for tibialis anterior (TA) muscle: 10-meter walk/run, 6-minute walk test, 4-stair climb (subjects from A083-02 only)) - Maintenance Phase and Follow-Up: Day 1, 113, 169, 337, 505, 673, 701 • FSHD-health index and CMT health index (CMT-HI): - Loading Phase: Screening, Day 1, 85 - Maintenance Phase and Follow-Up: Day 1, 113, 169, 337, 505, 673, 701 • PK samples: - Loading Phase: Day 1, 85 | — |
Countries
Canada, Spain, United States
Contacts
Public ContactKenneth M. Attie
Acceleron Pharma Inc.
Outcome results
None listed