Study of ACE-083 in Patients With Facioscapulohumeral Muscular Dystrophy (FSHD)
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| ClinicalTrials.gov Identifier: NCT02927080 |
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Recruitment Status :
Terminated
(Investigation of ACE-083 for use in patients with FSHD is being discontinued as it did not achieve functional secondary endpoints in the A083-02 trial.)
First Posted : October 6, 2016
Last Update Posted : November 6, 2019
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Facioscapulohumeral Muscular Dystrophy | Drug: ACE-083 Drug: ACE-083 or placebo | Phase 2 |
Part 1 (dose escalation, open-label) Part 1 will consist of up to 6 cohorts (A to F) of patients and will evaluate multiple ascending dose levels of ACE-083 in either the tibialis anterior (TA) or biceps brachii (BB) muscle. Patients in each cohort will be enrolled in a 4-week screening period before beginning treatment. A Safety Review Team (SRT) will meet to review data for each cohort when at least 4 patients within a cohort have completed their Day 43 visit prior to dose escalation.
Part 2 (randomized, double-blind, placebo-controlled, with open-label extension) Prior to the initiation of Part 2, a review of safety and efficacy data from Part 1 will be conducted to determine whether cohorts for one or both muscles will be pursued in Part 2, as well as the recommended dose level for each muscle. A total of up to 56 new patients (28 patients per muscle) may be enrolled and randomized (1:1) to receive either ACE-083 (n=14/muscle) or placebo (n=14/muscle) bilaterally to either the TA or BB muscles (but not both). Patients will receive blinded study drug once every three weeks for approximately 6 months (9 doses).
Patients who complete the double-blind treatment period will immediately roll over to open-label treatment with ACE-083, receiving the same dose of active drug, bilaterally in either the TA or BB muscle, once every three weeks for approximately 6 months (8 doses). In Part 2, the SRT will periodically review blinded safety data for each muscle treated.
Study duration for Part 1 for each patient will be approximately 24 weeks, including a 4-week screening period, a 12-week treatment period, and an 8-week follow-up period after the last dose.
Study duration for Part 2 for each patient will be approximately 15 months, including a 1-month screening period, a 12-month treatment period (6-month double-blind, placebo-controlled and a 6-month open-label extension), and a 2-month follow-up period after the last dose
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 95 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study of ACE-083 in Patients With Facioscapulohumeral Muscular Dystrophy |
| Actual Study Start Date : | November 2016 |
| Actual Primary Completion Date : | September 17, 2019 |
| Actual Study Completion Date : | October 9, 2019 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: ACE-083 (Part 1, Cohort 1)
ACE-083 150 mg IM, once every 3 weeks for up to 5 doses.
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Drug: ACE-083
Recombinant fusion protein. |
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Experimental: ACE-083 (Part 1, Cohort 2)
ACE-083 200 mg IM, once every 3 weeks for up to 5 doses.
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Drug: ACE-083
Recombinant fusion protein. |
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Experimental: ACE-083 (Part 1, Cohort 3)
ACE-083 up to 250 mg IM, once every 3 weeks for up to 5 doses.
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Drug: ACE-083
Recombinant fusion protein. |
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Experimental: ACE-083 (Part 2, DB-PC, IM tibialis anterior muscle)
Double-Blind, Placebo-Controlled ACE-083 up to 250 mg IM (tibialis anterior muscle) or placebo, once every 3 weeks for up to 9 doses.
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Drug: ACE-083 or placebo
Recombinant fusion protein or normal saline. |
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Experimental: ACE-083 (Part 2, PL, IM tibialis anterior muscle)
Open-Label ACE-083 up to 250 mg IM (tibialis anterior muscle) once every 3 weeks for up to 8 doses.
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Drug: ACE-083
Recombinant fusion protein. |
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Experimental: ACE-083, (Part 2, DB-PC, IM biceps brachii muscle)
Double-Blind, Placebo-Controlled ACE-083 up to 250 mg IM (biceps brachii muscle) or placebo, once every 3 weeks for up to 9 doses.
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Drug: ACE-083 or placebo
Recombinant fusion protein or normal saline. |
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Experimental: ACE-083 (Part 2, OP, biceps brachii muscle)
Open-Label ACE-083 up to 250 mg IM (biceps brachii muscle), once every 3 weeks for up to 8 doses.
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Drug: ACE-083
Recombinant fusion protein. |
- Safety and Tolerability (data collection on the incidence, nature and severity of adverse events). [ Time Frame: From initiation of treatment (Study Day 1) to end-of-study visit (Study Day 141). ]Adverse events will be recorded and coded in accordance with MedDRA v.20,0
- Estimation of systemic exposure to ACE-083 following local intramuscular administration. [ Time Frame: From initiation of treatment (Study Day 1) to end-of-study visit (Study Day 141). ]Bioanlaytical assay for the quantitative of ACE-083 in serum
- Percent change from baseline in strength of injected muscle [ Time Frame: From initiation of treatment (Study Day 1) to end of treatment visit. ]Strength measurements by hand-held or fixed-system dynamometry (quantitative muscle testing).
- Percent change from baseline in function of injected muscle [ Time Frame: From initiation of treatment (Study Day 1) to end-of-study visit (Study Day 141). ]Function assessed by a battery of motor function tests; 4-stair climb, 6-minute walk test, gait analysis and performance of the upper limb (PUL) test
- Change from baseline in patient-reported outcome (PRO) measures [ Time Frame: From initiation of treatment (Study Day 1) to end-of-study visit (Study Day 141). ]PRO assessed by health-related quality of life and disease burden, as measured by the FSHD Health Index questionnaire (FSHD-HI).
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Key Inclusion Criteria:
- Age ≥ 18 years
- Genetically-confirmed FSHD1 or FSHD2 (or a first-degree relative with genetically confirmed FSHD1 or FSHD2) and clinical findings meeting FSHD criteria
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Part 1 TA cohorts:
- 6-minute walk distance (6MWD) ≥ 150 meters (without a brace)
- 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:
- 6MWD ≥ 150 and ≤ 500 meters (without a brace)
- 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
- 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:
- 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
- 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
- Renal impairment (serum creatinine ≥ 2 times the upper limit of normal [ULN])
- Aspartate transaminase (AST) and/or alanine transaminase (ALT) ≥ 3 times ULN
- 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)
- Major surgery within 4 weeks prior to Study Day 1
- 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
- Androgens or growth hormone within 6 months before Study Day 1 and for duration of study; topical physiologic androgen replacement is permitted
- 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)
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02927080
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| Responsible Party: | Acceleron Pharma, Inc. |
| ClinicalTrials.gov Identifier: | NCT02927080 |
| Other Study ID Numbers: |
A083-02 ACE-083 ( Other Identifier: Acceleron Pharma Inc. ) |
| First Posted: | October 6, 2016 Key Record Dates |
| Last Update Posted: | November 6, 2019 |
| Last Verified: | November 2019 |
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FSHD |
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Muscular Dystrophies Muscular Dystrophy, Facioscapulohumeral Muscular Disorders, Atrophic Muscular Diseases |
Musculoskeletal Diseases Neuromuscular Diseases Nervous System Diseases Genetic Diseases, Inborn |