Summary

for people ages 18 years and up (full criteria)
at UCLA UC Davis
study started
estimated completion:
(ucla) (ucdavis)

Description

Summary

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

Official Title

A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study of ACE-083 in Patients With Facioscapulohumeral Muscular Dystrophy

Details

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

Keywords

Facioscapulohumeral Muscular Dystrophy FSHD Muscular Dystrophies Muscular Dystrophy, Facioscapulohumeral

Eligibility

For people ages 18 years and up

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. Part 1 TA cohorts:
  4. 6-minute walk distance (6MWD) ≥ 150 meters (without a brace)
  5. Mild to moderate weakness in left and/or right ankle dorsiflexion

Part 1 BB cohorts:

  1. 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:

  1. Mild to moderate weakness in left and/or right elbow flexion
  2. 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.

Key Exclusion Criteria:

  1. Histor y 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. 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)

Locations

  • University of California Los Angeles Medical Center accepting new patients
    Los Angeles, California, United States
  • University of California Davis Medical Center accepting new patients
    Sacramento, California, United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Acceleron Pharma, Inc.
ID
NCT02927080
Phase
Phase 2
Lead Scientists
Perry Shieh
Nanette Joyce
Study Type
Interventional
Last Updated
June 5, 2018