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

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ClinicalTrials.gov Identifier: NCT02927080
Recruitment Status : Active, not recruiting
First Posted : October 6, 2016
Last Update Posted : April 8, 2019
Sponsor:
Information provided by (Responsible Party):
Acceleron Pharma, Inc.

Tracking Information
First Submitted Date  ICMJE October 5, 2016
First Posted Date  ICMJE October 6, 2016
Last Update Posted Date April 8, 2019
Study Start Date  ICMJE November 2016
Estimated Primary Completion Date March 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 27, 2018)
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
Original Primary Outcome Measures  ICMJE
 (submitted: October 5, 2016)
  • Part 1: Safety and Tolerability (adverse events) [ Time Frame: From initiation of treatment (Study Day 1) to end of follow-up period (Study Day 141). ]
  • Part 2: Percent change from baseline in muscle volume of injected muscle by MRI [ Time Frame: From initiation of treatment (Study Day 1) to end of follow-up period (Study Day 141). ]
Change History Complete list of historical versions of study NCT02927080 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 27, 2018)
  • 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).
Original Secondary Outcome Measures  ICMJE
 (submitted: October 5, 2016)
  • Estimation of systemic exposure to ACE-083 by quantitative LC-MS assay of serum samples following local intramuscular administration [ Time Frame: From initiation of treatment (Study Day 1) to end of follow-up period (Study Day 141) ]
  • Percent change from baseline in strength of injected muscle by quantitative muscle testing [ Time Frame: From initiation of treatment (Study Day 1) to end of treatment visit (Study Day 106) ]
  • Percent change from baseline in function of injected muscle by motor function tests [ Time Frame: From initiation of treatment (Study Day 1) to end of treatment visit (Study Day 106) ]
  • Change from baseline in Health-Related-Quality-of-Life (HRQoL) by FSHD-Health Index questionnaire [ Time Frame: From initiation of treatment (Study Day 1) to end of treatment visit (Study Day 106) ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of ACE-083 in Patients With Facioscapulohumeral Muscular Dystrophy (FSHD)
Official Title  ICMJE A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study of ACE-083 in Patients With Facioscapulohumeral Muscular Dystrophy
Brief 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.
Detailed Description

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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Facioscapulohumeral Muscular Dystrophy
Intervention  ICMJE
  • Drug: ACE-083
    Recombinant fusion protein.
  • Drug: ACE-083 or placebo
    Recombinant fusion protein or normal saline.
Study Arms  ICMJE
  • Experimental: ACE-083 (Part 1, Cohort 1)
    ACE-083 150 mg IM, once every 3 weeks for up to 5 doses.
    Intervention: Drug: ACE-083
  • Experimental: ACE-083 (Part 1, Cohort 2)
    ACE-083 200 mg IM, once every 3 weeks for up to 5 doses.
    Intervention: Drug: ACE-083
  • Experimental: ACE-083 (Part 1, Cohort 3)
    ACE-083 up to 250 mg IM, once every 3 weeks for up to 5 doses.
    Intervention: Drug: ACE-083
  • 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.
    Intervention: Drug: ACE-083 or placebo
  • 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.
    Intervention: Drug: ACE-083
  • 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.
    Intervention: Drug: ACE-083 or placebo
  • 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.
    Intervention: Drug: ACE-083
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: April 4, 2019)
58
Original Estimated Enrollment  ICMJE
 (submitted: October 5, 2016)
76
Estimated Study Completion Date  ICMJE June 2020
Estimated Primary Completion Date March 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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:

    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 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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02927080
Other Study ID Numbers  ICMJE A083-02
ACE-083 ( Other Identifier: Acceleron Pharma Inc. )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Acceleron Pharma, Inc.
Study Sponsor  ICMJE Acceleron Pharma, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Acceleron Pharma, Inc.
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP