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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2017 by Acceleron Pharma, Inc.
Sponsor:
Information provided by (Responsible Party):
Acceleron Pharma, Inc.
ClinicalTrials.gov Identifier:
NCT02927080
First received: October 5, 2016
Last updated: May 16, 2017
Last verified: May 2017
  Purpose
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.

Condition Intervention Phase
Facioscapulohumeral Muscular Dystrophy
Drug: ACE-083
Drug: ACE-083 or placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Participant, Investigator
Primary Purpose: Treatment
Official Title: A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study of ACE-083 in Patients With Facioscapulohumeral Muscular Dystrophy

Resource links provided by NLM:


Further study details as provided by Acceleron Pharma, Inc.:

Primary Outcome Measures:
  • 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). ]

Secondary Outcome Measures:
  • 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) ]

Estimated Enrollment: 76
Study Start Date: November 2016
Estimated Study Completion Date: April 2019
Estimated Primary Completion Date: January 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ACE-083 (Part 1, Cohort 1)
ACE-083 150 mg IM, once every 3 weeks for up to 5 doses.
Drug: ACE-083
Recombinant fusion protein.
Experimental: ACE-083 (Part 1, Cohort 2)
ACE-083 200 mg IM, once every 3 weeks for up to 5 doses.
Drug: ACE-083
Recombinant fusion protein.
Experimental: ACE-083 (Part 1, Cohort 3)
ACE-083 up to 250 mg IM, once every 3 weeks for up to 5 doses.
Drug: ACE-083
Recombinant fusion protein.
Experimental: ACE-083 or placebo (Part 2, Cohort 1)
ACE-083 up to 250 mg IM (tibialis anterior muscle) or placebo, once every 3 weeks for up to 5 doses.
Drug: ACE-083 or placebo
Recombinant fusion protein or buffer solution.
Experimental: ACE-083 or placebo (Part 2, Cohort 2)
ACE-083 up to 250 mg IM (biceps brachii muscle) or placebo, once every 3 weeks for up to 5 doses.
Drug: ACE-083 or placebo
Recombinant fusion protein or buffer solution.

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) 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 40 new patients (20 patients per muscle) may be enrolled and randomized (3:2) to receive either ACE-083 (n=12) or placebo (n=8) unilaterally or bilaterally (if both sides are affected per inclusion criteria) to either the TA or BB muscles (but not both). The SRT will meet to review Part 2 patient safety data after the first 10 patients reach Day 43 in the study and approximately every 3 months thereafter.

Study duration for Parts 1 and 2 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

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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. For tibialis anterior (TA) cohorts:

    1. Able to walk independently for at least 10 meters, without a brace
    2. Mild to moderate weakness in left and/or right ankle dorsiflexion

    Note: Opposite side must not be severely affected.

    For biceps brachii (BB) cohorts: 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. 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.
  5. Ability to adhere to the study visit schedule/procedures, and to understand and comply with protocol requirements
  6. Signed written informed consent

Key Exclusion Criteria:

  1. History 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. Systemic corticosteroids within 2 weeks before Study Day 1 and for duration of study; inhaled therapeutic or physiologic doses of corticosteroids are permitted
  8. Any change in medications potentially affecting muscle function within 4 weeks of Study Day 1 and for duration of study
  9. Previous exposure to any marketed or investigational agent potentially affecting muscle volume, strength, or function within 5 half-lives of last dose or 4 weeks of Study Day 1 if half-life is unknown, or any prior exposure to ACE-083
  10. 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
  11. 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)
  12. Known active substance abuse, including alcohol
  13. History of sensitivity to protein pharmaceuticals
  14. Female that is lactating/breast-feeding
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02927080

Contacts
Contact: Clinical Trial Manager clinicaltrials083@acceleronpharma.com

Locations
United States, California
University of California Los Angeles Medical Center Recruiting
Los Angeles, California, United States
Contact: Angela Ho, CRC    310-825-3264    ALHo@mednet.ucla.edu   
Principal Investigator: Perry Shieh, MD         
University of California Davis Medical Center Recruiting
Sacramento, California, United States
Contact: Colleen Anthonisen, CRC       canthonisen@ucdavis.edu   
Principal Investigator: Nanette Joyce, MD         
United States, Kansas
University of Kansas Medical Center Recruiting
Kansas City, Kansas, United States
Contact: Ayla McCalley, CRC    913-945-9937    amccalley2@kumc.edu   
Principal Investigator: Jeffrey Statland, MD         
United States, Massachusetts
Brigham & Women's Hospital Recruiting
Boston, Massachusetts, United States
Contact: Kristen Roe       kroe@partners.org   
Principal Investigator: Anthony Amato, MD         
United States, Minnesota
University of Minnesita Not yet recruiting
Minneapolis, Minnesota, United States
Contact: Paul & Sheila Wellstone Muscular Dystrophy Center    612-626-0822    mdcenter@umn.edu   
Principal Investigator: Georgios Manousakis, MD         
United States, Missouri
Washington University School of Medicine Recruiting
Saint Louis, Missouri, United States
Contact: Julaine Florence    314-362-6983      
Principal Investigator: Alan Pestronk, MD         
United States, New York
University of Rochester School of Medicine Recruiting
Rochester, New York, United States
Contact: Leann Lewis    585-275-7680      
Principal Investigator: Rabi Tawil, MD         
United States, North Carolina
Carolinas Healthcare System Neurosciences Institute Recruiting
Charlotte, North Carolina, United States
Contact: Lisa Ranzinger    704-446-0803      
Principal Investigator: Elena Bravver, MD         
United States, Ohio
The Ohio State University Recruiting
Columbus, Ohio, United States
Contact: Julie Agriesti    614-293-4098    Julie.Agriesti@osumc.edu   
Principal Investigator: John Kissel, MD         
United States, Oregon
Oregon Health & Science University Recruiting
Portland, Oregon, United States
Contact: Diana Dimitrova, CRC    503-494-7269    dimitrov@ohsu.edu   
Principal Investigator: Chafic Karam, MD         
United States, Pennsylvania
University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States
Contact: Lauren Elman, MD       Lauren.Elman@uphs.upenn.edu   
Principal Investigator: Lauren Elman, MD         
United States, Utah
University of Utah Recruiting
Salt Lake City, Utah, United States
Contact: Bryant Gordon, CRC    801-585-5052    bryant.gordon@genetics.utah.edu   
Principal Investigator: Nicholas Johnson, MD         
Canada, Alberta
University of Calgary Recruiting
Calgary, Alberta, Canada
Contact: Jose Martinez    403-210-7009    jamarti@ucalgary.ca   
Principal Investigator: Lawrence Korngut, MD         
Canada, Ontario
London Health Sciences Centre Not yet recruiting
London, Ontario, Canada
Contact: Rhiannon Hicks    519-685-8441    Rhiannon.hicks@lhsc.on.ca   
Principal Investigator: Craig Campbell, MD         
Sponsors and Collaborators
Acceleron Pharma, Inc.
  More Information

Responsible Party: Acceleron Pharma, Inc.
ClinicalTrials.gov Identifier: NCT02927080     History of Changes
Other Study ID Numbers: A083-02
ACE-083 ( Other Identifier: Acceleron Pharma Inc. )
Study First Received: October 5, 2016
Last Updated: May 16, 2017

Keywords provided by Acceleron Pharma, Inc.:
FSHD

Additional relevant MeSH terms:
Muscular Dystrophies
Muscular Dystrophy, Facioscapulohumeral
Muscular Disorders, Atrophic
Muscular Diseases
Musculoskeletal Diseases
Neuromuscular Diseases
Nervous System Diseases
Genetic Diseases, Inborn

ClinicalTrials.gov processed this record on May 25, 2017