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

NCT02927080 | Terminated Phase 2 Results DMC

• 2 other identifiers: A083-02ACE-083
• Study Type: interventional
• Target: 95
• Locations: 3 countries
• Sites: 24

Brief Summary

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

Conditions

Facioscapulohumeral Muscular Dystrophy

Keywords

FSHD

Outcome Measures

Primary Outcomes (5)

• Safety and Tolerability (Incidence of Adverse Events)

  The number of participants that had a least one Treatment Emergent Adverse Event for the duration of each of the respective study parts.

  From initiation of treatment to Day 106 for Part 1 and Day 190 for Part 2

• Safety and Tolerability (Severity of Adverse Events, Grade 3 or Higher).

  The number of participants that had a least one Treatment Emergent Adverse Event with CTCAE Grade 3 or Higher for the duration of each of the respective study parts.

  From initiation of treatment to Day 106 for Part 1 and Day 190 for Part 2

• Safety and Tolerability (Severity of Adverse Events- Dose Interruption, Reduction and/or Drug Withdrawal)

  The number of participants that had a least one Treatment Emergent Adverse Event that led to dose interruption, dose reduction and/or drug withdrawn.

  From initiation of treatment to Day 106 for Part 1 and Day 190 for Part 2

• Total Muscle Volume (TMV) of the Treated Muscle in Patients With FSHD Administered ACE-083 or Placebo During Part 2 (Randomized, Controlled Portion)

  Total Muscle Volume (TMV)of the treated muscle in Patients with FSHD administered ACE-083 or placebo During Part 2 (randomized, controlled portion) from Baseline to Day 190. Total Muscle volume was measured by Magnetic Resonance Imaging (MRI). MRI was performed bilaterally on the tibialis anterior and the biceps brachii on Day 1, Day Day 43, Day 106, and Day 190. Baseline and Day 190 total muscle volume, means and standard deviations are reported.

  Time Frame: From initiation of treatment to Study Visit Day 190

• Percent Change of Total Muscle Volume (TMV) of the Treated Muscle in Patients With FSHD Administered ACE-083 or Placebo During Part 2 (Randomized, Controlled Portion)

  Percent Change of Total Muscle Volume (TMV)of the treated muscle in Patients with FSHD administered ACE-083 or placebo During Part 2 (randomized, controlled portion) from Baseline to Day 190. Total Muscle volume was measured by Magnetic Resonance Imaging (MRI). MRI was performed bilaterally on the tibialis anterior and the biceps brachii on Day 1, Day Day 43, Day 106, and Day 190. Percent Change from Baseline to Day 190 total muscle volume, mean and standard deviation is reported.

  Time Frame: From initiation of treatment to Study Visit Day 190

Secondary Outcomes (14)

• Percent Change in Total Muscle Volume (TMV) in Muscle in Patients With FSHD Administered ACE-083 During Part 1 (Open-label, Dose-escalation Portion)

  Time Frame: From initiation of treatment to Study Visit Day 106

• Absolute Change in Fat Fraction (FF) of the Muscle in Patients With FSHD Administered ACE-083 or Placebo During Part 2 (Randomized, Controlled Portion)

  Time Frame: From initiation of treatment to Study Visit Day 190

• Percent Change From Baseline in Function of Tibialis Anterior, Part 2 (Randomized, Controlled Portion)

  From initiation of treatment (Study Day 1) to Study Visit Day 190

• Percent Change From Baseline in Strength of Biceps Brachii, Part 2, Randomized-controlled

  From initiation of treatment (Study Day 1) to Study Visit Day 190

• Percent Change From Baseline in Performance of the Upper Limb (PUL) Mid-Level Elbow Dimension, Part 2, Randomized-controlled

  From initiation of treatment (Study Day 1) to Study Visit Day 190

Study Arms (10)

ACE-083 (Part 1, Cohort 1a) Tibialis Anterior (TA) 150mg

EXPERIMENTAL

ACE-083 150 mg TA unilaterally, once every 3 weeks for up to 5 doses. Drug: ACE-083 Recombinant fusion protein

Drug: ACE-083

ACE-083 (Part 1, Cohort 2a) Tibialis Anterior (TA) 200mg

EXPERIMENTAL

ACE-083 200 mg TA unilaterally, once every 3 weeks for up to 5 doses. Drug: ACE-083 Recombinant fusion protein

Drug: ACE-083

ACE-083 (Part 1, Cohort 3a) Tibialis Anterior (TA) 200mg

EXPERIMENTAL

ACE-083 200 mg TA bilaterally, once every 3 weeks for up to 5 doses. Drug: ACE-083 Recombinant fusion protein

Drug: ACE-083

ACE-083 (Part 1, Cohort 1b) Biceps Brachii (BB) 150 mg

EXPERIMENTAL

ACE-083 150 mg BB unilaterally, once every 3 weeks for up to 5 doses. Drug: ACE-083 Recombinant fusion protein

Drug: ACE-083

ACE-083 (Part 1, Cohort 2b) Biceps Brachii (BB) 200 mg

EXPERIMENTAL

ACE-083 200 mg BB unilaterally, once every 3 weeks for up to 5 doses. Drug: ACE-083 Recombinant fusion protein

Drug: ACE-083

ACE-083 (Part 1, Cohort 3b) Biceps Brachii (BB) 240 mg

EXPERIMENTAL

ACE-083 240 mg BB unilaterally, once every 3 weeks for up to 5 doses. Drug: ACE-083 Recombinant fusion protein

Drug: ACE-083

Placebo (Part 2, DB-PC) Tibialis Anterior (TA)

PLACEBO COMPARATOR

Part 2, double-blind (DB) placebo-controlled (PC). Placebo TA bilaterally, once every 3 weeks for up to 9 doses. Drug: Placebo Normal saline Afterwards, participants were rolled over into the open-label portion and received ACE-083 240 mg TA bilaterally, once every 3 weeks for up to 8 doses. Drug: ACE-083 Recombinant fusion protein

Drug: ACE-083 or placebo

ACE-083 (Part 2, DB-PC) Tibialis Anterior (TA) 240 mg

EXPERIMENTAL

Part 2, double-blind placebo-controlled. ACE-083 240 mg TA bilaterally, once every 3 weeks for up to 9 doses. Drug: ACE-083 Recombinant fusion protein Afterwards, participants were rolled over into the open-label portion and received ACE-083 240 mg TA bilaterally, once every 3 weeks for up to 8 doses. Drug: ACE-083 Recombinant fusion protein

Drug: ACE-083

Placebo (Part 2, DB-PC) Biceps Brachii (BB)

PLACEBO COMPARATOR

Part 2, double-blind placebo-controlled. Placebo BB bilaterally, once every 3 weeks for up to 9 doses. Drug: Placebo Normal saline Afterwards, participants were rolled over into the open-label portion and received ACE-083 240 mg Biceps Brachii (BB) bilaterally, once every 3 weeks for up to 8 doses. Drug: ACE-083 Recombinant fusion protein

Drug: ACE-083 or placebo

ACE-083 (Part 2, DB-PC) Biceps Brachii (BB) 240 mg

EXPERIMENTAL

Part 2, double-blind placebo-controlled. ACE-083 240 mg Biceps Brachii (BB) bilaterally, once every 3 weeks for up to 9 doses. Drug: ACE-083 Recombinant fusion protein Afterwards, participants were rolled over into the open-label portion and received ACE-083 240 mg Biceps Brachii (BB) bilaterally, once every 3 weeks for up to 8 doses. Drug: ACE-083 Recombinant fusion protein

Drug: ACE-083

Interventions

ACE-083 DRUG

Recombinant fusion protein.

ACE-083 (Part 1, Cohort 1a) Tibialis Anterior (TA) 150mg; ACE-083 (Part 1, Cohort 1b) Biceps Brachii (BB) 150 mg; ACE-083 (Part 1, Cohort 2a) Tibialis Anterior (TA) 200mg; ACE-083 (Part 1, Cohort 2b) Biceps Brachii (BB) 200 mg; ACE-083 (Part 1, Cohort 3a) Tibialis Anterior (TA) 200mg; ACE-083 (Part 1, Cohort 3b) Biceps Brachii (BB) 240 mg; ACE-083 (Part 2, DB-PC) Biceps Brachii (BB) 240 mg; ACE-083 (Part 2, DB-PC) Tibialis Anterior (TA) 240 mg

ACE-083 or placebo DRUG

Recombinant fusion protein or normal saline.

Placebo (Part 2, DB-PC) Biceps Brachii (BB); Placebo (Part 2, DB-PC) Tibialis Anterior (TA)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years
• Genetically confirmed Facioscapulohumeral muscular dystrophy type 1 (FSHD1) or FSHD2 (or a first-degree relative with genetically confirmed FSHD1 or FSHD2) and clinical findings meeting FSHD criteria
• Part 1 TA cohorts:
• 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:
• MWD ≥ 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.

You may not qualify if:

• 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 anti-coagulation/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)

Sponsors & Collaborators

• Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA: lead

Study Sites (24)

University of California Los Angeles Medical Center

Los Angeles, California, 90095, United States

Location

University of California Davis Medical Center

Sacramento, California, 95817, United States

Location

University of Colorado

Aurora, Colorado, 80045, United States

Location

Indiana University School of Medicine

Indianapolis, Indiana, 46202, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Johns Hopkins Hugo W. Moser Research Inst. at Kennedy Krieger Inc.

Baltimore, Maryland, 21205, United States

Location

Brigham & Women's Hospital

Boston, Massachusetts, 02115, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

University of Rochester School of Medicine

Rochester, New York, 14642, United States

Location

Carolinas Healthcare System Neurosciences Institute

Charlotte, North Carolina, 28203, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

The Ohio State University

Columbus, Ohio, 43210, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

University of Utah

Salt Lake City, Utah, 84112, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

University of Calgary

Calgary, Alberta, T2N4Z6, Canada

Location

London Health Sciences Centre

London, Ontario, N6A5W9, Canada

Location

Montreal Neurological Institute & Hospital

Montreal, Quebec, H3A 2B4, Canada

Location

Hospital Universitario Vall d'Hebrón

Barcelona, 08035, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, 08041, Spain

Location

Hospital Universitario y Politécnico La Fe

Valencia, 46026, Spain

Location

MeSH Terms

Conditions

Muscular Dystrophy, Facioscapulohumeral

Condition Hierarchy (Ancestors)

Muscular Dystrophies; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme LLC

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 5, 2016
• First Posted: October 6, 2016
• Study Start: November 1, 2016
• Primary Completion: September 17, 2019
• Study Completion: October 9, 2019
• Last Updated: September 26, 2022
• Results First Posted: April 22, 2021

Record last verified: 2022-09

Locations

CA (3); ES (3); US (18)