Extension Study to Evaluate the Long-Term Effects of ACE-083 in Patients With Facioscapulohumeral Muscular Dystrophy (FSHD) and Charcot-Marie Tooth (CMT) Disease Types 1 and X (CMT1 and CMTX)

NCT03943290 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: A083-04ACE-083
• Study Type: interventional
• Target: 62
• Locations: 3 countries
• Sites: 24

Brief Summary

This is an open-label, multicenter, phase 2 extension study to evaluate the safety, tolerability, PK, PD, and efficacy of ACE-083 in subjects with FSHD previously enrolled in Study A083-02 and subjects with CMT1 and CMTX previously enrolled in Study A083-03. This study will be conducted in two Parts: Part 1, which is a loading phase of 6 months' duration, and Part 2, the maintenance phase, which will last up to 24 months.

Conditions

Charcot-Marie-Tooth Disease; Facioscapulohumeral Muscular Dystrophy

Outcome Measures

Primary Outcomes (3)

• Part 2- Frequency of Adverse Events - Presence and Nature of Adverse Events (AE) During Part 2

  The number of participants that had a least one Treatment Emergent Adverse Event during the Part 2 of the study. The pre-specified analysis for this outcome measure was for those participants in the part 2 cohorts of this study therefore, only data of part 2 portion of the study are reported.

  From baseline to end of participation of the Part 2 portion of the study

• Part 2: Frequency of Adverse Events - Presence and Nature of Grade 3 or Higher Adverse Events (AE) During the Part 2 of the Study.

  The number of participants that had a least one grade 3 or higher Treatment Emergent Adverse Event during Part 2 of the study. The pre-specified analysis for this outcome measure was for those participants in the double-blind, placebo-controlled Part 2 of the study therefore, only data from the part 2 portion of the study are reported.

  From baseline to the end of the part 2 portion of the study

• Part 2: Change in Total Muscle Volume - Percent Change From Baseline to Day 113 in Total Muscle Volume of Injected Muscle by Magnetic Resonance Imaging (MRI) During the Part 2 Portion

  The primary pharmacodynamic variable was the difference in mean percent change in total muscle volume (average of left and right side) at the first 6 months of the maintenance phase (Day 169; q4w or q8w) from the total muscle volume (average of left and right sides) at the start of the maintenance phase (or equivalently the end of the loading phase). Due to the early termination of this trial, percent change is only able to be reported as percent change from baseline to Day 113. The pre-specified analysis for this outcome measure was for those participants in the part 2 portion in cohorts with data to Day 113. Therefore, only data from these part 2 arms- 2b, 2c, 3b and 3c of the study are reported.

  During the Part 2 portion of the study: Baseline to Day 113

Secondary Outcomes (20)

• Part 2: Change in Muscle Function. Absolute Change From Baseline in Functional Assessment for Tibialis Anterior (TA) Muscle:10-meter Walk/Run During Part 2 of the Study

  Baseline and End of Treatment visit for Part 2 of the study

• Part 2: Change in Muscle Function. Percent Change From Baseline in Functional Assessment for Tibialis Anterior (TA) Muscle:10-meter Walk/Run During Part 2 of the Study

  Baseline and End of Treatment visit for Part 2 of the study

• Part 2: Change in Muscle Function. Absolute Change From Baseline in Functional Assessment for Tibialis Anterior (TA) Muscle: 6-minute Walk Test

  Baseline and End of Treatment Visit during Part 2 of the study

• Part 2: Change in Muscle Function - Percent Change From Baseline in Functional Assessment for Tibialis Anterior (TA) Muscle in 6-minute Walk Test

  Baseline and End of Treatment visit during Part 2 of the study

• Part 2: Change in Muscle Function. Absolute Change From Baseline in Functional Assessment for Tibialis Anterior (TA) Muscle: 4-stair Climb Up (in Participants With FSHD Only)

  Baseline, End of Treatment visit during Part 2

Study Arms (9)

Part 1 Cohort 1a

EXPERIMENTAL

ACE-083 240 mg/muscle administered bilaterally by injection into the TA muscle every 4 weeks for up to 6 doses for FSHD patients

Drug: ACE-083

Part 1 Cohort 1b

EXPERIMENTAL

ACE-083 240 mg/muscle administered bilaterally by injection into the BB muscle every 4 weeks for up to 6 doses for FSHD patients

Drug: ACE-083

Part 1 Cohort 1c

EXPERIMENTAL

ACE-083 240 mg/muscle administered bilaterally by injection into the TA muscle every 4 weeks for up to 6 doses for CMT patients

Drug: ACE-083

Part 2 Cohort 2a

EXPERIMENTAL

ACE-083 Administered into the TA muscle q4w for up to 24 months (24 doses) for FSHD patients

Drug: ACE-083

Part 2 Cohort 2b

EXPERIMENTAL

ACE-083 Administered into the BB muscle q4w for up to 24 months (24 doses) for FSHD patients

Drug: ACE-083

Part 2 Cohort 2c

EXPERIMENTAL

ACE-083 Administered into the TA muscle q4w for up to 24 months (24 doses) for CMT patients

Drug: ACE-083

Part 2 Cohort 3a

EXPERIMENTAL

ACE-083 Administered into the TA muscle q8w for up to 24 months (12 doses) for FSHD patients

Drug: ACE-083

Part 2 Cohort 3b

EXPERIMENTAL

ACE-083 Administered into the BB muscle q8w for up to 24 months (12 doses) for FSHD patients

Drug: ACE-083

Part 2 Cohort 3c

EXPERIMENTAL

ACE-083 Administered into the TA muscle q8w for up to 24 months (12 doses) for CMT patients

Drug: ACE-083

Interventions

ACE-083 DRUG

Recombinant fusion protein

Part 1 Cohort 1a; Part 1 Cohort 1b; Part 1 Cohort 1c; Part 2 Cohort 2a; Part 2 Cohort 2b; Part 2 Cohort 2c; Part 2 Cohort 3a; Part 2 Cohort 3b; Part 2 Cohort 3c

Eligibility Criteria

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

You may qualify if:

• Completion of treatment with study drug per protocol and completion of the end of treatment (ET) visit in Study A083-02 or Study A083-03.
• Females of childbearing potential (defined as sexually mature women who have not undergone hysterectomy or bilateral oophorectomy or are not naturally postmenopausal ≥ 24 consecutive months) must have negative urine pregnancy test prior to enrollment and use highly effective birth control methods (abstinence, oral contraceptives, barrier method with spermicide, or surgical sterilization) during study participation and for 8 weeks following the last dose of ACE-083. 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 and for 8 weeks following the last dose of ACE-083, even if they have undergone a vasectomy. Subjects must be counseled about contraception prior to the first dose of ACE-083 and every three months thereafter during the study.
• Ability to adhere to the study visit schedule/procedures and to understand and comply with protocol requirements
• Signed written informed consent

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
• Co-morbidities, including symptomatic cardiopulmonary disease, significant orthopedic or neuropathic pain, or other conditions that, in the opinion of the investigator, would limit a subject's ability to complete strength and/or functional assessments
• Type 1 or type 2 diabetes mellitus
• Thyroid disorder unless condition is stable with no change in treatment for at least 4 weeks before the first dose and no expected change for duration of 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 and for duration of study; single agent low dose aspirin \[≤ 100 mg daily\] is permitted)
• Severe deformity or ankle fixation that would sufficiently limit passive range of motion to affect functional assessments (TA patients only)
• Major surgery within 4 weeks prior to Study Day 1
• Chronic pharmacologic doses of systemic corticosteroids (≥ 2 weeks) within 4 weeks before Study Day 1 and for duration of study; intra-articular/topical/inhaled/intranasal physiologic doses of systemic corticosteroids are permitted
• Androgens, growth hormone, insulin or oral hormone replacement therapy within 6 months before Study Day 1 and for duration of study; topical physiologic androgen replacement is permitted. Chronic insulin therapy is permitted for diabetic FSHD patients. Oral HRT is permitted if started at least 3 months prior to receiving study drug
• Any change in medications potentially affecting muscle strength or function within 4 weeks of Study Day 1 and for duration of study (e.g., creatinine, CoQ10, systemic beta-adrenergic agonists)
• Previous exposure to any other investigational agent (not including ACE-083) potentially affecting muscle volume, muscle strength, or muscle or nerve function within 5 half-lives of last dose plus an additional 8-week washout period (or 12 weeks prior to Study Day 1 if half-life is unknown)
• 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
• Any condition that would prevent MRI scanning or compromise the ability to obtain a clear and interpretable scan of the treated muscles (e.g., knee/hip replacement 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-Irvine

Orange, California, 92697, United States

Location

University of California Davis Medical Center

Sacramento, California, 95817, United States

Location

University of Colorado

Aurora, Colorado, 80045, United States

Location

University of Florida

Gainesville, Florida, 32611, United States

Location

Indiana University

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

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

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Columbia University

New York, New York, 10027, United States

Location

University of Rochester School of Medicine

Rochester, New York, 14642, United States

Location

Carolinas Healthcare System Neurosciences Institute

Charlotte, North Carolina, 28207, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, 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, 23284, United States

Location

University of Calgary

Calgary, Alberta, Canada

Location

London Health Sciences Centre

London, Ontario, Canada

Location

Montreal Neurological Institute & Hospital

Montreal, Quebec, Canada

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, Spain

Location

Hospital Universitario Vall d'Hebrón

Barcelona, Spain

Location

MeSH Terms

Conditions

Muscular Dystrophy, Facioscapulohumeral; Charcot-Marie-Tooth Disease

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; Hereditary Sensory and Motor Neuropathy; Nervous System Malformations; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Polyneuropathies; Peripheral Nervous System Diseases; Congenital Abnormalities

Limitations and Caveats

In this open-label, multicenter, phase 2 extension study in participants with FSHD and CMT (types 1 and X), treatment with ACE-083 q4w or q8w was generally safe and well tolerated. Participants were discontinued from this study when their respective parent studies were terminated by the sponsor, and as such, this study was also terminated. Due to premature termination of this study, insufficient efficacy data were obtained to enable meaningful efficacy analyses.

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
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 17, 2019
• First Posted: May 9, 2019
• Study Start: May 10, 2019
• Primary Completion: March 11, 2020
• Study Completion: March 11, 2020
• Last Updated: September 26, 2022
• Results First Posted: June 2, 2021

Record last verified: 2022-09

Locations

CA (3); ES (2); US (19)