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)

NCT ID: NCT03943290

Last Updated: 2022-09-26

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 62 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-05-10
• Study Completion Date: 2020-03-11

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.

Detailed Description

Part 1 (6-month, non-randomized, open-label, loading phase for subjects from A083-02 Part 1 and A083-03 Part 1) Part 1 will consist of 3 cohorts of up to 18 subjects each. Subjects enrolled in Cohorts 1a and 1b will have completed Part 1 of Study A083-02; subjects enrolled in Cohort 1c will have completed Part 1 of Study A083-03. In this loading phase, 240 mg/muscle ACE-083 will be administered bilaterally every 4 weeks (q4w) for 6 doses (6 months) into either the tibialis anterior (TA) muscle or the biceps brachii (BB) muscle, depending on the muscle injected in the previous study; subjects may not switch muscle cohort upon enrollment in this study. Subjects will participate in a screening period of up to 4 weeks before receiving the first dose of ACE-083.

Part 2 (24-month, randomized, open-label rollover maintenance phase for subjects from A083-02 Part 2, A083-03 Part 2, and A083-04 Part 1) Subjects who complete Part 1 of this study (the loading phase), Part 2 of A083-02, or Part 2 of A083-03 will enroll directly into the Part 2 open-label maintenance phase of treatment with ACE-083 and will consist of 6 cohorts of up to 23 FSHD or 29 CMT subjects each. These subjects will be randomized (1:1) to receive ACE-083, 240 mg/muscle bilaterally, either q4w or q8w. Thus, subjects enrolled in Cohorts 2a, 2b, and 2c will be FSHD TA, FSHD BB, and CMT TA treated q4w, and subjects enrolled in Cohorts 3a, 3b, and 3c will be FSHD TA, FSHD BB, and CMT TA treated q8w.

Study duration for a subject initially enrolled in Part 1 and then extended to Part 2 will be approximately 33 months, including a 1-month screening period, 6-month Part 1 loading phase, 24-month Part 2 maintenance phase, and 2-month follow-up period.

For subjects who enrolled directly into Part 2 of this study from Part 2 of Studies A083-02 and A083-03, the duration of the study will be approximately 26 months, including a 24-month maintenance phase and a 2-month follow-up period.

Conditions

Facioscapulohumeral Muscular Dystrophy; Charcot-Marie-Tooth Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part 1 Cohort 1a

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

Group Type: EXPERIMENTAL

ACE-083

Intervention Type: DRUG

Recombinant fusion protein

Part 1 Cohort 1b

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

Group Type: EXPERIMENTAL

ACE-083

Intervention Type: DRUG

Recombinant fusion protein

Part 1 Cohort 1c

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

Group Type: EXPERIMENTAL

ACE-083

Intervention Type: DRUG

Recombinant fusion protein

Part 2 Cohort 2a

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

Group Type: EXPERIMENTAL

ACE-083

Intervention Type: DRUG

Recombinant fusion protein

Part 2 Cohort 2b

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

Group Type: EXPERIMENTAL

ACE-083

Intervention Type: DRUG

Recombinant fusion protein

Part 2 Cohort 2c

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

Group Type: EXPERIMENTAL

ACE-083

Intervention Type: DRUG

Recombinant fusion protein

Part 2 Cohort 3a

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

Group Type: EXPERIMENTAL

ACE-083

Intervention Type: DRUG

Recombinant fusion protein

Part 2 Cohort 3b

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

Group Type: EXPERIMENTAL

ACE-083

Intervention Type: DRUG

Recombinant fusion protein

Part 2 Cohort 3c

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

Group Type: EXPERIMENTAL

ACE-083

Intervention Type: DRUG

Recombinant fusion protein

Interventions

ACE-083

Recombinant fusion protein

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. 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.

2. 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.

3. Ability to adhere to the study visit schedule/procedures and to understand and comply with protocol requirements

4. Signed written informed consent

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. 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

3. Type 1 or type 2 diabetes mellitus

4. 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

5. Renal impairment (serum creatinine ≥ 2 times the upper limit of normal [ULN])

6. Aspartate transaminase (AST) and/or alanine transaminase (ALT) ≥ 3 times ULN

7. 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)

8. Severe deformity or ankle fixation that would sufficiently limit passive range of motion to affect functional assessments (TA patients only)

9. Major surgery within 4 weeks prior to Study Day 1

10. 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

11. 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

12. 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)

13. 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)

14. 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

15. 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)

16. Known active substance abuse, including alcohol

17. History of sensitivity to protein pharmaceuticals

18. Female that is pregnant or lactating/breast-feeding

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

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

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University of California-Irvine

Orange, California, United States

University of California Davis Medical Center

Sacramento, California, United States

University of Colorado

Aurora, Colorado, United States

University of Florida

Gainesville, Florida, United States

Indiana University

Indianapolis, Indiana, United States

University of Iowa

Iowa City, Iowa, United States

University of Kansas Medical Center

Kansas City, Kansas, United States

Brigham & Women's Hospital

Boston, Massachusetts, United States

University of Minnesota

Minneapolis, Minnesota, United States

Washington University School of Medicine

St Louis, Missouri, United States

Hackensack University Medical Center

Hackensack, New Jersey, United States

Columbia University

New York, New York, United States

University of Rochester School of Medicine

Rochester, New York, United States

Carolinas Healthcare System Neurosciences Institute

Charlotte, North Carolina, United States

Duke University Medical Center

Durham, North Carolina, United States

Oregon Health & Science University

Portland, Oregon, United States

University of Pennsylvania

Philadelphia, Pennsylvania, United States

University of Utah

Salt Lake City, Utah, United States

Virginia Commonwealth University

Richmond, Virginia, United States

University of Calgary

Calgary, Alberta, Canada

London Health Sciences Centre

London, Ontario, Canada

Montreal Neurological Institute & Hospital

Montreal, Quebec, Canada

Hospital de la Santa Creu i Sant Pau

Barcelona, , Spain

Hospital Universitario Vall d'Hebrón

Barcelona, , Spain

Countries

United States; Canada; Spain

Provided Documents

Document Type: Study Protocol

View Document

Other Identifiers

ACE-083

Identifier Type: OTHER

Identifier Source: secondary_id

A083-04

Identifier Type: -

Identifier Source: org_study_id