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

NCT ID: NCT02927080

Last Updated: 2022-09-26

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 95 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-11-30
• Study Completion Date: 2019-10-09

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.

Detailed Description

Part 1 (dose escalation, open-label) Part 1 will consist of up to 6 cohorts of patients and will evaluate multiple ascending dose levels of ACE-083 administered unilaterally or bilaterally to either the tibialis anterior (TA) or biceps brachii (BB) muscle(s). 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 of the next cohort. 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.

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 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

Conditions

Facioscapulohumeral Muscular Dystrophy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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

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

Group Type: EXPERIMENTAL

ACE-083

Intervention Type: DRUG

Recombinant fusion protein.

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

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

Group Type: EXPERIMENTAL

ACE-083

Intervention Type: DRUG

Recombinant fusion protein.

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

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

Group Type: EXPERIMENTAL

ACE-083

Intervention Type: DRUG

Recombinant fusion protein.

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

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

Group Type: EXPERIMENTAL

ACE-083

Intervention Type: DRUG

Recombinant fusion protein.

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

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

Group Type: EXPERIMENTAL

ACE-083

Intervention Type: DRUG

Recombinant fusion protein.

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

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

Group Type: EXPERIMENTAL

ACE-083

Intervention Type: DRUG

Recombinant fusion protein.

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

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

Group Type: PLACEBO_COMPARATOR

ACE-083 or placebo

Intervention Type: DRUG

Recombinant fusion protein or normal saline.

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

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

Group Type: EXPERIMENTAL

ACE-083

Intervention Type: DRUG

Recombinant fusion protein.

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

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

Group Type: PLACEBO_COMPARATOR

ACE-083 or placebo

Intervention Type: DRUG

Recombinant fusion protein or normal saline.

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

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

Group Type: EXPERIMENTAL

ACE-083

Intervention Type: DRUG

Recombinant fusion protein.

Interventions

ACE-083

Recombinant fusion protein.

Intervention Type: DRUG

ACE-083 or placebo

Recombinant fusion protein or normal saline.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Age ≥ 18 years

2. 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

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.

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 anti-coagulation/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)

• 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 Los Angeles Medical Center

Los Angeles, California, United States

University of California Davis Medical Center

Sacramento, California, United States

University of Colorado

Aurora, Colorado, United States

Indiana University School of Medicine

Indianapolis, Indiana, United States

University of Iowa

Iowa City, Iowa, United States

University of Kansas Medical Center

Kansas City, Kansas, United States

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

Baltimore, Maryland, 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

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

The Ohio State University

Columbus, Ohio, 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 Universitario Vall d'Hebrón

Barcelona, , Spain

Hospital de la Santa Creu i Sant Pau

Barcelona, , Spain

Hospital Universitario y Politécnico La Fe

Valencia, , Spain

Countries

United States; Canada; Spain

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

ACE-083

Identifier Type: OTHER

Identifier Source: secondary_id

A083-02

Identifier Type: -

Identifier Source: org_study_id