Study of ACE-083 in Patients With Facioscapulohumeral Muscular Dystrophy (FSHD)
Facioscapulohumeral Muscular Dystrophy
About this trial
This is an interventional treatment trial for Facioscapulohumeral Muscular Dystrophy focused on measuring FSHD
Eligibility Criteria
Key Inclusion Criteria:
- 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:
- 6-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:
- 6MWD ≥ 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.
Key Exclusion Criteria:
- 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)
Sites / Locations
- University of California Los Angeles Medical Center
- University of California Davis Medical Center
- University of Colorado
- Indiana University School of Medicine
- University of Iowa
- University of Kansas Medical Center
- Johns Hopkins Hugo W. Moser Research Inst. at Kennedy Krieger Inc.
- Brigham & Women's Hospital
- University of Minnesota
- Washington University School of Medicine
- University of Rochester School of Medicine
- Carolinas Healthcare System Neurosciences Institute
- Duke University Medical Center
- The Ohio State University
- Oregon Health & Science University
- University of Pennsylvania
- University of Utah
- Virginia Commonwealth University
- University of Calgary
- London Health Sciences Centre
- Montreal Neurological Institute & Hospital
- Hospital Universitario Vall d'Hebrón
- Hospital de la Santa Creu i Sant Pau
- Hospital Universitario y Politécnico La Fe
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm 8
Arm 9
Arm 10
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Placebo Comparator
Experimental
Placebo Comparator
Experimental
ACE-083 (Part 1, Cohort 1a) Tibialis Anterior (TA) 150mg
ACE-083 (Part 1, Cohort 2a) Tibialis Anterior (TA) 200mg
ACE-083 (Part 1, Cohort 3a) Tibialis Anterior (TA) 200mg
ACE-083 (Part 1, Cohort 1b) Biceps Brachii (BB) 150 mg
ACE-083 (Part 1, Cohort 2b) Biceps Brachii (BB) 200 mg
ACE-083 (Part 1, Cohort 3b) Biceps Brachii (BB) 240 mg
Placebo (Part 2, DB-PC) Tibialis Anterior (TA)
ACE-083 (Part 2, DB-PC) Tibialis Anterior (TA) 240 mg
Placebo (Part 2, DB-PC) Biceps Brachii (BB)
ACE-083 (Part 2, DB-PC) Biceps Brachii (BB) 240 mg
ACE-083 150 mg TA unilaterally, once every 3 weeks for up to 5 doses. Drug: ACE-083 Recombinant fusion protein
ACE-083 200 mg TA unilaterally, once every 3 weeks for up to 5 doses. Drug: ACE-083 Recombinant fusion protein
ACE-083 200 mg TA bilaterally, once every 3 weeks for up to 5 doses. Drug: ACE-083 Recombinant fusion protein
ACE-083 150 mg BB unilaterally, once every 3 weeks for up to 5 doses. Drug: ACE-083 Recombinant fusion protein
ACE-083 200 mg BB unilaterally, once every 3 weeks for up to 5 doses. Drug: ACE-083 Recombinant fusion protein
ACE-083 240 mg BB unilaterally, once every 3 weeks for up to 5 doses. Drug: ACE-083 Recombinant fusion protein
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
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
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
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