Facioscapulohumeral Muscular Dystrophy Clinical Trial
Official title:
A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study of ACE-083 in Patients With Facioscapulohumeral Muscular Dystrophy
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.
Status | Terminated |
Enrollment | 95 |
Est. completion date | October 9, 2019 |
Est. primary completion date | September 17, 2019 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | Key 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. Key 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) |
Country | Name | City | State |
---|---|---|---|
Canada | University of Calgary | Calgary | Alberta |
Canada | London Health Sciences Centre | London | Ontario |
Canada | Montreal Neurological Institute & Hospital | Montréal | Quebec |
Spain | Hospital de la Santa Creu i Sant Pau | Barcelona | |
Spain | Hospital Universitario Vall d'Hebrón | Barcelona | |
Spain | Hospital Universitario y Politécnico La Fe | Valencia | |
United States | University of Colorado | Aurora | Colorado |
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 | Carolinas Healthcare System Neurosciences Institute | Charlotte | North Carolina |
United States | The Ohio State University | Columbus | Ohio |
United States | Duke University Medical Center | Durham | North Carolina |
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 | University of California Los Angeles Medical Center | Los Angeles | California |
United States | University of Minnesota | Minneapolis | Minnesota |
United States | University of Pennsylvania | Philadelphia | Pennsylvania |
United States | Oregon Health & Science University | Portland | Oregon |
United States | Virginia Commonwealth University | Richmond | Virginia |
United States | University of Rochester School of Medicine | Rochester | New York |
United States | University of California Davis Medical Center | Sacramento | California |
United States | Washington University School of Medicine | Saint Louis | Missouri |
United States | University of Utah | Salt Lake City | Utah |
Lead Sponsor | Collaborator |
---|---|
Acceleron Pharma Inc. (a wholly owned subsidiary of Merck Sharp and Dohme, a subsidiary of Merck & Co., Inc.) |
United States, Canada, Spain,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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 | |
Primary | 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 | |
Primary | 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 | |
Primary | 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 | |
Primary | 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 | Percent Change in Total Muscle Volume (TMV) in Muscle in Patients With FSHD Administered ACE-083 During Part 1 (Open-label, Dose-escalation Portion) | Percent Change in Total Muscle Volume (TMV) in muscle in patients with FSHD administered ACE-083 During 1 (open-label, dose-escalation portion) from Baseline to Day 106. 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, and Day 106, change from Baseline and Day 106 reported. | Time Frame: From initiation of treatment to Study Visit Day 106 | |
Secondary | Absolute Change in Fat Fraction (FF) of the Muscle in Patients With FSHD Administered ACE-083 or Placebo During Part 2 (Randomized, Controlled Portion) | Absolute change in Fat Fraction (FF) of the muscle in patients with FSHD administered ACE-083 or Placebo During Part 2 (randomized, controlled portion) from Baseline to Day 190. Absolute change in intramuscular fat fraction in the tibialis anterior and biceps brachii were 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, change from Baseline and Day 190 reported. | Time Frame: From initiation of treatment to Study Visit Day 190 | |
Secondary | Percent Change From Baseline in Function of Tibialis Anterior, Part 2 (Randomized, Controlled Portion) | Percent change from baseline in function of Tibialis Anterior during Part 2 assessed by: 6-minute walk test, 10 meter walk/run and 4-stair climb (ascend) | From initiation of treatment (Study Day 1) to Study Visit Day 190 | |
Secondary | Percent Change From Baseline in Strength of Biceps Brachii, Part 2, Randomized-controlled | Elbow flexion strength measured by hand-held dynamometry (quantitative muscle testing), maximum voluntary isometric contraction (MVIC). | From initiation of treatment (Study Day 1) to Study Visit Day 190 | |
Secondary | Percent Change From Baseline in Performance of the Upper Limb (PUL) Mid-Level Elbow Dimension, Part 2, Randomized-controlled | Percent Change from Baseline in Performance of the Upper Limb (PUL) Mid-Level Elbow Dimension, Part 2, Randomized-controlled, PUL from baseline to end of treatment (Day 190). The Performance of the Upper Limb is an assessment specifically designed for patients with Duchenne muscular dystrophy. The measures used in this study was a subset of the assessment. PUL was assessment by measures of high-level of movement (lifting weights of 50g, 200g, 500g and 1000g at shoulder height and above shoulder height) and mid-level movement by performing tasks with and without weights: hand to mouth with and without weights (50, 200g), hand to table, moving weights on table (100g, 200g, 500g and 1000g), lift light and heavy cans, stack light and heavy cans, remove lid from container, tearing paper). | From initiation of treatment (Study Day 1) to Study Visit Day 190 | |
Secondary | Change From Baseline in Facioscapulohumeral Muscular Dystrophy-health Index (FSHD-HI), Patient-reported Outcome (PRO) Measures Part 2 (Randomized, Controlled Portion)- Total Score | The facioscapulohumeral muscular dystrophy-health index (FSHD-HI) is a disease-specific patient-reported outcome (PRO) tool assessed by health-related quality of life and disease burden. The FSHD-HI questionnaire was designed to measure both overall FSHD health-related quality-of-life and 14 separate subdomains designed and based on patient interviews to measure total FSHD health-related quality-of-life, including both motor impairment and the social and emotional impact of FSHD. The 116 questions are combined into a total score, the score is transformed onto a percentage scale; with a range of 0-100, with 100 representing maximal disability, and lower scores representing decreasing disability, 0 representing no disability. The mean and standard deviation for baseline and day 190 are reported as is the absolute change from baseline to Day 190 during the randomized controlled portion of Part 2. | Time Frame: From initiation of treatment (Study Day 1) to Study Visit Day 190 | |
Secondary | ACE-083 Serum Concentration Following Local Intramuscular Administration (200 mg Tibialis Anterior (TA) Bilaterally) Day 2, 24-hours After Dose | Pharmacokinetic assessment included ACE-083 serum concentration collection and on a dosing day had a ±15 minute window for post-dose sample collection, based on the time of the first injection. Timepoints that have data are reported; Day 2, 24-hours after dose is reported. | Day 2, 24-hours after dose | |
Secondary | ACE-083 Serum Concentration Following Local Intramuscular Administration (200 mg Tibialis Anterior (TA) Bilaterally) Day 85, 6-hours After Dose | Pharmacokinetic assessment included ACE-083 serum concentration and on a dosing day had a ±15 minute window for post-dose sample collection, based on the time of the first injection. The timepoints for which data is available are reported. Day 86, 6-hours post-dose is reported. | Study Day 85 (6 hours post-dose) | |
Secondary | ACE-083 Serum Concentration Following Local Intramuscular Administration (200 mg Biceps Brachii (BB) Unilateral) Day 1, 6-hours Post-dose | Pharmacokinetic assessment included ACE-083 serum concentration and on a dosing day had a ±15 minute window for post-dose sample collection, based on the time of the first injection. The timepoints for which data is available are reported. Day 1, 6-hours post-dose, is reported. | Study Day 1, 6-hours post-dose | |
Secondary | ACE-083 Serum Concentration Following Local Intramuscular Administration (200 mg Biceps Brachii (BB) Unilateral) Day 85, 4-hours Post-dose | Pharmacokinetic assessment included ACE-083 serum concentration and on a dosing day had a ±15 minute window for post-dose sample collection, based on the time of the first injection. The timepoints for which data is available are reported. | Study Day 85, 4-hours post-dose | |
Secondary | ACE-083 Serum Concentration Following Local Intramuscular Administration (240 mg Tibialis Anterior (TA) Bilaterally) Day 2, 24- Hours Post-dose | Pharmacokinetic assessment included ACE-083 serum concentration and on a dosing day had a ±15 minute window for post-dose sample collection, based on the time of the first injection. The timepoints for which data is available are reported. Day 2, 24-hours post-dose is reported. | Day 2, 24-hours post-dose | |
Secondary | ACE-083 Serum Concentration Following Local Intramuscular Administration (240 mg Tibialis Anterior (TA) Bilaterally) Day 86, 24- Hours Post-dose | Pharmacokinetic assessment included ACE-083 serum concentration and on a dosing day had a ±15 minute window for post-dose sample collection, based on the time of the first injection. The timepoints for which data is available are reported. Day 86, 24-hours post-dose is reported. | Day 86, 24-hours post-dose | |
Secondary | ACE-083 Serum Concentration Following Local Intramuscular Administration (240 mg Biceps Brachii (BB) Bilaterally) Day 2, 24- Hours Post-dose | Pharmacokinetic assessment included ACE-083 serum concentration and on a dosing day had a ±15 minute window for post-dose sample collection, based on the time of the first injection. The timepoints for which data is available are reported. Day 2, 24-hours post-dose is reported. | Day 2, 24-hours post-dose | |
Secondary | ACE-083 Serum Concentration Following Local Intramuscular Administration (240 mg Biceps Brachii (BB) Bilaterally) Day 86, 24 Hours Post-dose | Pharmacokinetic assessment included ACE-083 serum concentration and on a dosing day had a ±15 minute window for post-dose sample collection, based on the time of the first injection. The timepoints for which data is available are reported. Day 86, 24-hours post-dose is reported. | Day 86, 24- hours post-dose |
Status | Clinical Trial | Phase | |
---|---|---|---|
Recruiting |
NCT00082108 -
Myotonic Dystrophy and Facioscapulohumeral Muscular Dystrophy Registry
|
||
Completed |
NCT02579239 -
Evaluate Safety and Biological Activity of ATYR1940 in Participants With Limb Girdle Muscular Dystrophy 2B (LGMD2B) and Facioscapulohumeral Muscular Dystrophy (FSHD)
|
Phase 1/Phase 2 | |
Completed |
NCT02625662 -
Facioscapulohumeral Dystrophy in Children
|
||
Recruiting |
NCT04001582 -
The United Kingdom Facioscapulohumeral Muscular Dystrophy Patient Registry
|
||
Recruiting |
NCT06425445 -
Quantitative Assessment of Orofacial Muscle Function in FSHD
|
N/A | |
Terminated |
NCT03943290 -
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)
|
Phase 2 | |
Completed |
NCT01596803 -
Effects Antioxidants Supplementation on Muscular Function Patients Facioscapulohumeral Dystrophy (FSHD)
|
N/A | |
Active, not recruiting |
NCT03458832 -
Clinical Trial Readiness to Solve Barriers to Drug Development in FSHD
|
||
Completed |
NCT02766985 -
Rasch-analysis of Clinical Severity in FSHD
|
||
Active, not recruiting |
NCT01671865 -
Magnetic Resonance Imaging and Spectroscopy Biomarkers for Facioscapulohumeral Muscular Dystrophy
|
||
Completed |
NCT02413190 -
Bone Health in Facioscapulohumeral Muscular Dystrophy
|
||
Completed |
NCT01931644 -
At-Home Research Study for Patients With Autoimmune, Inflammatory, Genetic, Hematological, Infectious, Neurological, CNS, Oncological, Respiratory, Metabolic Conditions
|
||
Completed |
NCT01437345 -
A Multicenter Collaborative Study on the Clinical Features, Expression Profiling, and Quality of Life of Infantile Onset FSHD
|
N/A | |
Completed |
NCT02836418 -
Study to Evaluate the Long-Term Safety, Tolerability, and Biological Activity of ATYR1940 in Participants With Limb Girdle and Facioscapulohumeral Muscular Dystrophy (FSHD)
|
Phase 1/Phase 2 | |
Not yet recruiting |
NCT06086548 -
Unraveling Metabolic Involvement in Facioscapulohumeral Dystrophy Through Metabolomics
|
||
Completed |
NCT00821548 -
Electrostimulation of Shoulder Girdle and Quadriceps Muscles in Facioscapulohumeral Muscular Dystrophy Patients
|
N/A | |
Completed |
NCT05178706 -
Effectiveness of Upper Extremity Rehabilitation in pwFSHD (Patient With Facioscapulohumeral Dystrophia)
|
||
Completed |
NCT00104078 -
Study Evaluating MYO-029 in Adult Muscular Dystrophy
|
Phase 1/Phase 2 | |
Recruiting |
NCT05019625 -
Biomarker Development for Muscular Dystrophies
|
||
Completed |
NCT03123913 -
Study of Testosterone and rHGH in FSHD
|
Phase 1 |