Study of ACE-083 in Patients With Facioscapulohumeral Mus... | NCT02927080 | Trialant
NCT02927080
Sponsor
Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA
Status
Terminated
Last Update Posted
Sep 26, 2022Actual
Enrollment
95Actual
Phase
Phase 2
Conditions
Facioscapulohumeral Muscular Dystrophy
Interventions
ACE-083
ACE-083 or placebo
Countries
United States
Canada
Spain
Protocol Section
Identification Module
NCT ID
NCT02927080
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
A083-02
Secondary IDs
ID
Type
Description
Link
ACE-083
Other Identifier
Acceleron Pharma Inc.
Brief Title
Study of ACE-083 in Patients With Facioscapulohumeral Muscular Dystrophy (FSHD)
Official Title
A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study of ACE-083 in Patients With Facioscapulohumeral Muscular Dystrophy
Acronym
Not provided
Organization
Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USAINDUSTRY
Status Module
Record Verification Date
Sep 2022
Overall Recruitment Status or Expanded Access Status
Terminated
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Study was discontinued as it did not achieve functional secondary endpoints.
Expanded Access Info
No
Start Date
Nov 2016Actual
Primary Completion Date
Sep 17, 2019Actual
Completion Date
Oct 9, 2019Actual
First Submitted Date
Oct 5, 2016
First Submission Date that Met QC Criteria
Oct 5, 2016
First Posted Date
Oct 6, 2016Estimated
Results Waived
Not provided
Results First Submitted Date
Sep 18, 2020
Results First Submitted that Met QC Criteria
Mar 29, 2021
Results First Posted Date
Apr 22, 2021Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Sep 14, 2022
Last Update Posted Date
Sep 26, 2022Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USAINDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
Yes
Is FDA Regulated Drug
Not provided
Is FDA Regulated Device
Not provided
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
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
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
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
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
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
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)
Secondary Outcomes
Measure
Description
Time Frame
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.
Other Outcomes
Not provided
Eligibility Module
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))
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)
Accepts Healthy Volunteers
No
Sex
All
Sex/Gender Based
Not provided
Sex/Gender Description
Not provided
Minimum Age
18 Years
Maximum Age
Not provided
Standard Ages
AdultOlder Adult
Study Population
Not provided
Sampling Method
Not provided
Contacts/Locations Module
Central Contacts
Not provided
Overall Officials
Not provided
Locations
Facility
Status
City
State
ZIP
Country
Contacts
University of California Los Angeles Medical Center
Los Angeles
California
90095
United States
References Module
No data available
No data is available for this block.
IPD Sharing Statement Module
No data available
No data is available for this block.
Results Section
Participant Flow Module
Pre-assignment Details
Not provided
Recruitment Details
First subject enrolled 22 November 2016, last subject completed 09 October 2019. The study was divided into parts; Part 1 was an open-label dose escalation study and had 6 cohorts and Part 2 was a randomized double-blind placebo controlled trial. Participants were recruited from 23 study centers in 3 countries (US, Canada and Spain).
ACE-083 240 mg BB unilaterally, once every 3 weeks for up to 5 doses. Drug: ACE-083 Recombinant fusion protein
Drug: ACE-083
Placebo (Part 2, DB-PC) Tibialis Anterior (TA)
Placebo Comparator
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.
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
Drug: ACE-083
Placebo (Part 2, DB-PC) Biceps Brachii (BB)
Placebo Comparator
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.
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.
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
Time Frame: From initiation of treatment to Study Visit Day 106
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
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
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
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
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
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
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)
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
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
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
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
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
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
University of California Davis Medical Center
Sacramento
California
95817
United States
University of Colorado
Aurora
Colorado
80045
United States
Indiana University School of Medicine
Indianapolis
Indiana
46202
United States
University of Iowa
Iowa City
Iowa
52242
United States
University of Kansas Medical Center
Kansas City
Kansas
66160
United States
Johns Hopkins Hugo W. Moser Research Inst. at Kennedy Krieger Inc.
Baltimore
Maryland
21205
United States
Brigham & Women's Hospital
Boston
Massachusetts
02115
United States
University of Minnesota
Minneapolis
Minnesota
55455
United States
Washington University School of Medicine
St Louis
Missouri
63110
United States
University of Rochester School of Medicine
Rochester
New York
14642
United States
Carolinas Healthcare System Neurosciences Institute
Charlotte
North Carolina
28203
United States
Duke University Medical Center
Durham
North Carolina
27710
United States
The Ohio State University
Columbus
Ohio
43210
United States
Oregon Health & Science University
Portland
Oregon
97239
United States
University of Pennsylvania
Philadelphia
Pennsylvania
19104
United States
University of Utah
Salt Lake City
Utah
84112
United States
Virginia Commonwealth University
Richmond
Virginia
23298
United States
University of Calgary
Calgary
Alberta
T2N4Z6
Canada
London Health Sciences Centre
London
Ontario
N6A5W9
Canada
Montreal Neurological Institute & Hospital
Montreal
Quebec
H3A 2B4
Canada
Hospital Universitario Vall d'Hebrón
Barcelona
08035
Spain
Hospital de la Santa Creu i Sant Pau
Barcelona
08041
Spain
Hospital Universitario y Politécnico La Fe
Valencia
46026
Spain
ACE-083 200 mg TA unilaterally, once every 3 weeks for up to 5 doses. Drug: ACE-083 Recombinant fusion protein
Double-Blind, Placebo-Controlled ACE-083 240 mg BB bilaterally, once every 3 weeks for up to 9 doses.
Drug: ACE-083 Recombinant fusion protein
FG0006 subjects
FG0016 subjects
FG0026 subjects
FG0036 subjects
FG0047 subjects
FG0056 subjects
FG00615 subjects
FG00714 subjects
FG00815 subjects
FG00914 subjects
Open-Label Extension From Part 2 Double Blind-Placebo Controlled
Patients who completed the double-blind (DB) treatment period continued into the open-label extension (OLE) period. Patients who received ACE-083 in the DB treatment period continued to receive the same dose of ACE-083 during the OLE period, and patients who received placebo during the DB treatment period were switched to receive ACE-083, 240 mg/muscle. In the OLE period, ACE-083 was administered bilaterally in either the TA or BB muscle once every 3 weeks for approximately 6 months (8 doses).
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG00614 subjects
FG00713 subjects
FG00814 subjects
FG00912 subjects
COMPLETED
FG0006 subjects
FG0015 subjects
FG0026 subjects
FG0036 subjects
FG0046 subjects
FG0056 subjects
FG0067 subjects
FG0075 subjects
FG00812 subjects
FG0097 subjects
NOT COMPLETED
FG0000 subjects
FG0011 subjects
FG0020 subjects
FG0030 subjects
FG0041 subjects
FG0050 subjects
FG0068 subjects
FG0079 subjects
FG0083 subjects
FG0097 subjects
Type
Comment
Reasons
Withdrawal by Subject
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0041 subjects
FG0050 subjects
FG0061 subjects
FG0071 subjects
FG0080 subjects
FG0092 subjects
Willingness to comply with protocol
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Study terminated by Sponsor
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Adverse Event
FG0000 subjects
FG0011 subjects
FG0020 subjects
FG0030 subjects
FG004
Other
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
The Safety population was used for the results posting for both parts of the study. The Safety Set consists of all patients who received at least one dose of the study drug (including placebo).
Double-Blind, Placebo-Controlled ACE-083 240 mg BB bilaterally, once every 3 weeks for up to 9 doses.
Drug: ACE-083 Recombinant fusion protein
Units
Counts
Participants
OG0006
OG0016
OG0026
OG003
Title
Denominators
Categories
Title
Measurements
OG0006
OG0016
OG0025
OG003
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.
The safety set population is all participants that received at least one dose of ACE-083 or placebo during the study.
Posted
Count of Participants
Participants
From initiation of treatment to Day 106 for Part 1 and Day 190 for Part 2
ACE-083 200 mg TA bilaterally, once every 3 weeks for up to 5 doses. Drug: ACE-083 Recombinant fusion protein
OG003
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.
The Per Protocol Set: All patients enrolled/randomized in the study who received at least one dose of the study drug (includes placebo) with no major protocol violations.
Posted
Mean
Standard Deviation
mm3
Time Frame: From initiation of treatment to Study Visit Day 190
ID
Title
Description
OG000
Placebo (Part 2, DB-PC) Tibialis Anterior (TA)
Double-Blind, Placebo-Controlled Placebo- TA bilaterally, once every 3 weeks for up to 9 doses.
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.
OG002
Placebo (Part 2, DB-PC) Biceps Brachii (BB)
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.
The Per Protocol Set: All patients enrolled/randomized in the study who received at least one dose of the study drug (includes placebo) with no major protocol violations.
Posted
Mean
Standard Deviation
percent change
Time Frame: From initiation of treatment to Study Visit Day 190
ID
Title
Description
OG000
Placebo (Part 2, DB-PC) Tibialis Anterior (TA)
Double-Blind, Placebo-Controlled Placebo- TA bilaterally, once every 3 weeks for up to 9 doses.
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.
OG002
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.
The Per Protocol Set: All patients enrolled/randomized in the study who received at least one dose of the study drug (includes placebo) with no major protocol violations.
Posted
Mean
Standard Error
percent change
Time Frame: From initiation of treatment to Study Visit Day 106
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.
The Per Protocol Set: All patients enrolled/randomized in the study who received at least one dose of the study drug (includes placebo) with no major protocol violations.
Posted
Least Squares Mean
Standard Error
Percent change
Time Frame: From initiation of treatment to Study Visit Day 190
ID
Title
Description
OG000
Placebo (Part 2, DB-PC) Tibialis Anterior (TA)
Double-Blind, Placebo-Controlled Placebo-TA bilaterally, once every 3 weeks for up to 9 doses.
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
OG002
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)
Per Protocol Set: All patients enrolled/randomized in the study who received at least one dose of the study drug (includes placebo) with no major protocol violations.
Posted
Least Squares Mean
Standard Error
percent change
From initiation of treatment (Study Day 1) to Study Visit Day 190
ID
Title
Description
OG000
Placebo (Part 2, DB-PC) Tibialis Anterior (TA)
Double-Blind, Placebo-Controlled Placebo- TA bilaterally, once every 3 weeks for up to 9 doses.
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
Units
Counts
Participants
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).
Per Protocol Set: All patients enrolled/randomized in the study who received at least one dose of the study drug (includes placebo) with no major protocol violations.
Posted
Least Squares Mean
Standard Error
percent change
From initiation of treatment (Study Day 1) to Study Visit Day 190
ID
Title
Description
OG000
Placebo (Part 2, DB-PC) Biceps Brachii (BB)
Double-Blind, Placebo-Controlled Placebo-BB bilaterally, once every 3 weeks for up to 9 doses.
Double-Blind, Placebo-Controlled ACE-083 240 mg BB bilaterally, once every 3 weeks for up to 9 doses.
Drug: ACE-083 Recombinant fusion protein
Units
Counts
Participants
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).
Per Protocol Set: All patients enrolled/randomized in the study who received at least one dose of the study drug (includes placebo) with no major protocol violations.
Posted
Least Squares Mean
Standard Error
percent change
From initiation of treatment (Study Day 1) to Study Visit Day 190
ID
Title
Description
OG000
Placebo (Part 2, DB-PC) Biceps Brachii (BB)
Double-Blind, Placebo-Controlled Placebo- BB bilaterally, once every 3 weeks for up to 9 doses.
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.
The Per Protocol Set: All patients enrolled/randomized in the study who received at least one dose of the study drug (includes placebo) with no major protocol violations.
Posted
Mean
Standard Deviation
score on a scale
Time Frame: From initiation of treatment (Study Day 1) to Study Visit Day 190
ID
Title
Description
OG000
Placebo (Part 2, DB-PC) Tibialis Anterior (TA)
Double-Blind, Placebo-Controlled Placebo- TA bilaterally, once every 3 weeks for up to 9 doses.
Drug: Placebo Normal saline
OG001
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.
Pharmacokinetics Population: All patients who have received at least one dose of study drug and have sufficient pharmacokinetic (PK) samples collected and assayed for PK analysis
ACE-083 200 mg TA bilaterally, once every 3 weeks for up to 5 doses. Drug: ACE-083 Recombinant fusion protein
Units
Counts
Participants
OG000
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.
Pharmacokinetics Population: All patients who have received at least one dose of study drug and have sufficient pharmacokinetic (PK) samples collected and assayed for PK analysis
ACE-083 200 mg TA bilaterally, once every 3 weeks for up to 5 doses. Drug: ACE-083 Recombinant fusion protein
Units
Counts
Participants
OG000
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.
Pharmacokinetics Population: All patients who have received at least one dose of study drug and have sufficient pharmacokinetic (PK) samples collected and assayed for PK analysis
ACE-083 200 mg BB unilaterally, once every 3 weeks for up to 5 doses. Drug: ACE-083 Recombinant fusion protein
Units
Counts
Participants
OG000
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.
Pharmacokinetics Population: All patients who have received at least one dose of study drug and have sufficient pharmacokinetic (PK) samples collected and assayed for PK analysis
ACE-083 200 mg BB unilaterally, once every 3 weeks for up to 5 doses. Drug: ACE-083 Recombinant fusion protein
Units
Counts
Participants
OG000
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.
Pharmacokinetics Population: All patients who have received at least one dose of study drug and have sufficient pharmacokinetic (PK) samples collected and assayed for PK analysis
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
Units
Counts
Participants
OG000
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.
Pharmacokinetics Population: All patients who have received at least one dose of study drug and have sufficient pharmacokinetic (PK) samples collected and assayed for PK analysis
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
Units
Counts
Participants
OG000
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.
Pharmacokinetics Population: All patients who have received at least one dose of study drug and have sufficient pharmacokinetic (PK) samples collected and assayed for PK analysis
Double-Blind, Placebo-Controlled ACE-083 240 mg BB bilaterally, once every 3 weeks for up to 9 doses.
Drug: ACE-083 Recombinant fusion protein
Units
Counts
Participants
OG000
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.
Pharmacokinetics Population: All patients who have received at least one dose of study drug and have sufficient pharmacokinetic (PK) samples collected and assayed for PK analysis
Double-Blind, Placebo-Controlled ACE-083 240 mg BB bilaterally, once every 3 weeks for up to 9 doses.
Drug: ACE-083 Recombinant fusion protein
Units
Counts
Participants
OG000
Time Frame
For part 1 (open-label; dose-escalation) the time frame is six months For part 2, there are two parts: randomized, double-blind, placebo-controlled and then an open-label portion- the total time frame for part 2 is fifteen months
Double-Blind, Placebo-Controlled ACE-083 240 mg BB bilaterally, once every 3 weeks for up to 9 doses.
Drug: ACE-083 Recombinant fusion protein
Units
Counts
Participants
OG00014
OG00113
OG00214
OG00314
Title
Denominators
Categories
Title
Measurements
OG0005.46± 7.32
OG00114.20± 10.72
OG0021.07± 8.08
OG00320.41± 16.64
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
D190 Percent change from baseline in TMV
ANCOVA
0.0138
Mean Difference (Net)
9.54
Standard Error of the Mean
3.876
2-Sided
90
3.17
15.92
Superiority
Percent Change in Total Muscle Volume (TMV) of the TA muscle in patients with FSHD administered ACE-083 when compared to placebo During Part 2 (randomized, controlled portion)
OG002
OG003
D190 Percent change from baseline in TMV
ANCOVA
<0.0001
Mean Difference (Net)
16.39
Standard Error of the Mean
4.032
2-Sided
90
9.75
23.02
Superiority
Percent Change in Total Muscle Volume (TMV) of the BB muscle in patients with FSHD administered ACE-083 when compared to placebo During Part 2 (randomized, controlled portion)
ACE-083 200 mg TA bilaterally, once every 3 weeks for up to 5 doses. Drug: ACE-083 Recombinant fusion protein
Double-Blind, Placebo-Controlled ACE-083 240 mg BB bilaterally, once every 3 weeks for up to 9 doses.
Drug: ACE-083 Recombinant fusion protein
Units
Counts
Participants
OG00014
OG00113
OG00214
OG00314
Title
Denominators
Categories
Baseline FSHD-HI total score
Title
Measurements
OG00037.65± 15.60
OG00145.51± 28.44
OG00245.52± 23.38
OG00325.89± 21.78
Day 190 FSHD-HI total score
Title
Measurements
OG00039.44± 18.76
OG00146.18± 29.15
OG00247.27± 22.73
OG003
Absolute Change Day 190 from Baseline
Title
Measurements
OG0001.79± 4.83
OG0010.67± 6.02
OG0021.75± 6.90
OG003
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Change from baseline in FSHD-HI, patient-reported outcome (PRO) measures Part 2 (Randomized, Controlled Portion)- Total Score for TA group part 2; compared to Placebo
ANCOVA
0.5661
Mean Difference (Final Values)
-1.98
Standard Error of the Mean
3.459
2-Sided
90
-7.67
3.70
Superiority
OG002
OG003
Change from baseline in FSHD-HI, patient-reported outcome (PRO) measures Part 2 (Randomized, Controlled Portion)- Total Score for BB group part 2; compared to Placebo