Facioscapulohumeral Muscular DystrophyPhase 2NCT02927080
Study of ACE-083 in Patients With Facioscapulohumeral Muscular Dystrophy (FSHD)
A Phase 2 study testing ACE-083 in people with Facioscapulohumeral Muscular Dystrophy, run by Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA at 24 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Facioscapulohumeral Muscular Dystrophy
- What is being tested?
- ACE-083
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 95 participants
- Where
- 24 sitesin 3 countries
- Study dates
- Nov 2016to 9 Oct 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 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:
- 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.
Who cannot join
- 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
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- 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)
Trial locations and contacts
24 sites in 3 countries.
24 sites in 3 countries
United States18 sites
University of Colorado
Aurora, Colorado, 80045
Johns Hopkins Hugo W. Moser Research Inst. at Kennedy Krieger Inc.
Baltimore, Maryland, 21205
Brigham & Women's Hospital
Boston, Massachusetts, 02115
Carolinas Healthcare System Neurosciences Institute
Charlotte, North Carolina, 28203
The Ohio State University
Columbus, Ohio, 43210
Duke University Medical Center
Durham, North Carolina, 27710
Indiana University School of Medicine
Indianapolis, Indiana, 46202
University of Iowa
Iowa City, Iowa, 52242
University of Kansas Medical Center
Kansas City, Kansas, 66160
University of California Los Angeles Medical Center
Los Angeles, California, 90095
University of Minnesota
Minneapolis, Minnesota, 55455
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Oregon Health & Science University
Portland, Oregon, 97239
Virginia Commonwealth University
Richmond, Virginia, 23298
University of Rochester School of Medicine
Rochester, New York, 14642
University of California Davis Medical Center
Sacramento, California, 95817
University of Utah
Salt Lake City, Utah, 84112
Washington University School of Medicine
St Louis, Missouri, 63110
Canada3 sites
University of Calgary
Calgary, Alberta, T2N4Z6
London Health Sciences Centre
London, Ontario, N6A5W9
Montreal Neurological Institute & Hospital
Montreal, Quebec, H3A 2B4
Spain3 sites
Hospital Universitario Vall d'Hebrón
Barcelona, 08035
Hospital de la Santa Creu i Sant Pau
Barcelona, 08041
Hospital Universitario y Politécnico La Fe
Valencia, 46026
About this study
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.
Read the 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
- Being tested
- ACE-083, ACE-083 or placebo
- Keywords
- FSHD
- Medical subject headings
- Muscular Dystrophy, Facioscapulohumeral
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ACE-083Drug
Recombinant fusion protein.
ACE-083 or placeboDrug
Recombinant fusion protein or normal saline.
| Study group | Role | What they receive |
|---|---|---|
| ACE-083 (Part 1, Cohort 1a) Tibialis Anterior (TA) 150mg | Experimental | ACE-083 150 mg TA unilaterally, once every 3 weeks for up to 5 doses. Drug: ACE-083 Recombinant fusion protein Receives: Drug: ACE-083 |
| ACE-083 (Part 1, Cohort 2a) Tibialis Anterior (TA) 200mg | Experimental | ACE-083 200 mg TA unilaterally, once every 3 weeks for up to 5 doses. Drug: ACE-083 Recombinant fusion protein Receives: Drug: ACE-083 |
| ACE-083 (Part 1, Cohort 3a) Tibialis Anterior (TA) 200mg | Experimental | ACE-083 200 mg TA bilaterally, once every 3 weeks for up to 5 doses. Drug: ACE-083 Recombinant fusion protein Receives: Drug: ACE-083 |
| ACE-083 (Part 1, Cohort 1b) Biceps Brachii (BB) 150 mg | Experimental | ACE-083 150 mg BB unilaterally, once every 3 weeks for up to 5 doses. Drug: ACE-083 Recombinant fusion protein Receives: Drug: ACE-083 |
| ACE-083 (Part 1, Cohort 2b) Biceps Brachii (BB) 200 mg | Experimental | ACE-083 200 mg BB unilaterally, once every 3 weeks for up to 5 doses. Drug: ACE-083 Recombinant fusion protein Receives: Drug: ACE-083 |
| ACE-083 (Part 1, Cohort 3b) Biceps Brachii (BB) 240 mg | Experimental | ACE-083 240 mg BB unilaterally, once every 3 weeks for up to 5 doses. Drug: ACE-083 Recombinant fusion protein Receives: 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.
Drug: ACE-083 Recombinant fusion protein Receives: Drug: ACE-083 or placebo |
| ACE-083 (Part 2, DB-PC) Tibialis Anterior (TA) 240 mg | Experimental | 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 Receives: 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.
Drug: ACE-083 Recombinant fusion protein Receives: Drug: ACE-083 or placebo |
| ACE-083 (Part 2, DB-PC) Biceps Brachii (BB) 240 mg | Experimental | 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 Receives: Drug: ACE-083 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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)
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.
Measured: Time Frame: From initiation of treatment to Study Visit Day 190
Secondary outcomes (14)
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.
Measured: 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.
Measured: 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)
Measured: 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).
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Day 86, 24- hours post-dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Oct 2016 (estimated)
- Study startNov 2016
- Primary completion17 Sep 2019
- Study completion9 Oct 2019
Why it stopped: Study was discontinued as it did not achieve functional secondary endpoints.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Facioscapulohumeral Muscular DystrophyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 95 participants (actual)
Sponsor and investigators
- Lead sponsor
- Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02927080
- Sponsor's protocol ID
- A083-02
- Other IDs
- ACE-083
- Status last verified
- Sep 2022
- First submitted
- 5 Oct 2016
- Last updated
- 26 Sep 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 26 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study of ACE-083 in Patients With Facioscapulohumeral Muscular Dystrophy
- ClinicalTrials.gov ID
- NCT02927080
- Acronym / sponsor ID
- A083-02
- Conditions
- Facioscapulohumeral Muscular Dystrophy
- Keywords
- FSHD
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study was discontinued as it did not achieve functional secondary endpoints.
- Enrolment
- 95 participants (actual)
- Lead sponsor
- Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USAIndustry (pharma, biotech, devices)
- Study start
- Nov 2016 (actual)
- Primary completion
- 17 Sep 2019 (actual)
- Study completion
- 9 Oct 2019 (actual)
- First posted
- 6 Oct 2016 (estimated)
- Results
- Posted 22 Apr 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 10
| Arm | Type | Receives |
|---|---|---|
| ACE-083 (Part 1, Cohort 1a) Tibialis Anterior (TA) 150mg | Experimental | Drug: ACE-083ACE-083 150 mg TA unilaterally, once every 3 weeks for up to 5 doses. Drug: ACE-083 Recombinant fusion protein |
| ACE-083 (Part 1, Cohort 2a) Tibialis Anterior (TA) 200mg | Experimental | Drug: ACE-083ACE-083 200 mg TA unilaterally, once every 3 weeks for up to 5 doses. Drug: ACE-083 Recombinant fusion protein |
| ACE-083 (Part 1, Cohort 3a) Tibialis Anterior (TA) 200mg | Experimental | Drug: ACE-083ACE-083 200 mg TA bilaterally, once every 3 weeks for up to 5 doses. Drug: ACE-083 Recombinant fusion protein |
| ACE-083 (Part 1, Cohort 1b) Biceps Brachii (BB) 150 mg | Experimental | Drug: ACE-083ACE-083 150 mg BB unilaterally, once every 3 weeks for up to 5 doses. Drug: ACE-083 Recombinant fusion protein |
| ACE-083 (Part 1, Cohort 2b) Biceps Brachii (BB) 200 mg | Experimental | Drug: ACE-083ACE-083 200 mg BB unilaterally, once every 3 weeks for up to 5 doses. Drug: ACE-083 Recombinant fusion protein |
| ACE-083 (Part 1, Cohort 3b) Biceps Brachii (BB) 240 mg | Experimental | Drug: ACE-083ACE-083 240 mg BB unilaterally, once every 3 weeks for up to 5 doses. Drug: ACE-083 Recombinant fusion protein |
| Placebo (Part 2, DB-PC) Tibialis Anterior (TA) | Placebo comparator | Drug: ACE-083 or placeboPart 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 |
| ACE-083 (Part 2, DB-PC) Tibialis Anterior (TA) 240 mg | Experimental | Drug: ACE-083Part 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 |
| Placebo (Part 2, DB-PC) Biceps Brachii (BB) | Placebo comparator | Drug: ACE-083 or placeboPart 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 |
| ACE-083 (Part 2, DB-PC) Biceps Brachii (BB) 240 mg | Experimental | Drug: ACE-083Part 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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:
- 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 (9 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ACE-083Recombinant fusion protein. | Drug | ACE-083 (Part 1, Cohort 1a) Tibialis Anterior (TA) 150mg, ACE-083 (Part 1, Cohort 1b) Biceps Brachii (BB) 150 mg, ACE-083 (Part 1, Cohort 2a) Tibialis Anterior (TA) 200mg, ACE-083 (Part 1, Cohort 2b) Biceps Brachii (BB) 200 mg, ACE-083 (Part 1, Cohort 3a) Tibialis Anterior (TA) 200mg, ACE-083 (Part 1, Cohort 3b) Biceps Brachii (BB) 240 mg, ACE-083 (Part 2, DB-PC) Biceps Brachii (BB) 240 mg, ACE-083 (Part 2, DB-PC) Tibialis Anterior (TA) 240 mg |
| ACE-083 or placeboRecombinant fusion protein or normal saline. | Drug | Placebo (Part 2, DB-PC) Biceps Brachii (BB), Placebo (Part 2, DB-PC) Tibialis Anterior (TA) |
Primary outcome
Safety and Tolerability (Incidence of Adverse Events)
Time frame: From initiation of treatment to Day 106 for Part 1 and Day 190 for Part 2
The number of participants that had a least one Treatment Emergent Adverse Event for the duration of each of the respective study parts.
Safety and Tolerability (Severity of Adverse Events, Grade 3 or Higher).
Time frame: From initiation of treatment to Day 106 for Part 1 and Day 190 for Part 2
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.
Safety and Tolerability (Severity of Adverse Events- Dose Interruption, Reduction and/or Drug Withdrawal)
Time frame: From initiation of treatment to Day 106 for Part 1 and Day 190 for Part 2
The number of participants that had a least one Treatment Emergent Adverse Event that led to dose interruption, dose reduction and/or drug withdrawn.
Total Muscle Volume (TMV) of the Treated Muscle in Patients With FSHD Administered ACE-083 or Placebo During Part 2 (Randomized, Controlled Portion)
Time frame: Time Frame: From initiation of treatment to Study Visit Day 190
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.
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)
Time frame: 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) 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.
14 secondary outcomes
Percent Change in Total Muscle Volume (TMV) in Muscle in Patients With FSHD Administered ACE-083 During Part 1 (Open-label, Dose-escalation Portion)
Time frame: 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)
Time frame: 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)
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Day 86, 24- hours post-dose
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Sep 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
24 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ACE-083 in people with Facioscapulohumeral Muscular Dystrophy, run by Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA at 24 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 26 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 24 sites in United States, Canada, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Apr 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and Tolerability (Incidence of Adverse Events) (time frame: From initiation of treatment to Day 106 for Part 1 and Day 190 for Part 2). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Sep 2022.