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Clinical trial information and results are updated daily from ClinicalTrials.gov. The latest data update was conducted on 01/21/2021.

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)

Clinicaltrials.gov identifier NCT03943290

Recruitment Status Terminated (Investigation of ACE-083 for use in patients with CMT is being discontinued as it did not achieve functional secondary endpoints in the A083-03 trial.)

First Posted May 9, 2019

Last update posted March 13, 2020

Study Description

Brief summary:

This is an open-label, multicenter, phase 2 extension study to evaluate the safety, tolerability, PK, PD, and efficacy of ACE-083 in subjects with FSHD previously enrolled in Study A083-02 and subjects with CMT1 and CMTX previously enrolled in Study A083-03. This study will be conducted in two Parts: Part 1, which is a loading phase of 6 months' duration, and Part 2, the maintenance phase, which will last up to 24 months.

  • Condition or Disease:Facioscapulohumeral Muscular Dystrophy
    Charcot-Marie-Tooth Disease
  • Intervention/Treatment: Drug: ACE-083
  • Phase: Phase 2
Detailed Description

Part 1 (6-month, non-randomized, open-label, loading phase for subjects from A083-02 Part 1 and A083-03 Part 1) Part 1 will consist of 3 cohorts of up to 18 subjects each. Subjects enrolled in Cohorts 1a and 1b will have completed Part 1 of Study A083-02; subjects enrolled in Cohort 1c will have completed Part 1 of Study A083-03. In this loading phase, 240 mg/muscle ACE-083 will be administered bilaterally every 4 weeks (q4w) for 6 doses (6 months) into either the tibialis anterior (TA) muscle or the biceps brachii (BB) muscle, depending on the muscle injected in the previous study; subjects may not switch muscle cohort upon enrollment in this study. Subjects will participate in a screening period of up to 4 weeks before receiving the first dose of ACE-083. Part 2 (24-month, randomized, open-label rollover maintenance phase for subjects from A083-02 Part 2, A083-03 Part 2, and A083-04 Part 1) Subjects who complete Part 1 of this study (the loading phase), Part 2 of A083-02, or Part 2 of A083-03 will enroll directly into the Part 2 open-label maintenance phase of treatment with ACE-083 and will consist of 6 cohorts of up to 23 FSHD or 29 CMT subjects each. These subjects will be randomized (1:1) to receive ACE-083, 240 mg/muscle bilaterally, either q4w or q8w. Thus, subjects enrolled in Cohorts 2a, 2b, and 2c will be FSHD TA, FSHD BB, and CMT TA treated q4w, and subjects enrolled in Cohorts 3a, 3b, and 3c will be FSHD TA, FSHD BB, and CMT TA treated q8w. Study duration for a subject initially enrolled in Part 1 and then extended to Part 2 will be approximately 33 months, including a 1-month screening period, 6-month Part 1 loading phase, 24-month Part 2 maintenance phase, and 2-month follow-up period. For subjects who enrolled directly into Part 2 of this study from Part 2 of Studies A083-02 and A083-03, the duration of the study will be approximately 26 months, including a 24-month maintenance phase and a 2-month follow-up period.

Study Design
  • Study Type: Interventional
  • Actual Enrollment: 62 participants
  • Allocation: Randomized
  • Intervention Model: Parallel Assignment
  • Masking: None (Open Label) ()
  • Primary Purpose: Treatment
  • Official Title: An Open-Label Extension Study to Evaluate the Long-Term Effects of ACE-083 in Patients With Facioscapulohumeral Muscular Dystrophy (FSHD) Previously Enrolled in Study A083-02 and in Patients With Charcot-Marie Tooth (CMT) Disease Types 1 and X Previously Enrolled in Study A083-03
  • Actual Study Start Date: May 2019
  • Actual Primary Completion Date: March 2020
  • Actual Study Completion Date: March 2020
Arms and interventions
Arm Intervention/treatment
Experimental: Part 1 Cohort 1a
ACE-083 240 mg/muscle administered bilaterally by injection into the TA muscle every 4 weeks for up to 6 doses for FSHD patients
Drug: ACE-083
Recombinant fusion protein
Experimental: Part 1 Cohort 1b
ACE-083 240 mg/muscle administered bilaterally by injection into the BB muscle every 4 weeks for up to 6 doses for FSHD patients
Drug: ACE-083
Recombinant fusion protein
Experimental: Part 1 Cohort 1c
ACE-083 240 mg/muscle administered bilaterally by injection into the TA muscle every 4 weeks for up to 6 doses for CMT patients
Drug: ACE-083
Recombinant fusion protein
Experimental: Part 2 Cohort 2a
ACE-083 Administered into the TA muscle q4w for up to 24 months (24 doses) for FSHD patients
Drug: ACE-083
Recombinant fusion protein
Experimental: Part 2 Cohort 2b
ACE-083 Administered into the BB muscle q4w for up to 24 months (24 doses) for FSHD patients
Drug: ACE-083
Recombinant fusion protein
Experimental: Part 2 Cohort 2c
ACE-083 Administered into the TA muscle q4w for up to 24 months (24 doses) for CMT patients
Drug: ACE-083
Recombinant fusion protein
Experimental: Part 2 Cohort 3a
ACE-083 Administered into the TA muscle q8w for up to 24 months (12 doses) for FSHD patients
Drug: ACE-083
Recombinant fusion protein
Experimental: Part 2 Cohort 3b
ACE-083 Administered into the BB muscle q8w for up to 24 months (12 doses) for FSHD patients
Drug: ACE-083
Recombinant fusion protein
Experimental: Part 2 Cohort 3c
ACE-083 Administered into the TA muscle q8w for up to 24 months (12 doses) for CMT patients
Drug: ACE-083
Recombinant fusion protein
Outcome Measures
  • Primary Outcome Measures: 1. Frequency of adverse events - Presence and nature of adverse events (AE) [ Time Frame: From baseline to Month 23 in Part 2 ]
  • 2. Change in muscle volume - Percent change from baseline in muscle volume of injected muscle by magnetic resonance imaging (MRI) [ Time Frame: From baseline to Month 23 in Part 2 ]
  • Secondary Outcome Measures: 1. Change in muscle function - percent change from baseline for tibialis anterior (TA) muscle in 6-minute walk test [ Time Frame: From baseline to Month 23 in Part 2 ]
  • 2. Change in muscle function - percent change from baseline for tibialis anterior (TA) muscle in 4-stair climb (subjects from A083-02 only) [ Time Frame: From baseline to Month 23 in Part 2 ]
  • 3. Pharmacokinetics parameter of time to maximum serum concentration following administration (Tmax) [ Time Frame: From baseline to Month 5 in Part 1 ]
  • 4. Pharmacokinetics parameter of area under the plasma concentration versus time curve (AUC) [ Time Frame: From baseline to Month 5 in Part 1 ]
  • 5. Change in muscle function. Percent and absolute change from baseline in functional assessment for tibialis anterior (TA) muscle:10-meter walk/run [ Time Frame: From baseline to Month 23 in Part 2 ]
  • 6. Change in muscle function. Percent and absolute change from baseline in functional assessment for tibialis anterior (TA) muscle: 6-minute walk test [ Time Frame: From baseline to Month 23 in Part 2 ]
  • 7. Change in muscle function. Percent and absolute change from baseline in functional assessment for tibialis anterior (TA) muscle: 4-stair climb (subjects from A083-02 only) [ Time Frame: From baseline to Month 23 in Part 2 ]
  • 8. Change in muscle function. Percent and absolute change from baseline in functional assessment for tibialis anterior (TA) muscle: 100-meter timed test [ Time Frame: From baseline to Month 23 in Part 2 ]
  • 9. Change in muscle function. Percent and absolute change from baseline in functional assessment for biceps brachii (BB) muscle: mid-level and high level performance of the upper limb (PUL) test [ Time Frame: From baseline to Month 23 in Part 2 ]
  • 10. Change in muscle function - percent change from baseline for tibialis anterior (TA) muscle in 10-meter walk/run [ Time Frame: From baseline to Month 23 in Part 2 ]
  • 11. Change in muscle function - percent change from baseline for tibialis anterior (TA) muscle in 100-meter timed test [ Time Frame: From baseline to Month 23 in Part 2 ]
  • 12. Change in muscle function - percent change from baseline for biceps brachii (BB) muscle in mid-level an high level performance of the upper limb (PUL) test [ Time Frame: From baseline to Month 23 in Part 2 ]
  • 13. Change in patient-reported quality of life. Absolute change from baseline in FSHD-health index score (FSHD-HI, subjects from A083-02) [ Time Frame: From baseline to Month 23 in Part 2 ]
    The FSHD Health Index (FSHD-HI) is a disease-specific patient reported outcome questionnaire that uses direct patient input to measure disease burden. For this index, the total score and all subscales are scored from 0 to 100 with 0 representing no disease burden and 100 representing the maximum amount of disease burden in the particular domain
  • 14. Change in patient-reported quality of life. Absolute change from baseline in CMT health index score (CMT-HI, subjects from A083-03) [ Time Frame: From baseline to Month 23 in Part 2 ]
    The CMT-Health Index (CMT-HI) is a disease-specific patient reported outcome measure designed to measure patient reported disease burden during clinical trials in patients with Charcot-Marie-Tooth Disease. For this index, the total score and all subscales are scored from 0 to 100 with 0 representing no disease burden and 100 representing the maximum amount of disease burden in the particular domain.
  • 15. Pharmacokinetics parameter of peak plasma concentration (Cmax) [ Time Frame: From baseline to Month 5 in Part 1 ]
Eligibility Criteria
  • Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
  • Sexes Eligible for Study: All
  • Accepts Healthy Volunteers: No
Criteria

Key Inclusion Criteria:

1. Completion of treatment with study drug per protocol and completion of the end of
treatment (ET) visit in Study A083-02 or Study A083-03.

2. Females of childbearing potential (defined as sexually mature women who have not
undergone hysterectomy or bilateral oophorectomy or are not naturally postmenopausal ≥
24 consecutive months) must have negative urine pregnancy test prior to enrollment and
use highly effective birth control methods (abstinence, oral contraceptives, barrier
method with spermicide, or surgical sterilization) during study participation and for
8 weeks following the last dose of ACE-083. 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
and for 8 weeks following the last dose of ACE-083, even if they have undergone a
vasectomy. Subjects must be counseled about contraception prior to the first dose of
ACE-083 and every three months thereafter during the study.

3. Ability to adhere to the study visit schedule/procedures and to understand and comply
with protocol requirements

4. Signed written informed consent

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. Co-morbidities, including symptomatic cardiopulmonary disease, significant orthopedic
or neuropathic pain, or other conditions that, in the opinion of the investigator,
would limit a subject's ability to complete strength and/or functional assessments

3. Type 1 or type 2 diabetes mellitus

4. Thyroid disorder unless condition is stable with no change in treatment for at least 4
weeks before the first dose and no expected change for duration of study

5. Renal impairment (serum creatinine ≥ 2 times the upper limit of normal [ULN])

6. Aspartate transaminase (AST) and/or alanine transaminase (ALT) ≥ 3 times ULN

7. Increased risk of bleeding (i.e., due to hemophilia, platelet disorders, or use of any
anticoagulation/platelet modifying therapies up to 2 weeks prior to Study Day 1 and
for duration of study; single agent low dose aspirin [≤ 100 mg daily] is permitted)

8. Severe deformity or ankle fixation that would sufficiently limit passive range of
motion to affect functional assessments (TA patients only)

9. Major surgery within 4 weeks prior to Study Day 1

10. Chronic pharmacologic doses of systemic corticosteroids (≥ 2 weeks) within 4 weeks
before Study Day 1 and for duration of study;
intra-articular/topical/inhaled/intranasal physiologic doses of systemic
corticosteroids are permitted

11. Androgens, growth hormone, insulin or oral hormone replacement therapy within 6 months
before Study Day 1 and for duration of study; topical physiologic androgen replacement
is permitted

12. Any change in medications potentially affecting muscle strength or function within 4
weeks of Study Day 1 and for duration of study (e.g., creatinine, CoQ10, systemic
beta-adrenergic agonists)

13. Previous exposure to any other investigational agent (not including ACE-083)
potentially affecting muscle volume, muscle strength, or muscle or nerve function
within 5 half-lives of last dose plus an additional 8-week washout period (or 12 weeks
prior to Study Day 1 if half-life is unknown)

14. Significant change in physical activity or exercise (e.g., significant increase or
decrease in intensity or frequency) within 8 weeks before Study Day 1 or inability to
maintain the baseline level of physical activity throughout the study

15. Any condition that would prevent MRI scanning or compromise the ability to obtain a
clear and interpretable scan of the treated muscles (e.g., knee/hip replacement
metallic implants)

16. Known active substance abuse, including alcohol

17. History of sensitivity to protein pharmaceuticals

18. Female that is pregnant or lactating/breast-feeding

Contacts and Locations
Contacts
Locations
Show 27 Study Locations
Sponsors and Collaborators

Acceleron Pharma, Inc.

More Information
  • Responsible Party: Acceleron Pharma, Inc.
  • ClinicalTrials.gov Identifier: NCT03943290 History of Changes
  • Other Study ID Numbers: A083-04, ACE-083
  • First Posted: May 9, 2019 Key Record Dates
  • Last Update Posted: March 13, 2020
  • Last Verified: March 2020
  • Studies a U.S. FDA-regulated Drug Product: Yes
  • Studies a U.S. FDA-regulated Device Product: No
  • Additional relevant MeSH terms: Tooth Diseases
    Charcot-Marie-Tooth Disease
    Nerve Compression Syndromes
    Hereditary Sensory and Motor Neuropathy
    Muscular Dystrophies
    Muscular Dystrophy, Facioscapulohumeral