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Trial record 2 of 4 for:    ACE-083

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)

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ClinicalTrials.gov Identifier: NCT03943290
Recruitment Status : Enrolling by invitation
First Posted : May 9, 2019
Last Update Posted : September 30, 2019
Sponsor:
Information provided by (Responsible Party):
Acceleron Pharma, Inc.

Tracking Information
First Submitted Date  ICMJE April 17, 2019
First Posted Date  ICMJE May 9, 2019
Last Update Posted Date September 30, 2019
Actual Study Start Date  ICMJE May 10, 2019
Estimated Primary Completion Date June 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 7, 2019)
  • Frequency of adverse events - Presence and nature of adverse events (AE) [ Time Frame: From baseline to Month 23 in Part 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 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03943290 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 7, 2019)
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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
  • 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.
  • Pharmacokinetics parameter of peak plasma concentration (Cmax) [ Time Frame: From baseline to Month 5 in Part 1 ]
  • Pharmacokinetics parameter of time to maximum serum concentration following administration (Tmax) [ Time Frame: From baseline to Month 5 in Part 1 ]
  • Pharmacokinetics parameter of area under the plasma concentration versus time curve (AUC) [ Time Frame: From baseline to Month 5 in Part 1 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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)
Official Title  ICMJE 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
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.
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Facioscapulohumeral Muscular Dystrophy
  • Charcot-Marie-Tooth Disease
Intervention  ICMJE Drug: ACE-083
Recombinant fusion protein
Study Arms  ICMJE
  • 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
    Intervention: Drug: ACE-083
  • 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
    Intervention: Drug: ACE-083
  • 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
    Intervention: Drug: ACE-083
  • Experimental: Part 2 Cohort 2a
    ACE-083 Administered into the TA muscle q4w for up to 24 months (24 doses) for FSHD patients
    Intervention: Drug: ACE-083
  • Experimental: Part 2 Cohort 2b
    ACE-083 Administered into the BB muscle q4w for up to 24 months (24 doses) for FSHD patients
    Intervention: Drug: ACE-083
  • Experimental: Part 2 Cohort 2c
    ACE-083 Administered into the TA muscle q4w for up to 24 months (24 doses) for CMT patients
    Intervention: Drug: ACE-083
  • Experimental: Part 2 Cohort 3a
    ACE-083 Administered into the TA muscle q8w for up to 24 months (12 doses) for FSHD patients
    Intervention: Drug: ACE-083
  • Experimental: Part 2 Cohort 3b
    ACE-083 Administered into the BB muscle q8w for up to 24 months (12 doses) for FSHD patients
    Intervention: Drug: ACE-083
  • Experimental: Part 2 Cohort 3c
    ACE-083 Administered into the TA muscle q8w for up to 24 months (12 doses) for CMT patients
    Intervention: Drug: ACE-083
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Enrolling by invitation
Estimated Enrollment  ICMJE
 (submitted: May 7, 2019)
150
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE August 2022
Estimated Primary Completion Date June 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03943290
Other Study ID Numbers  ICMJE A083-04
ACE-083 ( Other Identifier: Acceleron Pharma Inc. )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Acceleron Pharma, Inc.
Study Sponsor  ICMJE Acceleron Pharma, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Acceleron Pharma, Inc.
Verification Date September 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP