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Study of ACE-083 in Patients With Charcot-Marie-Tooth Disease

This study is currently recruiting participants.
See Contacts and Locations
Verified August 2017 by Acceleron Pharma, Inc.
Sponsor:
Information provided by (Responsible Party):
Acceleron Pharma, Inc.
ClinicalTrials.gov Identifier:
NCT03124459
First received: April 12, 2017
Last updated: August 3, 2017
Last verified: August 2017
  Purpose
This is a multicenter, phase 2 study to evaluate the safety, tolerability, pharmacodynamics (PD), efficacy, and pharmacokinetics (PK) of ACE-083 in patients with CMT1 and CMTX, to be conducted in two parts. Part 1 is non-randomized, open-label, dose-escalation and Part 2 is randomized, double-blind, and placebo-controlled.

Condition Intervention Phase
Charcot-Marie-Tooth Disease Drug: ACE-083 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study of ACE-083 in Patients With Charcot-Marie-Tooth Disease Types 1 and X

Resource links provided by NLM:


Further study details as provided by Acceleron Pharma, Inc.:

Primary Outcome Measures:
  • Part 1: Frequency of adverse events [ Time Frame: From initiation of treatment (Study Day 1) to end of follow-up period (Study Day 141). ]
    Number of subjects with adverse events related to treatment intervention

  • Part 2: Change in muscle volume [ Time Frame: From initiation of treatment (Study Day 1) to end of follow-up period (Study Day 141). ]
    Percent change from baseline in volume of injected muscle, by MRI


Secondary Outcome Measures:
  • Change in amount of intramuscular fat tissue [ Time Frame: From initiation of treatment (Study Day 1) to end of follow-up period (Study Day 141). ]
    Percent change from baseline in intramuscular fat fraction of the injected muscle, by MRI

  • Change in muscle strength [ Time Frame: From initiation of treatment (Study Day 1) to end of follow-up period (Study Day 141). ]
    Percent change from baseline in strength of the injected muscle, by Quantitative Muscle Testing (QMT)

  • Change in muscle function - walk/run time [ Time Frame: From initiation of treatment (Study Day 1) to end of follow-up period (Study Day 141). ]
    Percent change from baseline in functional assessments, as measured by 10-meter walk/run time

  • Change in muscle function - walk distance [ Time Frame: From initiation of treatment (Study Day 1) to end of follow-up period (Study Day 141). ]
    Percent change from baseline in functional assessments, as measured by 6-minute walk distance

  • Change in balance and fall risk [ Time Frame: From initiation of treatment (Study Day 1) to end of follow-up period (Study Day 141). ]
    Percent change from baseline in static and dynamic balance, as measured by the Berg Balance Scale, a 14-item scoring system to assess balance and fall risk in adults

  • Change in clinical examination score [ Time Frame: From initiation of treatment (Study Day 1) to end of follow-up period (Study Day 141). ]
    Percent change from baseline in the CMT Examination Score (CMTES2), a composite acoring system to assess sensory and motor impairment in subjects with CMT

  • Change in patient-reported quality of life [ Time Frame: From initiation of treatment (Study Day 1) to end of follow-up period (Study Day 141). ]
    Percent change from baseline in CMT-HI, a disease-specific, patient-reported health index score


Estimated Enrollment: 42
Actual Study Start Date: July 31, 2017
Estimated Study Completion Date: July 2019
Estimated Primary Completion Date: July 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part 1 Cohort 1
ACE-083 150 mg IM (tibialis anterior muscle), once every 3 weeks for up to 5 doses.
Drug: ACE-083
Part 1 - Recombinant fusion protein. Part 2 - Recombinant fusion protein or buffer solution.
Experimental: Part 1 Cohort 2
ACE-083 200 mg IM, (tibialis anterior muscle), once every 3 weeks for up to 5 doses.
Drug: ACE-083
Part 1 - Recombinant fusion protein. Part 2 - Recombinant fusion protein or buffer solution.
Experimental: Part 1 Cohort 3
ACE-083 up to 250 mg IM (tibialis anterior muscle), once every 3 weeks for up to 5 doses.
Drug: ACE-083
Part 1 - Recombinant fusion protein. Part 2 - Recombinant fusion protein or buffer solution.
Experimental: Part 2
ACE-083 up to 250 mg IM (tibialis anterior muscle) or placebo, once every 3 weeks for up to 5 doses.
Drug: ACE-083
Part 1 - Recombinant fusion protein. Part 2 - Recombinant fusion protein or buffer solution.

Detailed Description:

Part 1 (non-randomized, open-label, dose-escalation) Part 1 will consist of up to 3 cohorts of 6 patients each and will evaluate multiple ascending dose levels of ACE-083 administered bilaterally once every 3 weeks for up to 5 doses in the tibialis anterior (TA) muscle. Patients in each cohort will be enrolled in a 4-week screening period before beginning treatment.

Part 2 (randomized, double-blind, placebo-controlled) Prior to the initiation of Part 2, a review of safety and efficacy data from Part 1 will be conducted by the Safety Review Team (SRT) to determine the recommended dose level (maximum 250 mg/muscle). A total of up to 24 new patients may be enrolled and randomized (2:1 randomization) to receive either ACE-083 (n=16) or placebo (n=8) bilaterally by injection into both TA muscles once every 3 weeks for up to 5 doses.

Study duration for Parts 1 and 2 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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age ≥ 18 years
  2. Diagnosis of CMT with documented genetically-confirmed CMT1 or CMTX or a first-degree relative with documented genetically-confirmed CMT1 or CMTX and clinical signs/symptoms of CMT1 or CMTX
  3. Six-minute walk distance of at least 150 meters (without a brace or walker)
  4. Independent ambulation for at least 10 meters, without a brace
  5. Mild to moderate weakness in left and right ankle dorsiflexion as determined by Medical Research Council (MRC) manual muscle testing (MMT)
  6. Mild weakness in left and right ankle plantar flexion as determined by MRC MMT
  7. 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. 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 he has undergone a successful vasectomy. Patients must be counseled concerning measures to be used to prevent pregnancy prior to the first dose of ACE-083.
  8. Ability to adhere to the study visit schedule/procedures, and to understand and comply with protocol requirements
  9. Signed written informed consent

Exclusion Criteria:

  1. History of active malignancy, with the exception of fully excised or treated basal cell carcinoma, cervical carcinoma in-situ, or ≤ 2 squamous cell carcinomas of the skin
  2. Symptomatic cardiopulmonary disease, significant functional impairment, significant orthopedic or neuropathic pain, or other co-morbidities that in the opinion of the investigator would limit a patient's ability to complete strength and/or functional assessments on study
  3. Clinically significant endocrine or metabolic disease, such as hypothyroidism, unless corrected (e.g., with adequate replacement therapy)
  4. Renal impairment (serum creatinine ≥ 2 times the upper limit of normal [ULN])
  5. Aspartate transaminase (AST) and/or alanine transaminase (ALT) ≥ 3 times ULN
  6. 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; low dose aspirin [≤ 100 mg daily] is permitted)
  7. Severe deformity or ankle fixation that would sufficiently limit passive range of motion to affect assessment of dorsiflexion strength
  8. Major surgery within 4 weeks prior to Study Day 1
  9. Systemic corticosteroids within 2 weeks before Study Day 1 and for duration of study; inhaled or intranasal therapeutic or physiologic doses of systemic corticosteroids are permitted
  10. Exposure to any marketed or investigational agent 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 total of Study Day 1 if half-life is unknown)
  11. Any previous or current exposure to ACE-083
  12. 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
  13. Any condition that would prevent MRI scanning or compromise the ability to obtain a clear and interpretable scan of the lower leg, as applicable (e.g., knee/hip replacement metallic implants)
  14. Known active substance abuse, including alcohol
  15. History of sensitivity to protein pharmaceuticals
  16. Female that is lactating/breast-feeding
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT03124459

Contacts
Contact: Clinical Trial Manager 617-649-9200 clinicaltrials08303@acceleronpharma.com

Locations
United States, Kansas
University of Kansas Medical Center - Neurology Department Recruiting
Kansas City, Kansas, United States, 66160
Contact: Ayla McCalley, CRC    913-945-9937    amccalley2@kumc.edu   
Principal Investigator: Jeffrey Statland         
United States, New Jersey
Hackensack University Medical Center Recruiting
Hackensack, New Jersey, United States, 07601
Contact: Angelica Castro, BSN, RN       Angelica.Castro@hackenssackmeridian.org   
Principal Investigator: Florian Thomas, MD         
United States, New York
University of Rochester Medical Center, Neurology Not yet recruiting
Rochester, New York, United States, 14642
Contact: Janet Sowden    585-275-1267    Janet_sowden@urmc.rochester.edu   
Principal Investigator: David N Herrmann, MD         
United States, Pennsylvania
University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Sonya A Zaman       sonya.aziz-zaman@uphs.upenn.edu   
Principal Investigator: Colin Quinn, MD         
Sponsors and Collaborators
Acceleron Pharma, Inc.
Investigators
Study Chair: Kenneth M. Attie, MD Acceleron Pharma, Inc.
  More Information

Responsible Party: Acceleron Pharma, Inc.
ClinicalTrials.gov Identifier: NCT03124459     History of Changes
Other Study ID Numbers: A083-03
ACE-083 ( Other Identifier: Acceleron Pharma Inc. )
Study First Received: April 12, 2017
Last Updated: August 3, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Acceleron Pharma, Inc.:
CMT1 / CMTX

Additional relevant MeSH terms:
Tooth Diseases
Charcot-Marie-Tooth Disease
Nerve Compression Syndromes
Hereditary Sensory and Motor Neuropathy
Stomatognathic Diseases
Nervous System Malformations
Nervous System Diseases
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Polyneuropathies
Peripheral Nervous System Diseases
Neuromuscular Diseases
Congenital Abnormalities
Genetic Diseases, Inborn

ClinicalTrials.gov processed this record on August 22, 2017