ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 3 of 3 for:    ace-083

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03124459
Recruitment Status : Recruiting
First Posted : April 21, 2017
Last Update Posted : June 15, 2018
Sponsor:
Information provided by (Responsible Party):
Acceleron Pharma, Inc.

Brief Summary:
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 or disease Intervention/treatment Phase
Charcot-Marie-Tooth Disease Drug: ACE-083 Drug: Placebo Phase 2

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 SRT to determine the recommended dose level (maximum 250 mg/muscle). A total of up to 40 new patients may be enrolled and randomized (1:1 randomization) to receive either ACE 083 (n=20) or placebo (n=20) bilaterally by injection into both TA muscles once every 3 weeks for up to 17 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.

Study duration for Part 2 will be 15 months, including 4-week screening, 6 months double blind placebo-controlled , 6 months open-label and 8 week follow-up.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 42 participants
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
Actual Study Start Date : July 31, 2017
Estimated Primary Completion Date : February 2020
Estimated Study Completion Date : February 2020


Arm Intervention/treatment
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 (double-blind placebo controlled)
ACE-083 up to 250 mg IM (tibialis anterior muscle) or placebo, once every 3 weeks for up to 9 doses
Drug: ACE-083
Part 1 - Recombinant fusion protein. Part 2 - Recombinant fusion protein or buffer solution.

Drug: Placebo
Recombinant fusion protein or buffer solution

Experimental: Part 2 (open label)
ACE-083 up to 250 mg IM (tibialis anterior muscle), once every 3 weeks for up to 8 doses
Drug: ACE-083
Part 1 - Recombinant fusion protein. Part 2 - Recombinant fusion protein or buffer solution.




Primary Outcome Measures :
  1. 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

  2. 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 :
  1. 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

  2. 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)

  3. 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

  4. 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

  5. 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

  6. 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 scoring system to assess sensory and motor impairment in subjects with CMT

  7. 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



Information from the National Library of Medicine

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, Learn About Clinical Studies.


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. Age ≥ 18 years
  2. Diagnosis of CMT1 or CMTX confirmed by:

    1. Clinical presentation and electrodiagnostics
    2. Genetically-confirmed CMT1 or CMTX for the patient or first-degree relative
  3. Part 1:

    1. Six-minute walk distance (6MWD) of at least 150 meters (without a brace or walker)
    2. Independent ambulation for at least 10 meters, without a brace
    3. Left and right ankle plantar flexion MRC grade 4+ to 5, inclusive

    Part 2:

    1. 6MWD ≥ 150 and ≤ 500 meters (without a brace or walker); a maximum of 20% of enrolled patients with 6MWD ≥ 450 meters will be included
    2. Left and right ankle plantar flexion MRC grade 4- to 5, inclusive
  4. Left and right ankle dorsiflexion Medical Research Council (MRC) manual muscle testing (MMT) grade 4- to 4+, inclusive
  5. Females of childbearing potential must have negative urine pregnancy test prior to enrollment and use highly effective birth control methods 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.
  6. Ability to adhere to the study visit schedule/procedures, and to understand and comply with protocol requirements
  7. Signed written informed consent

Key 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. 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; low dose aspirin [≤ 100 mg daily] is permitted)
  8. Severe deformity or ankle fixation that would sufficiently limit passive range of motion to affect assessment of dorsiflexion strength
  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 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 prior to Study Day 1 if half-life is unknown)
  14. Any previous or current exposure to ACE-083
  15. 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
  16. 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)
  17. Known active substance abuse, including alcohol
  18. History of sensitivity to protein pharmaceuticals
  19. Female that is lactating/breast-feeding

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03124459


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

Locations
United States, California
University of California-Irvine Recruiting
Orange, California, United States, 92868
Contact: Jeanette Overton    714-456-8520    jtoverto@uci.edu   
Principal Investigator: Tahseen Mozaffar, MD         
United States, Florida
University of Florida Recruiting
Gainesville, Florida, United States, 32610
Contact: Amanda Cowsert, CRC    352-294-8778    Amanda.cowsert@ufl.edu   
Principal Investigator: Sankarsubramoney Subramony, MD         
United States, Iowa
University of Iowa Hospitals and Clinics Recruiting
Iowa City, Iowa, United States, 52242
Contact: Nicole Kressin    319-358-8596    Nicole-kressin@uiowa.edu   
Principal Investigator: Michael Shy, MD         
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, Minnesota
University of Minnesota, Neurology Department Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Natalya Burlakova       burla019@umn.edu   
Principal Investigator: David Walk, MD         
United States, New Jersey
Hackensack University Medical Center Recruiting
Hackensack, New Jersey, United States, 07601
Contact: Christine Cavallo    551-996-3079    Christine.cavallo@hackensackmeridian.org   
Principal Investigator: Florian Thomas, MD         
United States, New York
University of Rochester Medical Center, Neurology 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, Oregon
Oregon Health & Science University Recruiting
Portland, Oregon, United States, 97239
Contact: Diana Dimitrova, PhD    503-494-7269    dimitrov@ohsu.edu   
Contact: Chafic         
Principal Investigator: Chafic Karam, 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         
United States, Utah
University of Utah Recruiting
Salt Lake City, Utah, United States, 84112
Contact: Bryant Gordon, CRC    801-585-5052    Bryant.gordon@hsc.utah.edu   
Principal Investigator: Nicholas Johnson, MD         
Sponsors and Collaborators
Acceleron Pharma, Inc.
Investigators
Study Chair: Kenneth M. Attie, MD Acceleron Pharma, Inc.

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. )
First Posted: April 21, 2017    Key Record Dates
Last Update Posted: June 15, 2018
Last Verified: June 2018
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