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



Status:Recruiting
Conditions:Neurology, Dental
Therapuetic Areas:Dental / Maxillofacial Surgery, Neurology
Healthy:No
Age Range:18 - Any
Updated:1/17/2019
Start Date:July 31, 2017
End Date:February 2020
Contact:Clinical Trial Manager
Email:clinicaltrials08303@acceleronpharma.com
Phone:617-649-9200

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A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study of ACE-083 in Patients With Charcot-Marie-Tooth Disease Types 1 and X

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.

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.

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
We found this trial at
16
sites
Gainesville, Florida 32610
(352) 392-3261
Principal Investigator: Sankarsubramoney Subramony, MD
Phone: 352-294-8778
University of Florida The University of Florida (UF) is a major, public, comprehensive, land-grant, research...
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85 S Prospect St
Burlington, Vermont 5405
(802) 656-3131
Principal Investigator: Waqar Waheed, MD
University of Vermont The University of Vermont combines faculty-student relationships most commonly found in a...
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Burlington, VT
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116th St and Broadway
New York, New York 10027
(212) 854-1754
Principal Investigator: Thomas Brannagan, MD
Phone: 212-342-4447
Columbia University In 1897, the university moved from Forty-ninth Street and Madison Avenue, where it...
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New York, NY
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3181 Southwest Sam Jackson Park Road
Portland, Oregon 97239
503 494-8311
Principal Investigator: Chafic Karam, MD
Phone: 503-494-7269
Oregon Health and Science University In 1887, the inaugural class of the University of Oregon...
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Portland, OR
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201 Presidents Circle
Salt Lake City, Utah 84108
801) 581-7200
Principal Investigator: Russell Butterfield, MD
Phone: 801-585-5052
University of Utah Research is a major component in the life of the U benefiting...
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Salt Lake City, UT
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Aurora, Colorado 80045
Principal Investigator: Vera Fridman, MD
Phone: 303-724-4644
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1010 Edgehill Road North
Charlotte, North Carolina 28207
Principal Investigator: Urvi Desai, MD
Phone: 704-446-0803
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Charlotte, NC
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30 Prospect Ave
Hackensack, New Jersey 07601
(201) 996-2000
Principal Investigator: Florian Thomas, MD
Phone: 551-996-3079
Hackensack University Medical Center Hackensack University Medical Center, part of the Hackensack University Health Network,...
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200 Hawkins Dr,
Iowa City, Iowa 52242
866-452-8507
Principal Investigator: Michael Shy, MD
Phone: 319-358-8596
University of Iowa Hospitals and Clinics University of Iowa Hospitals and Clinics—recognized as one of...
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Iowa City, IA
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3901 Rainbow Boulevard
Kansas City, Kansas 66160
Principal Investigator: Jeffrey Statland
Phone: 913-945-9937
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909 Fulton Street Southeast
Minneapolis, Minnesota 55455
Principal Investigator: David Walk, MD
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Orange, California 92868
Principal Investigator: Tahseen Mozaffar, MD
Phone: 714-456-8520
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3451 Walnut St
Philadelphia, Pennsylvania 19104
1 (215) 898-5000
Principal Investigator: Colin Quinn, MD
Univ of Pennsylvania Penn has a long and proud tradition of intellectual rigor and pursuit...
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Richmond, Virginia 23298
(804) 828-0100
Principal Investigator: Scott Vota, MD
Virginia Commonwealth University Since our founding as a medical school in 1838, Virginia Commonwealth University...
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601 Elmwood Avenue
Rochester, New York 14642
Principal Investigator: David N Herrmann, MD
Phone: 585-275-1267
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Rochester, NY
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660 S Euclid Ave
Saint Louis, Missouri 63110
(314) 362-5000
Principal Investigator: Alan Pestronk, MD
Washington University School of Medicine Washington University Physicians is the clinical practice of the School...
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