Phase 3 Study of Ataluren in Patients With Nonsense Mutation Duchenne Muscular Dystrophy



Status:Completed
Conditions:Neurology, Orthopedic, Women's Studies
Therapuetic Areas:Neurology, Orthopedics / Podiatry, Reproductive
Healthy:No
Age Range:7 - 16
Updated:12/15/2017
Start Date:March 2013
End Date:August 2015

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A Phase 3 Efficacy and Safety Study of Ataluren (PTC124) in Patients With Nonsense Mutation Dystrophinopathy

Dystrophinopathy is a disease continuum that includes Duchenne muscular dystrophy, which
develops in boys. It is caused by a mutation in the gene for dystrophin, a protein that is
important for maintaining normal muscle structure and function. Loss of dystrophin causes
muscle fragility that leads to weakness and loss of walking ability. A specific type of
mutation, called a nonsense (premature stop codon) mutation is the cause of dystrophinopathy
in approximately 10-15% of boys with the disease. Ataluren is an orally delivered,
investigational drug that has the potential to overcome the effects of the nonsense mutation.
The main goal of this Phase 3 study is to evaluate the effect of ataluren on walking ability.
The effect of ataluren on physical function, quality of life, and activities of daily living
will be evaluated. This study will also provide additional information on the long-term
safety of ataluren.

This study is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study to
determine the efficacy and safety of ataluren 10, 10, 20 mg/kg in patients with
nonsense-mutation (nm) dystrophinopathy. Patients will be randomized in a 1:1 ratio to
ataluren 10-, 10-, 20-mg/kg dose level or placebo. Patients will receive study drug TID at
morning, midday, and evening. It is planned that 220 patients will be enrolled and patients
will undergo 48 weeks of blinded treatment prior to the final analysis. Study assessments
will be performed at clinic visits every 8 weeks. It is anticipated that an open-label
extension study will be available to patients (who successfully complete the double-blind
study) in countries where ataluren is not commercially available.

Inclusion Criteria:

- Ability to provide written informed consent (parental/guardian consent if
applicable)/assent per local requirements.

- Male sex.

- Age ≥7 and ≤16 years.

- Phenotypic evidence of dystrophinopathy based on the onset of characteristic clinical
symptoms or signs (eg. proximal muscle weakness, waddling gait, and Gowers' maneuver)
by 6 years of age, an elevated serum creatinine kinase level, and ongoing difficulty
with walking.

- Documentation of the presence of a nonsense point mutation in the dystrophin gene as
determined by gene sequencing from a laboratory certified by the College of American
Pathologists (CAP), the Clinical Laboratory Improvement Act/Amendment (CLIA) or an
equivalent organization.

- Documentation that a blood sample has been drawn for confirmation of the presence of a
nonsense mutation in the dystrophin gene.

- Use of systemic corticosteroids (prednisone, prednisolone, or deflazacort) for a
minimum of 6 months immediately prior to start of study treatment, with no significant
change in dosage or dosing regimen (not related to body weight change) for a minimum
of 3 months immediately prior to start of study treatment and a reasonable expectation
that dosage and dosing regimen will not change significantly for the duration of the
study.

- Ability to walk ≥150 meters unassisted during the screening 6-minute walk test.
Patients need to be below the protocol-specified threshold for %-predicted 6MWD.

- Results of the 2 Baseline 6MWD results must be determined as valid and results of the
Day 2 Baseline 6MWD must be within 20% of the Day 1 Baseline 6MWD.

- Baseline 6MWD (mean of valid Day 1 and Day 2 values) must be no more than a 20%
reduction from the valid Screening 6MWD.

- Confirmed screening laboratory values within the central laboratory ranges (hepatic,
renal, and serum electrolyte parameters)

- Willingness to abstain from sexual intercourse or employ an approved method of
contraception during the period of study drug administration and 6-week follow-up
period.

- Willingness and ability to comply with scheduled visits, drug administration plan,
study procedures, laboratory tests, and study restrictions.

Exclusion Criteria:

- Treatment with systemic aminoglycoside antibiotics within 3 months prior to start of
study treatment.

- Initiation of systemic corticosteroids therapy within 6 months prior to start of study
treatment.

- Change in systemic corticosteroid therapy (eg, change in type of drug, dose
modification not related to body weight change, schedule modification, interruption,
or reinitiation) within 3 months prior to start of study treatment.

- Any change (initiation, change in type of drug, dose modification, schedule
modification,interruption, discontinuation, or reinitiation) in prophylaxis/treatment
for congestive heart failure (CHF) within 3 months prior to start of study treatment.

- Ongoing use of coumarin-based anticoagulants (eg. warfarin), phenytoin, tolbutamide,
or paclitaxel.

- Prior therapy with ataluren.

- Known hypersensitivity to any of the ingredients or excipients of the study drug

- Exposure to another investigational drug within 3 months prior to start of study
treatment.

- History of major surgical procedure within 6 weeks prior to start of study treatment.

- Ongoing immunosuppressive therapy (other than corticosteroids).

- Ongoing participation in any clinical trial (except for studies specifically approved
by PTC Therapeutics).

- Expectation of major surgical procedure (eg, scoliosis surgery) during the 12-month
treatment period of the study.

- Requirement for daytime ventilator assistance. Note: Evening ventilator assistance and
use of bi-level positive airway pressure (Bi-PAP) therapy is allowed.

- Uncontrolled clinical symptoms and signs of CHF (American College of
Cardiology/American Heart Association Stage C or Stage D).

- Prior or ongoing medical condition (eg, concomitant illness, psychiatric condition,
behavioral disorder, alcoholism, drug abuse), medical history, physical findings (eg.
lower limb injury that may affect 6MWT performance), ECG findings, or laboratory
abnormality that, in the investigator's opinion, could adversely affect the safety of
the subject, makes it unlikely that the course of treatment or follow-up would be
completed, or could impair the assessment of study results.
We found this trial at
22
sites
3333 Burnet Avenue # Mlc3008
Cincinnati, Ohio 45229
 1-513-636-4200 
Cincinnati Children's Hospital Medical Center Patients and families from across the region and around the...
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700 Childrens Drive
Columbus, Ohio 43205
(616) 722-2000
Nationwide Children's Hospital At Nationwide Children’s, we are creating the future of pediatric health care....
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Columbus, OH
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101 Jessup Hall
Iowa City, Iowa 52242
(319) 335-3500
University of Iowa With just over 30,000 students, the University of Iowa is one of...
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Iowa City, IA
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Los Angeles, California 90095
310-825-4321
University of California at Los Angeles The University of California, Los Angeles (UCLA) is an...
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Los Angeles, CA
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Minneapolis, Minnesota 55455
(612) 625-5000
Univ of Minnesota With a flagship campus in the heart of the Twin Cities, and...
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Minneapolis, MN
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630 W 168th St
New York, New York 10032
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New York, NY
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South 34th Street
Philadelphia, Pennsylvania 19104
 215-590-1000
Children's Hospital of Philadelphia Since its start in 1855 as the nation's first hospital devoted...
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Philadelphia, PA
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3181 Southwest Sam Jackson Park Road
Portland, Oregon 97239
503 494-8311
Oregon Health and Science University In 1887, the inaugural class of the University of Oregon...
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Sacramento, California 95814
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201 Presidents Circle
Salt Lake City, Utah 84108
801) 581-7200
University of Utah Research is a major component in the life of the U benefiting...
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300 Longwood Ave
Boston, Massachusetts 02115
(617) 355-6000
Boston Children's Hospital Boston Children's Hospital is a 395-bed comprehensive center for pediatric health care....
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Boston, Massachusetts 02115
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1653 W. Congress Parkway
Chicago, Illinois 60612
(312) 942-5000
Rush University Medical Center Rush University Medical Center encompasses a 664-bed hospital serving adults and...
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Chicago, IL
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Dallas, TX
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Gulf Breeze, Florida 32561
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6621 Fannin St
Houston, Texas 77030
(832) 824-1000
Texas Children's Hospital Texas Children's Hospital, located in Houston, Texas, is a not-for-profit organization whose...
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3901 Rainbow Blvd
Kansas City, Kansas 66160
(913) 588-5000
University of Kansas Medical Center The University of Kansas Medical Center serves Kansas through excellence...
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3414 Fifth Avenue
Pittsburgh, Pennsylvania 15213
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Westmead, New South Wales 2145
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