Clinical trial NCT01247207: Study of Ataluren in Previously Treated Participants With Nonsense Mutation Dystrophinopathy (nmDBMD)
Official title: An Open-Label, Safety Study for Ataluren (PTC124) Patients With Nonsense Mutation Dystrophinopathy
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: PHASE3
Conditions: Duchenne Muscular Dystrophy
Keywords: Duchenne muscular dystrophy
Becker muscular dystrophy
Nonsense mutation
Premature stop codon
DMD
BMD
nmDBMD
DBMD
Ataluren
PTC124
Lead sponsor: PTC Therapeutics
Sponsor class: INDUSTRY
First posted: 2010-11-24
Enrollment: 270
Sex: MALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The objective of this study is to assess the safety and tolerability of 10, 10, 20 milligrams per kilogram (mg/kg) ataluren in participants with nmDBMD who had prior exposure to ataluren in a PTC sponsored clinical trial or treatment plan, and siblings of those participants (provided those participants have completed the placebo-controlled portion of the trial).

The treatment will continue under this protocol until consent withdrawal by participants, withdrawal due to worsen condition after initiating ataluren treatment, withdrawal by investigator, withdrawal due to participant unable to tolerate ataluren, participant is eligible to participate in another ataluren nmDBMD clinical trial program initiated by sponsor, study is discontinued by the relevant regulatory authority and/or sponsor, or until ataluren becomes commercially available.


Eligibility criteria: Inclusion Criteria:

* Evidence of signed and dated informed consent/assent document(s) indicating that the participant (and/or his parent/legal guardian) has been informed of all pertinent aspects of the trial. Note: If the study candidate is considered a child under local regulation, a parent or legal guardian must provide written consent prior to initiation of study screening procedures and the study candidate may be required to provide written assent. The rules of the responsible Institutional Review Board/Independent Ethic Committee (IRB/IEC) regarding whether one or both parents must provide consent and the appropriate ages for obtaining consent and assent from the participant should be followed.
* History of exposure to ataluren in a prior PTC study or treatment plan and effected nmDBMD siblings of those participants (provided those participants have completed the placebo-controlled portion of the trial).
* Fertile men, who are sexually active with women of childbearing potential and who have not had a vasectomy, must agree to use a barrier method of birth control during the study and for up to 50 days after the last dose of study drug.
* Willingness and ability to comply with scheduled visits, drug administration and return plan, study procedures, laboratory tests, and study restrictions Note: Psychological, social, familial, or geographical factors that might preclude adequate study participation should be considered.

Exclusion Criteria:

* Exposure to another investigational drug within 1 month prior to start of study treatment.
* Eligibility for another ataluren clinical trial that is actively enrolling study participants.
* Positive for Hepatitis B core antibody or Hepatitis C antibody at screening for ataluren naïve participants (siblings) or participants who have a temporary treatment gap of 1 year before entering study
* Known hypersensitivity to any of the ingredients or excipients of ataluren (refined polydextrose, polyethylene glycol 3350, poloxamer 407, mannitol 25C, crospovidone XL10, hydroxyethyl cellulose, colloidal silica, magnesium stearate).
* Ongoing intravenous (IV) aminoglycoside or IV vancomycin therapy.
* Ongoing uncontrolled medical/surgical condition, electrocardiogram (ECG) findings, or laboratory abnormality that, in the investigator's opinion, could adversely affect the safety of the participant or make it unlikely that follow-up would be completed.

Primary outcomes:
measure: Number of Participants With Adverse Events
timeFrame: Baseline up to end of study (up to approximately 8 years)
measure: Number of Participants With Laboratory Parameters Abnormalities
timeFrame: Baseline up to end of study (up to approximately 8 years)
measure: Number of Participants With Abnormal Physical Findings
timeFrame: Baseline up to end of study (up to approximately 8 years)
Secondary outcomes:
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix Childrens Hospital
state: Arizona
city: Los Angeles
country: United States
facility: Children's Hospital of Los Angeles
state: California
city: Los Angeles
country: United States
facility: UCLA
state: California
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: Sacramento
country: United States
facility: University of California-Davis
state: California
city: San Francisco
country: United States
facility: University of CA, San Francisco-Benioff Children's Hospital
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado - Center for Cancer and Blood Disorders
state: Colorado
city: Gulf Breeze
country: United States
facility: Child Neurology Center of NW Florida NW
state: Florida
city: Atlanta
country: United States
facility: Rare Disease Research, LLC
state: Georgia
city: Chicago
country: United States
facility: Rush Univ Medical Center
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa Children's Hospital
state: Iowa
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Boston
country: United States
facility: Children's Hospital of Boston/Harvard Medical School
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University Medical School
state: Missouri
city: New York
country: United States
facility: Columbia University Pediatric Neuromuscular Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Childrens Hospital Medical Center
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Portland
country: United States
facility: Shriners Hospital for Children-Portland
state: Oregon
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Dallas
country: United States
facility: Childrens Medical Center Dallas
state: Texas
city: Houston
country: United States
facility: Texas Children's Hospital
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Norfolk
country: United States
facility: Children's Hospital of the King's Daughters
state: Virginia
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Calgary
country: Canada
facility: Alberta Children's Hospital
state: Alberta
city: Vancouver
country: Canada
facility: British Columbia Children's Hospital
state: British Columbia
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Ottawa
country: Canada
facility: Children's Hospital of East Ontario
state: Ontario
city: Quebec
country: Canada
facility: CHU de Québec - Université Laval
Study officials:
affiliation: PTC Therapeutics, Inc.
name: Vinay Penematsa, MD
role: STUDY_DIRECTOR
References:
citation: Hirawat S, Welch EM, Elfring GL, Northcutt VJ, Paushkin S, Hwang S, Leonard EM, Almstead NG, Ju W, Peltz SW, Miller LL. Safety, tolerability, and pharmacokinetics of PTC124, a nonaminoglycoside nonsense mutation suppressor, following single- and multiple-dose administration to healthy male and female adult volunteers. J Clin Pharmacol. 2007 Apr;47(4):430-44. doi: 10.1177/0091270006297140.
citation: Welch EM, Barton ER, Zhuo J, Tomizawa Y, Friesen WJ, Trifillis P, Paushkin S, Patel M, Trotta CR, Hwang S, Wilde RG, Karp G, Takasugi J, Chen G, Jones S, Ren H, Moon YC, Corson D, Turpoff AA, Campbell JA, Conn MM, Khan A, Almstead NG, Hedrick J, Mollin A, Risher N, Weetall M, Yeh S, Branstrom AA, Colacino JM, Babiak J, Ju WD, Hirawat S, Northcutt VJ, Miller LL, Spatrick P, He F, Kawana M, Feng H, Jacobson A, Peltz SW, Sweeney HL. PTC124 targets genetic disorders caused by nonsense mutations. Nature. 2007 May 3;447(7140):87-91. doi: 10.1038/nature05756. Epub 2007 Apr 22.