Study of Ataluren for Previously Treated Patients With nmDBMD in Europe, Israel, Australia, and Canada - Full Text View

Purpose

Duchenne/Becker muscular dystrophy (DBMD) is a genetic disorder that 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 during childhood and teenage years. A specific type of mutation, called a nonsense (premature stop codon) mutation, is the cause of DBMD 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. This study is an open-label trial for patients with nonsense mutation dystrophinopathy who received ataluren in a prior PTC-sponsored study at a clinical trial site in Europe, Israel, Australia, or Canada. The primary objective of the study is to evaluate the long-term safety of ataluren, as determined by adverse events and laboratory abnormalities.

Condition	Intervention	Phase
Duchenne Muscular Dystrophy Becker Muscular Dystrophy Dystrophinopathy	Drug: Ataluren	Phase 3


Study Type:	Interventional
Study Design:	Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	An Open-Label Study for Previously Treated Ataluren (PTC124) Patients With Nonsense Mutation Dystrophinopathy

Resource links provided by NLM:

Genetics Home Reference related topics: Duchenne and Becker muscular dystrophy

MedlinePlus related topics: Muscular Dystrophy

Genetic and Rare Diseases Information Center resources: Muscular Dystrophy Duchenne Muscular Dystrophy Becker Muscular Dystrophy Dystrophinopathy

U.S. FDA Resources

Further study details as provided by PTC Therapeutics:

Primary Outcome Measures:

Safety and Tolerability [ Time Frame: 240 weeks ]
The safety profile of ataluren will be characterized by type, frequency, severity, timing, and relationship to ataluren of any adverse events or laboratory abnormalities

Secondary Outcome Measures:

Change from baseline in 6MWD as measured by the 6MWT (in ambulatory patients) [ Time Frame: 240 weeks ]
Change from baseline in subject and parent/caregiver-reported activities of daily living, as measured by the Egen Klassifikation (EK) scale (in nonambulatory patients) [ Time Frame: 240 weeks ]
Change from baseline in timed function tests (in ambulatory patients) [ Time Frame: 240 weeks ]
Change from baseline in pulmonary function as measured by spirometry (in nonambulatory patients) [ Time Frame: 240 weeks ]
Change from baseline in physical function as measured by the North Star Ambulatory Assessment (in ambulatory patients) [ Time Frame: 240 weeks ]
Changes in patient and/or parent/caregiver reports of disease status as measured by a standardized survey administered by site personnel [ Time Frame: 240 weeks ]


Enrollment:	95
Study Start Date:	May 2012
Estimated Study Completion Date:	November 2019
Estimated Primary Completion Date:	November 2019 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Ataluren Ataluren	Drug: Ataluren Oral powder for suspension taken 3 times per day (10 mg/kg in the morning, 10 mg/kg at mid-day, and 20mg/kg in the evening). Other Name: PTC124

Detailed Description:

The study will enroll boys with nonsense mutation DBMD who have a history of exposure to ataluren in a prior PTC study in nmDBMD (PTC124-GD-004-DMD, PTC124-GD-004e-DMD, PTC124-GD-007-DMD, PTC124-GD-007e, and PTC124-GD-008-DMD) at a trial site in Europe, Israel, Australia, or Canada. Patients will receive study drug 3 times per day (at breakfast, lunch, and dinner). Study assessments will be performed at clinic visits during screening and every 12 weeks during the 96-week treatment period. Patients must also return to the clinic for a post-treatment visit 6 weeks after the last dose of ataluren.

Eligibility


Ages Eligible for Study:	Child, Adult, Senior
Sexes Eligible for Study:	Male
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Evidence of signed and dated informed consent/assent document(s) indicating that the subject (and/or his parent/legal guardian) has been informed of all pertinent aspects of the trial
History of exposure to ataluren in a prior PTC study in nmDBMD
Male sex
Confirmed screening laboratory values within the specified ranges
In subjects who are sexually active, willingness to abstain from sexual intercourse or employ a barrier or medical method of contraception during ataluren administration and the 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:

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
Known hypersensitivity to any of the ingredients or excipients of study drug
Ongoing use of the following medications: coumarin based anti-coagulants, phenytoin, tolbutamide, paclitaxel, or systemic aminoglycoside therapy
Ongoing uncontrolled medical/surgical condition, ECG findings, or laboratory abnormality that, in the investigator's opinion, could adversely affect the safety of the patient or make it unlikely that follow-up would be completed

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: NCT01557400

Locations


Australia
Royal Children's Hospital
Parkville, Victoria, Australia
Institute For Neuromuscular Research, The Children's Hospital at Westmead
Westmead, Australia
Belgium
University Hospital KU Leuven
Leuven, Belgium
Canada, Alberta
Alberta Children's Hospital
Calgary, Alberta, Canada
Canada, British Columbia
British Columbia Children's Hospital
Vancouver, British Columbia, Canada
Canada, Ontario
Children's Hospital of Western Ontario
London, Ontario, Canada
France
Hôpital d'Enfants CHU Timone
Marseille, France
Laboratoire d'Exploration Fonctionnelles
Nantes, France
Groupe Hospitalier La Pitie-Salpetriere
Paris, France
Germany
University of Essen - Clinic for Children
Essen, Germany
University Hospital
Freiburg, Germany
Israel
Hadassah Medical Center, Hebrew University Hospital
Jerusalem, Israel
Italy
Ospedale Maggiore Policlinico in Milan
Milan, Italy
Ospedale Pediatrico Bambino Gesu
Rome, Italy
U.O. Complessa di Neuropsichiatria Infantile
Rome, Italy
Spain
Hospital Sant Joan de déu
Barcelona, Spain
Hospital Universitari La Fe
Valencia, Spain
Sweden
Queen Silvia Children's Hospital
Goteburg, Sweden
Astrid Lindgren Pediatric Hospital
Stockholm, Sweden
United Kingdom
Great Ormond Street Hospital
London, United Kingdom
University of Newcastle Institute of Human Genetics
Newcastle Upon Tyne, United Kingdom

Sponsors and Collaborators

PTC Therapeutics

Investigators


Study Director:	Edward O'Mara, MD	PTC Therapeutics

More Information

Publications:

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. Epub 2007 Apr 22.

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.


Responsible Party:	PTC Therapeutics
ClinicalTrials.gov Identifier:	NCT01557400 History of Changes
Other Study ID Numbers:	PTC124-GD-019-DMD
Study First Received:	March 15, 2012
Last Updated:	July 26, 2016

Keywords provided by PTC Therapeutics:


Duchenne muscular dystrophy Becker muscular dystrophy Nonsense mutation Premature stop codon DMD	BMD nmDBMD DBMD Ataluren PTC124

Additional relevant MeSH terms:


Muscular Dystrophies Muscular Dystrophy, Duchenne Muscular Disorders, Atrophic Muscular Diseases Musculoskeletal Diseases	Neuromuscular Diseases Nervous System Diseases Genetic Diseases, Inborn Genetic Diseases, X-Linked

ClinicalTrials.gov processed this record on July 25, 2017