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

Study Description

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Brief Summary:

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 comprises a Phase 3, open-label study of ataluren in patients with nmDBMD who previously received ataluren at an investigator site in a prior PTC-sponsored clinical study. A separate open-label study (PTC124-GD-016-DMD) is being conducted for nmDBMD patients who previously received ataluren at an investigator site in the United States (US).

Condition or disease	Intervention/treatment	Phase
Duchenne Muscular Dystrophy; Becker Muscular Dystrophy; Dystrophinopathy	Drug: Ataluren	Phase 3

Detailed Description:

All participating sites must have had at least 1 patient that received ataluren treatment in a prior PTC-sponsored clinical study in DBMD. It is planned that up to ~96 patients will be enrolled.

Subjects will receive ataluren 3 times per day (TID) at respective morning, midday, and evening doses of 10 mg/kg, 10 mg/kg, and 20 mg/kg, for approximately 336 weeks. Study assessments will be performed at clinic visits during screening, on the first day of ataluren dosing, and then every48 weeks during the ataluren treatment period, except for weight, which will be measured every 24 weeks at a primary care physician (PCP). No measures of efficacy will be captured.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	95 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	An Open-Label Study for Previously Treated Ataluren (PTC124) Patients With Nonsense Mutation Dystrophinopathy
Study Start Date :	May 2012
Estimated Primary Completion Date :	March 2018
Estimated Study Completion Date :	March 2018

Arms and Interventions

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Arm	Intervention/treatment
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

Outcome Measures

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Primary Outcome Measures :

1. Long term Safety and Tolerability of Ataluren. [ Time Frame: 336 weeks ]
   The primary objective of this study is to assess the long-term safety and tolerability of 10, 10, 20 mg/kg ataluren in patients with nmDBMD who had prior exposure to ataluren in a PTC-sponsored clinical trial.Safety profile characterized by type, frequency, severity, timing, and relationship to Ataluren of any adverse events or laboratory abnormalities.

Eligibility Criteria

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

Criteria

1. 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.

   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 Ethics Committee (IRB/IEC) regarding whether one or both parents must provide consent and the appropriate ages for obtaining consent and assent from the subject should be followed.

2. History of exposure to ataluren in a prior PTC study in nmDBMD . Note: Patients are considered eligible only if they received ataluren during their participation in one or more prior PTC-sponsored studies of ataluren in nmDBMD. Note: Subjects who have participated in a prior or ongoing PTC study with ataluren in nmDBMD at a trial site in the US or Canada, but reside outside of the US and Canada, may be eligible for this study (with the approval of the PTC Therapeutics Medical Monitor).
3. Male sex.
4. In patients 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.
5. Willingness and ability to comply with scheduled visits, drug administration 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:

1. Exposure to another investigational drug within 1 month prior to start of study treatment.
2. Eligibility for another ataluren clinical trial that is actively enrolling study participants.
3. Known hypersensitivity to any of the ingredients or excipients of ataluren (Litesse® UltraTM [refined polydextrose], polyethylene glycol 3350, Lutrol® micro F127 [poloxamer 407], mannitol 25C, crospovidone XL10, hydroxyethyl cellulose, vanilla, Cab-O-Sil® M5P [colloidal silica], magnesium stearate).

4. Ongoing use of the following medications:

   1. Coumarin-based anticoagulants (eg, warfarin), phenytoin, tolbutamide, or paclitaxel.
   2. Systemic aminoglycoside therapy
5. 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

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Locations

Australia, Melbourne
Royal Children's Hospital
Parkville, Melbourne, Australia
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
Göteborg, 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

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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
First Posted:	March 19, 2012
Last Update Posted:	January 18, 2018
Last Verified:	January 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No

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