Clinical trial NCT02090959: An Extension Study of Ataluren (PTC124) in Participants With Nonsense Mutation Dystrophinopathy
Official title: A Phase 3 Extension Study of Ataluren (PTC124) in Patients With Nonsense Mutation Dystrophinopathy
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Muscular Dystrophy, Duchenne
Muscular Dystrophies
Muscular Disorders, Atrophic
Muscular Diseases
Musculoskeletal Diseases
Neuromuscular Diseases
Nervous System Diseases
Genetic Diseases, X-Linked
Genetic Diseases, Inborn
Keywords: Duchenne muscular dystrophy
Dystrophinopathy
Nonsense mutation
Premature stop codon
Becker muscular dystrophy
DMD/BMD
PTC124
Ataluren
Lead sponsor: PTC Therapeutics
Sponsor class: INDUSTRY
First posted: 2014-03-19
Enrollment: 219
Sex: MALE
Minimum age (years): 7
Maximum age (years): 15
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to obtain long term safety data of ataluren in male participants with nonsense mutation dystrophinopathy (who participated and completed a previous Phase 3 study of ataluren \[PTC124-GD-020-DMD {NCT01826487}\]) to augment the overall safety database. Screening and baseline procedures are structured to avoid a gap in treatment between the double-blind study (PTC124-GD-020-DMD) and this extension study.

This study may be further extended by amendment until either ataluren becomes commercially available or the clinical development of ataluren in duchenne muscular dystrophy (DMD) is discontinued.


Eligibility criteria: Inclusion Criteria:

* Completion of study treatment in the previous Phase 3, double-blind study (PTC124-GD-020-DMD).
* 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 1 or both parents must provide consent and the appropriate ages for obtaining consent and assent from the participant should be followed.
* In participants who are sexually active, willingness to abstain from sexual intercourse or employ a barrier or medical method of contraception during the period of study drug administration and 6-week follow-up period.
* Willingness and ability to comply with scheduled visits, ataluren administration plan, study procedures, laboratory tests, and study restrictions.

Exclusion Criteria:

* Known hypersensitivity to any of the ingredients or excipients of the study drug (Litesse® UltraTM \[refined polydextrose\], polyethylene glycol 3350, Lutrol® micro F127 \[poloxamer 407\], mannitol 25C, crospovidone XL10, hydroxyethyl cellulose, vanilla, Cab-O-Sil® M5P \[colloidal silica\], and magnesium stearate).
* Ongoing participation in any other therapeutic clinical trial.
* Prior or ongoing medical condition (for example, concomitant illness, psychiatric condition, behavioral disorder, alcoholism, drug abuse), medical history, physical findings, electrocardiogram (ECG) findings, or laboratory abnormality that, in the investigator's opinion, could adversely affect the safety of the participant, makes it unlikely that the course of treatment or follow-up would be completed, or could impair the assessment of study results.

Primary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: Baseline (Day 1) up to 6 weeks post-treatment (Week 150)
measure: Number of Participants With Abnormalities in Clinical Laboratory Parameters
timeFrame: Baseline (Day 1) up to 6 weeks post-treatment (Week 150)
Secondary outcomes:
measure: Change From Baseline in 6MWD at Week 144
timeFrame: Baseline, Week 144
measure: Change From Baseline in Time to Stand From Supine Position at Week 144
timeFrame: Baseline, Week 144
measure: Change From Baseline in Time to Walk/Run 10 Meters at Week 144
timeFrame: Baseline, Week 144
measure: Change From Baseline in Time to Climb 4 Stairs at Week 144
timeFrame: Baseline, Week 144
measure: Change From Baseline in Time to Descend 4 Stairs at Week 144
timeFrame: Baseline, Week 144
measure: Change From Baseline in Physical Function Total Score as Measured by NSAA at Week 144
timeFrame: Baseline, Week 144
measure: Change From Baseline in PUL Total Score at Week 144
timeFrame: Baseline, Week 144
measure: Change From Baseline in Percent Predicted FVC as Measured by Spirometry at Week 144
timeFrame: Baseline, Week 144
measure: Change From Baseline in Percent Predicted FEV1 as Measured by Spirometry at Week 144
timeFrame: Baseline, Week 144
measure: Change From Baseline in PEF as Measured by Spirometry at Week 144
timeFrame: Baseline, Week 144
measure: Change From Baseline in PCF as Measured by Spirometry at Week 144
timeFrame: Baseline, Week 144
measure: Change From Baseline in PODCI Transfers/Basic Mobility Score at Week 144
timeFrame: Baseline, Week 144
measure: Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 144, as Assessed by a Standardized Survey Administered by Site Personnel
timeFrame: Baseline, Week 144
measure: Ataluren Plasma Concentration
timeFrame: Pre-dose at Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, and 144
measure: Change From Baseline in Systolic and Diastolic Blood Pressure at Week 144
timeFrame: Baseline, Week 144
measure: Change From Baseline in Pulse Rate at Week 144
timeFrame: Baseline, Week 144
measure: Change From Baseline in Body Temperature at Week 144
timeFrame: Baseline, Week 144
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of California, Los Angeles
state: California
city: Sacramento
country: United States
facility: UC Davis Medical Center
state: California
city: Stanford
country: United States
facility: Stanford University Medical Center
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 Northwest Florida
state: Florida
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa
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 Boston
state: Massachusetts
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine, Division of Endocrinology, Metabolism and Lipid Research
state: Missouri
city: New York
country: United States
facility: Columbia University College of Physicians & Surgeons
state: New York
city: Cincinnati
country: United States
facility: Children's Hospital Cincinnati
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Philadelphia
country: United States
facility: The Children's Hospital of Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh
state: Pennsylvania
city: Dallas
country: United States
facility: Childrens Medical Center Dallas, Texas
state: Texas
city: Houston
country: United States
facility: Texas Children's Hospital
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Seattle
country: United States
facility: Seattle Children's Hospital - Childhood Cancer and Blood Disorders
state: Washington
city: Westmead
country: Australia
facility: The Children's Hospital at Westmead
state: New South Wales
city: Parkville
country: Australia
facility: The Royal Children's Hospital
state: Victoria
city: Leuven
country: Belgium
facility: UZ Leuven
city: Rio de Janeiro
country: Brazil
facility: Universidade Federal do Rio de Janeiro - Instituto de Puericultura e Pediatria Martagao Gesteira
city: São Paulo
country: Brazil
facility: Sao Paulo University -HC/FMUSP
city: Sofia
country: Bulgaria
facility: Aleksandrovska Hospital
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: Children's Hospital of Western Ontario
state: Ontario
city: Santiago
country: Chile
facility: Hospital Luis Calvo Mackenna
state: Región Metropolitana
city: Santiago
country: Chile
facility: Hospital Clinico Universidad Catolica
city: Brno
country: Czechia
facility: University Hospital Brno
city: Praha
country: Czechia
facility: Motol University Hospital
city: Marseille
country: France
facility: Hospital de la Timone
city: Nantes Cedex 1
country: France
facility: CHU de Nantes
city: Paris Cedex 13
country: France
facility: Groupe Hospitalier Pitie-Salpetriere
city: Paris
country: France
facility: Hopital Necker - Enfants Malades
city: Essen
country: Germany
facility: Universitaetsklinikum Essen
city: Freiburg
country: Germany
facility: University Medical Center Freiburg
city: Munchen
country: Germany
facility: Universitat Munchen - von Haunersche Kinder Clinic
city: Jerusalem
country: Israel
facility: Hadassah University Hospital
city: Milano
country: Italy
facility: Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico di Milano
city: Rome
country: Italy
facility: Bambino Gesu Hospital
city: Rome
country: Italy
facility: U.O. Complessa di Neuropsichiatria Infantile
city: Sicily
country: Italy
facility: Policlinico Universitario G. Martino
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Warsaw
country: Poland
facility: Medical University of Warsaw
city: Barcelona
country: Spain
facility: Hospital Sant Joan de Deu
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic la Fe
city: Goteburg
country: Sweden
facility: Queen Silvia Children's Hospital
city: Stockholm
country: Sweden
facility: Astrid Lindgren Childrens Hospital
city: Lausanne
country: Switzerland
facility: CHUV Lausanne
city: Ankara
country: Turkey
facility: Hacettepe Childrens Hospital
city: Talas/Kayseri
country: Turkey
facility: Erciyes University Faculty of Medicine
city: London
country: United Kingdom
facility: University College London Institute of Child Health
city: Manchester
country: United Kingdom
facility: Royal Manchester Children's Hospital
city: Newcastle upon Tyne
country: United Kingdom
facility: The Newcastle upon Tyne Hospitals, NHS Foundation Trust
Study officials:
affiliation: PTC Therapeutics
name: Francesco Bibbiani, M.D.
role: STUDY_DIRECTOR
References:
citation: Thangarajh M, Elfring GL, Trifillis P, McIntosh J, Peltz SW; Ataluren Phase 2b Study Group. The relationship between deficit in digit span and genotype in nonsense mutation Duchenne muscular dystrophy. Neurology. 2018 Sep 25;91(13):e1215-e1219. doi: 10.1212/WNL.0000000000006245. Epub 2018 Aug 22.