An Extension Study of Ataluren (PTC124) in Participants With Nonsense Mutation Dystrophinopathy

NCT02090959 | Terminated Phase 3 Results DMC

• 1 other identifier: PTC124-GD-020e-DMD
• Study Type: interventional
• Target: 219
• Locations: 19 countries
• Sites: 58

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.

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

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

  An adverse event (AE): any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Severity of AEs: graded per Common Terminology Criteria for AEs (CTCAE), Version 3.0 as Grade 1 (mild), 2 (moderate), 3 (severe), 4 (life-threatening), 5 (death). Drug-related AEs: AEs with possible, probable, unlikely relationship, or unrelated to study drug. Serious AEs (SAEs): death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention. TEAE: an AE that occurred or worsened in the period extending from first dose of study drug in this study to 6 weeks after last dose of study drug in this study. A summary of other non-serious AEs and all SAEs, regardless of causality is located in Reported AE section.

  Baseline (Day 1) up to 6 weeks post-treatment (Week 150)

• Number of Participants With Abnormalities in Clinical Laboratory Parameters

  Abnormalities in laboratory variables as pre-defined in protocol for safety-monitoring were: Hepatic (Serum alanine aminotransferase \[ALT\]: increase of greater than \[\>\] 150 units/liter \[U/L\] with stable or decrease of creatinine kinese \[CK\]; Serum glutamyl amino transferase \[GGT\] \[U/L\]: Grade 2 \[\>2.5 - 5.0 \* upper limit of normal {ULN}\]), renal (Serum cystatin C miiligrams/liter \[mg/L\] \>1.33 - 2.00 mg/L; Serum blood urea nitrogen \[UREAN\] \[millimoles/liter {mmol/L}\] greater than or equal to \[≥\]1.5 - 3.0 \* ULN; Urine occult blood: 2+ \[Small\], 3+ \[Moderate\], 4+ \[Large\]), and electrolytes (Serum sodium: low \[mmol/L\], Grade 3-4 \[less than {\<}130 mmol/L\]; serum potassium: high \[mmol/L\], Grade 3-4 \[\>6.0 mmol/L\]; and Serum bicarbonate \[mmol/L\]: Grade 2 \[\<16 - 11 mmol/L\]).

  Baseline (Day 1) up to 6 weeks post-treatment (Week 150)

Secondary Outcomes (17)

• Change From Baseline in 6MWD at Week 144

  Baseline, Week 144

• Change From Baseline in Time to Stand From Supine Position at Week 144

  Baseline, Week 144

• Change From Baseline in Time to Walk/Run 10 Meters at Week 144

  Baseline, Week 144

• Change From Baseline in Time to Climb 4 Stairs at Week 144

  Baseline, Week 144

• Change From Baseline in Time to Descend 4 Stairs at Week 144

  Baseline, Week 144

Study Arms (1)

Ataluren

EXPERIMENTAL

Participants will receive ataluren suspension orally 3 times a day (TID), 10 milligrams/kilogram (mg/kg) at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for up to 144 weeks.

Drug: Ataluren

Interventions

Ataluren DRUG

Ataluren will be administered per the dose and schedule specified in the arm.

Also known as: PTC124

Ataluren

Eligibility Criteria

• Age: 7 Years - 15 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• PTC Therapeutics: lead

Study Sites (58)

University of California, Los Angeles

Los Angeles, California, 90095, United States

Location

UC Davis Medical Center

Sacramento, California, 95817, United States

Location

Stanford University Medical Center

Stanford, California, 94305, United States

Location

Children's Hospital Colorado - Center for Cancer and Blood Disorders

Aurora, Colorado, 80045, United States

Location

Child Neurology Center of Northwest Florida

Gulf Breeze, Florida, 32561, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Children's Hospital Boston

Boston, Massachusetts, 02115, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Washington University School of Medicine, Division of Endocrinology, Metabolism and Lipid Research

St Louis, Missouri, 63110, United States

Location

Columbia University College of Physicians & Surgeons

New York, New York, 10032, United States

Location

Children's Hospital Cincinnati

Cincinnati, Ohio, 45229, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43209, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15224, United States

Location

Childrens Medical Center Dallas, Texas

Dallas, Texas, 75207, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

University of Utah

Salt Lake City, Utah, 84112, United States

Location

Seattle Children's Hospital - Childhood Cancer and Blood Disorders

Seattle, Washington, 98105, United States

Location

The Children's Hospital at Westmead

Westmead, New South Wales, 2145, Australia

Location

The Royal Children's Hospital

Parkville, Victoria, 3052, Australia

Location

UZ Leuven

Leuven, 3000, Belgium

Location

Universidade Federal do Rio de Janeiro - Instituto de Puericultura e Pediatria Martagao Gesteira

Rio de Janeiro, 21.941-912, Brazil

Location

Sao Paulo University -HC/FMUSP

São Paulo, 05403-900, Brazil

Location

Aleksandrovska Hospital

Sofia, 1431, Bulgaria

Location

Alberta Children's Hospital

Calgary, Alberta, T3B 6A8, Canada

Location

British Columbia Children's Hospital

Vancouver, British Columbia, V6H 3V4, Canada

Location

Children's Hospital of Western Ontario

London, Ontario, N6C 2RC, Canada

Location

Hospital Luis Calvo Mackenna

Santiago, Santiago Metropolitan, Chile

Location

Hospital Clinico Universidad Catolica

Santiago, 8330073, Chile

Location

University Hospital Brno

Brno, 635 00, Czechia

Location

Motol University Hospital

Prague, 150 06, Czechia

Location

Hospital de la Timone

Marseille, 13385, France

Location

CHU de Nantes

Nantes, 44093, France

Location

Hopital Necker - Enfants Malades

Paris, 75015, France

Location

Groupe Hospitalier Pitie-Salpetriere

Paris, 75651, France

Location

Universitaetsklinikum Essen

Essen, 45122, Germany

Location

University Medical Center Freiburg

Freiburg im Breisgau, 79106, Germany

Location

Universitat Munchen - von Haunersche Kinder Clinic

München, 80337, Germany

Location

Hadassah University Hospital

Jerusalem, 91240, Israel

Location

Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico di Milano

Milan, 20122, Italy

Location

Bambino Gesu Hospital

Rome, 00165, Italy

Location

U.O. Complessa di Neuropsichiatria Infantile

Rome, 00168, Italy

Location

Policlinico Universitario G. Martino

Sicily, 98125, Italy

Location

Medical University of Warsaw

Warsaw, 502-097, Poland

Location

Seoul National University Hospital

Seoul, 110-744, South Korea

Location

Hospital Sant Joan de Deu

Barcelona, 08950, Spain

Location

Hospital Universitari i Politecnic la Fe

Valencia, 46026, Spain

Location

Queen Silvia Children's Hospital

Gothenburg, SE-416 85, Sweden

Location

Astrid Lindgren Childrens Hospital

Stockholm, 17176, Sweden

Location

CHUV Lausanne

Lausanne, 1011, Switzerland

Location

Hacettepe Childrens Hospital

Ankara, 06100, Turkey (Türkiye)

Location

Erciyes University Faculty of Medicine

Talas/Kayseri, 38039, Turkey (Türkiye)

Location

University College London Institute of Child Health

London, WC1N 3JH, United Kingdom

Location

Royal Manchester Children's Hospital

Manchester, M13 9WL, United Kingdom

Location

The Newcastle upon Tyne Hospitals, NHS Foundation Trust

Newcastle upon Tyne, NE1 3BZ, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 30135256 DERIVED

Related Links

• Related Info

MeSH Terms

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

Interventions

ataluren

Condition Hierarchy (Ancestors)

Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Limitations and Caveats

The study was terminated early per Sponsor decision due to commercial availability of ataluren.

Results Point of Contact

• Title: Patient Advocacy
• Organization: PTC Therapeutics, Inc.

medinfo@ptcbio.com

1-866-562-4620

Study Officials

• Francesco Bibbiani, M.D.

  PTC Therapeutics

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 17, 2014
• First Posted: March 19, 2014
• Study Start: March 20, 2014
• Primary Completion: June 12, 2018
• Study Completion: June 12, 2018
• Last Updated: August 11, 2020
• Results First Posted: August 11, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share

Locations

ES (2); IL (1); IT (4); GB (3); TU (2); CZ (2); SE (2); CH (1); US (21); CL (2); DE (3); BE (1); KR (1); FR (4); AU (2); PL (1); BU (1); BR (2); CA (3)