Study of Ataluren in ≥2 to <5 Year-Old Male Participants With Duchenne Muscular Dystrophy

NCT02819557 | Completed Phase 2 Results DMC

• 1 other identifier: PTC124-GD-030-DMD
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 6

Brief Summary

This is a Phase 2, multiple-dose, open-label study evaluating the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of ataluren in participants aged ≥2 to \<5 years old with Duchenne muscular dystrophy (DMD) caused by a nonsense mutation in the dystrophin gene.

Conditions

Duchenne Muscular Dystrophy

Outcome Measures

Primary Outcomes (4)

• Number of Participants With Treatment Emergent Adverse Events (TEAEs), TEAEs Leading to Discontinuation, and Serious Adverse Events (SAEs)

  A TEAE was any untoward medical occurrence or undesirable event that begins or worsens following administration of study drug, whether or not considered related to study drug by Investigator. An SAE was an adverse event (AE) resulting in any of the following outcomes or deemed significant for any other reason, death, initial or prolonged inpatient hospitalization, life-threatening experience (immediate risk of dying) or persistent or significant disability/incapacity not related to dystrophinopathy. An event was not reported as an SAE, if event was exclusively a relapse or expected change or progression of baseline dystrophinopathy. AEs included both SAEs and nonserious AEs. AEs classified according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 and coded using Medical Dictionary for Regulatory Activities. A summary of SAEs and all non-serious AEs, regardless of causality, is located in the Reported Adverse Events section.

  Baseline up to Week 56

• Number of Participants With a Clinically Meaningful Abnormal Clinical Laboratory (Biochemistry, Hematology, and Urinalysis) Parameter

  Clinical laboratory results that were considered clinically meaningful were to be determined by the Investigator and Sponsor. Biochemistry parameters included sodium, potassium, chloride, bicarbonate, blood urea nitrogen, creatinine, magnesium, calcium, phosphorus, uric acid, glucose, total protein, albumin, bilirubin (total, direct, and indirect), aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase, creatine kinase, lactate dehydrogenase, alkaline phosphatase, total cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides, and cystatin C. Hematology parameters included white blood cell count with differential, hemoglobin, hematocrit, other red cell parameters, and platelet count. Urinalysis parameters included pH, specific gravity, glucose, ketones, blood, protein, urobilinogen, bilirubin, nitrite, and leukocyte esterase. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.

  Baseline up to Week 56

• Number of Participants With a Clinically Meaningful Abnormal Electrocardiogram (ECG) Test Results

  ECG results that were considered clinically meaningful were to be determined by the Investigator. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.

  Baseline up to Week 56

• Number of Participants With a Dose-Limiting Toxicity as Measured by Hepatic and Renal Toxicity

  Dose-limiting toxicity was measured through clinical evaluations for potential hepatic and renal toxicities. The clinical evaluations included the following: * Hepatic: The participant's medical history, hepatitis screening results, all clinical blood values (particularly serum bilirubin, gamma-glutamyl transferase \[GGT\], aspartate aminotransferase \[AST\], and alanine aminotransferase \[ALT\] values), and all concomitant medications were reviewed. * Renal: The participant's medical history, all clinical blood and urine renal values, serum electrolytes, medications, and potential pre- or post-renal conditions were reviewed.

  Baseline up to Week 56

Secondary Outcomes (10)

• Pharmacokinetics: Maximum Observed Plasma Concentration From Time Zero up to 6 Hours After the Morning Dose (Cmax0-6hr)

  0 (predose), 1, 2, 4, and 6 (postdose) hours on Days 1 and 28

• Pharmacokinetics: Time to Reach Maximum Observed Plasma Concentration From Time Zero up to 6 Hours After the Morning Dose (Tmax0-6hr)

  0 (predose), 1, 2, 4, and 6 (postdose) hours on Days 1 and 28

• Area Under the Plasma Concentration Time Curve From Time Zero up to 10 Hours After the Morning Dose (AUC0-10hr)

  0 (predose), 1, 2, 4, 6, 8, and 10 (postdose) hours on Days 1 and 28

• Pharmacokinetics: Concentration at the End of the First (Morning) Dose Interval (Ctrough6hr)

  0 (predose), 1, 2, 4, and 6 (postdose) hours on Days 1 and 28

• Change From Baseline in Proximal Muscle Function as Assessed by Speed During TFTs

  Baseline, Week 28 and Week 52

Study Arms (1)

Ataluren

EXPERIMENTAL

Participants will be administered ataluren orally at a dose of 10 milligrams/kilograms (mg/kg) in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening (for a total of 40 mg/kg/day) for up to 52 weeks. Dose will be provided based upon the weight of each participant, which will be assessed every 12 weeks.

Drug: Ataluren

Interventions

Ataluren DRUG

White to off-white powder for oral suspension.

Also known as: PTC124, Translarna

Ataluren

Eligibility Criteria

• Age: 2 Years - 5 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Males ≥2 to \<5 years of age
• Body weight ≥12 kg
• Diagnosis of DMD
• Nonsense mutation in at least 1 allele of the dystrophin gene

You may not qualify if:

• Participation in any other drug or device clinical investigation
• Ongoing use of prohibited concomitant medications

Sponsors & Collaborators

• PTC Therapeutics: lead

Study Sites (6)

Child Neuro NWF

Gulf Breeze, Florida, 32561, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Children's Hospital Boston

Boston, Massachusetts, 02115, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Children's Medical Center Dallas

Dallas, Texas, 75390-8843, United States

Location

University of Utah

Salt Lake City, Utah, 84112, United States

Location

MeSH Terms

Conditions

Muscular Dystrophy, Duchenne

Interventions

ataluren

Condition Hierarchy (Ancestors)

Muscular Dystrophies; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Results Point of Contact

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

medinfo@ptcbio.com

1-866-562-4620

Study Officials

• Francesco Bibbiani, MD

  PTC Therapeutics

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 16, 2016
• First Posted: June 30, 2016
• Study Start: June 9, 2016
• Primary Completion: February 9, 2018
• Study Completion: February 9, 2018
• Last Updated: August 28, 2020
• Results First Posted: August 28, 2020

Record last verified: 2020-08

Locations

US (6)