Clinical trial NCT03648827: A Study to Assess Dystrophin Levels in Participants With Nonsense Mutation Duchenne Muscular Dystrophy (nmDMD)
Official title: Phase 2 Clinical Pharmacology Study to Assess Dystrophin Levels in Subjects With nmDMD Before and After Treatment With Ataluren
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Duchenne Muscular Dystrophy
Lead sponsor: PTC Therapeutics
Sponsor class: INDUSTRY
First posted: 2018-08-27
Enrollment: 20
Sex: MALE
Minimum age (years): 2
Maximum age (years): 7
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study is designed to evaluate the ability of ataluren to increase dystrophin protein levels in muscle cells of participants with nmDMD. The study will evaluate the levels of dystrophin before and after 40 weeks of ataluren therapy using muscle biopsies and 2 validated assay methods, electrochemiluminescence (ECL) and immunohistochemistry.


Eligibility criteria: Inclusion Criteria:

* 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.
* Phenotypic evidence of duchenne muscular dystrophy (DMD) based on the onset of characteristic clinical symptoms or signs (for example, proximal muscle weakness, waddling gait, and Gowers' maneuver) and an elevated serum creatine kinase (CK). Medical documentation of phenotypic evidence of DMD needs to be provided upon request by the Sponsor's medical monitor.
* Documentation of the presence of a nonsense point mutation in the dystrophin gene as determined by gene sequencing. Review and approval of documentation by sponsor or designee is required prior to enrollment.
* Willing to undergo muscle biopsy.

Exclusion Criteria:

* Ongoing intravenous (IV) aminoglycoside or IV vancomycin therapy.
* Known contra-indication to muscle biopsy (such as bleeding or clotting disorders).
* Prior or ongoing therapy with ataluren.
* Known hypersensitivity to any of the ingredients or excipients of the study drug (for example, refined polydextrose, polyethylene glycol 3350, poloxamer 407, mannitol 25C, crospovidone XL10, hydroxyethyl cellulose, colloidal silica, magnesium stearate).
* Exposure to another investigational drug within 2 months prior to start of study treatment, or ongoing participation in any interventional clinical trial.
* Requirement for daytime ventilator assistance or any use of invasive mechanical ventilation via tracheostomy. Evening non-invasive mechanical ventilation such as use of bilevel positive airway pressure (Bi-PAP) therapy is allowed.
* Elevated serum creatinine or cystatin C levels at screening.
* Prior or ongoing medical condition (for example, concomitant illness, psychiatric condition, behavioral disorder), medical history, physical 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: Percent Change From Baseline in Dystrophin Level at Week 40, as Measured by ECL
timeFrame: Baseline, Week 40
Secondary outcomes:
measure: Percent Change From Baseline in Dystrophin Level at Week 40, as Determined by Immunohistochemistry (IHC) Membrane Stain Density
timeFrame: Baseline, Week 40
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix Childrens Hospital
state: Arizona
city: Los Angeles
country: United States
facility: University of California, Los Angeles (UCLA)
state: California
city: Sacramento
country: United States
facility: University of California (UC) Davis Medical Center
state: California
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: New York
country: United States
facility: Columbia University College of Physicians & Surgeons
state: New York
city: Houston
country: United States
facility: Texas Children's Hospital
state: Texas
city: San Antonio
country: United States
facility: University of Texas Heath Science Center at San Antonio
state: Texas
city: Norfolk
country: United States
facility: Children's Hospital of the King's Daughters
state: Virginia
Study officials:
affiliation: PTC Therapeutics, Inc.
name: Francesco Bibbiani, MD
role: STUDY_DIRECTOR
References: