Duchenne Muscular Dystrophy
Conditions
Brief summary
This study is designed to generate additional data on the effect of ataluren for producing dystrophin protein in nonsense mutation nmDMD participants. This study will evaluate dystrophin levels from participants with nmDMD who currently have been receiving ataluren for ≥9 months. The study will have a single visit (Visit 1).
Interventions
DRUGAtaluren
Ataluren will be administered as per the dose and schedule specified in the arm.
Sponsors
PTC Therapeutics
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
MALE
Healthy volunteers
No
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. * Ambulatory (10 meters walk/run in less than \[\<\] 30 seconds) and functional grade on the Brooke Upper Extremity Scale of a 1 or a 2. * Currently being treated with ataluren 10, 10, 20 mg/kg for \>=9 months, with no gap in treatment of greater than (\>) 1 month, in an ongoing PTC-sponsored nmDMD clinical trial prior to study entry. * 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) by 6 years of age and an elevated serum creatine kinase (CK). Medical documentation of phenotypic evidence of DMD needs to be provided upon request by the medical monitor. * Willing to undergo muscle biopsy.
Exclusion criteria
* Known contra-indication to muscle biopsy (such as bleeding or clotting disorders). * Exposure to another investigational drug within 2 months prior to study enrollment or ongoing participation in any non-ataluren interventional clinical trial. * Requirement for daytime ventilator assistance or any use of invasive mechanical ventilation via tracheostomy. Note: Evening non-invasive mechanical ventilation such as use of bilevel positive airway pressure (Bi-PAP) therapy is allowed. * 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Dystrophin Levels as Measured by Electrochemiluminescence (ECL) | Day 1 of biopsy | The mean dystrophin protein levels were measured by ECL. Dystrophin levels are reported by muscle group (gastrocnemius, tibialis anterior, and across muscle locations). Results below the limit of quantitation were imputed as half of lower limit of quantitation (LLOQ). LLOQ = 0.5 micrograms (μg)/milliliter (mL) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Dystrophin Protein Levels as Determined by Immunohistochemistry | Day 1 of biopsy | Dystrophin levels by IHC mean membrane stain density are reported by muscle group (gastrocnemius, tibialis anterior, and across muscle locations). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ataluren Participants who had been receiving ataluren, were dosed daily 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening, for ≥9 months from ongoing PTC-sponsored nmDMD clinical trials. | 6 |
| Total | 6 |
Baseline characteristics
| Characteristic | Ataluren |
|---|---|
| Age, Continuous | 10.2 years STANDARD_DEVIATION 2.04 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 6 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 6 |
| other Total, other adverse events | 2 / 6 |
| serious Total, serious adverse events | 0 / 6 |
Outcome results
Primary
Mean Dystrophin Levels as Measured by Electrochemiluminescence (ECL)
The mean dystrophin protein levels were measured by ECL. Dystrophin levels are reported by muscle group (gastrocnemius, tibialis anterior, and across muscle locations). Results below the limit of quantitation were imputed as half of lower limit of quantitation (LLOQ). LLOQ = 0.5 micrograms (μg)/milliliter (mL)
Time frame: Day 1 of biopsy
Population: ITT population included all enrolled participants with a valid assessment of dystrophin level, as measured by ECL.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ataluren | Mean Dystrophin Levels as Measured by Electrochemiluminescence (ECL) | Gastrocnemius | 0.0844 nanograms (ng)/mg | Standard Deviation 0.05874 |
| Ataluren | Mean Dystrophin Levels as Measured by Electrochemiluminescence (ECL) | Tibialis Anterior | 0.1002 nanograms (ng)/mg | Standard Deviation 0.0806 |
| Ataluren | Mean Dystrophin Levels as Measured by Electrochemiluminescence (ECL) | Across Muscle Locations | 0.1054 nanograms (ng)/mg | Standard Deviation 0.083 |
Secondary
Dystrophin Protein Levels as Determined by Immunohistochemistry
Dystrophin levels by IHC mean membrane stain density are reported by muscle group (gastrocnemius, tibialis anterior, and across muscle locations).
Time frame: Day 1 of biopsy
Population: ITT population included all enrolled participants with a valid assessment of dystrophin level, as measured by ECL.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ataluren | Dystrophin Protein Levels as Determined by Immunohistochemistry | Gastrocnemius | 0.28817 ng/mg | Standard Deviation 0.220547 |
| Ataluren | Dystrophin Protein Levels as Determined by Immunohistochemistry | Tibialis Anterior | 0.26578 ng/mg | Standard Deviation 0.22651 |
| Ataluren | Dystrophin Protein Levels as Determined by Immunohistochemistry | Across Muscle Locations | 0.30483 ng/mg | Standard Deviation 0.2186 |