Trial Outcomes & Findings for A Study to Assess Dystrophin Levels in Participants With Nonsense Mutation Duchenne Muscular Dystrophy (nmDMD) (NCT NCT03648827)
NCT ID: NCT03648827
Last Updated: 2022-04-05
Results Overview
The percent change in dystrophin level from baseline in ambulatory nonsense mutation duchenne muscular dystrophy (nmDMD) participants after treatment with ataluren for 40 weeks was analyzed using quantitative assay (ECL).The least square (LS) mean and 90% confidence interval (CI) were analyzed from a mixed-model repeated measures (MMRM) with factors of muscle locations and visits as fixed effects, and participants as a random effect.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
20 participants
Primary outcome timeframe
Baseline, Week 40
Results posted on
2022-04-05
Participant Flow
Participant milestones
| Measure |
Ataluren
Participants received ataluren oral suspension 10 milligrams per kilogram (mg/kg) in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening each day for 40 weeks.
|
|---|---|
|
Overall Study
STARTED
|
20
|
|
Overall Study
Received at Least 1 Dose of Study Drug
|
20
|
|
Overall Study
COMPLETED
|
20
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Study to Assess Dystrophin Levels in Participants With Nonsense Mutation Duchenne Muscular Dystrophy (nmDMD)
Baseline characteristics by cohort
| Measure |
Ataluren
n=20 Participants
Participants received ataluren oral suspension 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening each day for 40 weeks.
|
|---|---|
|
Age, Continuous
|
4.8 years
STANDARD_DEVIATION 1.77 • n=5 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
20 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
5 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
15 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
17 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline, Week 40Population: ITT population included all enrolled participants with a valid assessment of dystrophin level at baseline, as measured by ECL.
The percent change in dystrophin level from baseline in ambulatory nonsense mutation duchenne muscular dystrophy (nmDMD) participants after treatment with ataluren for 40 weeks was analyzed using quantitative assay (ECL).The least square (LS) mean and 90% confidence interval (CI) were analyzed from a mixed-model repeated measures (MMRM) with factors of muscle locations and visits as fixed effects, and participants as a random effect.
Outcome measures
| Measure |
Ataluren
n=20 Participants
Participants received ataluren oral suspension 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening each day for 40 weeks.
|
|---|---|
|
Percent Change From Baseline in Dystrophin Level at Week 40, as Measured by ECL
|
6.559 percent change
Interval -8.402 to 23.963
|
SECONDARY outcome
Timeframe: Baseline, Week 40Population: ITT population included all enrolled participants with a valid assessment of dystrophin level at baseline, as measured by ECL.
The percent change in dystrophin level from baseline in ambulatory nmDMD participants after 40 weeks of ataluren therapy was determined by IHC membrane stain density. The LS mean and 90% CI were analyzed from an MMRM with factors of muscle locations and visits as fixed effects, and participants as a random effect.
Outcome measures
| Measure |
Ataluren
n=20 Participants
Participants received ataluren oral suspension 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening each day for 40 weeks.
|
|---|---|
|
Percent Change From Baseline in Dystrophin Level at Week 40, as Determined by Immunohistochemistry (IHC) Membrane Stain Density
|
4.914 percent change
Interval -1.642 to 11.906
|
Adverse Events
Ataluren
Serious events: 2 serious events
Other events: 18 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Ataluren
n=20 participants at risk
Participants received ataluren oral suspension 10 milligrams per kilogram (mg/kg) in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening each day for 40 weeks.
|
|---|---|
|
Infections and infestations
COVID-19
|
5.0%
1/20 • Baseline up to Week 40
Safety Population included all participants who received at least 1 dose of ataluren.
|
|
Injury, poisoning and procedural complications
Femur fracture
|
5.0%
1/20 • Baseline up to Week 40
Safety Population included all participants who received at least 1 dose of ataluren.
|
Other adverse events
| Measure |
Ataluren
n=20 participants at risk
Participants received ataluren oral suspension 10 milligrams per kilogram (mg/kg) in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening each day for 40 weeks.
|
|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
30.0%
6/20 • Baseline up to Week 40
Safety Population included all participants who received at least 1 dose of ataluren.
|
|
Gastrointestinal disorders
Vomiting
|
15.0%
3/20 • Baseline up to Week 40
Safety Population included all participants who received at least 1 dose of ataluren.
|
|
Gastrointestinal disorders
Abdominal pain
|
10.0%
2/20 • Baseline up to Week 40
Safety Population included all participants who received at least 1 dose of ataluren.
|
|
Gastrointestinal disorders
Abdominal pain upper
|
5.0%
1/20 • Baseline up to Week 40
Safety Population included all participants who received at least 1 dose of ataluren.
|
|
Gastrointestinal disorders
Constipation
|
5.0%
1/20 • Baseline up to Week 40
Safety Population included all participants who received at least 1 dose of ataluren.
|
|
Gastrointestinal disorders
Dyspepsia
|
5.0%
1/20 • Baseline up to Week 40
Safety Population included all participants who received at least 1 dose of ataluren.
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
5.0%
1/20 • Baseline up to Week 40
Safety Population included all participants who received at least 1 dose of ataluren.
|
|
General disorders
Pyrexia
|
10.0%
2/20 • Baseline up to Week 40
Safety Population included all participants who received at least 1 dose of ataluren.
|
|
General disorders
Gait inability
|
5.0%
1/20 • Baseline up to Week 40
Safety Population included all participants who received at least 1 dose of ataluren.
|
|
General disorders
Oedema peripheral
|
5.0%
1/20 • Baseline up to Week 40
Safety Population included all participants who received at least 1 dose of ataluren.
|
|
Infections and infestations
Ear infection
|
10.0%
2/20 • Baseline up to Week 40
Safety Population included all participants who received at least 1 dose of ataluren.
|
|
Infections and infestations
Nasopharyngitis
|
10.0%
2/20 • Baseline up to Week 40
Safety Population included all participants who received at least 1 dose of ataluren.
|
|
Infections and infestations
Upper respiratory tract infection
|
10.0%
2/20 • Baseline up to Week 40
Safety Population included all participants who received at least 1 dose of ataluren.
|
|
Infections and infestations
COVID-19
|
5.0%
1/20 • Baseline up to Week 40
Safety Population included all participants who received at least 1 dose of ataluren.
|
|
Infections and infestations
Conjunctivitis bacterial
|
5.0%
1/20 • Baseline up to Week 40
Safety Population included all participants who received at least 1 dose of ataluren.
|
|
Infections and infestations
Gastroenteritis
|
5.0%
1/20 • Baseline up to Week 40
Safety Population included all participants who received at least 1 dose of ataluren.
|
|
Infections and infestations
Influenza
|
5.0%
1/20 • Baseline up to Week 40
Safety Population included all participants who received at least 1 dose of ataluren.
|
|
Infections and infestations
Pharyngitis streptococcal
|
5.0%
1/20 • Baseline up to Week 40
Safety Population included all participants who received at least 1 dose of ataluren.
|
|
Infections and infestations
Pneumonia bacterial
|
5.0%
1/20 • Baseline up to Week 40
Safety Population included all participants who received at least 1 dose of ataluren.
|
|
Infections and infestations
Sinusitis
|
5.0%
1/20 • Baseline up to Week 40
Safety Population included all participants who received at least 1 dose of ataluren.
|
|
Infections and infestations
Viral upper respiratory tract infection
|
5.0%
1/20 • Baseline up to Week 40
Safety Population included all participants who received at least 1 dose of ataluren.
|
|
Injury, poisoning and procedural complications
Procedural pain
|
30.0%
6/20 • Baseline up to Week 40
Safety Population included all participants who received at least 1 dose of ataluren.
|
|
Injury, poisoning and procedural complications
Post procedural haemorrhage
|
15.0%
3/20 • Baseline up to Week 40
Safety Population included all participants who received at least 1 dose of ataluren.
|
|
Injury, poisoning and procedural complications
Femur fracture
|
5.0%
1/20 • Baseline up to Week 40
Safety Population included all participants who received at least 1 dose of ataluren.
|
|
Investigations
Urine output increased
|
5.0%
1/20 • Baseline up to Week 40
Safety Population included all participants who received at least 1 dose of ataluren.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
5.0%
1/20 • Baseline up to Week 40
Safety Population included all participants who received at least 1 dose of ataluren.
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
5.0%
1/20 • Baseline up to Week 40
Safety Population included all participants who received at least 1 dose of ataluren.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
5.0%
1/20 • Baseline up to Week 40
Safety Population included all participants who received at least 1 dose of ataluren.
|
|
Nervous system disorders
Headache
|
5.0%
1/20 • Baseline up to Week 40
Safety Population included all participants who received at least 1 dose of ataluren.
|
|
Psychiatric disorders
Aggression
|
5.0%
1/20 • Baseline up to Week 40
Safety Population included all participants who received at least 1 dose of ataluren.
|
|
Psychiatric disorders
Behaviour disorder
|
5.0%
1/20 • Baseline up to Week 40
Safety Population included all participants who received at least 1 dose of ataluren.
|
|
Psychiatric disorders
Sleep disorder
|
5.0%
1/20 • Baseline up to Week 40
Safety Population included all participants who received at least 1 dose of ataluren.
|
|
Renal and urinary disorders
Pollakiuria
|
5.0%
1/20 • Baseline up to Week 40
Safety Population included all participants who received at least 1 dose of ataluren.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
10.0%
2/20 • Baseline up to Week 40
Safety Population included all participants who received at least 1 dose of ataluren.
|
|
Skin and subcutaneous tissue disorders
Rash
|
10.0%
2/20 • Baseline up to Week 40
Safety Population included all participants who received at least 1 dose of ataluren.
|
|
Skin and subcutaneous tissue disorders
Miliaria
|
5.0%
1/20 • Baseline up to Week 40
Safety Population included all participants who received at least 1 dose of ataluren.
|
|
Skin and subcutaneous tissue disorders
Rash pruritic
|
5.0%
1/20 • Baseline up to Week 40
Safety Population included all participants who received at least 1 dose of ataluren.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The Sponsor can review results and/or communications prior to public release and can embargo communications regarding trial results for a period that is up to 180 days from the time submitted to the sponsor for review. The sponsor may consult with the PI to require changes to the communication or extend the embargo.
- Publication restrictions are in place
Restriction type: OTHER