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Clinical Trial Results:
A Phase 3, Randomised, Double-blind, Placebo-controlled Efficacy and Safety Study of Ataluren in Patients With Nonsense Mutation Duchenne Muscular Dystrophy and Open-label Extension

Summary
EudraCT number	2017-001223-49
Trial protocol	BG PL
Global end of trial date	25 Jul 2023

Results information
Results version number	v1(current)
This version publication date	24 Jan 2026
First version publication date	24 Jan 2026
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

PTC124-GD-041-DMD

ISRCTN number

US NCT number

NCT03179631

WHO universal trial number (UTN)

Sponsor organisation name

PTC Therapeutics, Inc.

Sponsor organisation address

100 Corporate Court, South Plainfield, United States, NJ 07080

Public contact

Medical Information, PTC Therapeutics, Inc., +011 44 1-866-562-4620, medinfo@ptcbio.com

Scientific contact

Medical Information, PTC Therapeutics International Limited, +353 19068700, medinfo@ptcbio.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Yes

Analysis stage

Final

Date of interim/final analysis

27 Sep 2023

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

25 Jul 2023

Was the trial ended prematurely?

Main objective of the trial

The primary objective of this trial was to determine the effect of ataluren on ambulation and endurance as assessed by the 6-minute walk test (6MWT).

Protection of trial subjects

This study was designed and monitored in accordance with sponsor procedures, which comply with the ethical principles of Good Clinical Practice (GCP) as required by the major regulatory authorities, and in accordance with the Declaration of Helsinki.

Background therapy

Evidence for comparator

Actual start date of recruitment

15 Aug 2017

Long term follow-up planned

Yes

Long term follow-up rationale

Safety, Efficacy

Long term follow-up duration

17 Months

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

United States: 360

Worldwide total number of subjects

360

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

340

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

The study consisted of a 72-week double-blind (DB) treatment period followed by a 72-week open-label (OL) treatment period. For confidentiality reasons, all participants have been reported for “United States” instead of their respective countries in "Section F. Population of Trial Subjects".

Screening details

A total of 439 participants were screened for the study. Of these, 363 participants were randomized to DB treatment, and 360 participants received at least 1 dose of study drug (176 participants received placebo and 184 participants received ataluren). Three participants who were randomized in error did not receive treatment.

Period 1 title

DB Treatment Period (72 Weeks)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Carer, Assessor

Are arms mutually exclusive

Yes

Ataluren

Arm description

Participants received ataluren oral suspension 10 milligrams (mg)/kilogram (kg) in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening each day for 72 weeks in DB treatment period and for an additional 72 weeks in OL treatment period.

Arm type

Experimental

Investigational medicinal product name

Ataluren

Investigational medicinal product code

Other name

Pharmaceutical forms

Oral suspension

Routes of administration

Oral use

Dosage and administration details

Ataluren was administered per dose and schedule specified in the arm description.

Placebo

Arm description

Participants received placebo matched to ataluren oral suspension for 72 weeks in DB treatment period. After completion of DB treatment period, 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 72 weeks in OL treatment period.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Oral suspension

Routes of administration

Oral use

Dosage and administration details

Placebo matched to ataluren was administered per schedule specified in the arm description.

Number of subjects in period 1	Ataluren	Placebo
Started	184	176
Intent-to-treat (ITT) Population	183	176
Completed	179	172
Not completed	5	4
Consent withdrawn by subject	1	3
Other than specified	1	1
Lost to follow-up	1	-
Protocol deviation	2	-

Period 2 title

OL Treatment Period (72 Weeks)

Is this the baseline period?

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Ataluren

Arm description

Arm type

Experimental

Investigational medicinal product name

Ataluren

Investigational medicinal product code

Other name

Pharmaceutical forms

Oral suspension

Routes of administration

Oral use

Dosage and administration details

Ataluren was administered per dose and schedule specified in the arm description.

Placebo

Arm description

Arm type

Placebo

Investigational medicinal product name

Ataluren

Investigational medicinal product code

Other name

Pharmaceutical forms

Oral suspension

Routes of administration

Oral use

Dosage and administration details

Ataluren was administered per dose and schedule specified in the arm description.

Number of subjects in period 2	Ataluren	Placebo
Started	179	172
Completed	174	165
Not completed	5	7
Consent withdrawn by subject	1	1
Investigator decision	-	1
Receiving commercially available product	1	5
Other than specified	2	-
Protocol deviation	1	-

Baseline characteristics

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Reporting group title

Ataluren

Reporting group description

Reporting group title

Placebo

Reporting group description

Reporting group values	Ataluren	Placebo	Total
Number of subjects	184	176	360
Age Categorical
Units: Subjects
Age Continuous
Units: years
arithmetic mean (standard deviation)	8.1 ( 1.91 )	8.2 ( 2.10 )	-
Gender Categorical
Units: Subjects
Female	0	0	0
Male	184	176	360
Race
Units: Subjects
American Indian or Alaska Native	0	1	1
Asian	112	109	221
Black or African American	2	3	5
Native Hawaiian or Other Pacific Islander	2	0	2
White	46	55	101
Other	22	8	30
Ethnicity
Units: Subjects
Hispanic or Latino	18	10	28
Not Hispanic or Latino	166	166	332

End points

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Reporting group title

Ataluren

Reporting group description

Reporting group title

Placebo

Reporting group description

Reporting group title

Ataluren

Reporting group description

Reporting group title

Placebo

Reporting group description

Subject analysis set title

Ataluren/Ataluren

Subject analysis set type

Intention-to-treat

Subject analysis set description

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 72 weeks in DB treatment period and for an additional 72 weeks in OL treatment period.

Subject analysis set title

Placebo/Ataluren

Subject analysis set type

Intention-to-treat

Subject analysis set description

Subject analysis set title

Ataluren/Ataluren

Subject analysis set type

Safety analysis

Subject analysis set description

Subject analysis set title

Ataluren/Placebo

Subject analysis set type

Safety analysis

Subject analysis set description

Primary: DB Period: Change From Baseline in 6-Minute Walk Distance (6MWD) at Week 72 - Modified Intention-to-treat (mITT) Population

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End point title

DB Period: Change From Baseline in 6-Minute Walk Distance (6MWD) at Week 72 - Modified Intention-to-treat (mITT) Population

End point description

The 6MWD test is a non-encouraged test performed in a 30 meters long flat corridor, where the participant is instructed to walk as far as possible, back and forth around two cones, with the permission to slow down, rest, or stop if needed. Ambulation was assessed via the 6MWD test following standardized procedures. Participants were not permitted to use assistive devices (walker, long leg braces, or short leg braces) during the 6MWD test. Participants with confirmed loss of ambulation at a particular visit were assigned a 6MWD result of 0. Baseline was defined as the maximum measurement of valid Day 1 and Day 2 6MWD values. Least square (LS) mean and standard error (SE) was calculated using the mixed-model repeated measures (MMRM). The mITT population included all randomized participants who met the following additional criteria: 7 to 16 years old with 6MWD ≥300 meters and time to stand from supine ≥5 seconds at baseline.

End point type

Primary

End point timeframe

Baseline, Week 72

End point values	Ataluren	Placebo
Number of subjects analysed	92	93
Units: meters
least squares mean (standard error)	-81.83 ( 6.461 )	-90.09 ( 6.377 )

Statistical Analysis 1

Comparison groups

Ataluren v Placebo

Number of subjects included in analysis

185

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.3626

Method

Mixed models analysis

Parameter type

LS Mean Difference

Point estimate

8.26

Confidence interval

level

95%

sides

2-sided

lower limit

-9.53

upper limit

26.05

Variability estimate

Standard error of the mean

Dispersion value

9.064

Primary: DB Period: Average Rate of Change From Baseline in 6MWD at Week 72 - mITT Population

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End point title

DB Period: Average Rate of Change From Baseline in 6MWD at Week 72 - mITT Population

End point description

The 6MWD test is a non-encouraged test performed in a 30 meters long flat corridor, where the participant is instructed to walk as far as possible, back and forth around two cones, with the permission to slow down, rest, or stop if needed. Ambulation was assessed via the 6MWD test following standardized procedures. Participants were not permitted to use assistive devices (walker, long leg braces, or short leg braces) during the 6MWD test. Participants with confirmed loss of ambulation at a particular visit were assigned a 6MWD result of 0. Baseline was defined as the maximum measurement of valid Day 1 and Day 2 6MWD values. LS mean and SE was calculated using the MMRM. The mITT population included all randomized participants who met the following additional criteria: 7 to 16 years old with 6MWD ≥300 meters and time to stand from supine ≥5 seconds at baseline.

End point type

Primary

End point timeframe

Baseline, Week 72

End point values	Ataluren	Placebo
Number of subjects analysed	92	93
Units: meters/week
least squares mean (standard error)	-1.14 ( 0.090 )	-1.25 ( 0.089 )

Statistical Analysis 1

Comparison groups

Ataluren v Placebo

Number of subjects included in analysis

185

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.3626

Method

Mixed models analysis

Parameter type

LS Mean Difference

Point estimate

0.11

Confidence interval

level

95%

sides

2-sided

lower limit

-0.13

upper limit

0.36

Variability estimate

Standard error of the mean

Dispersion value

0.126

Primary: DB Period: Change From Baseline in 6MWD at Week 72 - Intention-to-treat (ITT) Population

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End point title

DB Period: Change From Baseline in 6MWD at Week 72 - Intention-to-treat (ITT) Population

End point description

The 6MWD test is a non-encouraged test performed in a 30 meters long flat corridor, where the participant is instructed to walk as far as possible, back and forth around two cones, with the permission to slow down, rest, or stop if needed. Ambulation was assessed via the 6MWD test following standardized procedures. Participants were not permitted to use assistive devices (walker, long leg braces, or short leg braces) during the 6MWD test. Participants with confirmed loss of ambulation at a particular visit were assigned a 6MWD result of 0. Baseline was defined as the maximum measurement of valid Day 1 and Day 2 6MWD values. LS mean and SE was calculated using the MMRM. The ITT population included all participants who were randomized, with treatment assignments designated according to initial randomization, regardless of whether participants received a different study treatment from the one randomized.

End point type

Primary

End point timeframe

Baseline, Week 72

End point values	Ataluren	Placebo
Number of subjects analysed	183	176
Units: meters
least squares mean (standard error)	-53.01 ( 5.169 )	-67.43 ( 5.403 )

Statistical Analysis 1

Comparison groups

Ataluren v Placebo

Number of subjects included in analysis

359

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0248

Method

Mixed models analysis

Parameter type

LS Mean Difference

Point estimate

14.42

Confidence interval

level

95%

sides

2-sided

lower limit

1.83

upper limit

27.01

Variability estimate

Standard error of the mean

Dispersion value

6.42

Primary: DB Period: Average Rate of Change From Baseline in 6MWD at Week 72 - ITT Population

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End point title

DB Period: Average Rate of Change From Baseline in 6MWD at Week 72 - ITT Population

End point description

The 6MWD test is a non-encouraged test performed in a 30 meters long flat corridor, where the participant is instructed to walk as far as possible, back and forth around two cones, with the permission to slow down, rest, or stop if needed. Ambulation was assessed via the 6MWD test following standardized procedures. Participants were not permitted to use assistive devices (walker, long leg braces, or short leg braces) during the 6MWD test. Participants with confirmed loss of ambulation at a particular visit were assigned a 6MWD result of 0. Baseline was defined as the maximum measurement of valid Day 1 and Day 2 6MWD values. LS mean and SE was calculated using the MMRM. The ITT population included all participants who were randomized, with treatment assignments designated according to initial randomization, regardless of whether participants received a different study treatment from the one randomized.

End point type

Primary

End point timeframe

Baseline, Week 72

End point values	Ataluren	Placebo
Number of subjects analysed	183	176
Units: meters/week
least squares mean (standard error)	-0.74 ( 0.072 )	-0.94 ( 0.075 )

Statistical Analysis 1

Comparison groups

Ataluren v Placebo

Number of subjects included in analysis

359

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0248

Method

Mixed models analysis

Parameter type

LS Mean Difference

Point estimate

0.2

Confidence interval

level

95%

sides

2-sided

lower limit

0.03

upper limit

0.38

Variability estimate

Standard error of the mean

Dispersion value

0.089

Secondary: DB Period: Change From Baseline in Time to Run/Walk 10 Meters at Week 72 - mITT Population

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End point title

DB Period: Change From Baseline in Time to Run/Walk 10 Meters at Week 72 - mITT Population

End point description

During the test for walking/running 10 meters, the method of walk/run used by the participant was categorized as follows: 1. Unable to walk independently; 2. Unable to walk independently but can walk with support from a person or with assistive device (full leg calipers [knee-ankle-foot orthoses] or walker); 3. Highly adapted gait, wide-based lordotic gait, cannot increase walking speed; 4. Moderately adapted gait, can pick up speed but cannot run; 5. Able to pick up speed but runs with a double stance phase (that is, cannot achieve both feet off the ground); 6. Runs and gets both feet off the ground (with no double stance phase). Participants who could not perform a timed function test (TFT) within 30 seconds, including those who loss of ambulation or the TFT was above 30 seconds, a value of 30 seconds was used. Baseline was defined as the last observed measurement on or prior to the first dose of study drug. LS mean and SE was calculated using the MMRM. mITT population.

End point type

Secondary

End point timeframe

Baseline, Week 72

End point values	Ataluren	Placebo
Number of subjects analysed	92	93
Units: seconds
least squares mean (standard error)	3.06 ( 0.393 )	3.79 ( 0.389 )

Statistical Analysis 1

Comparison groups

Ataluren v Placebo

Number of subjects included in analysis

185

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.1877

Method

Mixed models analysis

Parameter type

LS Mean Difference

Point estimate

-0.73

Confidence interval

level

95%

sides

2-sided

lower limit

-1.81

upper limit

0.36

Variability estimate

Standard error of the mean

Dispersion value

0.552

Secondary: DB Period: Change From Baseline in Time to Run/Walk 10 Meters at Week 72 - ITT Population

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End point title

DB Period: Change From Baseline in Time to Run/Walk 10 Meters at Week 72 - ITT Population

End point description

During the test for walking/running 10 meters, the method of walk/run used by the participant was categorized as follows: 1. Unable to walk independently; 2. Unable to walk independently but can walk with support from a person or with assistive device (full leg calipers [knee-ankle-foot orthoses ] or walker); 3. Highly adapted gait, wide-based lordotic gait, cannot increase walking speed; 4. Moderately adapted gait, can pick up speed but cannot run; 5. Able to pick up speed but runs with a double stance phase (that is, cannot achieve both feet off the ground); 6. Runs and gets both feet off the ground (with no double stance phase). Participants who could not perform a TFT within 30 seconds, including those who loss of ambulation or the TFT was above 30 seconds, a value of 30 seconds was used. Baseline was defined as the last observed measurement on or prior to the first dose of study drug. LS mean and SE was calculated using the MMRM. ITT population.

End point type

Secondary

End point timeframe

Baseline, Week 72

End point values	Ataluren	Placebo
Number of subjects analysed	183	176
Units: seconds
least squares mean (standard error)	3.04 ( 0.287 )	3.82 ( 0.297 )

Statistical Analysis 1

Comparison groups

Ataluren v Placebo

Number of subjects included in analysis

359

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0422

Method

Mixed models analysis

Parameter type

LS Mean Difference

Point estimate

-0.78

Confidence interval

level

95%

sides

2-sided

lower limit

-1.53

upper limit

-0.03

Variability estimate

Standard error of the mean

Dispersion value

0.383

Secondary: DB Period: Change From Baseline in Time to Climb 4 Stairs at Week 72 - mITT Population

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End point title

DB Period: Change From Baseline in Time to Climb 4 Stairs at Week 72 - mITT Population

End point description

During the test for stair-climbing, the method of climbing used by the participant was categorized as follows: 1. Unable to up climb 4 standard stairs; 2. Climbs 4 standard stairs "marking time" (climbs one foot at a time, with both feet on a step before moving to next step), using both arms on one or both handrails; 3. Climbs 4 standard stairs "marking time", using one arm on one handrail; 4. Climbs 4 standard stairs "marking time", not needing handrail; 5. Climbs 4 standard stairs alternating feet, needs handrail for support; 6. Climbs 4 standard stairs alternating feet, not needing handrail support. Participants who could not perform a TFT within 30 seconds, including those who loss of ambulation or the TFT was above 30 seconds, a value of 30 seconds was used. Baseline was defined as the last observed measurement on or prior to the first dose of study drug. LS mean and SE was calculated using the MMRM. mITT population.

End point type

Secondary

End point timeframe

Baseline, Week 72

End point values	Ataluren	Placebo
Number of subjects analysed	92	93
Units: seconds
least squares mean (standard error)	5.25 ( 0.518 )	6.98 ( 0.513 )

Statistical Analysis 1

Comparison groups

Ataluren v Placebo

Number of subjects included in analysis

185

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0179

Method

Mixed models analysis

Parameter type

LS Mean Difference

Point estimate

-1.73

Confidence interval

level

95%

sides

2-sided

lower limit

-3.16

upper limit

-0.3

Variability estimate

Standard error of the mean

Dispersion value

0.729

Secondary: DB Period: Change From Baseline in Time to Climb 4 Stairs at Week 72 - ITT Population

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End point title

DB Period: Change From Baseline in Time to Climb 4 Stairs at Week 72 - ITT Population

End point description

End point type

Secondary

End point timeframe

Baseline, Week 72

End point values	Ataluren	Placebo
Number of subjects analysed	183	176
Units: seconds
least squares mean (standard error)	4.98 ( 0.364 )	6.04 ( 0.375 )

Statistical Analysis 1

Comparison groups

Ataluren v Placebo

Number of subjects included in analysis

359

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0293

Method

Mixed models analysis

Parameter type

LS Mean Difference

Point estimate

-1.06

Confidence interval

level

95%

sides

2-sided

lower limit

-2.02

upper limit

-0.11

Variability estimate

Standard error of the mean

Dispersion value

0.488

Secondary: DB Period: Change From Baseline in Time to Descend 4 Stairs at Week 72 - mITT Population

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End point title

DB Period: Change From Baseline in Time to Descend 4 Stairs at Week 72 - mITT Population

End point description

During the test for stair-descending, the method of descending used by the participant was categorized as follows: 1. Unable to descend 4 standard stairs; 2. Descends 4 standard stairs "marking time" (climbs one foot at a time, with both feet on a step before moving to next step), using both arms on one or both handrails; 3. Descends 4 standard stairs "marking time", using one arm on one handrail; 4. Descends 4 standard stairs "marking time", not needing handrail; 5. Descends 4 standard stairs alternating feet, needs handrail for support; 6. Descends 4 standard stairs alternating feet, not needing handrail support. Participants who could not perform a TFT within 30 seconds, including those who loss of ambulation or the TFT was above 30 seconds, a value of 30 seconds was used. Baseline was defined as the last observed measurement on or prior to the first dose of study drug. LS mean and SE was calculated using the MMRM. mITT population.

End point type

Secondary

End point timeframe

Bseline, Week 72

End point values	Ataluren	Placebo
Number of subjects analysed	92	93
Units: seconds
least squares mean (standard error)	4.58 ( 0.545 )	4.78 ( 0.541 )

Statistical Analysis 1

Comparison groups

Ataluren v Placebo

Number of subjects included in analysis

185

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.7997

Method

Mixed models analysis

Parameter type

LS Mean Difference

Point estimate

-0.19

Confidence interval

level

95%

sides

2-sided

lower limit

-1.7

upper limit

1.31

Variability estimate

Standard error of the mean

Dispersion value

0.768

Secondary: DB Period: Change From Baseline in Time to Descend 4 Stairs at Week 72 - ITT Population

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End point title

DB Period: Change From Baseline in Time to Descend 4 Stairs at Week 72 - ITT Population

End point description

End point type

Secondary

End point timeframe

Baseline, Week 72

End point values	Ataluren	Placebo
Number of subjects analysed	183	176
Units: seconds
least squares mean (standard error)	4.96 ( 0.384 )	5.25 ( 0.396 )

Statistical Analysis 1

Comparison groups

Ataluren v Placebo

Number of subjects included in analysis

359

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.5749

Method

Mixed models analysis

Parameter type

LS Mean Difference

Point estimate

-0.29

Confidence interval

level

95%

sides

2-sided

lower limit

-1.3

upper limit

0.72

Variability estimate

Standard error of the mean

Dispersion value

0.516

Secondary: DB Period: Composite of Average Change From Baseline in TFTs at Week 72 - mITT Population

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End point title

DB Period: Composite of Average Change From Baseline in TFTs at Week 72 - mITT Population

End point description

The composite TFT was defined as the average in times to run/walk 10 meters, climb 4 stairs, and descend 4 stairs. Participants who could not perform a TFT within 30 seconds, including those who loss of ambulation or the TFT was above 30 seconds, a value of 30 seconds was used. Baseline was defined as the last observed measurement (average in times to run/walk 10 meters, climb 4 stairs, and descend 4 stairs) on or prior to the first dose of study drug. LS mean and SE was calculated using the MMRM. The mITT population included all randomized participants who met the following additional criteria: 7 to 16 years old with 6MWD ≥300 meters and time to stand from supine ≥5 seconds at baseline.

End point type

Secondary

End point timeframe

Baseline, Week 72

End point values	Ataluren	Placebo
Number of subjects analysed	92	93
Units: seconds
least squares mean (standard error)	4.15 ( 0.435 )	5.19 ( 0.431 )

Statistical Analysis 1

Comparison groups

Ataluren v Placebo

Number of subjects included in analysis

185

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0892

Method

Mixed models analysis

Parameter type

LS Mean Difference

Point estimate

-1.04

Confidence interval

level

95%

sides

2-sided

lower limit

-2.24

upper limit

0.16

Variability estimate

Standard error of the mean

Dispersion value

0.611

Secondary: DB Period: Composite of Average Change From Baseline in TFTs at Week 72 - ITT Population

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End point title

DB Period: Composite of Average Change From Baseline in TFTs at Week 72 - ITT Population

End point description

The composite TFT was defined as the average in times to run/walk 10 meters, climb 4 stairs, and descend 4 stairs. Participants who could not perform a TFT within 30 seconds, including those who loss of ambulation or the TFT was above 30 seconds, a value of 30 seconds was used. Baseline was defined as the last observed measurement (average in times to run/walk 10 meters, climb 4 stairs, and descend 4 stairs) on or prior to the first dose of study drug. LS mean and SE was calculated using the MMRM. The ITT population included all participants who were randomized, with treatment assignments designated according to initial randomization, regardless of whether participants received a different study treatment from the one randomized.

End point type

Secondary

End point timeframe

Baseline, Week 72

End point values	Ataluren	Placebo
Number of subjects analysed	183	176
Units: seconds
least squares mean (standard error)	4.24 ( 0.309 )	4.93 ( 0.319 )

Statistical Analysis

Comparison groups

Ataluren v Placebo

Number of subjects included in analysis

359

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0904

Method

Mixed models analysis

Parameter type

LS Mean Difference

Point estimate

-0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-1.51

upper limit

0.11

Variability estimate

Standard error of the mean

Dispersion value

0.412

Secondary: DB Period: Composite of Average Rate of Change From Baseline in TFTs at Week 72 - mITT Population

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End point title

DB Period: Composite of Average Rate of Change From Baseline in TFTs at Week 72 - mITT Population

End point description

End point type

Secondary

End point timeframe

Baseline, Week 72

End point values	Ataluren	Placebo
Number of subjects analysed	92	93
Units: seconds/week
least squares mean (standard error)	0.058 ( 0.006 )	0.072 ( 0.006 )

Statistical Analysis 1

Comparison groups

Ataluren v Placebo

Number of subjects included in analysis

185

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0892

Method

Mixed models analysis

Parameter type

LS Mean Difference

Point estimate

-0.014

Confidence interval

level

95%

sides

2-sided

lower limit

-0.031

upper limit

0.002

Variability estimate

Standard error of the mean

Dispersion value

0.008

Secondary: DB Period: Composite of Average Rate of Change From Baseline in TFTs at Week 72 - ITT Population

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End point title

DB Period: Composite of Average Rate of Change From Baseline in TFTs at Week 72 - ITT Population

End point description

The composite TFT was defined as the average in times to run/walk 10 meters, climb 4 stairs, and descend 4 stairs. Participants who could not perform a TFT within 30 seconds, including those who loss of ambulation or the TFT was above 30 seconds, a value of 30 seconds was used. Baseline was defined as the last observed measurement (average in times to run/walk 10 meters, climb 4 stairs, and descend 4 stairs) on or prior to the first dose of study drug. LS mean and SE was calculated using the MMRM. The ITT population included all participants who were randomized, with treatment assignments designated according to initial randomization, regardless of whether participants received a different study treatment from the one randomized.

End point type

Secondary

End point timeframe

Baseline, Week 72

End point values	Ataluren	Placebo
Number of subjects analysed	183	176
Units: seconds/week
least squares mean (standard error)	0.059 ( 0.004 )	0.069 ( 0.004 )

Statistical Analysis 1

Comparison groups

Ataluren v Placebo

Number of subjects included in analysis

359

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0904

Method

Mixed models analysis

Parameter type

LS Mean Difference

Point estimate

-0.01

Confidence interval

level

95%

sides

2-sided

lower limit

-0.021

upper limit

0.002

Variability estimate

Standard error of the mean

Dispersion value

0.006

Secondary: DB Period: Time to Persistent 10% Worsening in 6MWD at Week 72 - mITT Population

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End point title

DB Period: Time to Persistent 10% Worsening in 6MWD at Week 72 - mITT Population

End point description

The 6MWD test is a non-encouraged test performed in a 30 meters long flat corridor, where the participant is instructed to walk as far as possible, back and forth around two cones, with the permission to slow down, rest, or stop if needed. Ambulation was assessed via the 6MWD test following standardized procedures. Participants were not permitted to use assistive devices (walker, long leg braces, or short leg braces) during the 6MWD test. Time to 10% persistent worsening in 6MWD was defined as the last time that 6MWD was not 10% worse compared with baseline. Participants who did not have 10% 6MWD worsening were censored at the time of the last 6-minute walk test during the DB period. The mITT population included all randomized participants who met the following additional criteria: 7 to 16 years old with 6MWD ≥300 meters and time to stand from supine ≥5 seconds at baseline. Here, ‘Overall number of participants analyzed’ = participants with 10% persistent worsening by Week 72.

End point type

Secondary

End point timeframe

Baseline to Week 72

End point values	Ataluren	Placebo
Number of subjects analysed	58	71
Units: weeks
median (confidence interval 95%)	36.7 (36.0 to 60.0)	35.6 (23.7 to 48.0)

Statistical Analysis 1

Comparison groups

Ataluren v Placebo

Number of subjects included in analysis

129

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0659

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.73

Confidence interval

level

95%

sides

2-sided

lower limit

0.52

upper limit

1.03

Secondary: DB Period: Time to Persistent 10% Worsening in 6MWD at Week 72 - ITT Population

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End point title

DB Period: Time to Persistent 10% Worsening in 6MWD at Week 72 - ITT Population

End point description

6MWD test is a non-encouraged test performed in a 30 meters long flat corridor, where participant is instructed to walk as far as possible, back and forth around two cones, with permission to slow down, rest, or stop if needed. Ambulation was assessed via 6MWD test following standardized procedures. Participants were not permitted to use assistive devices (walker, long leg braces, or short leg braces) during 6MWD test. Time to 10% persistent worsening in 6MWD was defined as the last time that 6MWD was not 10% worse compared with baseline. Participants who did not have 10% 6MWD worsening were censored at the time of last 6-minute walk test during DB period. ITT population. ‘Overall number of participants analyzed’ = participants with 10% persistent worsening by Week 72. '99999' = Due to the low number of events, the data could not be estimated.

End point type

Secondary

End point timeframe

Baseline to Week 72

End point values	Ataluren	Placebo
Number of subjects analysed	88	109
Units: weeks
median (confidence interval 95%)	74.3 (59.1 to 99999)	48.0 (36.0 to 60.9)

Statistical Analysis 1

Comparison groups

Ataluren v Placebo

Number of subjects included in analysis

197

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0078

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.69

Confidence interval

level

95%

sides

2-sided

lower limit

0.52

upper limit

0.91

Secondary: DB Period: Change From Baseline in North Start Ambulatory Assessment (NSAA) Total Score at Week 72 - mITT Population

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End point title

DB Period: Change From Baseline in North Start Ambulatory Assessment (NSAA) Total Score at Week 72 - mITT Population

End point description

The NSAA total score in the original scale is the sum of scores from 16 activities (excluding head lift). Each activity was scored as 0 (activity couldn't be performed), 1 (modified method, achieved goal without assistance), or 2 (normal, achieved goal without assistance). The total score ranges from 0 to 32, where higher scores indicate better functioning. If fewer than 13 of the 16 activities were performed, the total score was considered missing. If from 13 to 16 activities were performed, the total score was standardized by (observed total score / number of non-missing activities) x 16. If an activity could not be performed due to disease progression, a score of 0 was assigned. Baseline was defined as the last observed measurement on or prior to the first dose of study drug. LS mean and SE was calculated using the MMRM. mITT population.

End point type

Secondary

End point timeframe

Baseline, Week 72

End point values	Ataluren	Placebo
Number of subjects analysed	92	93
Units: units on a scale
least squares mean (standard error)	-5.2 ( 0.40 )	-6.1 ( 0.40 )

Statistical Analysis 1

Comparison groups

Ataluren v Placebo

Number of subjects included in analysis

185

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.1258

Method

Mixed models analysis

Parameter type

LS Mean Difference

Point estimate

0.9

Confidence interval

level

95%

sides

2-sided

lower limit

-0.2

upper limit

Variability estimate

Standard error of the mean

Dispersion value

0.57

Secondary: DB Period: Change From Baseline in NSAA Total Score at Week 72 - ITT Population

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End point title

DB Period: Change From Baseline in NSAA Total Score at Week 72 - ITT Population

End point description

End point type

Secondary

End point timeframe

Baseline, Week 72

End point values	Ataluren	Placebo
Number of subjects analysed	183	176
Units: units on a scale
least squares mean (standard error)	-3.7 ( 0.28 )	-4.5 ( 0.29 )

Statistical Analysis 1

Comparison groups

Ataluren v Placebo

Number of subjects included in analysis

359

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0235

Method

Mixed models analysis

Parameter type

LS Mean Difference

Point estimate

0.9

Confidence interval

level

95%

sides

2-sided

lower limit

0.1

upper limit

1.6

Variability estimate

Standard error of the mean

Dispersion value

0.38

Secondary: DB Period: Time to Loss of Ambulation Over 72 Weeks - mITT Population

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End point title

DB Period: Time to Loss of Ambulation Over 72 Weeks - mITT Population

End point description

Time to loss of ambulation was defined as persistent inability to perform the 10-meter run/walk test within 30 seconds at any post-baseline visit and for all remaining visits. The mITT population included all randomized participants who met the following additional criteria: 7 to 16 years old with 6MWD ≥300 meters and time to stand from supine ≥5 seconds at baseline. Here, 'Overall number of participants analyzed' = participants with loss of ambulation by Week 72. '99999' = Due to the low number of events, the data could not be estimated.

End point type

Secondary

End point timeframe

Baseline up to Week 72

End point values	Ataluren	Placebo
Number of subjects analysed	5	9
Units: weeks
median (confidence interval 95%)	84.1 (84.1 to 99999)	99999 (99999 to 99999)

Statistical Analysis 1

Comparison groups

Ataluren v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.4803

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.66

Confidence interval

level

95%

sides

2-sided

lower limit

0.21

upper limit

2.08

Secondary: DB Period: Time to Loss of Ambulation Over 72 Weeks - ITT Population

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End point title

DB Period: Time to Loss of Ambulation Over 72 Weeks - ITT Population

End point description

Time to loss of ambulation was defined as persistent inability to perform the 10-meter run/walk test within 30 seconds at any post-baseline visit and for all remaining visits. The ITT population included all participants who were randomized, with treatment assignments designated according to initial randomization, regardless of whether participants received a different study treatment from the one randomized. Here, 'Overall number of participants analyzed' = participants with loss of ambulation by Week 72. '99999' = Due to the low number of events, the data could not be estimated.

End point type

Secondary

End point timeframe

Baseline up to Week 72

End point values	Ataluren	Placebo
Number of subjects analysed	12	20
Units: weeks
median (confidence interval 95%)	99999 (99999 to 99999)	99999 (99999 to 99999)

Statistical Analysis 1

Comparison groups

Ataluren v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.1768

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.67

Confidence interval

level

95%

sides

2-sided

lower limit

0.32

upper limit

1.39

Secondary: DB Period: Time to Loss of Stair-Climbing Over 72 Weeks - mITT Population

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End point title

DB Period: Time to Loss of Stair-Climbing Over 72 Weeks - mITT Population

End point description

Time to loss of stair-climbing was defined as persistent inability to perform the 4-stair climb test within 30 seconds at any post-baseline visit and for all remaining visits. The mITT population included all randomized participants who met the following additional criteria: 7 to 16 years old with 6MWD ≥300 meters and time to stand from supine ≥5 seconds at baseline. Here, 'Overall number of participants analyzed' = participants with loss of stair-climbing by Week 72. '99999' = Due to the low number of events, the data could not be estimated.

End point type

Secondary

End point timeframe

Baseline up to Week 72

End point values	Ataluren	Placebo
Number of subjects analysed	11	15
Units: weeks
median (confidence interval 95%)	84.1 (82.6 to 99999)	99999 (99999 to 99999)

Statistical Analysis 1

Comparison groups

Ataluren v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.5452

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.72

Confidence interval

level

95%

sides

2-sided

lower limit

0.33

upper limit

1.59

Secondary: DB Period: Time to Loss of Stair-Climbing Over 72 Weeks - ITT Population

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End point title

DB Period: Time to Loss of Stair-Climbing Over 72 Weeks - ITT Population

End point description

Time to loss of stair-climbing was defined as persistent inability to perform the 4-stair climb test within 30 seconds at any post-baseline visit and for all remaining visits. The ITT population included all participants who were randomized, with treatment assignments designated according to initial randomization, regardless of whether participants received a different study treatment from the one randomized. Here, 'Overall number of participants analyzed' = participants with loss of stair-climbing by Week 72. '99999' = Due to the low number of events, the data could not be estimated.

End point type

Secondary

End point timeframe

Baseline up to Week 72

End point values	Ataluren	Placebo
Number of subjects analysed	24	31
Units: weeks
median (confidence interval 95%)	87.1 (84.1 to 99999)	99999 (99999 to 99999)

Statistical Analysis 1

Comparison groups

Ataluren v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.3055

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.69

Confidence interval

level

95%

sides

2-sided

lower limit

0.4

upper limit

1.19

Secondary: DB Period: Time to Loss of Stair-Descending Over 72 Weeks - mITT Population

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End point title

DB Period: Time to Loss of Stair-Descending Over 72 Weeks - mITT Population

End point description

Time to loss of stair-descending was defined as persistent inability to perform the 4-stair descend test within 30 seconds at any post-baseline visit and for all remaining visits. The mITT population included all randomized participants who met the following additional criteria: 7 to 16 years old with 6MWD ≥300 meters and time to stand from supine ≥5 seconds at baseline. Here, 'Overall number of participants analyzed' = participants with loss of stair-descending by Week 72. '99999' = Due to the low number of events, the data could not be estimated.

End point type

Secondary

End point timeframe

Baseline up to Week 72

End point values	Ataluren	Placebo
Number of subjects analysed	12	10
Units: weeks
median (confidence interval 95%)	84.1 (80.9 to 99999)	99999 (99999 to 99999)

Statistical Analysis 1

Comparison groups

Ataluren v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.3906

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

1.58

Confidence interval

level

95%

sides

2-sided

lower limit

0.65

upper limit

3.84

Secondary: DB Period: Time to Loss of Stair-Descending Over 72 Weeks - ITT Population

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End point title

DB Period: Time to Loss of Stair-Descending Over 72 Weeks - ITT Population

End point description

Time to loss of stair-descending was defined as persistent inability to perform the 4-stair descend test within 30 seconds at any post-baseline visit and for all remaining visits. The ITT population included all participants who were randomized, with treatment assignments designated according to initial randomization, regardless of whether participants received a different study treatment from the one randomized. Here, 'Overall number of participants analyzed' = participants with loss of stair-descending by Week 72. '99999' = Due to the low number of events, the data could not be estimated.

End point type

Secondary

End point timeframe

Baseline up to Week 72

End point values	Ataluren	Placebo
Number of subjects analysed	24	26
Units: weeks
median (confidence interval 95%)	87.1 (84.1 to 99999)	99999 (99999 to 99999)

Statistical Analysis 1

Comparison groups

Ataluren v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.8165

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.99

Confidence interval

level

95%

sides

2-sided

lower limit

0.56

upper limit

1.74

Secondary: DB Period: Number of Participants With Function Loss of NSAA Items at Week 72 - mITT Population

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End point title

DB Period: Number of Participants With Function Loss of NSAA Items at Week 72 - mITT Population

End point description

Function loss was defined as a drop of score from 1 or 2 at baseline to a score of 0 at the specified post-baseline. The missing assessments at post baseline visits were imputed using last observation carried forward (LOCF). The mITT population included all randomized participants who met the following additional criteria: 7 to 16 years old with 6MWD ≥300 meters and time to stand from supine ≥5 seconds at baseline. Here, 'n' = number of participants with baseline score of 2 or 1 and at least one post-baseline assessment for the specific activity.

End point type

Secondary

End point timeframe

Week 72

End point values	Ataluren	Placebo
Number of subjects analysed	92	93
Units: participants
Stand (n = 92, 93)	6	10
Walk (10m) (n = 92, 93)	5	10
Stand up from chair (n = 90, 92)	22	23
Stand on one leg - right (n = 92, 92)	13	16
Stand on one leg - left (n = 90, 92)	12	15
Climb box step - right (n = 76, 81)	22	38
Descend box step - right (n = 91, 90)	24	25
Climb box step - left (n = 79, 86)	24	38
Descend box step - left (n = 90, 89)	25	20
Lifts head (n = 78, 83)	13	15
Gets to sitting (n = 92, 92)	6	10
Rise from floor (n = 92, 92)	32	33
Stand on heels (n = 56, 54)	26	30
Jump (n = 82, 76)	26	22
Hop right (n = 56, 68)	26	30
Hop left (n = 50, 67)	22	28
Run (10m) (n = 89, 89)	19	22

No statistical analyses for this end point

Secondary: DB Period: Number of Participants With Function Loss of NSAA Items at Week 72 - ITT Population

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End point title

DB Period: Number of Participants With Function Loss of NSAA Items at Week 72 - ITT Population

End point description

Function loss was defined as a drop of score from 1 or 2 at baseline to a score of 0 at the specified post-baseline. The missing assessments at post baseline visits were imputed using LOCF. The ITT population included all participants who were randomized, with treatment assignments designated according to initial randomization, regardless of whether participants received a different study treatment from the one randomized. Here, 'n' = number of participants with baseline score of 2 or 1 and at least one post-baseline assessment for the specific activity.

End point type

Secondary

End point timeframe

Week 72

End point values	Ataluren	Placebo
Number of subjects analysed	183	176
Units: participants
Stand (n = 182, 176)	14	21
Walk (10m) (n = 183, 176)	14	21
Stand up from chair (n = 177, 171)	36	35
Stand on one leg - right (n = 180, 171)	25	25
Stand on one leg - left (n = 177, 171)	22	23
Climb box step - right (n = 155, 154)	28	50
Descend box step - right (n = 173, 167)	33	39
Climb box step - left (n = 158, 160)	30	51
Descend box step - left (n = 170, 164)	32	34
Lifts head (n = 160, 154)	19	28
Gets to sitting (n = 183, 175)	13	22
Rise from floor (n = 182, 173)	50	53
Stand on heels (n = 130, 112)	40	38
Jump (n = 160, 143)	32	31
Hop right (n = 125, 126)	30	37
Hop left (n = 120, 125)	27	34
Run (10m) (n = 174, 164)	29	35

No statistical analyses for this end point

Secondary: DB Period: Number of Participants With Treatment-emergent Adverse Events (TEAEs)

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End point title

DB Period: Number of Participants With Treatment-emergent Adverse Events (TEAEs)

End point description

An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event (SAE) was an 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); persistent or significant disability/incapacity; congenital anomaly. AEs included both SAEs and non-serious AEs. A TEAE was defined as an AE that occurred or worsened on or after the first dose of study drug and up to 4 weeks after the last dose of double-blind study drug and prior to the first dose of open-label treatment. A summary of other non-serious AEs and all SAEs, regardless of causality is located in the 'Reported AE section'. The as-treated population included all randomized participants who received study treatment, with treatment assignments designated according to actual treatment received.

End point type

Secondary

End point timeframe

Baseline up to Week 76

End point values	Ataluren	Placebo
Number of subjects analysed	184	176
Units: participants	157	149

No statistical analyses for this end point

Secondary: Overall Treatment period: Composite of Average Change From Baseline in TFTs at Week 144

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End point title

Overall Treatment period: Composite of Average Change From Baseline in TFTs at Week 144

End point description

The composite TFT was defined as the average in times to run/walk 10 meters, climb 4 stairs, and descend 4 stairs. Participants who could not perform a TFT within 30 seconds, including those who loss of ambulation or the TFT was above 30 seconds, a value of 30 seconds was used. Baseline was defined as the last observed measurement (average in times to run/walk 10 meters, climb 4 stairs, and descend 4 stairs) on or prior to the first dose of study drug. LS mean and SE was calculated using the MMRM. The ITT population included all participants who were randomized, with treatment assignments designated according to initial randomization, regardless of whether participants received a different study treatment from the one randomized.

End point type

Secondary

End point timeframe

Baseline, Week 144

End point values	Ataluren/Ataluren	Placebo/Ataluren
Number of subjects analysed	183	176
Units: seconds
least squares mean (standard error)	9.00 ( 0.432 )	9.29 ( 0.448 )

Statistical Analysis 1

Comparison groups

Ataluren/Ataluren v Placebo/Ataluren

Number of subjects included in analysis

359

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

LS Mean Difference

Point estimate

-0.29

Confidence interval

level

95%

sides

2-sided

lower limit

-1.43

upper limit

0.85

Variability estimate

Standard error of the mean

Dispersion value

0.581

Secondary: Overall Treatment period: Change From Baseline in 6MWD at Week 144

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End point title

Overall Treatment period: Change From Baseline in 6MWD at Week 144

End point description

The 6MWD test is a non-encouraged test performed in a 30 meters long flat corridor, where the participant is instructed to walk as far as possible, back and forth around two cones, with the permission to slow down, rest, or stop if needed. Ambulation was assessed via the 6MWD test following standardized procedures. Participants were not permitted to use assistive devices (walker, long leg braces, or short leg braces) during the 6MWD test. Participants with confirmed loss of ambulation at a particular visit were assigned a 6MWD result of 0. Baseline was defined as the maximum measurement of valid Day 1 and Day 2 6MWD values. LS mean and SE was calculated using the MMRM. The ITT population included all participants who were randomized, with treatment assignments designated according to initial randomization, regardless of whether participants received a different study treatment from the one randomized.

End point type

Secondary

End point timeframe

Baseline, Week 144

End point values	Ataluren/Ataluren	Placebo/Ataluren
Number of subjects analysed	183	176
Units: meters
least squares mean (standard error)	-130.49 ( 6.913 )	-140.00 ( 7.277 )

Statistical Analysis 1

Comparison groups

Placebo/Ataluren v Ataluren/Ataluren

Number of subjects included in analysis

359

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

LS Mean Difference

Point estimate

9.51

Confidence interval

level

95%

sides

2-sided

lower limit

-7.49

upper limit

26.51

Variability estimate

Standard error of the mean

Dispersion value

8.671

Secondary: Overall Treatment period: Change From Baseline in Time to Run/Walk 10 Meters at Week 144

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End point title

Overall Treatment period: Change From Baseline in Time to Run/Walk 10 Meters at Week 144

End point description

During the test for walking/running 10 meters, the method of walk/run used by the participant was categorized as follows: 1. Unable to walk independently; 2. Unable to walk independently but can walk with support from a person or with assistive device (full leg calipers [knee-ankle-foot orthoses ] or walker); 3. Highly adapted gait, wide-based lordotic gait, cannot increase walking speed; 4. Moderately adapted gait, can pick up speed but cannot run; 5. Able to pick up speed but runs with a double stance phase (that is, cannot achieve both feet off the ground); 6. Runs and gets both feet off the ground (with no double stance phase). Participants who could not perform a TFT within 30 seconds, including those who loss of ambulation or the TFT was above 30 seconds, a value of 30 seconds was used. Baseline was defined as the last observed measurement on or prior to the first dose of study drug. LS mean and SE was calculated using the MMRM. ITT population.

End point type

Secondary

End point timeframe

Baseline, Week 144

End point values	Ataluren/Ataluren	Placebo/Ataluren
Number of subjects analysed	183	176
Units: seconds
least squares mean (standard error)	7.99 ( 0.400 )	8.16 ( 0.415 )

Statistical Analysis 1

Comparison groups

Ataluren/Ataluren v Placebo/Ataluren

Number of subjects included in analysis

359

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

LS Mean Difference

Point estimate

-0.16

Confidence interval

level

95%

sides

2-sided

lower limit

-1.23

upper limit

0.9

Variability estimate

Standard error of the mean

Dispersion value

0.541

Secondary: Overall Treatment period: Change From Baseline in Time to Climb 4 Stairs at Week 144

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End point title

Overall Treatment period: Change From Baseline in Time to Climb 4 Stairs at Week 144

End point description

End point type

Secondary

End point timeframe

Baseline, Week 144

End point values	Ataluren/Ataluren	Placebo/Ataluren
Number of subjects analysed	183	176
Units: seconds
least squares mean (standard error)	9.89 ( 0.480 )	10.18 ( 0.496 )

Statistical Analysis 1

Comparison groups

Ataluren/Ataluren v Placebo/Ataluren

Number of subjects included in analysis

359

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

LS Mean Difference

Point estimate

-0.29

Confidence interval

level

95%

sides

2-sided

lower limit

-1.56

upper limit

0.98

Variability estimate

Standard error of the mean

Dispersion value

0.649

Secondary: Overall Treatment period: Change From Baseline in Time to Descend 4 Stairs at Week 144

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End point title

Overall Treatment period: Change From Baseline in Time to Descend 4 Stairs at Week 144

End point description

End point type

Secondary

End point timeframe

Baseline, Week 144

End point values	Ataluren/Ataluren	Placebo/Ataluren
Number of subjects analysed	183	176
Units: seconds
least squares mean (standard error)	9.56 ( 0.512 )	10.15 ( 0.530 )

Statistical Analysis 1

Comparison groups

Ataluren/Ataluren v Placebo/Ataluren

Number of subjects included in analysis

359

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

LS Mean Difference

Point estimate

-0.59

Confidence interval

level

95%

sides

2-sided

lower limit

-1.96

upper limit

0.77

Variability estimate

Standard error of the mean

Dispersion value

0.696

Secondary: Overall Treatment period: Change From Baseline in NSAA Total Score at Week 144

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End point title

Overall Treatment period: Change From Baseline in NSAA Total Score at Week 144

End point description

End point type

Secondary

End point timeframe

Baseline, Week 144

End point values	Ataluren/Ataluren	Placebo/Ataluren
Number of subjects analysed	183	176
Units: units on a scale
least squares mean (standard error)	-7.0 ( 0.54 )	-7.2 ( 0.56 )

Statistical Analysis 1

Comparison groups

Ataluren/Ataluren v Placebo/Ataluren

Number of subjects included in analysis

359

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

LS Mean Difference

Point estimate

0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-1.1

upper limit

1.6

Variability estimate

Standard error of the mean

Dispersion value

0.68

Secondary: Overall Treatment period: Time to Loss of Ambulation Over 144 Weeks

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End point title

Overall Treatment period: Time to Loss of Ambulation Over 144 Weeks

End point description

Time to loss of ambulation was defined as persistent inability to perform the 10-meter run/walk test within 30 seconds at any post-baseline visit and for all remaining visits. The ITT population included all participants who were randomized, with treatment assignments designated according to initial randomization, regardless of whether participants received a different study treatment from the one randomized. Here, 'Overall number of participants analyzed' = participants with loss of ambulation by Week 144. '99999' = Due to the low number of events, the data could not be estimated.

End point type

Secondary

End point timeframe

Baseline up to Week 144

End point values	Ataluren/Ataluren	Placebo/Ataluren
Number of subjects analysed	40	42
Units: weeks
median (confidence interval 95%)	99999 (99999 to 99999)	99999 (99999 to 99999)

Statistical Analysis 1

Comparison groups

Ataluren/Ataluren v Placebo/Ataluren

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Hazard ratio (HR)

Point estimate

0.89

Confidence interval

level

95%

sides

2-sided

lower limit

0.57

upper limit

1.39

Secondary: Overall Treatment period: Time to Loss of Stair-Climbing Over 144 Weeks

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End point title

Overall Treatment period: Time to Loss of Stair-Climbing Over 144 Weeks

End point description

Time to loss of stair-climbing was defined as persistent inability to perform the 4-stair climb test within 30 seconds at any post-baseline visit and for all remaining visits. The ITT population included all participants who were randomized, with treatment assignments designated according to initial randomization, regardless of whether participants received a different study treatment from the one randomized. Here, 'Overall number of participants analyzed' = participants with loss of stair-climbing by Week 144. '99999' = Due to the low number of events, the data could not be estimated.

End point type

Secondary

End point timeframe

Baseline up to Week 144

End point values	Ataluren/Ataluren	Placebo/Ataluren
Number of subjects analysed	53	59
Units: weeks
median (confidence interval 95%)	99999 (99999 to 99999)	99999 (99999 to 99999)

Statistical Analysis 1

Comparison groups

Ataluren/Ataluren v Placebo/Ataluren

Number of subjects included in analysis

112

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Hazard ratio (HR)

Point estimate

0.75

Confidence interval

level

95%

sides

2-sided

lower limit

0.51

upper limit

1.11

Secondary: Overall Treatment period: Number of Participants With Function Loss of NSAA Items at Week 144

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End point title

Overall Treatment period: Number of Participants With Function Loss of NSAA Items at Week 144

End point description

Function loss was defined as a drop of score from 1 or 2 at baseline to a score of 0 at the specified post-baseline. The missing assessments at post baseline visits were imputed using LOCF. The ITT population included all participants who were randomized, with treatment assignments designated according to initial randomization, regardless of whether participants received a different study treatment from the one randomized. Here, 'n' = number of participants with baseline score of 2 or 1 and at least one post-baseline assessment for the specific activity.

End point type

Secondary

End point timeframe

Week 144

End point values	Ataluren/Ataluren	Placebo/Ataluren
Number of subjects analysed	183	176
Units: participants
Stand (n = 182, 176)	49	49
Walk (10m) (n = 183, 176)	49	48
Stand up from chair (n = 177, 171)	64	73
Stand on one leg - right (n = 180, 171)	58	52
Stand on one leg - left (n = 177, 171)	57	50
Climb box step - right (n = 155, 154)	68	72
Descend box step - right (n = 173, 167)	72	69
Climb box step - left (n = 158, 160)	60	76
Descend box step - left (n = 170, 164)	69	70
Lifts head (n = 160, 154)	46	57
Gets to sitting (n = 183, 175)	53	49
Rise from floor (n = 182, 173)	85	91
Stand on heels (n = 130, 112)	57	49
Jump (n = 160, 143)	63	56
Hop right (n = 125, 126)	48	58
Hop left (n = 120, 125)	46	56
Run (10m) (n = 174, 164)	60	60

No statistical analyses for this end point

Secondary: Overall Treatment period: Time to Loss of Stair- Descending Over 144 Weeks

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End point title

Overall Treatment period: Time to Loss of Stair- Descending Over 144 Weeks

End point description

Time to loss of stair-descending was defined as persistent inability to perform the 4-stair descend test within 30 seconds at any post-baseline visit and for all remaining visits. The ITT population included all participants who were randomized, with treatment assignments designated according to initial randomization, regardless of whether participants received a different study treatment from the one randomized. Here, 'Overall number of participants analyzed' = participants with loss of stair-descending by Week 144. '99999' = Due to the low number of events, the data could not be estimated.

End point type

Secondary

End point timeframe

Baseline up to Week 144

End point values	Ataluren/Ataluren	Placebo/Ataluren
Number of subjects analysed	53	59
Units: weeks
median (confidence interval 95%)	99999 (99999 to 99999)	99999 (99999 to 99999)

Statistical Analysis 1

Comparison groups

Ataluren/Ataluren v Placebo/Ataluren

Number of subjects included in analysis

112

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Hazard ratio (HR)

Point estimate

0.85

Confidence interval

level

95%

sides

2-sided

lower limit

0.58

upper limit

1.25

Secondary: Overall Treatment period: Number of Participants With TEAEs

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End point title

Overall Treatment period: Number of Participants With TEAEs

End point description

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an 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); persistent or significant disability/incapacity; congenital anomaly. AEs included both SAEs and non-serious AEs. A TEAE was defined as an AE that occurs or worsens on or after the first dose of ataluren (regardless of double-blind or open-label) and up to 4 weeks after the last dose of ataluren. A summary of other non-serious AEs and all SAEs, regardless of causality is located in the 'Reported AE section'. The as-treated-OA population included all randomized participants who received at least 1 dose of ataluren anytime during the study.

End point type

Secondary

End point timeframe

Baseline up to Week 148

End point values	Ataluren/Ataluren	Ataluren/Placebo
Number of subjects analysed	184	172
Units: participants	170	110

No statistical analyses for this end point

Secondary: OL Period: Plasma Pharmacokinetic (PK) Concentration of Ataluren

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End point title

OL Period: Plasma Pharmacokinetic (PK) Concentration of Ataluren

End point description

The ITT population included all participants who were randomized, with treatment assignments designated according to initial randomization, regardless of whether participants received a different study treatment from the one randomized. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure. 'n' = participants evaluab le at specified timepoint.

End point type

Secondary

End point timeframe

Predose and 2 hours postdose at Week 144

End point values	Ataluren	Placebo
Number of subjects analysed	165	157
Units: micrograms (µg)/milliliter (mL)
geometric mean (geometric coefficient of variation)
Predose (n = 161, 157)	4.45 ( 120.5 )	4.11 ( 102.7 )
2 hours postdose (n = 165, 156)	12.16 ( 57.2 )	12.21 ( 57.3 )

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Baseline up to Week 148

Adverse event reporting additional description

As-treated population included all randomized participants who received study treatment, with treatment assignments designated according to actual treatment received. AEs were summarized separately for DB period and for the overall ataluren experience, which included all participants who received ataluren throughout the study (DB and OL Period).

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

24.1

Reporting group title

DB Period: Ataluren

Reporting group description

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 72 weeks in DB treatment period.

Reporting group title

Ataluren/Placebo‌

Reporting group description

Reporting group title

Ataluren‌/Ataluren

Reporting group description

Reporting group title

DB Period: Placebo

Reporting group description

Participants received placebo matched to ataluren oral suspension for 72 weeks in DB treatment period.

Serious adverse events	DB Period: Ataluren	Ataluren/Placebo‌	Ataluren‌/Ataluren	DB Period: Placebo
Total subjects affected by serious adverse events
subjects affected / exposed	13 / 184 (7.07%)	11 / 172 (6.40%)	22 / 184 (11.96%)	12 / 176 (6.82%)
number of deaths (all causes)	0	0	0	0
number of deaths resulting from adverse events
Injury, poisoning and procedural complications
Femur fracture
subjects affected / exposed	0 / 184 (0.00%)	1 / 172 (0.58%)	1 / 184 (0.54%)	3 / 176 (1.70%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Humerus fracture
subjects affected / exposed	0 / 184 (0.00%)	0 / 172 (0.00%)	0 / 184 (0.00%)	1 / 176 (0.57%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Spinal compression fracture
subjects affected / exposed	1 / 184 (0.54%)	0 / 172 (0.00%)	1 / 184 (0.54%)	0 / 176 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Lower limb fracture
subjects affected / exposed	1 / 184 (0.54%)	0 / 172 (0.00%)	1 / 184 (0.54%)	1 / 176 (0.57%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Tibia fracture
subjects affected / exposed	1 / 184 (0.54%)	0 / 172 (0.00%)	1 / 184 (0.54%)	0 / 176 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Compression fracture
subjects affected / exposed	0 / 184 (0.00%)	1 / 172 (0.58%)	0 / 184 (0.00%)	0 / 176 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Femoral neck fracture
subjects affected / exposed	0 / 184 (0.00%)	1 / 172 (0.58%)	1 / 184 (0.54%)	0 / 176 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Lumbar vertebral fracture
subjects affected / exposed	0 / 184 (0.00%)	0 / 172 (0.00%)	1 / 184 (0.54%)	0 / 176 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hip fracture
subjects affected / exposed	0 / 184 (0.00%)	1 / 172 (0.58%)	0 / 184 (0.00%)	0 / 176 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Congenital, familial and genetic disorders
Sebaceous naevus
subjects affected / exposed	1 / 184 (0.54%)	0 / 172 (0.00%)	1 / 184 (0.54%)	0 / 176 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Vascular disorders
Hypertension
subjects affected / exposed	1 / 184 (0.54%)	0 / 172 (0.00%)	1 / 184 (0.54%)	0 / 176 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Myocarditis
subjects affected / exposed	0 / 184 (0.00%)	0 / 172 (0.00%)	0 / 184 (0.00%)	1 / 176 (0.57%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Atrial fibrillation
subjects affected / exposed	0 / 184 (0.00%)	1 / 172 (0.58%)	0 / 184 (0.00%)	0 / 176 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac failure chronic
subjects affected / exposed	0 / 184 (0.00%)	1 / 172 (0.58%)	0 / 184 (0.00%)	0 / 176 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cardiomyopathy
subjects affected / exposed	0 / 184 (0.00%)	0 / 172 (0.00%)	2 / 184 (1.09%)	0 / 176 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Surgical and medical procedures
Medical device removal
subjects affected / exposed	0 / 184 (0.00%)	0 / 172 (0.00%)	1 / 184 (0.54%)	0 / 176 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Seizure
subjects affected / exposed	1 / 184 (0.54%)	0 / 172 (0.00%)	1 / 184 (0.54%)	0 / 176 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Acute disseminated encephalomyelitis
subjects affected / exposed	0 / 184 (0.00%)	0 / 172 (0.00%)	0 / 184 (0.00%)	1 / 176 (0.57%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Abdominal pain upper
subjects affected / exposed	1 / 184 (0.54%)	0 / 172 (0.00%)	1 / 184 (0.54%)	0 / 176 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Chronic gastritis
subjects affected / exposed	0 / 184 (0.00%)	0 / 172 (0.00%)	0 / 184 (0.00%)	1 / 176 (0.57%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Inguinal hernia
subjects affected / exposed	1 / 184 (0.54%)	0 / 172 (0.00%)	2 / 184 (1.09%)	0 / 176 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Vomiting
subjects affected / exposed	1 / 184 (0.54%)	0 / 172 (0.00%)	1 / 184 (0.54%)	0 / 176 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Intussusception
subjects affected / exposed	0 / 184 (0.00%)	0 / 172 (0.00%)	0 / 184 (0.00%)	1 / 176 (0.57%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Abdominal pain
subjects affected / exposed	0 / 184 (0.00%)	0 / 172 (0.00%)	1 / 184 (0.54%)	0 / 176 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Enteritis
subjects affected / exposed	0 / 184 (0.00%)	1 / 172 (0.58%)	0 / 184 (0.00%)	0 / 176 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Rhabdomyolysis
subjects affected / exposed	0 / 184 (0.00%)	1 / 172 (0.58%)	0 / 184 (0.00%)	1 / 176 (0.57%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pain in extremity
subjects affected / exposed	0 / 184 (0.00%)	0 / 172 (0.00%)	1 / 184 (0.54%)	0 / 176 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Back pain
subjects affected / exposed	0 / 184 (0.00%)	1 / 172 (0.58%)	0 / 184 (0.00%)	0 / 176 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Appendicitis
subjects affected / exposed	1 / 184 (0.54%)	0 / 172 (0.00%)	1 / 184 (0.54%)	0 / 176 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	0 / 184 (0.00%)	1 / 172 (0.58%)	0 / 184 (0.00%)	1 / 176 (0.57%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Influenza
subjects affected / exposed	1 / 184 (0.54%)	0 / 172 (0.00%)	1 / 184 (0.54%)	1 / 176 (0.57%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	0 / 184 (0.00%)	0 / 172 (0.00%)	1 / 184 (0.54%)	1 / 176 (0.57%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia mycoplasmal
subjects affected / exposed	1 / 184 (0.54%)	0 / 172 (0.00%)	1 / 184 (0.54%)	0 / 176 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Upper respiratory tract infection
subjects affected / exposed	1 / 184 (0.54%)	0 / 172 (0.00%)	1 / 184 (0.54%)	0 / 176 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Tracheitis
subjects affected / exposed	0 / 184 (0.00%)	0 / 172 (0.00%)	0 / 184 (0.00%)	1 / 176 (0.57%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis yersinia
subjects affected / exposed	0 / 184 (0.00%)	1 / 172 (0.58%)	0 / 184 (0.00%)	0 / 176 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hand-foot-and-mouth disease
subjects affected / exposed	0 / 184 (0.00%)	0 / 172 (0.00%)	1 / 184 (0.54%)	0 / 176 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Viral infection
subjects affected / exposed	0 / 184 (0.00%)	1 / 172 (0.58%)	1 / 184 (0.54%)	0 / 176 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	DB Period: Ataluren	Ataluren/Placebo‌	Ataluren‌/Ataluren	DB Period: Placebo
Total subjects affected by non serious adverse events
subjects affected / exposed	157 / 184 (85.33%)	107 / 172 (62.21%)	170 / 184 (92.39%)	148 / 176 (84.09%)
Injury, poisoning and procedural complications
Ligament sprain
subjects affected / exposed	17 / 184 (9.24%)	5 / 172 (2.91%)	20 / 184 (10.87%)	6 / 176 (3.41%)
occurrences all number	17	6	22	6
Fall
subjects affected / exposed	19 / 184 (10.33%)	6 / 172 (3.49%)	25 / 184 (13.59%)	23 / 176 (13.07%)
occurrences all number	35	7	48	30
Nervous system disorders
Headache
subjects affected / exposed	19 / 184 (10.33%)	6 / 172 (3.49%)	22 / 184 (11.96%)	15 / 176 (8.52%)
occurrences all number	38	29	56	22
General disorders and administration site conditions
Pyrexia
subjects affected / exposed	19 / 184 (10.33%)	3 / 172 (1.74%)	25 / 184 (13.59%)	9 / 176 (5.11%)
occurrences all number	23	3	29	10
Disease progression
subjects affected / exposed	11 / 184 (5.98%)	24 / 172 (13.95%)	47 / 184 (25.54%)	18 / 176 (10.23%)
occurrences all number	11	24	47	18
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	13 / 184 (7.07%)	4 / 172 (2.33%)	16 / 184 (8.70%)	14 / 176 (7.95%)
occurrences all number	22	4	27	15
Diarrhoea
subjects affected / exposed	15 / 184 (8.15%)	2 / 172 (1.16%)	18 / 184 (9.78%)	12 / 176 (6.82%)
occurrences all number	17	2	20	15
Vomiting
subjects affected / exposed	30 / 184 (16.30%)	4 / 172 (2.33%)	33 / 184 (17.93%)	9 / 176 (5.11%)
occurrences all number	46	4	52	10
Constipation
subjects affected / exposed	0 / 184 (0.00%)	4 / 172 (2.33%)	11 / 184 (5.98%)	0 / 176 (0.00%)
occurrences all number	0	4	12	0
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
subjects affected / exposed	12 / 184 (6.52%)	3 / 172 (1.74%)	16 / 184 (8.70%)	5 / 176 (2.84%)
occurrences all number	16	4	20	9
Cough
subjects affected / exposed	18 / 184 (9.78%)	6 / 172 (3.49%)	25 / 184 (13.59%)	20 / 176 (11.36%)
occurrences all number	23	7	35	32
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	0 / 184 (0.00%)	6 / 172 (3.49%)	11 / 184 (5.98%)	0 / 176 (0.00%)
occurrences all number	0	8	13	0
Pain in extremity
subjects affected / exposed	0 / 184 (0.00%)	3 / 172 (1.74%)	12 / 184 (6.52%)	0 / 176 (0.00%)
occurrences all number	0	4	17	0
Infections and infestations
Upper respiratory tract infection
subjects affected / exposed	27 / 184 (14.67%)	17 / 172 (9.88%)	33 / 184 (17.93%)	44 / 176 (25.00%)
occurrences all number	50	32	70	77
Nasopharyngitis
subjects affected / exposed	27 / 184 (14.67%)	7 / 172 (4.07%)	34 / 184 (18.48%)	12 / 176 (6.82%)
occurrences all number	42	11	70	17
Influenza
subjects affected / exposed	8 / 184 (4.35%)	1 / 172 (0.58%)	10 / 184 (5.43%)	9 / 176 (5.11%)
occurrences all number	9	1	11	9
Gastroenteritis
subjects affected / exposed	0 / 184 (0.00%)	2 / 172 (1.16%)	14 / 184 (7.61%)	0 / 176 (0.00%)
occurrences all number	0	2	17	0
COVID-19
subjects affected / exposed	0 / 184 (0.00%)	12 / 172 (6.98%)	8 / 184 (4.35%)	0 / 176 (0.00%)
occurrences all number	0	13	8	0

More information

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Were there any global substantial amendments to the protocol? Yes

01 Aug 2019

It included the following changes: - Added collection of blood samples for determination of ataluren plasma concentrations. Addition of secondary objectives of ataluren PK profile evaluation and correlation between ataluren plasma concentrations and functional outcomes. - Facilitated enrolment of the mITT Population by limiting enrolment to participants aged ≥7 to ≤16 years who met the mITT criteria after approximately 270 participants were enrolled in the study. - Increased the sample size from approximately 250 participants to a maximum of 340 participants to achieve up to 162 participants in the mITT Population.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results: A Phase 3, Randomised, Double-blind, Placebo-controlled Efficacy and Safety Study of Ataluren in Patients With Nonsense Mutation Duchenne Muscular Dystrophy and Open-label Extension

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: DB Period: Change From Baseline in 6-Minute Walk Distance (6MWD) at Week 72 - Modified Intention-to-treat (mITT) Population

Primary: DB Period: Change From Baseline in 6-Minute Walk Distance (6MWD) at Week 72 - Modified Intention-to-treat (mITT) Population

Primary: DB Period: Average Rate of Change From Baseline in 6MWD at Week 72 - mITT Population

Primary: DB Period: Average Rate of Change From Baseline in 6MWD at Week 72 - mITT Population

Primary: DB Period: Change From Baseline in 6MWD at Week 72 - Intention-to-treat (ITT) Population

Primary: DB Period: Change From Baseline in 6MWD at Week 72 - Intention-to-treat (ITT) Population

Primary: DB Period: Average Rate of Change From Baseline in 6MWD at Week 72 - ITT Population

Primary: DB Period: Average Rate of Change From Baseline in 6MWD at Week 72 - ITT Population

Secondary: DB Period: Change From Baseline in Time to Run/Walk 10 Meters at Week 72 - mITT Population

Secondary: DB Period: Change From Baseline in Time to Run/Walk 10 Meters at Week 72 - mITT Population

Secondary: DB Period: Change From Baseline in Time to Run/Walk 10 Meters at Week 72 - ITT Population

Secondary: DB Period: Change From Baseline in Time to Run/Walk 10 Meters at Week 72 - ITT Population

Secondary: DB Period: Change From Baseline in Time to Climb 4 Stairs at Week 72 - mITT Population

Secondary: DB Period: Change From Baseline in Time to Climb 4 Stairs at Week 72 - mITT Population

Secondary: DB Period: Change From Baseline in Time to Climb 4 Stairs at Week 72 - ITT Population

Secondary: DB Period: Change From Baseline in Time to Climb 4 Stairs at Week 72 - ITT Population

Secondary: DB Period: Change From Baseline in Time to Descend 4 Stairs at Week 72 - mITT Population

Secondary: DB Period: Change From Baseline in Time to Descend 4 Stairs at Week 72 - mITT Population

Secondary: DB Period: Change From Baseline in Time to Descend 4 Stairs at Week 72 - ITT Population

Secondary: DB Period: Change From Baseline in Time to Descend 4 Stairs at Week 72 - ITT Population

Secondary: DB Period: Composite of Average Change From Baseline in TFTs at Week 72 - mITT Population

Secondary: DB Period: Composite of Average Change From Baseline in TFTs at Week 72 - mITT Population

Secondary: DB Period: Composite of Average Change From Baseline in TFTs at Week 72 - ITT Population

Secondary: DB Period: Composite of Average Change From Baseline in TFTs at Week 72 - ITT Population

Secondary: DB Period: Composite of Average Rate of Change From Baseline in TFTs at Week 72 - mITT Population

Secondary: DB Period: Composite of Average Rate of Change From Baseline in TFTs at Week 72 - mITT Population

Secondary: DB Period: Composite of Average Rate of Change From Baseline in TFTs at Week 72 - ITT Population

Secondary: DB Period: Composite of Average Rate of Change From Baseline in TFTs at Week 72 - ITT Population

Secondary: DB Period: Time to Persistent 10% Worsening in 6MWD at Week 72 - mITT Population

Secondary: DB Period: Time to Persistent 10% Worsening in 6MWD at Week 72 - mITT Population

Secondary: DB Period: Time to Persistent 10% Worsening in 6MWD at Week 72 - ITT Population

Secondary: DB Period: Time to Persistent 10% Worsening in 6MWD at Week 72 - ITT Population

Secondary: DB Period: Change From Baseline in North Start Ambulatory Assessment (NSAA) Total Score at Week 72 - mITT Population

Secondary: DB Period: Change From Baseline in North Start Ambulatory Assessment (NSAA) Total Score at Week 72 - mITT Population

Secondary: DB Period: Change From Baseline in NSAA Total Score at Week 72 - ITT Population

Secondary: DB Period: Change From Baseline in NSAA Total Score at Week 72 - ITT Population

Secondary: DB Period: Time to Loss of Ambulation Over 72 Weeks - mITT Population

Secondary: DB Period: Time to Loss of Ambulation Over 72 Weeks - mITT Population

Secondary: DB Period: Time to Loss of Ambulation Over 72 Weeks - ITT Population

Secondary: DB Period: Time to Loss of Ambulation Over 72 Weeks - ITT Population

Secondary: DB Period: Time to Loss of Stair-Climbing Over 72 Weeks - mITT Population

Secondary: DB Period: Time to Loss of Stair-Climbing Over 72 Weeks - mITT Population

Secondary: DB Period: Time to Loss of Stair-Climbing Over 72 Weeks - ITT Population

Secondary: DB Period: Time to Loss of Stair-Climbing Over 72 Weeks - ITT Population

Secondary: DB Period: Time to Loss of Stair-Descending Over 72 Weeks - mITT Population

Secondary: DB Period: Time to Loss of Stair-Descending Over 72 Weeks - mITT Population

Secondary: DB Period: Time to Loss of Stair-Descending Over 72 Weeks - ITT Population

Secondary: DB Period: Time to Loss of Stair-Descending Over 72 Weeks - ITT Population

Secondary: DB Period: Number of Participants With Function Loss of NSAA Items at Week 72 - mITT Population

Secondary: DB Period: Number of Participants With Function Loss of NSAA Items at Week 72 - mITT Population

Secondary: DB Period: Number of Participants With Function Loss of NSAA Items at Week 72 - ITT Population

Secondary: DB Period: Number of Participants With Function Loss of NSAA Items at Week 72 - ITT Population

Secondary: DB Period: Number of Participants With Treatment-emergent Adverse Events (TEAEs)

Secondary: DB Period: Number of Participants With Treatment-emergent Adverse Events (TEAEs)

Secondary: Overall Treatment period: Composite of Average Change From Baseline in TFTs at Week 144

Secondary: Overall Treatment period: Composite of Average Change From Baseline in TFTs at Week 144

Secondary: Overall Treatment period: Change From Baseline in 6MWD at Week 144

Secondary: Overall Treatment period: Change From Baseline in 6MWD at Week 144

Secondary: Overall Treatment period: Change From Baseline in Time to Run/Walk 10 Meters at Week 144

Secondary: Overall Treatment period: Change From Baseline in Time to Run/Walk 10 Meters at Week 144

Secondary: Overall Treatment period: Change From Baseline in Time to Climb 4 Stairs at Week 144

Secondary: Overall Treatment period: Change From Baseline in Time to Climb 4 Stairs at Week 144

Secondary: Overall Treatment period: Change From Baseline in Time to Descend 4 Stairs at Week 144

Secondary: Overall Treatment period: Change From Baseline in Time to Descend 4 Stairs at Week 144

Secondary: Overall Treatment period: Change From Baseline in NSAA Total Score at Week 144

Secondary: Overall Treatment period: Change From Baseline in NSAA Total Score at Week 144

Secondary: Overall Treatment period: Time to Loss of Ambulation Over 144 Weeks

Secondary: Overall Treatment period: Time to Loss of Ambulation Over 144 Weeks

Secondary: Overall Treatment period: Time to Loss of Stair-Climbing Over 144 Weeks

Secondary: Overall Treatment period: Time to Loss of Stair-Climbing Over 144 Weeks

Clinical Trial Results:
A Phase 3, Randomised, Double-blind, Placebo-controlled Efficacy and Safety Study of Ataluren in Patients With Nonsense Mutation Duchenne Muscular Dystrophy and Open-label Extension