Trial Outcomes & Findings for Study of Ataluren in Participants With Nonsense Mutation Aniridia (NCT NCT02647359)

Last Updated: 2022-05-27

Results Overview

MNREAD Acuity Chart can only be used to assess participants ≥8 years old. MNREAD Acuity Chart measures reading speed as a function of print size in participants with normal and low vision. The test consists of short sentences with print size decreasing by 0.1 log unit steps from a maximum of 1.3 logarithm of the minimum angle of resolution (logMAR) (equivalent to 20/400 or 6/120 when viewed at 40 centimeters \[cm\]) to -0.5 logMAR (equivalent to 20/6 or 6/2). An MNREAD Acuity Chart curve of reading speed vs print size has a typical shape for normally sighted persons and many low-vision individuals. This curve is characterized by 3 summary values. At large print sizes, reading speed remains fairly constant, forming a plateau that represents the maximum reading speed. As the print size decreases, a critical print size (CPS) is reached at which reading speed begins to decline rapidly. Finally, the smallest print size that can be read is defined as the reading acuity (RA).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

39 participants

Primary outcome timeframe

Baseline, Week 48

Results posted on

2022-05-27

Participant Flow

Participant milestones

Participant milestones
Measure	Ataluren Participants received ataluren orally 3 times a day (TID) at a dose of 10 milligrams (mg)/kilogram (kg) in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 48 weeks in Stage 1 (double-masked period) and for additional 96 weeks in Stage 2 (open-label extension period). Participants, who completed Stage 2 and agreed to continue in open-label sub-study, continued to receive ataluren treatment at same dose as mentioned above, for 96 weeks.	Placebo Participants received placebo matched to ataluren TID orally in the morning, at midday, and in the evening for 48 weeks in Stage 1 (double-masked period) and ataluren orally TID at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for additional 96 weeks in Stage 2 (open-label extension period). Participants, who completed Stage 2 and agreed to continue in open-label sub-study, continued to receive ataluren treatment at same dose as mentioned above, for 96 weeks.
Stage 1: Double-Masked Period (48 Weeks) STARTED	26	13
Stage 1: Double-Masked Period (48 Weeks) Received at Least 1 Dose of Study Drug	26	13
Stage 1: Double-Masked Period (48 Weeks) COMPLETED	22	12
Stage 1: Double-Masked Period (48 Weeks) NOT COMPLETED	4	1
Stage 2: Open-Label Extension (96 Weeks) STARTED	22	11
Stage 2: Open-Label Extension (96 Weeks) COMPLETED	12	7
Stage 2: Open-Label Extension (96 Weeks) NOT COMPLETED	10	4
Open-Label Sub-Study (96 Weeks) STARTED	10	7
Open-Label Sub-Study (96 Weeks) COMPLETED	2	3
Open-Label Sub-Study (96 Weeks) NOT COMPLETED	8	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Ataluren Participants received ataluren orally 3 times a day (TID) at a dose of 10 milligrams (mg)/kilogram (kg) in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 48 weeks in Stage 1 (double-masked period) and for additional 96 weeks in Stage 2 (open-label extension period). Participants, who completed Stage 2 and agreed to continue in open-label sub-study, continued to receive ataluren treatment at same dose as mentioned above, for 96 weeks.	Placebo Participants received placebo matched to ataluren TID orally in the morning, at midday, and in the evening for 48 weeks in Stage 1 (double-masked period) and ataluren orally TID at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for additional 96 weeks in Stage 2 (open-label extension period). Participants, who completed Stage 2 and agreed to continue in open-label sub-study, continued to receive ataluren treatment at same dose as mentioned above, for 96 weeks.
Stage 1: Double-Masked Period (48 Weeks) Non-compliance with study drug	0	1
Stage 1: Double-Masked Period (48 Weeks) Other than specified	4	0
Stage 2: Open-Label Extension (96 Weeks) Adverse Event	2	1
Stage 2: Open-Label Extension (96 Weeks) Other than specified	8	3
Open-Label Sub-Study (96 Weeks) Lost to Follow-up	1	0
Open-Label Sub-Study (96 Weeks) Other than specified	7	4

Baseline Characteristics

Study of Ataluren in Participants With Nonsense Mutation Aniridia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ataluren n=26 Participants Participants received ataluren orally TID at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 48 weeks in Stage 1 (double-masked period) and for additional 96 weeks in Stage 2 (open-label extension period). Participants, who completed Stage 2 and agreed to continue in open-label sub-study, continued to receive ataluren treatment at same dose as mentioned above, for 96 weeks.	Placebo n=13 Participants Participants received placebo matched to ataluren TID orally in the morning, at midday, and in the evening for 48 weeks in Stage 1 (double-masked period) and ataluren orally TID at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for additional 96 weeks in Stage 2 (open-label extension period). Participants, who completed Stage 2 and agreed to continue in open-label sub-study, continued to receive ataluren treatment at same dose as mentioned above, for 96 weeks.	Total n=39 Participants Total of all reporting groups
Age, Continuous	14.1 years STANDARD_DEVIATION 10.12 • n=5 Participants	19.2 years STANDARD_DEVIATION 19.43 • n=7 Participants	15.8 years STANDARD_DEVIATION 13.88 • n=5 Participants
Sex: Female, Male Female	10 Participants n=5 Participants	8 Participants n=7 Participants	18 Participants n=5 Participants
Sex: Female, Male Male	16 Participants n=5 Participants	5 Participants n=7 Participants	21 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	26 Participants n=5 Participants	12 Participants n=7 Participants	38 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	22 Participants n=5 Participants	11 Participants n=7 Participants	33 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Week 48

Population: The intent-to-treat (ITT) population included all randomized participants who received at least 1 dose of study drug. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.

Outcome measures

Outcome measures
Measure	Ataluren n=11 Participants Participants received ataluren orally TID at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 48 weeks in Stage 1 (double-masked period) and for additional 96 weeks in Stage 2 (open-label extension period). Participants, who completed Stage 2 and agreed to continue in open-label sub-study, continued to receive ataluren treatment at same dose as mentioned above, for 96 weeks.	Placebo n=5 Participants Participants received placebo matched to ataluren TID orally in the morning, at midday, and in the evening for 48 weeks in Stage 1 (double-masked period) and ataluren orally TID at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for additional 96 weeks in Stage 2 (open-label extension period). Participants, who completed Stage 2 and agreed to continue in open-label sub-study, continued to receive ataluren treatment at same dose as mentioned above, for 96 weeks.	Overall Ataluren Exposure Participants received ataluren orally TID at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 48 weeks in Stage 1 (double-masked period) and for additional 96 weeks in Stage 2 (open-label extension period). Participants, who completed Stage 2 and agreed to continue in open-label sub-study, continued to receive ataluren treatment at same dose as mentioned above, for 96 weeks.
Percent Change From Baseline in Maximum Reading Speed of Oculus Unitas (OU) (Both Eyes) at Week 48, as Measured Using the Minnesota Low Vision Reading Test (MNREAD) Acuity Charts	9.87 percent change Standard Error 7.425	-0.89 percent change Standard Error 11.809	—

SECONDARY outcome

Timeframe: Baseline, Week 48

Population: The ITT population included all randomized participants who received at least 1 dose of study drug. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.

Reading Accessibility Index is defined as the mean reading speed in words per minute (wpm) across the 10 largest physical print sizes on the MNREAD Acuity Chart, normalized by the value for a group of normally sighted young adults. For a viewing distance of 40 cm, this range of print sizes corresponds to 0.4 to 1.3 logMAR. This range of print sizes was chosen for 2 reasons. First, it sustains the manifest refraction spherical equivalent (MRS) in normally sighted persons. Second, it covers most contemporary printed text found in everyday life. Because the Reading Accessibility Index is normalized by the value for a group of normally sighted young adults (aged 18 to 39 years), a Reading Accessibility Index of 1.0 represents normal performance for this age group. Values less than 1.0 mean reduced accessibility to printed text within the range of print size encountered in daily life. Missing data was imputed using last observation carried forward (LOCF) method.

Outcome measures

Outcome measures
Measure	Ataluren n=11 Participants Participants received ataluren orally TID at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 48 weeks in Stage 1 (double-masked period) and for additional 96 weeks in Stage 2 (open-label extension period). Participants, who completed Stage 2 and agreed to continue in open-label sub-study, continued to receive ataluren treatment at same dose as mentioned above, for 96 weeks.	Placebo n=6 Participants Participants received placebo matched to ataluren TID orally in the morning, at midday, and in the evening for 48 weeks in Stage 1 (double-masked period) and ataluren orally TID at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for additional 96 weeks in Stage 2 (open-label extension period). Participants, who completed Stage 2 and agreed to continue in open-label sub-study, continued to receive ataluren treatment at same dose as mentioned above, for 96 weeks.	Overall Ataluren Exposure Participants received ataluren orally TID at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 48 weeks in Stage 1 (double-masked period) and for additional 96 weeks in Stage 2 (open-label extension period). Participants, who completed Stage 2 and agreed to continue in open-label sub-study, continued to receive ataluren treatment at same dose as mentioned above, for 96 weeks.
Change From Baseline in Reading Accessibility Index of Both Eyes at Week 48	0.10 units on a scale Standard Deviation 0.241	0.02 units on a scale Standard Deviation 0.267	—

SECONDARY outcome

Timeframe: Baseline, Week 48

The BCVA was evaluated using the Early Treatment Diabetic Retinopathy Study (ETDRS) Method. Missing data was imputed using LOCF method.

Outcome measures

Outcome measures
Measure	Ataluren n=24 Participants Participants received ataluren orally TID at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 48 weeks in Stage 1 (double-masked period) and for additional 96 weeks in Stage 2 (open-label extension period). Participants, who completed Stage 2 and agreed to continue in open-label sub-study, continued to receive ataluren treatment at same dose as mentioned above, for 96 weeks.	Placebo n=13 Participants Participants received placebo matched to ataluren TID orally in the morning, at midday, and in the evening for 48 weeks in Stage 1 (double-masked period) and ataluren orally TID at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for additional 96 weeks in Stage 2 (open-label extension period). Participants, who completed Stage 2 and agreed to continue in open-label sub-study, continued to receive ataluren treatment at same dose as mentioned above, for 96 weeks.	Overall Ataluren Exposure Participants received ataluren orally TID at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 48 weeks in Stage 1 (double-masked period) and for additional 96 weeks in Stage 2 (open-label extension period). Participants, who completed Stage 2 and agreed to continue in open-label sub-study, continued to receive ataluren treatment at same dose as mentioned above, for 96 weeks.
Change From Baseline in Best Corrected Visual Acuity (BCVA) at Week 48 Left Eye	-0.00 LogMAR Standard Deviation 0.076	0.01 LogMAR Standard Deviation 0.103	—
Change From Baseline in Best Corrected Visual Acuity (BCVA) at Week 48 Right Eye	0.03 LogMAR Standard Deviation 0.125	-0.04 LogMAR Standard Deviation 0.138	—

SECONDARY outcome

Timeframe: Baseline, Week 48

Maximum Reading Speed was measured using the MNREAD Acuity Chart, which can only be used to assess participants ≥8 years old. The MNREAD Acuity Chart measures reading speed as a function of print size in participants with normal and low vision. The test consists of short sentences with print size decreasing by 0.1 log unit steps from a maximum of 1.3 logMAR (equivalent to 20/400 or 6/120 when viewed at 40 cm) to -0.5 logMAR (equivalent to 20/6 or 6/2). An MNREAD Acuity Chart curve of reading speed vs print size has a typical shape for normally sighted persons and many low-vision individuals. This curve is characterized by 3 summary values. At large print sizes, reading speed remains fairly constant, forming a plateau that represents the maximum reading speed. As the print size decreases, a CPS is reached at which reading speed begins to decline rapidly. Finally, the smallest print size that can be read is defined as the RA.

Outcome measures

Outcome measures
Measure	Ataluren n=10 Participants Participants received ataluren orally TID at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 48 weeks in Stage 1 (double-masked period) and for additional 96 weeks in Stage 2 (open-label extension period). Participants, who completed Stage 2 and agreed to continue in open-label sub-study, continued to receive ataluren treatment at same dose as mentioned above, for 96 weeks.	Placebo n=6 Participants Participants received placebo matched to ataluren TID orally in the morning, at midday, and in the evening for 48 weeks in Stage 1 (double-masked period) and ataluren orally TID at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for additional 96 weeks in Stage 2 (open-label extension period). Participants, who completed Stage 2 and agreed to continue in open-label sub-study, continued to receive ataluren treatment at same dose as mentioned above, for 96 weeks.	Overall Ataluren Exposure Participants received ataluren orally TID at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 48 weeks in Stage 1 (double-masked period) and for additional 96 weeks in Stage 2 (open-label extension period). Participants, who completed Stage 2 and agreed to continue in open-label sub-study, continued to receive ataluren treatment at same dose as mentioned above, for 96 weeks.
Percent Change From Baseline in Maximum Reading Speed of Oculus Dexter (OD) (Right Eye) and Oculus Sinister (OS) (Left Eye) at Week 48 Left Eye	8.70 percent change Standard Deviation 36.464	-4.11 percent change Standard Deviation 38.380	—
Percent Change From Baseline in Maximum Reading Speed of Oculus Dexter (OD) (Right Eye) and Oculus Sinister (OS) (Left Eye) at Week 48 Right Eye	19.05 percent change Standard Deviation 39.116	-3.83 percent change Standard Deviation 21.091	—

SECONDARY outcome

Timeframe: Baseline, Week 48

Reading Accessibility Index is defined as the mean reading speed in wpm across the 10 largest physical print sizes on the MNREAD Acuity Chart, normalized by the value for a group of normally sighted young adults. For a viewing distance of 40 cm, this range of print sizes corresponds to 0.4 to 1.3 logMAR. This range of print sizes was chosen for 2 reasons. First, it sustains the MRS in normally sighted persons. Second, it covers most contemporary printed text found in everyday life. Because the Reading Accessibility Index is normalized by the value for a group of normally sighted young adults (aged 18 to 39 years), a Reading Accessibility Index of 1.0 represents normal performance for this age group. Values less than 1.0 mean reduced accessibility to printed text within the range of print size encountered in daily life. Missing data was imputed using LOCF method.

Outcome measures

Outcome measures
Measure	Ataluren n=11 Participants Participants received ataluren orally TID at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 48 weeks in Stage 1 (double-masked period) and for additional 96 weeks in Stage 2 (open-label extension period). Participants, who completed Stage 2 and agreed to continue in open-label sub-study, continued to receive ataluren treatment at same dose as mentioned above, for 96 weeks.	Placebo n=6 Participants Participants received placebo matched to ataluren TID orally in the morning, at midday, and in the evening for 48 weeks in Stage 1 (double-masked period) and ataluren orally TID at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for additional 96 weeks in Stage 2 (open-label extension period). Participants, who completed Stage 2 and agreed to continue in open-label sub-study, continued to receive ataluren treatment at same dose as mentioned above, for 96 weeks.	Overall Ataluren Exposure Participants received ataluren orally TID at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 48 weeks in Stage 1 (double-masked period) and for additional 96 weeks in Stage 2 (open-label extension period). Participants, who completed Stage 2 and agreed to continue in open-label sub-study, continued to receive ataluren treatment at same dose as mentioned above, for 96 weeks.
Change From Baseline in Reading Accessibility Index of Right Eye and Left Eye at Week 48 Left Eye	-0.70 units on a scale Standard Deviation 2.601	0.01 units on a scale Standard Deviation 0.224	—
Change From Baseline in Reading Accessibility Index of Right Eye and Left Eye at Week 48 Right Eye	0.04 units on a scale Standard Deviation 0.048	0.05 units on a scale Standard Deviation 0.128	—

SECONDARY outcome

Timeframe: Baseline, Week 48

The MNREAD Acuity Chart measures reading speed as a function of print size in participants with normal and low vision. The test consists of short sentences with print size decreasing by 0.1 log unit steps from a maximum of 1.3 logMAR (equivalent to 20/400 or 6/120 when viewed at 40 cm) to -0.5 logMAR (equivalent to 20/6 or 6/2). An MNREAD Acuity Chart curve of reading speed vs print size has a typical shape for normally sighted persons and many low-vision individuals. This curve is characterized by 3 summary values. At large print sizes, reading speed remains fairly constant, forming a plateau that represents the maximum reading speed. As the print size decreases, a CPS is reached at which reading speed begins to decline rapidly. Finally, the smallest print size that can be read is defined as the RA. Missing data was imputed using LOCF method.

Outcome measures

Outcome measures
Measure	Ataluren n=11 Participants Participants received ataluren orally TID at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 48 weeks in Stage 1 (double-masked period) and for additional 96 weeks in Stage 2 (open-label extension period). Participants, who completed Stage 2 and agreed to continue in open-label sub-study, continued to receive ataluren treatment at same dose as mentioned above, for 96 weeks.	Placebo n=6 Participants Participants received placebo matched to ataluren TID orally in the morning, at midday, and in the evening for 48 weeks in Stage 1 (double-masked period) and ataluren orally TID at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for additional 96 weeks in Stage 2 (open-label extension period). Participants, who completed Stage 2 and agreed to continue in open-label sub-study, continued to receive ataluren treatment at same dose as mentioned above, for 96 weeks.	Overall Ataluren Exposure Participants received ataluren orally TID at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 48 weeks in Stage 1 (double-masked period) and for additional 96 weeks in Stage 2 (open-label extension period). Participants, who completed Stage 2 and agreed to continue in open-label sub-study, continued to receive ataluren treatment at same dose as mentioned above, for 96 weeks.
Change From Baseline in Critical Print Size (CPS) of Both Eyes, Right Eye, and Left Eye at Week 48 Both Eyes	-0.19 LogMAR Standard Deviation 0.259	0.12 LogMAR Standard Deviation 0.433	—
Change From Baseline in Critical Print Size (CPS) of Both Eyes, Right Eye, and Left Eye at Week 48 Left Eye	-0.05 LogMAR Standard Deviation 0.198	0.07 LogMAR Standard Deviation 0.271	—
Change From Baseline in Critical Print Size (CPS) of Both Eyes, Right Eye, and Left Eye at Week 48 Right Eye	0.03 LogMAR Standard Deviation 0.275	-0.02 LogMAR Standard Deviation 0.452	—

SECONDARY outcome

Timeframe: Baseline, Week 48

Outcome measures

Outcome measures
Measure	Ataluren n=11 Participants Participants received ataluren orally TID at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 48 weeks in Stage 1 (double-masked period) and for additional 96 weeks in Stage 2 (open-label extension period). Participants, who completed Stage 2 and agreed to continue in open-label sub-study, continued to receive ataluren treatment at same dose as mentioned above, for 96 weeks.	Placebo n=6 Participants Participants received placebo matched to ataluren TID orally in the morning, at midday, and in the evening for 48 weeks in Stage 1 (double-masked period) and ataluren orally TID at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for additional 96 weeks in Stage 2 (open-label extension period). Participants, who completed Stage 2 and agreed to continue in open-label sub-study, continued to receive ataluren treatment at same dose as mentioned above, for 96 weeks.	Overall Ataluren Exposure Participants received ataluren orally TID at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 48 weeks in Stage 1 (double-masked period) and for additional 96 weeks in Stage 2 (open-label extension period). Participants, who completed Stage 2 and agreed to continue in open-label sub-study, continued to receive ataluren treatment at same dose as mentioned above, for 96 weeks.
Change From Baseline in Reading Acuity (RA) of Both Eyes, Right Eye, and Left Eye at Week 48 Both Eyes	-0.06 LogMAR Standard Deviation 0.239	-0.16 LogMAR Standard Deviation 0.339	—
Change From Baseline in Reading Acuity (RA) of Both Eyes, Right Eye, and Left Eye at Week 48 Left Eye	-0.15 LogMAR Standard Deviation 2.723	-0.16 LogMAR Standard Deviation 0.467	—
Change From Baseline in Reading Acuity (RA) of Both Eyes, Right Eye, and Left Eye at Week 48 Right Eye	-0.05 LogMAR Standard Deviation 0.142	-0.14 LogMAR Standard Deviation 0.236	—

SECONDARY outcome

Timeframe: Baseline to Week 48

The severity of corneal keratopathy was reported as worsened, not change, or improve. Missing data were imputed using LOCF.

Outcome measures

Outcome measures
Measure	Ataluren n=21 Participants Participants received ataluren orally TID at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 48 weeks in Stage 1 (double-masked period) and for additional 96 weeks in Stage 2 (open-label extension period). Participants, who completed Stage 2 and agreed to continue in open-label sub-study, continued to receive ataluren treatment at same dose as mentioned above, for 96 weeks.	Placebo n=12 Participants Participants received placebo matched to ataluren TID orally in the morning, at midday, and in the evening for 48 weeks in Stage 1 (double-masked period) and ataluren orally TID at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for additional 96 weeks in Stage 2 (open-label extension period). Participants, who completed Stage 2 and agreed to continue in open-label sub-study, continued to receive ataluren treatment at same dose as mentioned above, for 96 weeks.	Overall Ataluren Exposure Participants received ataluren orally TID at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 48 weeks in Stage 1 (double-masked period) and for additional 96 weeks in Stage 2 (open-label extension period). Participants, who completed Stage 2 and agreed to continue in open-label sub-study, continued to receive ataluren treatment at same dose as mentioned above, for 96 weeks.
Number of Participants With Change From Baseline in Severity of Corneal Keratopathy at Week 48 Left Eye · Worsened	4 Participants	2 Participants	—
Number of Participants With Change From Baseline in Severity of Corneal Keratopathy at Week 48 Left Eye · Not change	7 Participants	2 Participants	—
Number of Participants With Change From Baseline in Severity of Corneal Keratopathy at Week 48 Left Eye · Improved	8 Participants	3 Participants	—
Number of Participants With Change From Baseline in Severity of Corneal Keratopathy at Week 48 Right Eye · Worsened	4 Participants	2 Participants	—
Number of Participants With Change From Baseline in Severity of Corneal Keratopathy at Week 48 Right Eye · Not change	7 Participants	2 Participants	—
Number of Participants With Change From Baseline in Severity of Corneal Keratopathy at Week 48 Right Eye · Improved	10 Participants	4 Participants	—

SECONDARY outcome

Timeframe: Baseline, Week 48

Missing data were imputed using LOCF.

Outcome measures

Outcome measures
Measure	Ataluren n=9 Participants Participants received ataluren orally TID at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 48 weeks in Stage 1 (double-masked period) and for additional 96 weeks in Stage 2 (open-label extension period). Participants, who completed Stage 2 and agreed to continue in open-label sub-study, continued to receive ataluren treatment at same dose as mentioned above, for 96 weeks.	Placebo n=2 Participants Participants received placebo matched to ataluren TID orally in the morning, at midday, and in the evening for 48 weeks in Stage 1 (double-masked period) and ataluren orally TID at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for additional 96 weeks in Stage 2 (open-label extension period). Participants, who completed Stage 2 and agreed to continue in open-label sub-study, continued to receive ataluren treatment at same dose as mentioned above, for 96 weeks.	Overall Ataluren Exposure Participants received ataluren orally TID at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 48 weeks in Stage 1 (double-masked period) and for additional 96 weeks in Stage 2 (open-label extension period). Participants, who completed Stage 2 and agreed to continue in open-label sub-study, continued to receive ataluren treatment at same dose as mentioned above, for 96 weeks.
Change From Baseline in Iris Area at Week 48 Left Eye	-0.15 millimeter square (mm^2) Standard Deviation 0.333	0.14 millimeter square (mm^2) Standard Deviation 0.129	—
Change From Baseline in Iris Area at Week 48 Right Eye	-0.06 millimeter square (mm^2) Standard Deviation 0.257	-0.14 millimeter square (mm^2)	—

SECONDARY outcome

Timeframe: Baseline, Week 240

The BCVA was evaluated using the ETDRS Method. Missing data were imputed using LOCF method.

Outcome measures

Outcome measures
Measure	Ataluren n=2 Participants Participants received ataluren orally TID at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 48 weeks in Stage 1 (double-masked period) and for additional 96 weeks in Stage 2 (open-label extension period). Participants, who completed Stage 2 and agreed to continue in open-label sub-study, continued to receive ataluren treatment at same dose as mentioned above, for 96 weeks.	Placebo Participants received placebo matched to ataluren TID orally in the morning, at midday, and in the evening for 48 weeks in Stage 1 (double-masked period) and ataluren orally TID at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for additional 96 weeks in Stage 2 (open-label extension period). Participants, who completed Stage 2 and agreed to continue in open-label sub-study, continued to receive ataluren treatment at same dose as mentioned above, for 96 weeks.	Overall Ataluren Exposure Participants received ataluren orally TID at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 48 weeks in Stage 1 (double-masked period) and for additional 96 weeks in Stage 2 (open-label extension period). Participants, who completed Stage 2 and agreed to continue in open-label sub-study, continued to receive ataluren treatment at same dose as mentioned above, for 96 weeks.
Change From Baseline in BCVA at Week 240 Left Eye	0.02 logMAR Standard Deviation 0.141	—	—
Change From Baseline in BCVA at Week 240 Right Eye	0.11 logMAR Standard Deviation 0.240	—	—

SECONDARY outcome

Timeframe: Baseline up to Week 244

Population: The safety population included all randomized participants who received at least 1 dose of study drug.

An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AEs included both SAEs and non-serious AEs. A summary of other non-serious AEs and all SAEs, regardless of causality is located in the 'Reported AE section'. AEs were summarized separately for Stage 1 and for the overall ataluren experience, which included all participants who received ataluren throughput the study (Stage 1, open-label extension period \[Stage 2\], and sub-study).

Outcome measures

Outcome measures
Measure	Ataluren n=26 Participants Participants received ataluren orally TID at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 48 weeks in Stage 1 (double-masked period) and for additional 96 weeks in Stage 2 (open-label extension period). Participants, who completed Stage 2 and agreed to continue in open-label sub-study, continued to receive ataluren treatment at same dose as mentioned above, for 96 weeks.	Placebo n=13 Participants Participants received placebo matched to ataluren TID orally in the morning, at midday, and in the evening for 48 weeks in Stage 1 (double-masked period) and ataluren orally TID at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for additional 96 weeks in Stage 2 (open-label extension period). Participants, who completed Stage 2 and agreed to continue in open-label sub-study, continued to receive ataluren treatment at same dose as mentioned above, for 96 weeks.	Overall Ataluren Exposure n=37 Participants Participants received ataluren orally TID at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 48 weeks in Stage 1 (double-masked period) and for additional 96 weeks in Stage 2 (open-label extension period). Participants, who completed Stage 2 and agreed to continue in open-label sub-study, continued to receive ataluren treatment at same dose as mentioned above, for 96 weeks.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	22 Participants	10 Participants	35 Participants

Adverse Events

Stage 1: Ataluren

Serious events: 1 serious events

Other events: 22 other events

Deaths: 0 deaths

Stage 1: Placebo

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Overall Ataluren Exposure

Serious events: 1 serious events

Other events: 35 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Stage 1: Ataluren n=26 participants at risk Participants received ataluren orally TID at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 48 weeks in Stage 1 (double-masked period).	Stage 1: Placebo n=13 participants at risk Participants received placebo matched to ataluren TID orally in the morning, at midday, and in the evening for 48 weeks in Stage 1 (double-masked period).	Overall Ataluren Exposure n=37 participants at risk Participants received ataluren orally TID at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 48 weeks in Stage 1 (double-masked period) and for additional 96 weeks in Stage 2 (open-label extension period). Participants, who completed Stage 2 and agreed to continue in open-label sub-study, continued to receive ataluren treatment at same dose as mentioned above, for 96 weeks.
Psychiatric disorders Mental disorder	3.8% 1/26 • Baseline up to Week 244 The safety population included all randomized participants who received at least 1 dose of study drug. AEs were summarized separately for Stage 1 and for the overall ataluren experience, which included all participants who received ataluren throughput the study (Stage 1, open-label extension period \[Stage 2\], and sub-study).	0.00% 0/13 • Baseline up to Week 244 The safety population included all randomized participants who received at least 1 dose of study drug. AEs were summarized separately for Stage 1 and for the overall ataluren experience, which included all participants who received ataluren throughput the study (Stage 1, open-label extension period \[Stage 2\], and sub-study).	2.7% 1/37 • Baseline up to Week 244 The safety population included all randomized participants who received at least 1 dose of study drug. AEs were summarized separately for Stage 1 and for the overall ataluren experience, which included all participants who received ataluren throughput the study (Stage 1, open-label extension period \[Stage 2\], and sub-study).

Other adverse events

Additional Information

Medical Information

PTC Therapeutics, Inc.

Phone: 1-866-562-4620

Email: [email protected]

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