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This study is designed to evaluate the effect of ataluren on Maximum Reading Speed as measured using the Minnesota Low Vision Reading Test (MNREAD) Acuity Charts in participants with nonsense mutation aniridia. This study involves a 4-week screening period, a 144-week treatment period (Stage 1: Weeks 1 to 48 [double-masked treatment] and Stage 2: Weeks 49 to 144 [open label treatment]), an optional 96-week open label extension sub-study, and a 4-week post-treatment follow-up period (either study completion or early termination). Participants that choose not to participate in the sub-study will be required to complete the post-treatment follow-up visit at the end of the Stage 2 open-label extension.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Ataluren | Experimental | Participants will receive ataluren orally 3 times a day (TID) at a dose of 10 milligrams per kilogram (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 complete Stage 2 and agree to continue in open-label sub-study, will continue to receive ataluren treatment at same dose as mentioned above, for 96 weeks or until commercial availability of ataluren for this indication, whichever is first, or until a positive risk-benefit assessment in this indication is not demonstrated. |
|
| Placebo | Placebo Comparator | Participants will receive placebo matching 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 complete Stage 2 and agree to continue in open-label sub-study, will continue to receive ataluren treatment at same dose as mentioned above, for 96 weeks or until commercial availability of ataluren for this indication, whichever is first, or until a positive risk-benefit assessment in this indication is not demonstrated. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ataluren | Drug | Ataluren oral suspension will be administered as per the dose and schedule specified in the respective arms. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 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). | Baseline, Week 48 |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Reading Accessibility Index of Both Eyes at Week 48 | 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. |
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Inclusion Criteria:
Evidence of signed and dated informed consent document(s) indicating that the study candidate (and/or a parent/legal guardian) has been informed of all pertinent aspects of the study. Note: If the study candidate is considered a child under local regulation, a parent or legal guardian must provide written consent prior to initiation of study screening procedures and the study candidate may be required to provide written assent. The rules of the responsible institutional review board/independent ethics committee (IRB/IEC) regarding whether 1 or both parents must provide consent and the appropriate ages for obtaining consent and assent from the participant should be followed.
Body weight greater than or equal to (>=) 12 kg.
Documentation of the presence of a nonsense mutation in 1 allele of the PAX6 gene as determined by genotyping performed at a laboratory certified by the College of American Pathologists (CAP), or under the Clinical Laboratory Improvement Act/Amendment (CLIA), or by an equivalent organization.
Clinical diagnosis of aniridia.
Willingness and ability to comply with scheduled visits, drug administration plan, study procedures, and study restrictions.
Good general health, as determined at Screening by medical history and physical examination (including vital sign measurements).
No clinically significant abnormality based upon laboratory assessments at Screening, in the opinion of the investigator.
Female participants of childbearing potential are eligible for the study but must be willing to use adequate (at least 1 form of) contraceptive methods as described below during the study treatment period (starting from the day of first dose of study drug and ending 60 days after the last dose of study drug). Childbearing potential is defined as participants who have experienced menarche and who are neither postmenopausal nor have been permanently sterilized.
Male participants with partners of childbearing potential must agree to use adequate (at least 1 form of) contraception as described below during the study treatment period (starting from the day of first dose of study drug and ending 60 days after the last dose of study drug).
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Quintus Ngumah, OD, PhD | PTC Therapeutics | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Casey Eye Institute, Oregon Health & Science University | Portland | Oregon | 97239 | United States | ||
| University of Virginia |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Stage 1: Double-Masked Period (48 Weeks) |
|
| ||||||||||||||||||||||||
| Stage 2: Open-Label Extension (96 Weeks) |
| |||||||||||||||||||||||||
| Open-Label Sub-Study (96 Weeks) |
|
The safety population included all randomized participants who received at least 1 dose of study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | Ataluren | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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 | 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). | 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. | Posted | Least Squares Mean | Standard Error | percent change | Baseline, Week 48 |
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).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Stage 1: Ataluren | 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). |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Mental disorder | Psychiatric disorders | MedDRA | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Information | PTC Therapeutics, Inc. | 1-866-562-4620 | medinfo@ptcbio.com |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Dec 17, 2019 | May 3, 2022 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Feb 5, 2020 | May 3, 2022 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D015783 | Aniridia |
| ID | Term |
|---|---|
| D005124 | Eye Abnormalities |
| D005128 | Eye Diseases |
| D015785 | Eye Diseases, Hereditary |
| D007499 | Iris Diseases |
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| ID | Term |
|---|---|
| C515878 | ataluren |
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| Placebo | Drug | Placebo will be administered as per the schedule specified in the respective arm. |
|
| Baseline, Week 48 |
| Change From Baseline in Best Corrected Visual Acuity (BCVA) at Week 48 | The BCVA was evaluated using the Early Treatment Diabetic Retinopathy Study (ETDRS) Method. Missing data was imputed using LOCF method. | Baseline, Week 48 |
| Percent Change From Baseline in Maximum Reading Speed of Oculus Dexter (OD) (Right Eye) and Oculus Sinister (OS) (Left Eye) at 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. | Baseline, Week 48 |
| Change From Baseline in Reading Accessibility Index of Right Eye and Left Eye at 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. | Baseline, Week 48 |
| Change From Baseline in Critical Print Size (CPS) of Both Eyes, Right Eye, and Left Eye at 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. | Baseline, Week 48 |
| Change From Baseline in Reading Acuity (RA) of Both Eyes, Right Eye, and Left Eye at 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. | Baseline, Week 48 |
| Number of Participants With Change From Baseline in Severity of Corneal Keratopathy at Week 48 | The severity of corneal keratopathy was reported as worsened, not change, or improve. Missing data were imputed using LOCF. | Baseline to Week 48 |
| Change From Baseline in Iris Area at Week 48 | Missing data were imputed using LOCF. | Baseline, Week 48 |
| Change From Baseline in BCVA at Week 240 | The BCVA was evaluated using the ETDRS Method. Missing data were imputed using LOCF method. | Baseline, Week 240 |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 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). | Baseline up to Week 244 |
| Charlottesville |
| Virginia |
| 22908 |
| United States |
| University of British Columbia | Vancouver | British Columbia | V5Z3N9 | Canada |
| NOT COMPLETED |
|
|
| NOT COMPLETED |
|
|
| BG001 | 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. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
|
|
|
|
| Secondary | Change From Baseline in Reading Accessibility Index of Both Eyes at Week 48 | 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. | 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. | Posted | Mean | Standard Deviation | units on a scale | Baseline, Week 48 |
|
|
|
| Secondary | Change From Baseline in Best Corrected Visual Acuity (BCVA) at Week 48 | The BCVA was evaluated using the Early Treatment Diabetic Retinopathy Study (ETDRS) Method. Missing data was imputed using LOCF method. | 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. 'Number analyzed' = participants evaluable for specified category. | Posted | Mean | Standard Deviation | LogMAR | Baseline, Week 48 |
|
|
|
| Secondary | Percent Change From Baseline in Maximum Reading Speed of Oculus Dexter (OD) (Right Eye) and Oculus Sinister (OS) (Left Eye) at 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. | 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. 'Number analyzed' = participants evaluable for specified category. | Posted | Mean | Standard Deviation | percent change | Baseline, Week 48 |
|
|
|
| Secondary | Change From Baseline in Reading Accessibility Index of Right Eye and Left Eye at 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. | 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. 'Number analyzed' = participants evaluable for specified category. | Posted | Mean | Standard Deviation | units on a scale | Baseline, Week 48 |
|
|
|
| Secondary | Change From Baseline in Critical Print Size (CPS) of Both Eyes, Right Eye, and Left Eye at 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. | 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. 'Number analyzed' = participants evaluable for specified category. | Posted | Mean | Standard Deviation | LogMAR | Baseline, Week 48 |
|
|
|
| Secondary | Change From Baseline in Reading Acuity (RA) of Both Eyes, Right Eye, and Left Eye at 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. | 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. 'Number analyzed' = participants evaluable for specified category. | Posted | Mean | Standard Deviation | LogMAR | Baseline, Week 48 |
|
|
|
| Secondary | Number of Participants With Change From Baseline in Severity of Corneal Keratopathy at Week 48 | The severity of corneal keratopathy was reported as worsened, not change, or improve. Missing data were imputed using LOCF. | 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. 'Number analyzed' = participants evaluable for specified category. | Posted | Count of Participants | Participants | Baseline to Week 48 |
|
|
|
| Secondary | Change From Baseline in Iris Area at Week 48 | Missing data were imputed using LOCF. | 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. 'Number analyzed' = participants evaluable for specified category. | Posted | Mean | Standard Deviation | millimeter square (mm^2) | Baseline, Week 48 |
|
|
|
| Secondary | Change From Baseline in BCVA at Week 240 | The BCVA was evaluated using the ETDRS Method. Missing data were imputed using LOCF method. | 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. 'Number analyzed' = participants evaluable for specified category. | Posted | Mean | Standard Deviation | logMAR | Baseline, Week 240 |
|
|
|
| Secondary | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 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). | The safety population included all randomized participants who received at least 1 dose of study drug. | Posted | Count of Participants | Participants | Baseline up to Week 244 |
|
|
|
| 0 |
| 26 |
| 1 |
| 26 |
| 22 |
| 26 |
| EG001 | Stage 1: 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). | 0 | 13 | 0 | 13 | 10 | 13 |
| EG002 | 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. | 0 | 37 | 1 | 37 | 35 | 37 |
| Vomiting | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Flatulence | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Abdominal distension | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Frequent bowel movements | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Dental caries | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Faeces soft | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Tooth impacted | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Abdominal discomfort | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Gastrointestinal Pain | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Malaise | General disorders | MedDRA | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA | Systematic Assessment |
|
| Local swelling | General disorders | MedDRA | Systematic Assessment |
|
| Medical device site reaction | General disorders | MedDRA | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA | Systematic Assessment |
|
| Asthenia | General disorders | MedDRA | Systematic Assessment |
|
| Sensation of pressure | General disorders | MedDRA | Systematic Assessment |
|
| Pain | General disorders | MedDRA | Systematic Assessment |
|
| Dry eye | Eye disorders | MedDRA | Systematic Assessment |
|
| Lacrimation increased | Eye disorders | MedDRA | Systematic Assessment |
|
| Eye pruritus | Eye disorders | MedDRA | Systematic Assessment |
|
| Corneal opacity | Eye disorders | MedDRA | Systematic Assessment |
|
| Eye swelling | Eye disorders | MedDRA | Systematic Assessment |
|
| Eyelid ptosis | Eye disorders | MedDRA | Systematic Assessment |
|
| Lenticular opacities | Eye disorders | MedDRA | Systematic Assessment |
|
| Ocular hyperaemia | Eye disorders | MedDRA | Systematic Assessment |
|
| Eye discharge | Eye disorders | MedDRA | Systematic Assessment |
|
| Keratopathy | Eye disorders | MedDRA | Systematic Assessment |
|
| Vision blurred | Eye disorders | MedDRA | Systematic Assessment |
|
| Vitreous detachment | Eye disorders | MedDRA | Systematic Assessment |
|
| Photophobia | Eye disorders | MedDRA | Systematic Assessment |
|
| Eye pain | Eye disorders | MedDRA | Systematic Assessment |
|
| Lens discolouration | Eye disorders | MedDRA | Systematic Assessment |
|
| Blepharospasm | Eye disorders | MedDRA | Systematic Assessment |
|
| Cataract | Eye disorders | MedDRA | Systematic Assessment |
|
| Eye inflammation | Eye disorders | MedDRA | Systematic Assessment |
|
| Eye irritation | Eye disorders | MedDRA | Systematic Assessment |
|
| Photokeratitis | Eye disorders | MedDRA | Systematic Assessment |
|
| Punctate keratitis | Eye disorders | MedDRA | Systematic Assessment |
|
| Visual acuity reduced | Eye disorders | MedDRA | Systematic Assessment |
|
| Gastroenteritis viral | Infections and infestations | MedDRA | Systematic Assessment |
|
| Conjunctivitis | Infections and infestations | MedDRA | Systematic Assessment |
|
| Influenza | Infections and infestations | MedDRA | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA | Systematic Assessment |
|
| Pharyngitis streptococcal | Infections and infestations | MedDRA | Systematic Assessment |
|
| Roseola | Infections and infestations | MedDRA | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA | Systematic Assessment |
|
| Ear infection | Infections and infestations | MedDRA | Systematic Assessment |
|
| Atypical Pneumonia | Infections and infestations | MedDRA | Systematic Assessment |
|
| Cellulitis of male external genital organ | Infections and infestations | MedDRA | Systematic Assessment |
|
| Eye infection | Infections and infestations | MedDRA | Systematic Assessment |
|
| Lyme disease | Infections and infestations | MedDRA | Systematic Assessment |
|
| Respiratory tract infection | Infections and infestations | MedDRA | Systematic Assessment |
|
| Urine leukocyte esterase positive | Investigations | MedDRA | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA | Systematic Assessment |
|
| Upper respiratory tract infection | Investigations | MedDRA | Systematic Assessment |
|
| Blood uric acid increased | Investigations | MedDRA | Systematic Assessment |
|
| Nitrite urine present | Investigations | MedDRA | Systematic Assessment |
|
| Protein urine present | Investigations | MedDRA | Systematic Assessment |
|
| Urine ketone body present | Investigations | MedDRA | Systematic Assessment |
|
| Blood urea increased | Investigations | MedDRA | Systematic Assessment |
|
| Intraocular pressure increased | Investigations | MedDRA | Systematic Assessment |
|
| Urine Leukocyte esterase positive | Investigations | MedDRA | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA | Systematic Assessment |
|
| Bacterial test positive | Investigations | MedDRA | Systematic Assessment |
|
| Blood bilirubin increased | Investigations | MedDRA | Systematic Assessment |
|
| Hepatic enzyme increased | Investigations | MedDRA | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA | Systematic Assessment |
|
| Mood altered | Psychiatric disorders | MedDRA | Systematic Assessment |
|
| Attention deficit/Hyperactivity disorder | Psychiatric disorders | MedDRA | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA | Systematic Assessment |
|
| Depression | Psychiatric disorders | MedDRA | Systematic Assessment |
|
| Obsessive-compulsive disorder | Psychiatric disorders | MedDRA | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
|
| Erythema | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
|
| Dermatitis contact | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
|
| Skin discolouration | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
|
| Hypothyroidism | Endocrine disorders | MedDRA | Systematic Assessment |
|
| Fall | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
|
| Somnolence | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Migraine | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Concussion | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
|
| Corneal Abrasion | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
|
| Joint dislocation | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
|
| Ligament sprain | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
|
| Radius fracture | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
|
| Sunburn | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
|
| Haematuria | Renal and urinary disorders | MedDRA | Systematic Assessment |
|
| Dysuria | Renal and urinary disorders | MedDRA | Systematic Assessment |
|
| Epiphysiolysis | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
|
| Menorrhagia | Reproductive system and breast disorders | MedDRA | Systematic Assessment |
|
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
|
| Balanoposthitis | Reproductive system and breast disorders | MedDRA | Systematic Assessment |
|
| Metrorrhagia | Reproductive system and breast disorders | MedDRA | Systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
|
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
|
| Sneezing | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
|
| Throat irritation | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
|
| Wheezing | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
|
| Phimosis | Congenital, familial and genetic disorders | MedDRA | Systematic Assessment |
|
| Motion sickness | Ear and labyrinth disorders | MedDRA | Systematic Assessment |
|
| Seasonal allergy | Immune system disorders | MedDRA | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA | Systematic Assessment |
|
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.
| D014603 |
| Uveal Diseases |
| D000013 | Congenital Abnormalities |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D030342 | Genetic Diseases, Inborn |
| Right Eye |
|
|
| Right Eye |
|
|
| Right Eye |
|
|
| Left Eye |
|
|
| Right Eye |
|
|
| Left Eye |
|
|
| Right Eye |
|
|
| Not change |
|
| Improved |
|
| Right Eye |
|
|
| Right Eye |
|
|