Genetic Diseases, Inborn, Genetic Diseases, X-Linked, Muscular Diseases, Muscular Disorders, Atrophic, Muscular Dystrophies, Muscular Dystrophy, Duchenne, Musculoskeletal Disease, Nervous System Diseases, Neuromuscular Diseases
Conditions
Keywords
Duchenne Muscular Dystrophy, Dystrophinopathy, Nonsense Mutation, Premature Stop Codon, Becker Muscular Dystrophy, DMD/BMD, PTC124, Ataluren
Brief summary
This study is a long-term study of ataluren in participants with nonsense mutation Duchenne muscular dystrophy.
Detailed description
This study is a randomized, double-blind, placebo-controlled, 72-week study, followed by a 72-week open-label period. The purpose is to characterize the long-term effects of ataluren-mediated dystrophin restoration on disease progression. Participants will be randomized in a 1:1 ratio to ataluren or placebo. Participants will receive blinded study drug three times daily (TID) at morning, midday, and evening for 72 weeks, after which all participants will receive open-label ataluren for an additional 72 weeks (144 weeks in total). Study assessments will be performed at clinic visits every 12 weeks during the double-blind period and every 24 weeks during the open-label period.
Interventions
DRUGAtaluren
10, 20 mg/kg
DRUGPLACEBO
10, 20 mg/kg
Sponsors
PTC Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
A randomized, double-blind, placebo-controlled,72-week study and its 72-week open-label extension
Intervention model description
This study describes the randomized, double-blind, placebo-controlled, 72-week study and its 72-week open-label extension
Eligibility
Sex/Gender
MALE
Age
5 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male sex * Age ≥5 years * Phenotypic evidence of Duchenne Muscular Dystrophy * Nonsense point mutation in the dystrophin gene * Use of systemic corticosteroids (prednisone/prednisolone or deflazacort)for a minimum of 12 months immediately prior to start of study treatment, with no significant change in dosage or dosing regimen for a minimum of 3 months immediately prior to start of study treatment * 6MWD ≥150 meters * Ability to perform timed function tests within 30 seconds * Willingness and ability to comply with scheduled visits, drug administration plan, study procedures, laboratory tests, and study restrictions.
Exclusion criteria
* Any change in prophylaxis treatment for cardiomyopathy within 1 month prior to start of study treatment. * Ongoing intravenous (IV) aminoglycoside or IV vancomycin therapy. * Prior or ongoing therapy with ataluren. * Known hypersensitivity to any of the ingredients or excipients of the study drug * Exposure to another investigational drug within 6 months prior to start of study treatment, or ongoing participation in any interventional clinical trial. * History of major surgical procedure within 12 weeks prior to start of study treatment, or expectation of major surgical procedure during the 72-week placebo-controlled treatment period. * Requirement for daytime ventilator assistance or any use of invasive mechanical ventilation via tracheostomy. * Uncontrolled clinical symptoms and signs of congestive heart failure * Elevated serum creatinine or cystatin C at screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| DB Period: Change From Baseline in 6-Minute Walk Distance (6MWD) at Week 72 - Modified Intention-to-treat (mITT) Population | Baseline, Week 72 | 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). |
| DB Period: Change From Baseline in 6MWD at Week 72 - Intent-to-Treat (ITT) Population | Baseline, Week 72 | 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. |
| DB Period: Average Rate of Change From Baseline in 6MWD at Week 72 - mITT Population | Baseline, Week 72 | 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. |
| DB Period: Average Rate of Change From Baseline in 6MWD at Week 72 - ITT Population | Baseline, Week 72 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| DB Period: Change From Baseline in Time to Run/Walk 10 Meters at Week 72 - mITT Population | Baseline, Week 72 | 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. |
| DB Period: Change From Baseline in Time to Run/Walk 10 Meters at Week 72 - ITT Population | Baseline, Week 72 | 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. |
| DB Period: Change From Baseline in Time to Climb 4 Stairs at Week 72 - mITT Population | Baseline, Week 72 | 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. |
| DB Period: Change From Baseline in Time to Climb 4 Stairs at Week 72 - ITT Population | Baseline, Week 72 | 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. |
| DB Period: Change From Baseline in Time to Descend 4 Stairs at Week 72 - mITT Population | Baseline, Week 72 | 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. |
| DB Period: Change From Baseline in Time to Descend 4 Stairs at Week 72 - ITT Population | Baseline, Week 72 | 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. |
| DB Period: Composite of Average Change From Baseline in TFTs at Week 72 - mITT Population | Baseline, Week 72 | 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. |
| DB Period: Composite of Average Change From Baseline in TFTs at Week 72 - ITT Population | Baseline, Week 72 | 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. |
| DB Period: Composite of Average Rate of Change From Baseline in TFTs at Week 72 - mITT Population | Baseline, Week 72 | 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. |
| DB Period: Composite of Average Rate of Change From Baseline in TFTs at Week 72 - ITT Population | Baseline, Week 72 | 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. |
| DB Period: Time to Persistent 10% Worsening in 6MWD at Week 72 - mITT Population | Baseline to Week 72 | 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. |
| DB Period: Time to Persistent 10% Worsening in 6MWD - ITT Population | Baseline to approximately Week 72 (Due to COVID, many participants attended the protocol-defined Week 72 visit late) | 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. Due to COVID, there were many participants who participated in the protocol-defined Week 72 visit late. Due to this reason, the calculated median for the time to event for the Ataluren arm in the DB period were greater than Week 72. |
| DB Period: Change From Baseline in North Start Ambulatory Assessment (NSAA) Total Score at Week 72 - mITT Population | Baseline, Week 72 | 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. |
| DB Period: Change From Baseline in NSAA Total Score at Week 72 - ITT Population | Baseline, Week 72 | 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. |
| DB Period: Time to Loss of Ambulation - mITT Population | Baseline up to approximately Week 72 (Due to COVID, many participants attended the protocol-defined Week 72 visit late) | 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. Due to COVID, there were many participants who participated in the protocol-defined Week 72 visit late. Due to this reason, the calculated median and 95% CI for the time to event for the Ataluren arm in the DB period were greater than Week 72. |
| DB Period: Time to Loss of Ambulation Over 72 Weeks - ITT Population | Baseline up to Week 72 | 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. |
| DB Period: Time to Loss of Stair-Climbing - mITT Population | Baseline up to approximately Week 72 (Due to COVID, many participants attended the protocol-defined Week 72 visit late) | 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. Due to COVID, there were many participants who participated in the protocol-defined Week 72 visit late. Due to this reason, the calculated median and 95% CI for the time to event for the Ataluren arm in the DB period were greater than Week 72. |
| DB Period: Time to Loss of Stair-Climbing - ITT Population | Baseline up to approximately Week 72 (Due to COVID, many participants attended the protocol-defined Week 72 visit late) | 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. Due to COVID, there were many participants who participated in the protocol-defined Week 72 visit late. Due to this reason, the calculated median and 95% CI for the time to event for the Ataluren arm in the DB period were greater than Week 72. |
| DB Period: Time to Loss of Stair-Descending - mITT Population | Baseline up to approximately Week 72 (Due to COVID, many participants attended the protocol-defined Week 72 visit late) | 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. Due to COVID, there were many participants who participated in the protocol-defined Week 72 visit late. Due to this reason, the calculated median and 95% CI for the time to event for the Ataluren arm in the DB period were greater than Week 72. |
| DB Period: Time to Loss of Stair-Descending - ITT Population | Baseline up to approximately Week 72 (Due to COVID, many participants attended the protocol-defined Week 72 visit late) | 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. Due to COVID, there were many participants who participated in the protocol-defined Week 72 visit late. Due to this reason, the calculated median and 95% CI for the time to event for the Ataluren arm in the DB period were greater than Week 72. |
| DB Period: Number of Participants With Function Loss of NSAA Items at Week 72 - mITT Population | Week 72 | 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 of NSAA items. The missing assessments at post baseline visits were imputed using last observation carried forward (LOCF). |
| DB Period: Number of Participants With Function Loss of NSAA Items at Week 72 - ITT Population | Week 72 | 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 of NSAA items. The missing assessments at post baseline visits were imputed using LOCF. |
| DB Period: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Baseline up to Week 76 | 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'. |
| Overall Treatment Period: Change From Baseline in 6MWD at Week 144 | Baseline, Week 144 | 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. |
| Overall Treatment Period: Composite of Average Change From Baseline in TFTs at Week 144 | Baseline, Week 144 | 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. |
| Overall Treatment Period: Change From Baseline in Time to Run/Walk 10 Meters at Week 144 | Baseline, Week 144 | 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. |
| Overall Treatment Period: Change From Baseline in Time to Climb 4 Stairs at Week 144 | Baseline, Week 144 | 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. |
| Overall Treatment Period: Change From Baseline in Time to Descend 4 Stairs at Week 144 | Baseline, Week 144 | 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. |
| Overall Treatment Period: Change From Baseline in NSAA Total Score at Week 144 | Baseline, Week 144 | 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 analysis of covariation (ANCOVA) with multiple imputation. |
| Overall Treatment Period: Time to Loss of Ambulation Over 144 Weeks | Baseline up to Week 144 | 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. |
| Overall Treatment Period: Time to Loss of Stair-Climbing Over 144 Weeks | Baseline up to Week 144 | 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. |
| Overall Treatment Period: Time to Loss of Stair- Descending Over 144 Weeks | Baseline up to Week 144 | 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. |
| Overall Treatment Period: Number of Participants With Function Loss of NSAA Items at Week 144 | Week 144 | 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 in NSAA items. The missing assessments at post baseline visits were imputed using LOCF. |
| Overall Treatment Period: Number of Participants With TEAEs | Baseline up to Week 148 | 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'. |
| OL Period: Plasma Pharmacokinetic (PK) Concentration of Ataluren | Predose and 2 hours postdose at Week 144 | — |
Countries
Australia, Brazil, Bulgaria, Canada, China, Hong Kong, India, Japan, Malaysia, Mexico, Poland, Puerto Rico, Russia, South Korea, Taiwan, Thailand, Turkey (Türkiye), United States
Contacts
STUDY_DIRECTORVinay Penematsa, MD
PTC Therapeutics, Inc.
Participant flow
Pre-assignment details
The study consisted of a 72-week double-blind (DB) treatment period followed by a 72-week open-label (OL) treatment period.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 8.1 years STANDARD_DEVIATION 2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 18 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 166 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 221 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 8 Participants |
| Race (NIH/OMB) White | 101 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 184 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 184 | 0 / 176 | 0 / 184 | 0 / 172 |
| other Total, other adverse events | 157 / 184 | 148 / 176 | 170 / 184 | 107 / 172 |
| serious Total, serious adverse events | 13 / 184 | 12 / 176 | 22 / 184 | 11 / 172 |
Outcome results
None listed