Long-Term Outcomes of Ataluren in Duchenne Muscular Dystrophy

A Phase 3, Randomized, Double-blind, Placebo-controlled Efficacy and Safety Study of Ataluren in Patients With Nonsense Mutation Duchenne Muscular Dystrophy and Open-Label Extension

This study is a long-term study of ataluren in participants with nonsense mutation Duchenne muscular dystrophy.

Study Overview

• Status: Completed
• Conditions: Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Muscular Diseases; Neuromuscular Diseases; Muscular Dystrophies; Muscular Disorders, Atrophic; Muscular Dystrophy, Duchenne; Musculoskeletal Disease
• Intervention / Treatment: Drug: Ataluren; Drug: PLACEBO

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.

• Study Type: Interventional
• Enrollment (Actual): 360
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • South Brisbane, Australia, Q4101
    • Queensland Children's Hospital
  • New South Wales
    • Westmead, New South Wales, Australia, 2145
      • The Childrens Hospital at Westmead
  • Victoria
    • Parkville, Victoria, Australia, 3052
      • The Royal Childrens Hospital
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Perth Children's Hospital
• Brazil
  • Belo Horizonte, Brazil, 30130-100
    • Hospital de Clínicas da Universidade Federal de Minas Gerais
  • Rio de Janeiro, Brazil, 21.941-912
    • Universidade Federal do Rio de Janeiro
  • São Paulo, Brazil, 05403-000
    • Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo - FMUSP
• Bulgaria
  • Sofia, Bulgaria, 1793
    • UMHAT SofiaMed
• Canada
  • Ontario
    • London, Ontario, Canada, N6A5W9
      • Childrens Hospital London Health Sciences Centre
    • Ottawa, Ontario, Canada, K1H8L1
      • Childrens Hospital of Eastern Ontario
• China
  • Beijing, China, 100039
    • General Hospital of Chinese Armed Police Forces
  • Fuzhou, China, 350005
    • The First Affiliated Hospital of Fujian Medical University
  • Hunan, China, 410008
    • Xiangya Hospital Central South University
  • Shanghai, China, 200032
    • Children's Hospital of Fudan University
  • Shenzhen, China, 518038
    • Shenzhen Children's Hospital
• Hong Kong
  • Hong Kong, Hong Kong, SAR
    • Queen Mary Hospital
• India
  • Chandigarh, India, 160012
    • Postgraduate Institute of Medical Education and Research
  • New Delhi, India, 110029
    • All India Institute of Medical Sciences
  • Gujarat
    • Ahmedabad, Gujarat, India, 380005
      • Panchshil Hospital
  • Karnataka
    • Bengaluru, Karnataka, India, 560029
      • National Institute of Mental Health and Neurosciences
  • Maharashtra
    • Māhīm, Maharashtra, India, 400016
      • P.D. Hinduja Hospital
  • Tamil Nadu
    • Chennai, Tamil Nadu, India, 600006
      • Apollo Children's Hospital Chennai
    • Vellore, Tamil Nadu, India, 632004
      • Christian Medical College Hospital Vellore
  • Telangana
    • Hyderabad, Telangana, India, 500082
      • Nizam's Institute of Medical Sciences (NIMS)
  • West Bengal
    • Kolkata, West Bengal, India, 700054
      • Apollo Gleneagles Hospital
• Japan
  • Multiple Locations, Japan
    • PTC Clinical Site
• Malaysia
  • Kuala Lumpur, Malaysia, 50586
    • Hospital Tunku Azizah Kuala Lumpur
  • Pantai, Malaysia, 59100
    • University Malaya Medical Centre (UMMC)
• Mexico
  • Chihuahua City, Mexico, 31217
    • Hospital Angeles Chihuahua
  • Mexico City, Mexico, 04530
    • Instituto Nacional de Pediatría
  • Tlalpan, Mexico, 14389
    • Instituto Nacional De Rehabilitacion
• Poland
  • Warsaw, Poland, 02-097
    • Samodzielny Publiczny Centralny Szpital Kliniczny w Warszawie
• Puerto Rico
  • San Juan, Puerto Rico, 00936-5067
    • University of Puerto Rico - School of Medicine
• Russia
  • Moscow, Russia, 125412
    • Russian National Research Medical University n.a. N.I.Pirogov, structural branch - Research Clinical Institute of Pediatrics n.a. Academician Yu. E. Veltishchev
  • Saint Petersburg, Russia, 194100
    • "Saint Petersburg State Paediatric Medical University" based at Consultative and Diagnostic Centre
• South Korea
  • Seoul, South Korea, 06351
    • Samsung Medical Center
  • Seoul, South Korea, 3080
    • Seoul National University Hospital
  • Gyeongsangnam-do
    • Yangsan, Gyeongsangnam-do, South Korea, 50612
      • Pusan National University Yangsan Hospital
• Taiwan
  • Kaohsiung City, Taiwan, 80756
    • Kaohsiung Medical University Chung-Ho Memorial Hospital
  • Taipei, Taiwan, 10002
    • National Taiwan University Hospital
• Thailand
  • Bangkok, Thailand, 10700
    • Siriraj Hospital
• Turkey (Türkiye)
  • Istanbul, Turkey (Türkiye), 34093
    • Istanbul University- Instanbul Medical Faculty
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Phoenix Childrens Hospital
  • California
    • Los Angeles, California, United States, 90027
      • Children's Hospital of Los Angeles
    • Oakland, California, United States, 94143
      • University of California, San Francisco (UCSF) - Benioff Children's Hospital - Oakland
    • Palo Alto, California, United States, 94305
      • Stanford University Medical Center
    • Sacramento, California, United States, 95817
      • University of California (UC) Davis Medical Center
    • San Bernardino, California, United States, 92408
      • Loma Linda University Children's Hospital
  • Florida
    • Gulf Breeze, Florida, United States, 32561
      • Northwest Florida Clinical Research Group, LLC
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Health - Riley Child Neurology
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan - CS Mott Children's Hospital
    • Detroit, Michigan, United States, 48201
      • Children's Hospital of Michigan
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
  • New York
    • New York, New York, United States, 10032
      • Columbia University College of Physicians & Surgeons
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • Shriners Hospital for Children
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • University of Pittsburgh School of Medicine
  • Texas
    • Fort Worth, Texas, United States, 76104
      • Cook Childrens Medical Center
    • Houston, Texas, United States, 77030
      • Texas Children's Hospital
    • San Antonio, Texas, United States, 78229-3900
      • University of Texas Health Science Center at San Antonio
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • University of Utah
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • Children's Hospital of The King's Daughters
  • Washington
    • Seattle, Washington, United States, 98105
      • Seattle Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ataluren; Participants will receive ataluren oral suspension 10 milligrams (mg)/kilogram (kg) in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening each day for 72 weeks in DB treatment period and for an additional 72 weeks in open-label treatment period.	Drug: Ataluren; 10, 20 mg/kg; Other Names: PTC124
Placebo Comparator: Placebo; Participants will receive placebo matched to ataluren oral suspension for 72 weeks in DB treatment period. After completion of DB treatment period, participants will receive ataluren oral suspension 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening each day for 72 weeks in open-label treatment period.	Drug: PLACEBO; 10, 20 mg/kg; Other Names: Matching Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DB Period: Change From Baseline in 6-Minute Walk Distance (6MWD) at Week 72 - Modified Intention-to-treat (mITT) Population	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).	Baseline, Week 72
DB Period: Change From Baseline in 6MWD at Week 72 - Intent-to-Treat (ITT) Population	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.	Baseline, Week 72
DB Period: Average Rate of Change From Baseline in 6MWD at Week 72 - mITT Population	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.	Baseline, Week 72
DB Period: Average Rate of Change From Baseline in 6MWD at Week 72 - ITT Population	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.	Baseline, Week 72

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DB Period: Change From Baseline in Time to Run/Walk 10 Meters at Week 72 - mITT Population	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.	Baseline, Week 72
DB Period: Change From Baseline in Time to Run/Walk 10 Meters at Week 72 - ITT Population	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.	Baseline, Week 72
DB Period: Change From Baseline in Time to Climb 4 Stairs at Week 72 - mITT Population	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.	Baseline, Week 72
DB Period: Change From Baseline in Time to Climb 4 Stairs at Week 72 - ITT Population	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.	Baseline, Week 72
DB Period: Change From Baseline in Time to Descend 4 Stairs at Week 72 - mITT Population	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.	Baseline, Week 72
DB Period: Change From Baseline in Time to Descend 4 Stairs at Week 72 - ITT Population	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.	Baseline, Week 72
DB Period: Composite of Average Change From Baseline in TFTs at Week 72 - mITT Population	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.	Baseline, Week 72
DB Period: Composite of Average Change From Baseline in TFTs at Week 72 - ITT Population	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.	Baseline, Week 72
DB Period: Composite of Average Rate of Change From Baseline in TFTs at Week 72 - mITT Population	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.	Baseline, Week 72
DB Period: Composite of Average Rate of Change From Baseline in TFTs at Week 72 - ITT Population	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.	Baseline, Week 72
DB Period: Time to Persistent 10% Worsening in 6MWD at Week 72 - mITT Population	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.	Baseline to Week 72
DB Period: Time to Persistent 10% Worsening in 6MWD - ITT Population	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.	Baseline to approximately Week 72 (Due to COVID, many participants attended the protocol-defined Week 72 visit late)
DB Period: Change From Baseline in North Start Ambulatory Assessment (NSAA) Total Score at Week 72 - mITT Population	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.	Baseline, Week 72
DB Period: Change From Baseline in NSAA Total Score at Week 72 - ITT Population	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.	Baseline, Week 72
DB Period: Time to Loss of Ambulation - mITT Population	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.	Baseline up to approximately Week 72 (Due to COVID, many participants attended the protocol-defined Week 72 visit late)
DB Period: Time to Loss of Ambulation Over 72 Weeks - ITT Population	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.	Baseline up to Week 72
DB Period: Time to Loss of Stair-Climbing - mITT Population	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.	Baseline up to approximately Week 72 (Due to COVID, many participants attended the protocol-defined Week 72 visit late)
DB Period: Time to Loss of Stair-Climbing - ITT Population	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.	Baseline up to approximately Week 72 (Due to COVID, many participants attended the protocol-defined Week 72 visit late)
DB Period: Time to Loss of Stair-Descending - mITT Population	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.	Baseline up to approximately Week 72 (Due to COVID, many participants attended the protocol-defined Week 72 visit late)
DB Period: Time to Loss of Stair-Descending - ITT Population	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.	Baseline up to approximately Week 72 (Due to COVID, many participants attended the protocol-defined Week 72 visit late)
DB Period: Number of Participants With Function Loss of NSAA Items at Week 72 - mITT Population	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).	Week 72
DB Period: Number of Participants With Function Loss of NSAA Items at Week 72 - ITT Population	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.	Week 72
DB Period: 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. 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'.	Baseline up to Week 76
Overall Treatment Period: Change From Baseline in 6MWD at 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.	Baseline, Week 144
Overall Treatment Period: Composite of Average Change From Baseline in TFTs at 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.	Baseline, Week 144
Overall Treatment Period: Change From Baseline in Time to Run/Walk 10 Meters at 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.	Baseline, Week 144
Overall Treatment Period: Change From Baseline in Time to Climb 4 Stairs at 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.	Baseline, Week 144
Overall Treatment Period: Change From Baseline in Time to Descend 4 Stairs at 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.	Baseline, Week 144
Overall Treatment Period: Change From Baseline in NSAA Total Score at 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.	Baseline, Week 144
Overall Treatment Period: Time to Loss of Ambulation Over 144 Weeks	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.	Baseline up to Week 144
Overall Treatment Period: Time to Loss of Stair-Climbing Over 144 Weeks	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.	Baseline up to Week 144
Overall Treatment Period: Time to Loss of Stair- Descending Over 144 Weeks	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.	Baseline up to Week 144
Overall Treatment Period: Number of Participants With Function Loss of NSAA Items at 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.	Week 144
Overall Treatment Period: Number of Participants With TEAEs	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'.	Baseline up to Week 148
OL Period: Plasma Pharmacokinetic (PK) Concentration of Ataluren		Predose and 2 hours postdose at Week 144

Collaborators and Investigators

• Sponsor: PTC Therapeutics
• Investigators: Study Director: Vinay Penematsa, MD, PTC Therapeutics, Inc.

Publications and helpful links

Helpful Links

• References

Study record dates

Study Major Dates

• Study Start (Actual): July 6, 2017
• Primary Completion (Actual): March 5, 2022
• Study Completion (Actual): July 25, 2023

Study Registration Dates

• First Submitted: June 1, 2017
• First Submitted That Met QC Criteria: June 5, 2017
• First Posted (Actual): June 7, 2017

Study Record Updates

• Last Update Posted (Actual): March 10, 2026
• Last Update Submitted That Met QC Criteria: February 17, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Duchenne Muscular Dystrophy; Ataluren; PTC124; Becker Muscular Dystrophy; Dystrophinopathy; Nonsense Mutation; Premature Stop Codon; DMD/BMD
• Additional Relevant MeSH Terms: Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Muscular Dystrophies; Muscular Diseases; Muscular Dystrophy, Duchenne; Musculoskeletal Diseases; Nervous System Diseases; Genetic Diseases, X-Linked; Neuromuscular Diseases; Muscular Disorders, Atrophic; ataluren
• Other Study ID Numbers: PTC124-GD-041-DMD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No