COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC:

Get the latest research information from NIH: Menu

Study of Ataluren (PTC124) in Nonambulatory Participants With Nonsense-Mutation-Mediated Duchenne/Becker Muscular Dystrophy (nmDMD/BMD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01009294
Recruitment Status : Terminated (Terminated early because a similar study with Ataluren exhibited lack of efficacy at the high dose (not due to safety concerns).)
First Posted : November 6, 2009
Results First Posted : July 29, 2020
Last Update Posted : July 29, 2020
Genzyme, a Sanofi Company
Information provided by (Responsible Party):
PTC Therapeutics

Brief Summary:
Duchenne/Becker muscular dystrophy (DMD/BMD) is a genetic disorder that develops in boys. It is caused by a mutation in the gene for dystrophin, a protein that is important for maintaining normal muscle structure and function. Loss of dystrophin causes muscle fragility that leads to weakness and loss of walking ability during childhood and teenage years. A specific type of mutation, called a nonsense (premature stop codon) mutation is the cause of DMD/BMD in approximately 10-15% of boys with the disease. Ataluren (PTC124) is an orally delivered, investigational drug that has the potential to overcome the effects of the nonsense mutation. This study is a Phase 2a trial that enrolled boys with nonsense mutation DMD/BMD who have lost independent mobility due to the disease. This study evaluated the safety and tolerability of ataluren (PTC124) and also evaluated efficacy outcomes in this participant population.

Condition or disease Intervention/treatment Phase
Duchenne Muscular Dystrophy Becker Muscular Dystrophy Drug: Ataluren Drug: Chronic Corticosteroid Therapy Phase 2

Detailed Description:

It was planned that this Phase 2a, open-label, safety and efficacy study to be performed at 5 sites in the US and 1 site in the United Kingdom.

The study was to enroll ~30 boys with nonsense mutation DMD/BMD (nmDBMD) who have been nonambulatory for at least 1 year. Enrollment was to be stratified to ensure evaluation of ~15 participants who were receiving chronic corticosteroid therapy and of ~15 participants who were not receiving chronic corticosteroid therapy. Participants were to take ataluren 3 times per day (at breakfast, lunch, and dinner) for 48 weeks (~1 year). Study assessments were to be performed at clinic visits during screening, every 6 weeks for 2 visits and then every 12 weeks until the end of the study. Additional safety laboratory testing was to be required 4 times during the course of the study; this could have been performed at the investigational site, at an accredited local laboratory or clinic, or in the participant's home using a nursing service. When the blind for a similar study (PTC124-GD-007-DMD; NCT00592553) was revealed, the results indicated lack of efficacy for the high dose. Therefore, even though an independent data monitoring committee (DMC) agreed that both ataluren dose levels were well tolerated by the participants, the DMC recommended discontinuing ongoing studies with participants with nmDBMD receiving high-dose ataluren.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 6 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2a Study of Ataluren (PTC124) in Nonambulatory Patients With Nonsense-Mutation-Mediated Duchenne/Becker Muscular Dystrophy
Actual Study Start Date : January 13, 2010
Actual Primary Completion Date : March 23, 2010
Actual Study Completion Date : March 23, 2010

Arm Intervention/treatment
Experimental: Ataluren
Ataluren was provided as a vanilla-flavored powder to be mixed with water, apple juice, or milk. Study drug dosing was based on milligrams of drug per kilogram of body weight. The dose level for ataluren was 20 milligrams/kilograms (mg/kg) in the morning, 20 mg/kg at midday, and 40 mg/kg in the evening. Administration within 30 minutes after a meal was recommended. Study drug was taken for up to 50 days.
Drug: Ataluren
Oral powder
Other Name: PTC124

Drug: Chronic Corticosteroid Therapy
Enrollment was stratified to ensure evaluation of approximately half of the participants were receiving chronic corticosteroid therapy and approximately half of participants were not receiving chronic corticosteroid therapy. Therefore, 3 out of 6 participants were receiving chronic corticosteriod therapy. For the participants receiving chronic corticosteriod therapy, a stable corticosteriod regimen was to be maintained during the study.

Primary Outcome Measures :
  1. Number of Participants With Treatment Emergent Adverse Events (TEAEs) [ Time Frame: Baseline up to Day 50 ]
    A TEAE is any untoward medical occurrence or undesirable event(s) experienced in a participant that begins or worsens following administration of the study drug or study treatment, whether or not considered related to the treatment by the Investigator. A serious adverse event (SAE) was an adverse event (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), or persistent or significant disability/incapacity not related to nmDBMD. AEs included both SAEs and non-serious AEs. AEs were classified according to National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0 (CTCAE) and coded using the Medical Dictionary for Regulatory Activities (MedDRA). A summary of serious and all other non-serious adverse events, regardless of causality, is located in the Reported Adverse Events module.

Secondary Outcome Measures :
  1. Time to Complete Upper Limb Function Tasks as Measured by the Jebsen Test [ Time Frame: Baseline and Week 6 ]
    Arm and hand function were assessed using the Jebsen test, a standardized clinical evaluation of tasks important to daily living. The test comprises of unilateral subtests performed with each hand (the dominant [DOM] hand and the non-DOM hand): moving and stacking light (250 grams) and heavy (500 grams) objects; picking up small, commonly encountered objects; stacking checkers; simulated feeding; simulated page turning; and writing. Participant performance of each task was timed. Longer time to complete the test indicates worse hand function.

  2. Upper Limb Function as Measured by the Brooke Upper Extremity Functional Rating Scale [ Time Frame: Baseline and Week 6 ]
    Upper extremity function was assessed using the Brooke Upper Extremity Functional Rating Scale, following standardized procedures. The Brooke Upper Extremity Functional Rating Scale graded arm and shoulder function from 1 to 6, with higher values indicating less function. A rating of "1" was used when the participant was able to abduct his arms in a full circle until they touch above his head, whereas a rating of "6" was used when the participant was unable to raise his hands to his mouth and had no useful function of hands.

  3. Participant Activities of Daily Living as Assessed Using the Egen Klassifikation (EK) Scale [ Time Frame: Baseline and Week 6 ]
    Activities of daily living after loss of ambulation were measured using the EK scale. The EK scale is an ordinal scale ranging from 0 to 30 points where 0 represents the highest level of independent function and 30 the lowest. The scale consists of 10 categories (each scored 0 to 3), involving different functional domains including 1) ability to use wheelchair, 2) ability to transfer from wheelchair, 3) ability to stand, 4) ability to balance in the wheelchair, 5) ability to move arms, 6) ability to use hands and arms when eating, 7) ability to turn in bed, 8) ability to cough, 9) ability to speak, and 10) physical well-being. The administration of the EK scale consisted of an interview of the participant to capture how he performs the tasks of daily life (as described by Categories 1 to 9) and how he perceives his wellbeing (as described by Category 10). The interviewer observed the participant and assigned the final score for the tasks that could be observed in the clinic.

  4. Shoulder, Elbow, and Wrist Passive and Active Range of Motion as Measured by Goniometry [ Time Frame: Baseline and Week 6 ]
    Goniometry was performed to test active and passive range-of motion (RoM) of the left (L) and right (R) shoulder, elbow, and wrist following standardized procedures. The observed angle for passive and active motion for each joint was measured in degrees. Greater degree of motion indicates better response.

  5. Force Exerted During Elbow Flexion and Extension, Shoulder Abduction, Hand Grip, Key Grip, and Finger Pinch as Assessed by Upper Extremity Myometry [ Time Frame: Baseline and Week 6 ]
    Upper extremity myometry was performed using a hand-held dynamometer following standardized procedures. The measured strength (peak force) was reported in Newtons. There are 0.22 pounds (lbs) in 1 Newton and approximately 10 Newton (9.80665 Newton) in 1 kilogram (kg). The threshold/range of the hand-held dynamometer is 0 to 500 Newtons. Bilateral assessments were done, and 3 measurements were recorded from each muscle group on each side, when possible. When the measurements were done in duplicate or triplicate, the best value was used. Greater value indicates better measurement.

  6. Time to Complete Hand Fine Motor Coordination and Dexterity Tasks as Measured by 9-Hole Peg Test (9HPT) [ Time Frame: Baseline and Week 6 ]
    Hand fine motor coordination and dexterity were assessed using the 9HPT using standardized procedures. The 9HPT is a unilateral test in which 9 pegs were placed in a board and then removed with the dominate and non-dominate hand within a 5-minute time limit. The amount of time required to put the pegs in the holes and remove them again with each hand was recorded. Each test was conducted twice per hand. Longer time to complete the test indicates worse hand fine motor coordination and dexterity.

  7. Forced Vital Capacity (FVC) as Measured by Spirometry [ Time Frame: Baseline and Week 6 ]
    Pulmonary function was assessed as FVC in participants by spirometry using a study-specific spirometer. Multiple tests were conducted, if needed.

  8. Systolic and Diastolic Function as Measured by Echocardiography With Tissue Doppler [ Time Frame: Week 24 and Week 48 ]
    Cardiac function was assessed by echocardiography, which included standard parameters (for example, ejection fraction, left ventricle diastolic and systolic dimensions), as well as parameters integrating Doppler flow analysis with imaging to evaluate perturbations in wall motion. A standardized data collection process harmonized data from all participating institutions and allowed for centralized review.

  9. Heart Rate as Assessed by Radial Pulse [ Time Frame: Baseline and Week 6 ]
    Heart rate was measured with the radial pulse. Following the Jebsen test, the participant rested for 5 minutes in a sitting position, and the heart rate for the last minute of this rest period was collected as the resting heart rate.

  10. Verbal Memory and Attention as Assessed by the Digit Span Task [ Time Frame: Baseline and Week 6 ]
    A series of digits (0-9) were presented to the participant in an auditory format only. The task had 2 parts: in the Forward Condition, the participant was requested to repeat back the digits in the order they were presented, and in the Backward Condition, he was requested to reverse the order of presentation.

  11. HRQL as Measured by the PedsQL Inventory Generic Core Scale [ Time Frame: Week 6 ]
    Health-related quality of life (HRQL) was measured by the Pediatric Quality of Life Inventory (PedsQL) Inventory Generic Core Scale. The generic core module comprised of 23 questions evaluating physical, emotional, social, and school functioning. Examples of items in each of the generic core module scales included: "It is hard for me to run"; "I feel sad or blue"; "I cannot do things that other kids my age can do;" and "It is hard to pay attention in class." Each of the generic core module items was scored on a 5-point response scale from 0 (never a problem) to 4 (almost always a problem). The appropriate age-specific version was completed. PedsQL Inventory Generic Core Scale data at Week 6 is presented.

  12. HRQL as Measured by the PedsQL Multidimensional Fatigue Scale [ Time Frame: Week 6 ]
    HRQL was measured by the PedsQL Multidimensional Fatigue Scale. The fatigue-specific module comprised of 18 questions evaluating general fatigue, sleep/rest fatigue, and cognitive fatigue. Fatigue-specific module obtains information relating to items such as: "I feel too tired to do things that I like to do"; "I spend a lot of time in bed"; and "I have trouble remembering more than one thing at a time." Each of the fatigue-specific module items was scored on a 5-point response scale from 0 (never a problem) to 4 (almost always a problem). The appropriate age-specific version was completed. PedsQL Multidimensional Fatigue Scale data at Week 6 is presented.

  13. HRQL as Measured by the INQoL [ Time Frame: Week 24 and Week 48 ]
    HRQL was measured by the Individualized Neuromuscular Quality of Life Questionnaire (INQoL). The INQoL consisted of 45 questions within 10 sections. Four of the sections evaluate key muscle disease symptoms (that is, weakness, locking [myotonia], pain, and fatigue), 5 sections evaluate the degree and importance of the impact of muscle disease on particular areas of life, and 1 section asks about the positive and negative effects of treatment. A higher score indicates greater symptom impact or worse HRQL, with a range of 0-7.

  14. Muscle Fragility as Determined by Serum Creatine Kinase (CK) Levels [ Time Frame: Baseline and Week 6 ]
    Blood samples collected for chemistry assays were used to quantify serum CK concentrations. Serum CK was assessed as a potential biomarker for muscle fragility, with a reduction in serum CK considered to be a positive outcome. The reference range was based on the age of the participant.

  15. Gastrocnemius Muscle Dystrophin Expression as Determined by Immunofluoresence or by Western Blotting Techniques [ Time Frame: Week 36 ]
    The gastrocnemius muscle was to be biopsied from 1 leg to assess for the production of dystrophin at Week 36. The production of dystrophin was to be measured by immunofluorescene staining of the sarcolemmal membrane or by Western blotting techniques with an antibody to the C-terminal portion of the dystrophin protein (excluding revertant fibers).

  16. Study Drug Compliance [ Time Frame: Baseline to Day 50 ]
    Study drug compliance was assessed by the participant daily diary and quantification of used and unused study drug. Compliance was assessed in terms of the amount of drug actually taken relative to the amount that should have been taken during the study.

  17. Pharmacokinetics: Ataluren Plasma Exposure [ Time Frame: 0, 2, 3, 6, 8, 9, 12, 14, 15, and 24 hours after the morning dose ]
    Blood for ataluren concentrations over a 24-hour period was to be collected on Days 2 and 3 of Week 6. Analysis of the blood samples was to be conducted using a validated high performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS) method.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   7 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   Male
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Male participants only are being studied.
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Diagnosis of DMD or BMD
  • Presence of a nonsense mutation in the dystrophin gene
  • Unable to ambulate independently for ≥1 year due to DMD/BMD
  • Presence of sufficient shoulder and elbow function to perform study-related functional procedures (for example, 9-hole peg test)
  • Adequate hepatic, renal, and adrenal function
  • Ability to provide evaluable pretreatment echocardiogram and lung function assessments
  • Willingness and ability to comply with scheduled visits, drug administration plan, study procedures, laboratory tests, and study restrictions
  • Ability to provide written informed consent (parental/guardian consent if applicable)/assent (if <18 years of age)

Exclusion Criteria:

  • Initiation of systemic corticosteroid therapy within 6 months prior to start of study treatment or use of systemic aminoglycoside antibiotic within 3 months prior to start of study treatment
  • Use of any intermittent systemic corticosteroid therapy regimen (for example, 10 days on followed by 10 days off, weekend dosing, every-other-day dosing); note that participants must have either been receiving a daily dosing regimen of prednisone, prednisolone, or deflazacort at the time of enrollment into the study or must have not been receiving any systemic corticosteroids
  • Any change in treatment for congestive heart failure within 3 months prior to start of study treatment
  • Ongoing warfarin or phenytoin therapy
  • Prior therapy with ataluren
  • Known hypersensitivity to any of the ingredients or excipients of ataluren (Litesse® UltraTM [refined polydextrose], polyethylene glycol 3350, Lutrol® micro F127 [poloxamer 407], mannitol 25C, crospovidone XL10, hydroxyethyl cellulose, vanilla, Cab O Sil® M5P [colloidal silica], magnesium stearate).
  • Exposure to another investigational drug within 2 months prior to start of study treatment
  • History of major surgical procedure within 1 month prior to start of study treatment or expectation of major surgical procedure (for example, scoliosis surgery) during the 48-week treatment period of the study
  • Ongoing immunosuppressive therapy (other than corticosteroids)
  • Ongoing participation in any other clinical trial
  • Requirement for daytime ventilator assistance
  • Uncontrolled clinical symptoms and signs of congestive heart failure
  • Prior or ongoing medical condition (for example, concomitant illness, psychiatric condition, behavioral disorder, alcoholism, drug abuse), medical history, physical findings, electrocardiogram (ECG) findings, or laboratory abnormality that, in the investigator's opinion, could adversely affect the safety of the participant, makes it unlikely that the course of treatment or follow up would be completed, or could impair the assessment of study results

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01009294

Layout table for location information
United States, California
University of California-Davis
Davis, California, United States, 95616
United States, Massachusetts
Children's Hospital of Boston
Boston, Massachusetts, United States, 02115
United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States, 55455
United States, Missouri
Washington University Medical School
Saint Louis, Missouri, United States, 63110
United States, Ohio
Nationwide Children's Hospital
Columbus, Ohio, United States, 43205
United Kingdom
University of Newcastle
Newcastle upon Tyne, United Kingdom, NE1 3BZ
Sponsors and Collaborators
PTC Therapeutics
Genzyme, a Sanofi Company
Layout table for investigator information
Study Director: Leone Atkinson, MD, PhD PTC Therapeutics
Additional Information:
Layout table for additonal information
Responsible Party: PTC Therapeutics Identifier: NCT01009294    
Other Study ID Numbers: PTC124-GD-008-DMD
2009-013169-24 ( EudraCT Number )
First Posted: November 6, 2009    Key Record Dates
Results First Posted: July 29, 2020
Last Update Posted: July 29, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by PTC Therapeutics:
Duchenne muscular dystrophy
Becker muscular dystrophy
Nonsense mutation
Premature stop codon
Additional relevant MeSH terms:
Layout table for MeSH terms
Muscular Dystrophies
Muscular Dystrophy, Duchenne
Muscular Disorders, Atrophic
Muscular Diseases
Musculoskeletal Diseases
Neuromuscular Diseases
Nervous System Diseases
Genetic Diseases, Inborn
Genetic Diseases, X-Linked