Muscular Dystrophy, DuchennePhase 3ACT DMDNCT01826487
Phase 3 Study of Ataluren in Participants With Nonsense Mutation Duchenne Muscular Dystrophy (nmDMD)
A Phase 3 study testing Ataluren in people with Muscular Dystrophy, Duchenne and Muscular Dystrophies, run by PTC Therapeutics at 55 sites in 18 countries.
Trial summary
Dystrophinopathy is a disease continuum that includes Duchenne muscular dystrophy, which 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. Read more about this study
- Who is it for?
- Ages 7 to 16 years, men only
- Conditions the study is for
- Muscular Dystrophy, Duchenne, Muscular Dystrophies, Muscular Disorders, Atrophic
- What is being tested?
- Ataluren
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 230 participants
- Where
- 55 sitesin 18 countries
- Study dates
- 26 Mar 2013to 20 Aug 2015
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 7 to 16 years
- Men only
- No healthy volunteers
- Child
Who may be able to join
- Ability to provide written informed consent (parental/guardian consent if applicable)/assent per local requirements.
- Phenotypic evidence of dystrophinopathy based on the onset of characteristic clinical symptoms or signs (for example; proximal muscle weakness, waddling gait, and Gowers' maneuver) by 6 years of age, an elevated serum creatinine kinase level, and ongoing difficulty with walking.
- Documentation of the presence of a nonsense point mutation in the dystrophin gene as determined by gene sequencing from a laboratory certified by the College of American Pathologists (CAP), the Clinical Laboratory Improvement Act/Amendment (CLIA) or an equivalent organization.
- Documentation that a blood sample has been drawn for confirmation of the presence of a nonsense mutation in the dystrophin gene.
- Use of systemic corticosteroids (prednisone, prednisolone, or deflazacort) for a minimum of 6 months immediately prior to start of study treatment, with no significant change in dosage or dosing regimen (not related to body weight change) for a minimum of 3 months immediately prior to start of study treatment and a reasonable expectation that dosage and dosing regimen will not change significantly for the duration of the study.
- Valid Screening 6-minute walk distance (6MWD) greater than or equal to (≥) 150 meters. Valid Screening 6MWD must have been less than or equal to (≤) 80% of predicted for age and height.
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- Results of the 2 Baseline 6MWD results must be determined as valid and results of the Day 2 Baseline 6MWD must be within 20% of the Day 1 Baseline 6MWD.
- Baseline 6MWD (mean of valid Day 1 and Day 2 values) must be no more than a 20% change from the valid Screening 6MWD.
- Confirmed screening laboratory values within the central laboratory ranges (hepatic, renal, and serum electrolyte parameters).
- Willingness to abstain from sexual intercourse or employ an approved method of contraception during the period of study drug administration and 6-week follow-up period.
- Willingness and ability to comply with scheduled visits, drug administration plan, study procedures, laboratory tests, and study restrictions.
Who cannot join
- Treatment with systemic aminoglycoside antibiotics within 3 months prior to start of study treatment.
- Initiation of systemic corticosteroids therapy within 6 months prior to start of study treatment.
- Change in systemic corticosteroid therapy (for example; change in type of drug, dose modification not related to body weight change, schedule modification, interruption, or reinitiation) within 3 months prior to start of study treatment.
- Any change (initiation, change in type of drug, dose modification, schedule modification,interruption, discontinuation, or reinitiation) in prophylaxis/treatment for congestive heart failure (CHF) within 3 months prior to start of study treatment.
- Ongoing use of coumarin-based anticoagulants (for example; warfarin), phenytoin, tolbutamide, or paclitaxel.
- Prior therapy with ataluren.
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- Known hypersensitivity to any of the ingredients or excipients of the study drug.
- Exposure to another investigational drug within 3 months prior to start of study treatment.
- History of major surgical procedure within 6 weeks prior to start of study treatment.
- Ongoing immunosuppressive therapy (other than corticosteroids).
- Ongoing participation in any clinical trial (except for studies specifically approved by PTC Therapeutics).
- Expectation of major surgical procedure (for example; scoliosis surgery) during the 12-month treatment period of the study.
- Requirement for daytime ventilator assistance.
- Uncontrolled clinical symptoms and signs of CHF (American College of Cardiology/American Heart Association Stage C or Stage D).
- Prior or ongoing medical condition (for example; concomitant illness, psychiatric condition, behavioral disorder, alcoholism, drug abuse), medical history, physical findings (for example; lower limb injury that may affect 6MWT performance), 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.
Trial locations and contacts
55 sites in 18 countries.
55 sites in 18 countries
United States21 sites
Children's Hospital Colorado - Center for Cancer and Blood Disorders
Aurora, Colorado, 80045
Boston Children's Hospital
Boston, Massachusetts, 02115
Children's Hospital Boston
Boston, Massachusetts, 02115
Rush University Medical Center
Chicago, Illinois, 60612
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229-3039
Nationwide Children's Hospital
Columbus, Ohio, 43209
Childrens Medical Center Dallas, Texas
Dallas, Texas, 75207
Child Neurology Center of Northwest Florida
Gulf Breeze, Florida, 32561
Texas Children's Hospital
Houston, Texas, 77030
University of Iowa
Iowa City, Iowa, 52242
University of Kansas Medical Center
Kansas City, Kansas, 66160
University of California, Los Angeles
Los Angeles, California, 90095
University of Minnesota
Minneapolis, Minnesota, 55455
Columbia University College of Physicians & Surgeons
New York, New York, 10032
The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, 15224
Oregon Health & Science University
Portland, Oregon, 97239
UC Davis Medical Center
Sacramento, California, 95817
University of Utah
Salt Lake City, Utah, 84112
Seattle Children's Hospital - Childhood Cancer and Blood Disorders
Seattle, Washington, 98105
Washington University School of Medicine, Division of Endocrinology, Metabolism and Lipid Research
St Louis, Missouri, 63110
France4 sites
Hospital de la Timone
Marseille, 13385
CHU de Nantes
Nantes, 44093
Hopital Necker - Enfants Malades
Paris, 75015
Groupe Hospitalier La Pitie-Salpetriere
Paris, 75651
Italy4 sites
Policlinico Universitario G. Martino
Messina, Sicily, 98125
Fondazione IRCS Ca Granda Ospedale Maggiore Policlinico di Milano
Milan, 20122
Bambino Gesu Hospital
Rome, 00165
U.O. Complessa di Neuropsichiatria Infantile
Rome, 00168
Canada3 sites
Alberta Children's Hospital
Calgary, Alberta, T3B 6A8
Children's Hospital of Western Ontario
London, Ontario, N6A 2E3
British Columbia Children's Hospital
Vancouver, British Columbia, V6H 3V4
United Kingdom3 sites
University College London Institute of Child Health
London, WC1N 1EH
Royal Manchester Children's Hospital
Manchester, M13 9WL
The Newcastle upon Tyne Hospitals, NHS Foundation Trust
Newcastle upon Tyne, NE1 3BZ
Australia2 sites
The Royal Children's Hospital
Parkville, Victoria, 3052
The Children's Hospital at Westmead
Westmead, New South Wales, 2145
Brazil2 sites
Universidade Federal do Rio de Janeiro - Instituto de Puericultura e Pediatria Martagao Gesteira
Rio de Janeiro, 21.941-912
Sao Paulo University -HC/FMUSP
São Paulo, 05403-900
Chile2 sites
Hospital Luis Calvo Mackenna
Santiago, Santiago Metropolitan
Hospital Clinico Universidad Catolica
Santiago, 8330073
Czechia2 sites
University Hospital Brno
Brno, 635 00
Motol University Hospital
Prague, 150 06
Germany2 sites
University of Essen-Duisburg
Essen, 45122
University Hospital Medical Center Freiburg
Freiburg im Breisgau, 79106
Spain2 sites
Hospital Sant Joan de Deu
Barcelona, 08950
Hospital Universitari i Politecnic la Fe
Valencia, 46026
Sweden2 sites
Queen Silvia Children's Hospital
Gothenburg, SE-416 85
Astrid Lindgren Childrens Hospital
Stockholm, 17176
About this study
Official title: A Phase 3 Efficacy and Safety Study of Ataluren in Patients With Nonsense Mutation Dystrophinopathy
Dystrophinopathy is a disease continuum that includes Duchenne muscular dystrophy, which 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. A specific type of mutation, called a nonsense (premature stop codon) mutation is the cause of dystrophinopathy in approximately 10-15 percent (%) of boys with the disease. Ataluren is an orally delivered, investigational drug that has the potential to overcome the effects of the nonsense mutation. The main goal of this Phase 3 study is to evaluate the effect of ataluren on walking ability. The effect of ataluren on physical function, quality of life, and activities of daily living will be evaluated. This study will also provide additional information on the long-term safety of ataluren.
Read the detailed description
This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study to determine the efficacy and safety of ataluren in participants with nmDMD.
- Conditions
- Muscular Dystrophy, Duchenne, Muscular Dystrophies, Muscular Disorders, Atrophic, Muscular Diseases, Musculoskeletal Diseases, Neuromuscular Diseases
- Being tested
- Ataluren, Placebo
- Keywords
- Duchenne muscular dystrophy, Dystrophinopathy, Nonsense mutation, Premature stop codon, Becker muscular dystrophy, DMD/BMD, PTC124, Ataluren
- Medical subject headings
- Muscular Dystrophy, Duchenne, Muscular Dystrophies, Muscular Disorders, Atrophic, Muscular Diseases, Musculoskeletal Diseases, Neuromuscular Diseases, Nervous System Diseases, Genetic Diseases, X-Linked
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AtalurenDrug
Also called PTC124
Ataluren will be administered as per the dose and schedule specified in the arm.
PlaceboDrug
Placebo will be administered as per the schedule specified in the arm.
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Participants will receive placebo matching to ataluren orally 3 times a day (TID) at morning, midday, and evening for 48 weeks. Receives: Drug: Placebo |
| Ataluren | Experimental | Participants will receive ataluren suspension orally TID, 10 milligrams/kilogram (mg/kg) at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 48 weeks. Receives: Drug: Ataluren |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in 6MWD at Week 48
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 by measuring the 6MWD in meters. 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 and Week 48 6MWD values are each the average of two valid 6MWD values, or a single available value if one was missing.
Measured: Baseline, Week 48
Secondary outcomes (5)
Time to 10 Percent (%) Persistent Worsening in 6MWD
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 by measuring the 6MWD in meters. 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. Time to 10% persistent worsening in 6MWD <300 meters, >=300 to 400 meters, and >=400 meters was evaluated. For participants who did not have 10% 6MWD worsening or who were removed from study, time to 10% 6MWD worsening was censored at the time of the last 6MWD test. Participants who became non-ambulatory were considered to have 10% worsening.
Measured: Baseline to Week 48
Change From Baseline in Time to Walk/Run 10 Meters at Week 48
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). If the time taken to perform a test exceeded 30 seconds or if a participant could not perform the test due to disease progression, a value of 30 seconds was used. A cumulative change from baseline data has been reported.
Measured: Baseline, Week 48
Change From Baseline in Time to Climb 4 Stairs at Week 48
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" (climbs one foot at a time, with both feet on a step before moving to next step), using one arm on one handrail; 4. Climbs 4 standard stairs "marking time" (climbs one foot at a time, with both feet on a step before moving to next step), 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. A cumulative change from baseline data has been reported.
Measured: Baseline, Week 48
Change From Baseline in Time to Descend 4 Stairs at Week 48
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" (climbs one foot at a time, with both feet on a step before moving to next step), using one arm on one handrail; 4. Descends 4 standard stairs "marking time" (climbs one foot at a time, with both feet on a step before moving to next step), 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. A cumulative change from baseline data has been reported.
Measured: Baseline, Week 48
Percentage of Participants With Treatment-Emergent Adverse Events (AEs)
An 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. Treatment-emergent adverse event (TEAE) was defined as an adverse event that occurred or worsened in the period extending from first dose of study drug to 6 weeks after the last dose of study drug. A summary of other non-serious AEs and all SAEs, regardless of causality is located in the 'Reported AE section'.
Measured: Baseline up to Week 54
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Apr 2013 (estimated)
- Study start26 Mar 2013
- Primary completion20 Aug 2015
- Study completion20 Aug 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Muscular Dystrophy, DuchenneStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 230 participants (actual)
Sponsor and investigators
- Lead sponsor
- PTC Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Robert Spiegel, M.D., Study director, PTC Therapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01826487
- Sponsor's protocol ID
- PTC124-GD-020-DMD
- Other IDs
- 2012-004527-20
- Acronym
- ACT DMD
- Status last verified
- Jul 2020
- First submitted
- 26 Mar 2013
- Last updated
- 4 Aug 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Shieh PB, Elfring G, Trifillis P, Santos C, Peltz SW, Parsons JA, Apkon S, Darras BT, Campbell C, McDonald CM; Members of the Ataluren Phase IIb Study Group; Members of the Ataluren Phase IIb Study Clinical Evaluator Training Group; Members of the ACT DMD Study Group; Members of the ACT DMD Clinical Evaluator Training Group. Meta-analyses of deflazacort versus prednisone/prednisolone in patients with nonsense mutation Duchenne muscular dystrophy. J Comp Eff Res. 2021 Dec;10(18):1337-1347. doi: 10.2217/cer-2021-0018. Epub 2021 Oct 25.
PubMed 34693725McDonald CM, Wei LJ, Flanigan KM, Elfring G, Trifillis P, Muntoni F; ACT DMD Clinical Evaluator Training Group; ACT DMD Study Group. Evaluating longitudinal therapy effects via the North Star Ambulatory Assessment. Muscle Nerve. 2021 Nov;64(5):614-619. doi: 10.1002/mus.27396. Epub 2021 Sep 2.
PubMed 34383312Campbell C, Barohn RJ, Bertini E, Chabrol B, Comi GP, Darras BT, Finkel RS, Flanigan KM, Goemans N, Iannaccone ST, Jones KJ, Kirschner J, Mah JK, Mathews KD, McDonald CM, Mercuri E, Nevo Y, Pereon Y, Renfroe JB, Ryan MM, Sampson JB, Schara U, Sejersen T, Selby K, Tulinius M, Vilchez JJ, Voit T, Wei LJ, Wong BL, Elfring G, Souza M, McIntosh J, Trifillis P, Peltz SW, Muntoni F; PTC124-GD-007-DMD Study Group; ACT DMD Study Group; Clinical Evaluator Training Groups. Meta-analyses of ataluren randomized controlled trials in nonsense mutation Duchenne muscular dystrophy. J Comp Eff Res. 2020 Oct;9(14):973-984. doi: 10.2217/cer-2020-0095. Epub 2020 Aug 27.
PubMed 32851872McDonald CM, Campbell C, Torricelli RE, Finkel RS, Flanigan KM, Goemans N, Heydemann P, Kaminska A, Kirschner J, Muntoni F, Osorio AN, Schara U, Sejersen T, Shieh PB, Sweeney HL, Topaloglu H, Tulinius M, Vilchez JJ, Voit T, Wong B, Elfring G, Kroger H, Luo X, McIntosh J, Ong T, Riebling P, Souza M, Spiegel RJ, Peltz SW, Mercuri E; Clinical Evaluator Training Group; ACT DMD Study Group. Ataluren in patients with nonsense mutation Duchenne muscular dystrophy (ACT DMD): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017 Sep 23;390(10101):1489-1498. doi: 10.1016/S0140-6736(17)31611-2. Epub 2017 Jul 17.
PubMed 28728956
Study at a glance
From the registry record, last updated by the sponsor on 4 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3 Efficacy and Safety Study of Ataluren in Patients With Nonsense Mutation Dystrophinopathy
- ClinicalTrials.gov ID
- NCT01826487
- Acronym / sponsor ID
- ACT DMD / PTC124-GD-020-DMD
- Conditions
- Muscular Dystrophy, Duchenne, Muscular Dystrophies, Muscular Disorders, Atrophic, Muscular Diseases, Musculoskeletal Diseases, Neuromuscular Diseases
- Keywords
- Duchenne muscular dystrophy, Dystrophinopathy, Nonsense mutation, Premature stop codon, Becker muscular dystrophy, DMD/BMD, PTC124, Ataluren
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 230 participants (actual)
- Lead sponsor
- PTC TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 26 Mar 2013 (actual)
- Primary completion
- 20 Aug 2015 (actual)
- Study completion
- 20 Aug 2015 (actual)
- First posted
- 8 Apr 2013 (estimated)
- Results
- Posted 4 Aug 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Dystrophinopathy is a disease continuum that includes Duchenne muscular dystrophy, which 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. A specific type of mutation, called a nonsense (premature stop codon) mutation is the cause of dystrophinopathy in approximately 10-15 percent (%) of boys with the disease. Ataluren is an orally delivered, investigational drug that has the potential to overcome the effects of the nonsense mutation. The main goal of this Phase 3 study is to evaluate the effect of ataluren on walking ability. The effect of ataluren on physical function, quality of life, and activities of daily living will be evaluated. This study will also provide additional information on the long-term safety of ataluren.
Detailed description
This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study to determine the efficacy and safety of ataluren in participants with nmDMD.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboParticipants will receive placebo matching to ataluren orally 3 times a day (TID) at morning, midday, and evening for 48 weeks. |
| Ataluren | Experimental | Drug: AtalurenParticipants will receive ataluren suspension orally TID, 10 milligrams/kilogram (mg/kg) at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 48 weeks. |
Who may qualify
- Ages
- 7 to 16 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (11 listed)
- Ability to provide written informed consent (parental/guardian consent if applicable)/assent per local requirements.
- Phenotypic evidence of dystrophinopathy based on the onset of characteristic clinical symptoms or signs (for example; proximal muscle weakness, waddling gait, and Gowers' maneuver) by 6 years of age, an elevated serum creatinine kinase level, and ongoing difficulty with walking.
- Documentation of the presence of a nonsense point mutation in the dystrophin gene as determined by gene sequencing from a laboratory certified by the College of American Pathologists (CAP), the Clinical Laboratory Improvement Act/Amendment (CLIA) or an equivalent organization.
- Documentation that a blood sample has been drawn for confirmation of the presence of a nonsense mutation in the dystrophin gene.
- Use of systemic corticosteroids (prednisone, prednisolone, or deflazacort) for a minimum of 6 months immediately prior to start of study treatment, with no significant change in dosage or dosing regimen (not related to body weight change) for a minimum of 3 months immediately prior to start of study treatment and a reasonable expectation that dosage and dosing regimen will not change significantly for the duration of the study.
Key exclusion criteria (15 listed)
- Treatment with systemic aminoglycoside antibiotics within 3 months prior to start of study treatment.
- Initiation of systemic corticosteroids therapy within 6 months prior to start of study treatment.
- Change in systemic corticosteroid therapy (for example; change in type of drug, dose modification not related to body weight change, schedule modification, interruption, or reinitiation) within 3 months prior to start of study treatment.
- Any change (initiation, change in type of drug, dose modification, schedule modification,interruption, discontinuation, or reinitiation) in prophylaxis/treatment for congestive heart failure (CHF) within 3 months prior to start of study treatment.
- Ongoing use of coumarin-based anticoagulants (for example; warfarin), phenytoin, tolbutamide, or paclitaxel.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AtalurenAlso: PTC124Ataluren will be administered as per the dose and schedule specified in the arm. | Drug | Ataluren |
| PlaceboPlacebo will be administered as per the schedule specified in the arm. | Drug | Placebo |
Primary outcome
Change From Baseline in 6MWD at Week 48
Time frame: Baseline, Week 48
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 by measuring the 6MWD in meters. 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 and Week 48 6MWD values are each the average of two valid 6MWD values, or a single available value if one was missing.
5 secondary outcomes
Time to 10 Percent (%) Persistent Worsening in 6MWD
Time frame: Baseline to Week 48
Change From Baseline in Time to Walk/Run 10 Meters at Week 48
Time frame: Baseline, Week 48
Change From Baseline in Time to Climb 4 Stairs at Week 48
Time frame: Baseline, Week 48
Change From Baseline in Time to Descend 4 Stairs at Week 48
Time frame: Baseline, Week 48
Percentage of Participants With Treatment-Emergent Adverse Events (AEs)
Time frame: Baseline up to Week 54
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Aug 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 34693725Shieh PB, Elfring G, Trifillis P, Santos C, Peltz SW, Parsons JA, Apkon S, Darras BT, Campbell C, McDonald CM; Members of the Ataluren Phase IIb Study Group; Members of the Ataluren Phase IIb Study Clinical Evaluator Training Group; Members of the ACT DMD Study Group; Members of the ACT DMD Clinical Evaluator Training Group. Meta-analyses of deflazacort versus prednisone/prednisolone in patients with nonsense mutation Duchenne muscular dystrophy. J Comp Eff Res. 2021 Dec;10(18):1337-1347. doi: 10.2217/cer-2021-0018. Epub 2021 Oct 25.
- Derived from this study: PubMed 34383312McDonald CM, Wei LJ, Flanigan KM, Elfring G, Trifillis P, Muntoni F; ACT DMD Clinical Evaluator Training Group; ACT DMD Study Group. Evaluating longitudinal therapy effects via the North Star Ambulatory Assessment. Muscle Nerve. 2021 Nov;64(5):614-619. doi: 10.1002/mus.27396. Epub 2021 Sep 2.
- Derived from this study: PubMed 32851872Campbell C, Barohn RJ, Bertini E, Chabrol B, Comi GP, Darras BT, Finkel RS, Flanigan KM, Goemans N, Iannaccone ST, Jones KJ, Kirschner J, Mah JK, Mathews KD, McDonald CM, Mercuri E, Nevo Y, Pereon Y, Renfroe JB, Ryan MM, Sampson JB, Schara U, Sejersen T, Selby K, Tulinius M, Vilchez JJ, Voit T, Wei LJ, Wong BL, Elfring G, Souza M, McIntosh J, Trifillis P, Peltz SW, Muntoni F; PTC124-GD-007-DMD Study Group; ACT DMD Study Group; Clinical Evaluator Training Groups. Meta-analyses of ataluren randomized controlled trials in nonsense mutation Duchenne muscular dystrophy. J Comp Eff Res. 2020 Oct;9(14):973-984. doi: 10.2217/cer-2020-0095. Epub 2020 Aug 27.
- Derived from this study: PubMed 28728956McDonald CM, Campbell C, Torricelli RE, Finkel RS, Flanigan KM, Goemans N, Heydemann P, Kaminska A, Kirschner J, Muntoni F, Osorio AN, Schara U, Sejersen T, Shieh PB, Sweeney HL, Topaloglu H, Tulinius M, Vilchez JJ, Voit T, Wong B, Elfring G, Kroger H, Luo X, McIntosh J, Ong T, Riebling P, Souza M, Spiegel RJ, Peltz SW, Mercuri E; Clinical Evaluator Training Group; ACT DMD Study Group. Ataluren in patients with nonsense mutation Duchenne muscular dystrophy (ACT DMD): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017 Sep 23;390(10101):1489-1498. doi: 10.1016/S0140-6736(17)31611-2. Epub 2017 Jul 17.
- Related InfoLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Robert Spiegel, M.D. study director
PTC Therapeutics
55 sites in 18 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Ataluren in people with Muscular Dystrophy, Duchenne and Muscular Dystrophies, run by PTC Therapeutics at 55 sites in 18 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 55 sites in United States, France, Italy, Canada, United Kingdom and 13 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Aug 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in 6MWD at Week 48 (time frame: Baseline, Week 48). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01826487, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Aug 2020.