Duchenne Muscular DystrophyPhase 2NCT02819557
Study of Ataluren in ≥2 to <5 Year-Old Male Participants With Duchenne Muscular Dystrophy
A Phase 2 study testing Ataluren in people with Duchenne Muscular Dystrophy, run by PTC Therapeutics at 6 sites in United States.
Trial summary
This is a Phase 2, multiple-dose, open-label study evaluating the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of ataluren in participants aged ≥2 to <5 years old with Duchenne muscular dystrophy (DMD) caused by a nonsense mutation in the dystrophin gene. Read more about this study
- Who is it for?
- Ages 2 to 5 years, men only
- Conditions the study is for
- Duchenne Muscular Dystrophy
- What is being tested?
- Ataluren
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 6 sitesUnited States
- Study dates
- 9 Jun 2016to 9 Feb 2018
- Phase
- Phase 2
- 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 2 to 5 years
- Men only
- No healthy volunteers
- Child
Who may be able to join
- Males ≥2 to <5 years of age
- Body weight ≥12 kg
- Diagnosis of DMD
- Nonsense mutation in at least 1 allele of the dystrophin gene
Who cannot join
- Participation in any other drug or device clinical investigation
- Ongoing use of prohibited concomitant medications
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United States6 sites
Children's Hospital Boston
Boston, Massachusetts, 02115
Rush University Medical Center
Chicago, Illinois, 60612
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Children's Medical Center Dallas
Dallas, Texas, 75390-8843
Child Neuro NWF
Gulf Breeze, Florida, 32561
University of Utah
Salt Lake City, Utah, 84112
About this study
Official title: A Phase 2 Study of the Safety, Pharmacokinetics, and Pharmacodynamics of Ataluren (PTC124®) in Patients Aged ≥2 to <5 Years Old With Nonsense Mutation Dystrophinopathy
This is a Phase 2, multiple-dose, open-label study evaluating the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of ataluren in participants aged ≥2 to <5 years old with Duchenne muscular dystrophy (DMD) caused by a nonsense mutation in the dystrophin gene.
Read the detailed description
In nonsense mutation DMD (nmDMD), early start of treatment is important and necessary and, therefore, it is relevant to understand the correct and tolerable dose in this age group, particularly since ataluren is dosed by weight. This study included a 4-week screening period, a 52-week treatment period (the first 4 weeks of which included PK parameters), and a 4-week follow-up period for participants who completed the treatment period (60 weeks total duration). The objective of the extension period (treatment period after PK parameters have been completed) was to assess the long-term safety of chronic administration of ataluren in this participant population.
- Conditions
- Duchenne Muscular Dystrophy
- Being tested
- Ataluren
- Medical subject headings
- Muscular Dystrophy, Duchenne
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AtalurenDrug
Also called PTC124, Translarna
White to off-white powder for oral suspension.
| Study group | Role | What they receive |
|---|---|---|
| Ataluren | Experimental | Participants will be administered ataluren orally at a dose of 10 milligrams/kilograms (mg/kg) in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening (for a total of 40 mg/kg/day) for up to 52 weeks. Dose will be provided based upon the weight of each participant, which will be assessed every 12 weeks. Receives: Drug: Ataluren |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Treatment Emergent Adverse Events (TEAEs), TEAEs Leading to Discontinuation, and Serious Adverse Events (SAEs)
A TEAE was any untoward medical occurrence or undesirable event that begins or worsens following administration of study drug, whether or not considered related to study drug by Investigator. An 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 dystrophinopathy. An event was not reported as an SAE, if event was exclusively a relapse or expected change or progression of baseline dystrophinopathy. AEs included both SAEs and nonserious AEs. AEs classified according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 and coded using Medical Dictionary for Regulatory Activities. A summary of SAEs and all non-serious AEs, regardless of causality, is located in the Reported Adverse Events section.
Measured: Baseline up to Week 56
Number of Participants With a Clinically Meaningful Abnormal Clinical Laboratory (Biochemistry, Hematology, and Urinalysis) Parameter
Clinical laboratory results that were considered clinically meaningful were to be determined by the Investigator and Sponsor. Biochemistry parameters included sodium, potassium, chloride, bicarbonate, blood urea nitrogen, creatinine, magnesium, calcium, phosphorus, uric acid, glucose, total protein, albumin, bilirubin (total, direct, and indirect), aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase, creatine kinase, lactate dehydrogenase, alkaline phosphatase, total cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides, and cystatin C. Hematology parameters included white blood cell count with differential, hemoglobin, hematocrit, other red cell parameters, and platelet count. Urinalysis parameters included pH, specific gravity, glucose, ketones, blood, protein, urobilinogen, bilirubin, nitrite, and leukocyte esterase. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Measured: Baseline up to Week 56
Number of Participants With a Clinically Meaningful Abnormal Electrocardiogram (ECG) Test Results
ECG results that were considered clinically meaningful were to be determined by the Investigator. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Measured: Baseline up to Week 56
Number of Participants With a Dose-Limiting Toxicity as Measured by Hepatic and Renal Toxicity
Dose-limiting toxicity was measured through clinical evaluations for potential hepatic and renal toxicities. The clinical evaluations included the following:
- Hepatic: The participant's medical history, hepatitis screening results, all clinical blood values (particularly serum bilirubin, gamma-glutamyl transferase [GGT], aspartate aminotransferase [AST], and alanine aminotransferase [ALT] values), and all concomitant medications were reviewed.
- Renal: The participant's medical history, all clinical blood and urine renal values, serum electrolytes, medications, and potential pre- or post-renal conditions were reviewed.
Measured: Baseline up to Week 56
Secondary outcomes (10)
Pharmacokinetics: Maximum Observed Plasma Concentration From Time Zero up to 6 Hours After the Morning Dose (Cmax0-6hr)
Ataluren concentrations in plasma were analyzed using a validated high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method.
Measured: 0 (predose), 1, 2, 4, and 6 (postdose) hours on Days 1 and 28
Pharmacokinetics: Time to Reach Maximum Observed Plasma Concentration From Time Zero up to 6 Hours After the Morning Dose (Tmax0-6hr)
Ataluren concentrations in plasma were analyzed using a validated HPLC-MS/MS method.
Measured: 0 (predose), 1, 2, 4, and 6 (postdose) hours on Days 1 and 28
Area Under the Plasma Concentration Time Curve From Time Zero up to 10 Hours After the Morning Dose (AUC0-10hr)
Ataluren concentrations in plasma were analyzed using a validated HPLC-MS/MS method. AUC0-10hr was measured using the linear trapezoidal rule during the ascending portion of the curve and the log-trapezoidal rule during the descending portion of the curve.
Measured: 0 (predose), 1, 2, 4, 6, 8, and 10 (postdose) hours on Days 1 and 28
Pharmacokinetics: Concentration at the End of the First (Morning) Dose Interval (Ctrough6hr)
Ataluren concentrations in plasma were analyzed using a validated HPLC-MS/MS method.
Measured: 0 (predose), 1, 2, 4, and 6 (postdose) hours on Days 1 and 28
Change From Baseline in Proximal Muscle Function as Assessed by Speed During TFTs
TFTs included time to stand from supine position (rise to standing), time to run/walk 10 meters (m), and time to ascend/descend 4 stairs. A decrease from baseline reflects faster completion of the functional task and, thus, better muscle function. If the time taken to perform a test exceeded 30 seconds or if a participant could not perform the test due to disease progression (PD), a value of 30 seconds was used.
Measured: Baseline, Week 28 and Week 52
Change From Baseline in Physical Function as Measured by the NSAA
NSAA consists of 17 activities, including items assessing abilities necessary to remain functionally ambulant (that is, ability to rise from floor, to get from lying to sitting/sitting to standing, and that are known to progressively deteriorate); items that can be partly present in DMD early stages (that is, assessing head raise and standing on heels); and a number of activities such as hopping, jumping, and running. Since the boys were <5 years old, revised 16 point, 8-point, and 3-point scales were used over the 17 point scale. Scores for evaluations=0 (Unable to achieve independently), 1 (Modified method but achieved goal independent of physical assistance), or 2 (Normal, no obvious modification of activity). Maximum total score for the 16-point scale=32, 8-point scale=16, and 3-point scale=6. If an activity couldn't be performed due to PD/loss of ambulation, a score of 0 was assigned. Change from Baseline calculated by subtracting Baseline value from value at Week 28 and Week 52.
Measured: Baseline, Week 28 and Week 52
Change From Baseline in Height of Participants at Weeks 4, 16, 28, 40, 52, and 56
Measured: Baseline, Weeks 4, 16, 28, 40, 52, and 56
Change From Baseline in Weight of Participants at Weeks 4, 16, 28, 40, 52, and 56
Measured: Baseline, Weeks 4, 16, 28, 40, 52, and 56
Change From Baseline in Body Mass Index of Participants at Weeks 4, 16, 28, 40, 52, and 56
Body mass index is an estimate of body fat based on body weight divided by height squared.
Measured: Baseline, Weeks 4, 16, 28, 40, 52, and 56
Ataluren Palatability Characteristics as Determined by a Parent/Caregiver Questionnaire
To assess palatability characteristics, participants/parents or guardians were asked to provide a response of "Strongly disagree", "Disagree", "Neither agree or disagree", "Agree", or "Strongly Agree" to the following 3 questions:
Question 1. "Is the medicine palatable?"
Question 2. "On the basis of reaction / facial expression of your child, do you think that the medication is pleasant?"
Question 3."You sometimes have problems in giving the medication to your child because he/she refuses to take it or throws it up?"
Measured: Baseline up to Week 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jun 2016 (estimated)
- Study start9 Jun 2016
- Primary completion9 Feb 2018
- Study completion9 Feb 2018
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.
- Other trials for Duchenne Muscular DystrophyStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- PTC Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Francesco Bibbiani, MD, Study director, PTC Therapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02819557
- Sponsor's protocol ID
- PTC124-GD-030-DMD
- Status last verified
- Aug 2020
- First submitted
- 16 Jun 2016
- Last updated
- 28 Aug 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 28 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Study of the Safety, Pharmacokinetics, and Pharmacodynamics of Ataluren (PTC124®) in Patients Aged ≥2 to <5 Years Old With Nonsense Mutation Dystrophinopathy
- ClinicalTrials.gov ID
- NCT02819557
- Acronym / sponsor ID
- PTC124-GD-030-DMD
- Conditions
- Duchenne Muscular Dystrophy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- PTC TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 9 Jun 2016 (actual)
- Primary completion
- 9 Feb 2018 (actual)
- Study completion
- 9 Feb 2018 (actual)
- First posted
- 30 Jun 2016 (estimated)
- Results
- Posted 28 Aug 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase 2, multiple-dose, open-label study evaluating the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of ataluren in participants aged ≥2 to <5 years old with Duchenne muscular dystrophy (DMD) caused by a nonsense mutation in the dystrophin gene.
Detailed description
In nonsense mutation DMD (nmDMD), early start of treatment is important and necessary and, therefore, it is relevant to understand the correct and tolerable dose in this age group, particularly since ataluren is dosed by weight. This study included a 4-week screening period, a 52-week treatment period (the first 4 weeks of which included PK parameters), and a 4-week follow-up period for participants who completed the treatment period (60 weeks total duration). The objective of the extension period (treatment period after PK parameters have been completed) was to assess the long-term safety of chronic administration of ataluren in this participant population.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ataluren | Experimental | Drug: AtalurenParticipants will be administered ataluren orally at a dose of 10 milligrams/kilograms (mg/kg) in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening (for a total of 40 mg/kg/day) for up to 52 weeks. Dose will be provided based upon the weight of each participant, which will be assessed every 12 weeks. |
Who may qualify
- Ages
- 2 to 5 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- Males ≥2 to <5 years of age
- Body weight ≥12 kg
- Diagnosis of DMD
- Nonsense mutation in at least 1 allele of the dystrophin gene
Key exclusion criteria (2 listed)
- Participation in any other drug or device clinical investigation
- Ongoing use of prohibited concomitant medications
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: PTC124, TranslarnaWhite to off-white powder for oral suspension. | Drug | Ataluren |
Primary outcome
Number of Participants With Treatment Emergent Adverse Events (TEAEs), TEAEs Leading to Discontinuation, and Serious Adverse Events (SAEs)
Time frame: Baseline up to Week 56
A TEAE was any untoward medical occurrence or undesirable event that begins or worsens following administration of study drug, whether or not considered related to study drug by Investigator. An 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 dystrophinopathy. An event was not reported as an SAE, if event was exclusively a relapse or expected change or progression of baseline dystrophinopathy. AEs included both SAEs and nonserious AEs. AEs classified according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 and coded using Medical Dictionary for Regulatory Activities. A summary of SAEs and all non-serious AEs, regardless of causality, is located in the Reported Adverse Events section.
Number of Participants With a Clinically Meaningful Abnormal Clinical Laboratory (Biochemistry, Hematology, and Urinalysis) Parameter
Time frame: Baseline up to Week 56
Clinical laboratory results that were considered clinically meaningful were to be determined by the Investigator and Sponsor. Biochemistry parameters included sodium, potassium, chloride, bicarbonate, blood urea nitrogen, creatinine, magnesium, calcium, phosphorus, uric acid, glucose, total protein, albumin, bilirubin (total, direct, and indirect), aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase, creatine kinase, lactate dehydrogenase, alkaline phosphatase, total cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides, and cystatin C. Hematology parameters included white blood cell count with differential, hemoglobin, hematocrit, other red cell parameters, and platelet count. Urinalysis parameters included pH, specific gravity, glucose, ketones, blood, protein, urobilinogen, bilirubin, nitrite, and leukocyte esterase. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Number of Participants With a Clinically Meaningful Abnormal Electrocardiogram (ECG) Test Results
Time frame: Baseline up to Week 56
ECG results that were considered clinically meaningful were to be determined by the Investigator. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Number of Participants With a Dose-Limiting Toxicity as Measured by Hepatic and Renal Toxicity
Time frame: Baseline up to Week 56
Dose-limiting toxicity was measured through clinical evaluations for potential hepatic and renal toxicities. The clinical evaluations included the following: * Hepatic: The participant's medical history, hepatitis screening results, all clinical blood values (particularly serum bilirubin, gamma-glutamyl transferase [GGT], aspartate aminotransferase [AST], and alanine aminotransferase [ALT] values), and all concomitant medications were reviewed. * Renal: The participant's medical history, all clinical blood and urine renal values, serum electrolytes, medications, and potential pre- or post-renal conditions were reviewed.
10 secondary outcomes
Pharmacokinetics: Maximum Observed Plasma Concentration From Time Zero up to 6 Hours After the Morning Dose (Cmax0-6hr)
Time frame: 0 (predose), 1, 2, 4, and 6 (postdose) hours on Days 1 and 28
Pharmacokinetics: Time to Reach Maximum Observed Plasma Concentration From Time Zero up to 6 Hours After the Morning Dose (Tmax0-6hr)
Time frame: 0 (predose), 1, 2, 4, and 6 (postdose) hours on Days 1 and 28
Area Under the Plasma Concentration Time Curve From Time Zero up to 10 Hours After the Morning Dose (AUC0-10hr)
Time frame: 0 (predose), 1, 2, 4, 6, 8, and 10 (postdose) hours on Days 1 and 28
Pharmacokinetics: Concentration at the End of the First (Morning) Dose Interval (Ctrough6hr)
Time frame: 0 (predose), 1, 2, 4, and 6 (postdose) hours on Days 1 and 28
Change From Baseline in Proximal Muscle Function as Assessed by Speed During TFTs
Time frame: Baseline, Week 28 and Week 52
Change From Baseline in Physical Function as Measured by the NSAA
Time frame: Baseline, Week 28 and Week 52
Change From Baseline in Height of Participants at Weeks 4, 16, 28, 40, 52, and 56
Time frame: Baseline, Weeks 4, 16, 28, 40, 52, and 56
Change From Baseline in Weight of Participants at Weeks 4, 16, 28, 40, 52, and 56
Time frame: Baseline, Weeks 4, 16, 28, 40, 52, and 56
Change From Baseline in Body Mass Index of Participants at Weeks 4, 16, 28, 40, 52, and 56
Time frame: Baseline, Weeks 4, 16, 28, 40, 52, and 56
Ataluren Palatability Characteristics as Determined by a Parent/Caregiver Questionnaire
Time frame: Baseline up to Week 28
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Aug 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Undecided
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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.
Francesco Bibbiani, MD study director
PTC Therapeutics
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ataluren in people with Duchenne Muscular Dystrophy, run by PTC Therapeutics at 6 sites in United States.
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 4 inclusion and 2 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 28 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 6 sites in United States. 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. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 28 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?
Number of Participants With Treatment Emergent Adverse Events (TEAEs), TEAEs Leading to Discontinuation, and Serious Adverse Events (SAEs) (time frame: Baseline up to Week 56). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 28 Aug 2020.