EpilepsyPhase 2NCT02758626
Ataluren for Nonsense Mutation in CDKL5 and Dravet Syndrome
A Phase 2 study testing ataluren in people with Epilepsy, run by NYU Langone Health at 1 site in United States.
Trial summary
This is a phase 2, crossover study of Ataluren for the treatment of nonsense mutation Dravet syndrome or cyclin-dependent kinase-like 5 (CDKL5) deficiency, resulting in drug-resistant epilepsy. Patients will receive 12 weeks of ataluren or placebo during each treatment period. Read more about this study
- Who is it for?
- Ages 2 to 12 years
- Conditions the study is for
- Epilepsy
- What is being tested?
- ataluren
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2016to 27 Feb 2021
- 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 12 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Age ≥ 2 years old and ≤ 12 years old, male or female, at Week 0 (at time informed consent/assent is signed)
- Documentation of a diagnosis of Dravet syndrome or CDKL5 deficiency resulting from a nonsense mutation in 1 allele, as evidenced by medical records, genetic testing, and the following clinical feature:
- Failure to control seizures despite appropriate trial of 2 or more AEDs at therapeutic doses
- Between 1 to 3 baseline AEDs at stable doses for a minimum for 4 weeks prior to the Baseline visit
- Vagus nerve stimulator (VNS), ketogenic diet, and modified Atkins diet do not count towards this limit but must be unchanged for 3 months prior to enrollment (Baseline).
- VNS must be on stable settings for a minimum of 3 months prior to the Baseline visit
Show all 9Show fewer
- If on ketogenic or modified Atkins diet, must be on stable ratio for a minimum of 3 months prior to the Baseline visit
- Written consent obtained from the patient or patient's legal representative must be obtained prior to performing any study procedures
- Minimum of 6 convulsive or drop seizures with duration > 3 seconds over the 4 weeks of diary screening prior to randomization and ≥ 6 convulsive or drop seizures with duration > 3 seconds during the 4 weeks from Screening to Baseline.
Who cannot join
- Patient is < 2 years old or ≥ 12 years old
- Epilepsies associated with genetic disorders other than Dravet syndrome or CDKL5 deficiency
- Patient has Dravet or CDKL5 genetic mutations that are NOT nonsense mutations
- Felbatol has been initiated within the past 12 months prior to the Screening Visit
- Patients who are currently or have participated in clinical trials in the 30 days prior to enrollment (Baseline Visit)
- Prior or ongoing medical condition (eg, concomitant illness, psychiatric condition), medical history, physical findings, or laboratory abnormality that, in the investigator's opinion, could adversely affect the safety of the patient, makes it unlikely that the course of study drug administration or follow-up would be completed, or could impair the assessment of study results.
- Ongoing intravenous administration of aminoglycosides or vancomycin.
Trial locations and contacts
1 site in 1 country.
United States1 site
New York University School of Medicine
New York, New York, 10016
About this study
Official title: A Phase 2 Randomized, Double-Masked Placebo-Controlled Crossover Safety and Tolerability Study of Ataluren for Drug Resistant Epilepsy in Patients With Nonsense Mutation CDKL5 or Dravet Syndrome
This is a phase 2, crossover study of Ataluren for the treatment of nonsense mutation Dravet syndrome or cyclin-dependent kinase-like 5 (CDKL5) deficiency, resulting in drug-resistant epilepsy. Patients will receive 12 weeks of ataluren or placebo during each treatment period. Treatment Period 1 will be followed by a 4-week Washout Period. Based on ataluren PK and pharmacodynamic data, the 4-week washout period is deemed an appropriate length of time to eliminate any ataluren drug effects. Following the Washout Period, patients will crossover to receive the opposite treatment during Treatment Period 2 as follows: Patients receiving ataluren during Treatment Period 1 will receive placebo during Treatment Period 2. Patients receiving placebo during Treatment Period 1 will receive ataluren during Treatment Period 2.
Read the detailed description
Investigators will try to characterize the safety profile of ataluren in patients with CDKL5 or Dravet syndrome resulting from a nonsense mutation and evaluate changes in convulsive and/or drop seizure frequency from Baseline following ataluren treatment in patients with CDKL5 or Dravet syndrome resulting from a nonsense mutation. Investigators will measure changes in minor seizure types (absence, myoclonic, complex partial/focal dyscognitive) following ataluren treatment in patients with CDKL5 or Dravet syndrome resulting from a nonsense mutation and changes from Baseline in cognitive, motor, and behavioral function as well as QOL following ataluren treatment in patients with CDKL5 or Dravet syndrome resulting from a nonsense mutation.
- Conditions
- Epilepsy
- Being tested
- ataluren, Placebo
- Medical subject headings
- Epilepsy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
atalurenDrug
Also called PTC124
Powder formulation
PlaceboDrug
Powder formulation
| Study group | Role | What they receive |
|---|---|---|
| Ataluren Followed By Placebo | Active comparator | Cross Over Design: Treatment Period 1 with Ataluren (Week 0/Day 1 to Week 12), Washout Period (Week 12 to Week 16), crossover to Placebo Treatment Period 2 (Week 16 to Week 28), and Follow-up (Week 28 to Week 32). Receives: Drug: ataluren; Drug: Placebo |
| Placebo Followed by Ataluren | Active comparator | Treatment Period 1 with Placebo (Week 0/Day 1 to Week 12), Washout Period (Week 12 to Week 16), crossover to Treatment Period 2 with Ataluren(Week 16 to Week 28). Receives: Drug: ataluren; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent Change From Baseline in 28-Day Convulsive Seizure Frequency During Ataluren Treatment Period
Convulsive seizure frequency per 28 days is defined as total number of convulsive seizures reported during the period divided by number of days during the period seizures were assessed, multiplied by 28. Percent change from Baseline will be defined as the frequency of seizures per 28 days during the Ataluren Treatment Period minus frequency of seizures per 28 days at Baseline, divided by the frequency of seizures per 28 days at Baseline, multiplied by 100. Negative percent change from Baseline indicates improvement.
Measured: Baseline, Week 12 of Ataluren Treatment (Up to Week 28)
Percent Change From Baseline in 28-Day Convulsive Seizure Frequency During Placebo Treatment Period
Convulsive seizure frequency per 28 days is defined as total number of convulsive seizures reported during the period divided by number of days during the period seizures were assessed, multiplied by 28. Percent change from Baseline will be defined as the frequency of seizures per 28 days during the Placebo Treatment Period minus frequency of seizures per 28 days at Baseline, divided by the frequency of seizures per 28 days at Baseline, multiplied by 100. Negative percent change from Baseline indicates improvement.
Measured: Baseline, Week 12 of Placebo Treatment (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 posted2 May 2016 (estimated)
- Study startNov 2016
- Primary completion27 Feb 2021
- Study completion27 Feb 2021
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 (1)Papers the sponsor has linked to this study.
- Other trials for EpilepsyStudies of the same condition, open and under way.
- More trials run by NYU Langone HealthThe sponsor's other registered studies.
- 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
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- NYU Langone Health
- Sponsor type
- University, hospital or other
- Collaborators
- PTC Therapeutics
- Responsible party
- Sponsor
- Investigators
- Orrin Devinsky, MD, Principal investigator, NYU Langone Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02758626
- Sponsor's protocol ID
- 15-00426
- Status last verified
- Jan 2023
- First submitted
- 4 Apr 2016
- Last updated
- 16 Feb 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Devinsky O, King L, Bluvstein J, Friedman D. Ataluren for drug-resistant epilepsy in nonsense variant-mediated Dravet syndrome and CDKL5 deficiency disorder. Ann Clin Transl Neurol. 2021 Mar;8(3):639-644. doi: 10.1002/acn3.51306. Epub 2021 Feb 4.
PubMed 33538404
Study at a glance
From the registry record, last updated by the sponsor on 16 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Randomized, Double-Masked Placebo-Controlled Crossover Safety and Tolerability Study of Ataluren for Drug Resistant Epilepsy in Patients With Nonsense Mutation CDKL5 or Dravet Syndrome
- ClinicalTrials.gov ID
- NCT02758626
- Acronym / sponsor ID
- 15-00426
- Conditions
- Epilepsy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- NYU Langone HealthUniversity, hospital or other
- Collaborators
- PTC Therapeutics
- Study start
- Nov 2016
- Primary completion
- 27 Feb 2021 (actual)
- Study completion
- 27 Feb 2021 (actual)
- First posted
- 2 May 2016 (estimated)
- Results
- Posted 16 Feb 2023
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, crossover study of Ataluren for the treatment of nonsense mutation Dravet syndrome or cyclin-dependent kinase-like 5 (CDKL5) deficiency, resulting in drug-resistant epilepsy. Patients will receive 12 weeks of ataluren or placebo during each treatment period. Treatment Period 1 will be followed by a 4-week Washout Period. Based on ataluren PK and pharmacodynamic data, the 4-week washout period is deemed an appropriate length of time to eliminate any ataluren drug effects. Following the Washout Period, patients will crossover to receive the opposite treatment during Treatment Period 2 as follows: Patients receiving ataluren during Treatment Period 1 will receive placebo during Treatment Period 2. Patients receiving placebo during Treatment Period 1 will receive ataluren during Treatment Period 2.
Detailed description
Investigators will try to characterize the safety profile of ataluren in patients with CDKL5 or Dravet syndrome resulting from a nonsense mutation and evaluate changes in convulsive and/or drop seizure frequency from Baseline following ataluren treatment in patients with CDKL5 or Dravet syndrome resulting from a nonsense mutation. Investigators will measure changes in minor seizure types (absence, myoclonic, complex partial/focal dyscognitive) following ataluren treatment in patients with CDKL5 or Dravet syndrome resulting from a nonsense mutation and changes from Baseline in cognitive, motor, and behavioral function as well as QOL following ataluren treatment in patients with CDKL5 or Dravet syndrome resulting from a nonsense mutation.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ataluren Followed By Placebo | Active comparator | Drug: ataluren, Drug: PlaceboCross Over Design: Treatment Period 1 with Ataluren (Week 0/Day 1 to Week 12), Washout Period (Week 12 to Week 16), crossover to Placebo Treatment Period 2 (Week 16 to Week 28), and Follow-up (Week 28 to Week 32). |
| Placebo Followed by Ataluren | Active comparator | Drug: ataluren, Drug: PlaceboTreatment Period 1 with Placebo (Week 0/Day 1 to Week 12), Washout Period (Week 12 to Week 16), crossover to Treatment Period 2 with Ataluren(Week 16 to Week 28). |
Who may qualify
- Ages
- 2 to 12 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (9 listed)
- Age ≥ 2 years old and ≤ 12 years old, male or female, at Week 0 (at time informed consent/assent is signed)
- Documentation of a diagnosis of Dravet syndrome or CDKL5 deficiency resulting from a nonsense mutation in 1 allele, as evidenced by medical records, genetic testing, and the following clinical feature:
- Between 1 to 3 baseline AEDs at stable doses for a minimum for 4 weeks prior to the Baseline visit
- VNS must be on stable settings for a minimum of 3 months prior to the Baseline visit
- If on ketogenic or modified Atkins diet, must be on stable ratio for a minimum of 3 months prior to the Baseline visit
Key exclusion criteria (7 listed)
- Patient is < 2 years old or ≥ 12 years old
- Epilepsies associated with genetic disorders other than Dravet syndrome or CDKL5 deficiency
- Patient has Dravet or CDKL5 genetic mutations that are NOT nonsense mutations
- Felbatol has been initiated within the past 12 months prior to the Screening Visit
- Patients who are currently or have participated in clinical trials in the 30 days prior to enrollment (Baseline Visit)
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: PTC124Powder formulation | Drug | Ataluren Followed By Placebo, Placebo Followed by Ataluren |
| PlaceboPowder formulation | Drug | Ataluren Followed By Placebo, Placebo Followed by Ataluren |
Primary outcome
Percent Change From Baseline in 28-Day Convulsive Seizure Frequency During Ataluren Treatment Period
Time frame: Baseline, Week 12 of Ataluren Treatment (Up to Week 28)
Convulsive seizure frequency per 28 days is defined as total number of convulsive seizures reported during the period divided by number of days during the period seizures were assessed, multiplied by 28. Percent change from Baseline will be defined as the frequency of seizures per 28 days during the Ataluren Treatment Period minus frequency of seizures per 28 days at Baseline, divided by the frequency of seizures per 28 days at Baseline, multiplied by 100. Negative percent change from Baseline indicates improvement.
Percent Change From Baseline in 28-Day Convulsive Seizure Frequency During Placebo Treatment Period
Time frame: Baseline, Week 12 of Placebo Treatment (Up to Week 28)
Convulsive seizure frequency per 28 days is defined as total number of convulsive seizures reported during the period divided by number of days during the period seizures were assessed, multiplied by 28. Percent change from Baseline will be defined as the frequency of seizures per 28 days during the Placebo Treatment Period minus frequency of seizures per 28 days at Baseline, divided by the frequency of seizures per 28 days at Baseline, multiplied by 100. Negative percent change from Baseline indicates improvement.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Feb 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 33538404Devinsky O, King L, Bluvstein J, Friedman D. Ataluren for drug-resistant epilepsy in nonsense variant-mediated Dravet syndrome and CDKL5 deficiency disorder. Ann Clin Transl Neurol. 2021 Mar;8(3):639-644. doi: 10.1002/acn3.51306. Epub 2021 Feb 4.
- 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.
Orrin Devinsky, MD principal investigator
NYU Langone Health
1 site 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 Epilepsy, run by NYU Langone Health at 1 site 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 9 inclusion and 7 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 16 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 16 Feb 2023). 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?
Percent Change From Baseline in 28-Day Convulsive Seizure Frequency During Ataluren Treatment Period (time frame: Baseline, Week 12 of Ataluren Treatment (Up to Week 28)). The study lists 2 primary outcomes in all. 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 NCT02758626, which also lists 1 linked publication.
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 16 Feb 2023.