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Seizures Associated With EMASPhase 3NCT05288283

Efficacy and Safety of GWP42003-P Oral Solution in Children With Epilepsy With Myoclonic-atonic Seizures

A Phase 3 study testing GWP42003-P in people with Seizures Associated With EMAS, run by Jazz Pharmaceuticals at 14 sites in 2 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

The primary aim of Part A of the study to assess the efficacy and tolerability of GWP42003-P compared to placebo as an adjunctive treatment for children with Epilepsy with myoclonic-atonic seizures (EMAS) -associated seizures. Read more about this study

Who is it for?
Ages 1 year to 18 years
Conditions the study is for
Seizures Associated With EMAS
What is being tested?
GWP42003-P
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
3 participants
Where
14 sitesin 2 countries
Study dates
31 Oct 2022to 28 Sep 2023
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 1 year to 18 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Participant has a current diagnosis of epilepsy with myoclonic-atonic seizures (EMAS), also known as Doose syndrome, myoclonic-astatic epilepsy, or myoclonic-atonic epilepsy, consistent with the International League Against Epilepsy (ILAE) guidelines. Presence of myoclonic-atonic seizures is mandatory to support a diagnosis of EMAS as determined by medical history and independent approval by The Epilepsy Study Consortium (TESC).
  • Participant's initial seizure onset occurred from ≥ 6 months to < 6 years of age, with normal or mildly impaired/delayed neurodevelopment reported prior to onset of seizures. During the first year of seizure onset, the majority of seizures experienced by the participant were myoclonic-atonic seizures or generalized tonic-clonic seizures as determined by medical history.
  • Participant is currently treated with one or more antiepileptic drug (AED) on a stable regimen (≥ 28 days prior to starting the baseline period [Part A Visit 2]) or on a stable ketogenic diet (≥ 3 months prior to starting the baseline period [Part A Visit 2]) and no changes to treatment are planned for the duration of the study.
  • Participant is refractory to anticonvulsant medication and failed at least 1 AED (e.g., valproic acid, clobazam, clonazepam, and levetiracetam) at therapeutic doses.
  • Participant is able to provide a historical electroencephalogram (EEG) report, which was performed within 12 months of Screening (Part A Visit 1), or is willing to complete an EEG at Screening (Part A Visit 1), that confirms a 3 to 6 Hertz (Hz) generalized spike-and-slow-wave or polyspike-and-slow-wave pattern.
  • Contraceptive use by male and female participants should be consistent with Clinical Trial Facilitation Group (CTFG) guidelines and any applicable local regulations regarding the methods of contraception for those participating in clinical studies.
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  • Fertile male participants with partners of childbearing potential (CBP) must be willing to use a male barrier method of contraception in addition to a second method of acceptable contraception used by their female of CBP partners, from the time of Screening (Part A Visit 1) until 3 months after the follow-up visit.
  • Female participants of CBP will not be pregnant or lactating and have a confirmed negative highly sensitive serum pregnancy test at Screening (Part A Visit 1).
  • Female participants must also have a confirmed negative urine pregnancy test prior to receiving their first dose of blinded investigational medicinal product (IMP) at Part A Visit 3.
  • Female participants who are continuing to Part B must have a confirmed negative urine pregnancy test prior to receiving their first dose of open-label GWP42003-P at Part B Visit 1.
  • Female participants of CBP must be willing to use a highly effective method of contraception from the time of signing the Informed Consent Form (ICF) until 3 months after the follow-up visit.
  • Participant or participant's caregiver(s) (according to local laws) is/are willing and able to give signed informed consent for participation in the study including compliance with the requirements and restrictions listed in the ICF and in the protocol.
  • Participant's caregiver(s) are willing to allow the responsible authorities to be notified of participation in the study, if mandated by local law.
  • Participant's caregiver completes at least 89% of Seizure eDiary entries during the first 28 days of the Baseline period (≥ 25 days of entries).
  • Part B only:
  • Has completed Part A of this study
  • Was compliant with all requirements of Part A (e.g., dosing, seizure eDiary, visits/procedures), in the judgement of the investigator and sponsor

Who cannot join

  • Has a history of psychogenic non-epileptic seizures that confounds the assessment of the primary efficacy measure
  • Has clinically significant unstable medical condition(s), other than EMAS
  • Has a clinically significant illness in the 28 days prior to Screening (Visit 1) or randomization (Part A Visit 3), other than epilepsy, which in the opinion of the investigator could affect seizure frequency
  • Has presence of focal seizures or persistent focal epileptiform discharges on EEG
  • Has a history of infantile spasms
  • Has moderate to severe neurocognitive and/or developmental delay prior to seizure onset
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  • Has a progressive neurological condition
  • Has known or suspected hypersensitivity to cannabinoids or any of the excipients of GWP42003-P such as sesame oil
  • Is unwilling or unable to remain stable on concurrent AEDs throughout the study.
  • Has, in the opinion of the investigator, clinically significant abnormalities in the electrocardiogram (ECG) measured at Screening (Part A Visit 1), or any concurrent cardiovascular conditions, which will interfere with the ability to read their ECGs
  • Has significantly impaired hepatic function at the Screening visit (Visit 1) or prior to dosing, defined as any of the following:
  • alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 5 × upper limit of normal (ULN);
  • total bilirubin (TBL) (serum) ≥ 2 × ULN or International Normalized Ratio (INR) > 1.5 (TBL ≥ 2 × ULN exclusion will not apply for participants diagnosed with Gilbert's disease);
  • serum ALT or AST ≥ 3 × ULN with the presence of fatigue, nausea, vomiting, right upper quadrant pain or tenderness, fever, rash, and/or eosinophilia (> 5%);
  • elevated ALT or AST at Screening (Part A Visit 1), should be discussed with the medical monitor prior to Randomization (Part A Visit 3); the medical monitor may allow for a confirmatory re-draw prior to randomization.
  • This criterion can only be confirmed once the laboratory results are available.
  • Has clinically significant impaired renal function at Screening (Part A Visit 1), as evidenced by an estimated creatinine clearance lower than 60 milliliters per minute (mL/min)
  • Is a female participant of CBP, who is pregnant (positive pregnancy test), lactating or planning pregnancy during the course of the study and for 3 months thereafter
  • Participant has any known or suspected history of alcohol or substance abuse
  • Any clinically significant abnormalities identified following a physical examination or laboratory assessments of the participant that, in the opinion of the investigator, would jeopardize the safety of the participant if they take part in the study
  • Participant has any other clinically significant disease or disorder which, in the opinion of the investigator, may either put the participant, other participants, or site staff at risk because of participation in the study, may influence the result of the study, or may affect the participant's ability to take part in the study
  • Has a change in anticonvulsant therapies within 28 days of starting the baseline period (Part A Visit 2), including AEDs or settings on vagal nerve stimulator
  • Has any planned clinical interventions or intends to change any or all medications that may impact seizures during the study
  • Has been treated with a general anesthetic in the 28 days prior to screening (Part A Visit 1) or randomization (Part A Visit 3 [Week 0])
  • Has undergone surgery for epilepsy in the 6 months prior to Screening (Part A Visit 1)
  • Is being considered for epilepsy surgery or any procedure involving general anesthesia during the study
  • Has initiated a ketogenic diet within 3 months prior to the Baseline period (Part A Visit 2). Participants who are stable on a ketogenic diet for ≥ 3 months and willing to remain on a stable epilepsy dietary therapy (e.g., ketogenic diet, Atkins diet, low glycemic index diet) during the study, are eligible for inclusion.
  • Has initiated felbamate within 12 months prior to screening (Part A Visit 1). Participants who are stable on a felbamate for ≥ 12 months are eligible for inclusion.
  • Is currently being treated with or had previously (within 3 months prior to screening [Part A Visit 1] received intravenous immunoglobulin treatment or plasma exchange for the treatment of seizures
  • Has participated in a clinical study involving administration of an IMP (new chemical entity) or medical device (e.g., vagal nerve stimulator) within 1 month prior to screening (Part A Visit 1)
  • Have previously been randomized, completed, or withdrawn from this study
  • Is currently using a drug of abuse or current non-prescribed use of any prescription drug
  • Is currently using or has used recreational or medicinal cannabis, cannabinoid-based medications, products, or supplements (botanical or synthetic) within 28 days prior to screening (Part A Visit 1).
  • Mother (if breastfeeding the participant) is currently using or has used recreational or medicinal cannabis, cannabinoid-based medications, products, or supplements (botanical or synthetic) within 28 days of screening (Part A Visit 1).
  • Has any history of suicidal behavior or serious suicidal ideation, defined as Category 4 or greater on the Columbia Suicide Severity Rating Scale (C-SSRS) at any visit prior to dosing with IMP. This criterion applies only to participants 4 to 18 years of age.
  • Is unwilling or unable to comply with all study requirements, including accurate eDiary completion
  • Participants who, in the opinion of the investigator (or designee), should not participate in this study
  • Has travel planned outside their country of residence during the study, unless the participant has confirmation that the IMP is permitted in the destination country and all stops along the way
  • Part B only:
  • Has significantly impaired hepatic function at Part A Visit 9, defined as any of the following:
  • ALT or AST > 5 × ULN;
  • TBL (serum) ≥ 2 × ULN or INR > 1.5 (TBL ≥ 2 × ULN exclusion will not apply for participants diagnosed with Gilbert's disease.
  • Serum ALT or AST ≥ 3 × ULN with the presence of fatigue, nausea, vomiting, right upper quadrant pain or tenderness, fever, rash, and/or eosinophilia (> 5%). The medical monitor may allow for a confirmatory redraw prior to rollover.
  • Meets any exclusion criteria at Part B Visit 1

Trial locations and contacts

14 sites in 2 countries.

14 sites in 2 countries

United States10 sites

  • Healthcare of Atlanta

    Atlanta, Georgia, 30329

  • Dell's Children's Hospital

    Austin, Texas, 78723

  • Children's Hospital of Alabama

    Birmingham, Alabama, 35233

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • Ann & Robert H. Lurie Children's Hospital

    Chicago, Illinois, 60611

  • Cincinnati Children's Hospital Medical Center - TS Clinic

    Cincinnati, Ohio, 45229

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • University of California Davis Health

    Sacramento, California, 95817

  • Seattle Children's Hospital

    Seattle, Washington, 98105

  • Wake Forest Baptist Health Sciences, Department of Neurology

    Winston-Salem, North Carolina, 27157

Other trials in United States

Italy4 sites

  • Azienda Ospedaliero Universitaria Ospedale Pediatrico Meyer

    Florence, 50139

  • Istituto Giannina Gaslini-Ospedale Pediatrico IRCCS

    Genova, 16147

  • IRCCS Fondazione Istituto Neurologico Nazionale D. Mondino Pavia

    Pavia, 27100

  • UOC Neuropsichiatria Infantile AOUI Verona

    Verona, 37126

Other trials in Italy

About this study

Official title: A Randomized, Double-blind, Placebo-controlled, Multisite, Phase 3 Study to Investigate the Efficacy and Safety of Cannabidiol Oral Solution (GWP42003-P) in Children and Adolescents With Epilepsy With Myoclonic-Atonic Seizures

The primary aim of Part A of the study to assess the efficacy and tolerability of GWP42003-P compared to placebo as an adjunctive treatment for children with Epilepsy with myoclonic-atonic seizures (EMAS) -associated seizures.

Part B of this study will be conducted to evaluate the long-term safety and tolerability of GWP42003-P in participants with EMAS.

Read the detailed description

The duration of study participation in Part A will be approximately 26 weeks, which includes a 1- to 3-week Screening Period, 4-week Baseline Observation Period, 14-week Dose Optimization Treatment Period, 10-day Taper Period, and a Safety Follow-up Period (4 weeks after end of taper visit). Participants will be randomized centrally in a 1:1 ratio to receive either GWP42003-P or matching placebo. Randomization will be stratified by clobazam use (on/off) and age of seizure onset (3 years of age and younger or older than 3 years of age). Upon completion of the double-blind phase (Part A), participants will have an option to continue in a 54-week open-label extension (Part B).

Being tested
GWP42003-P, Placebo
Keywords
Epilepsy, Seizures, Epilepsy with Myoclonic-Atonic Seizures (EMAS), Myoclonic-Atonic Epilepsy, Doose syndrome, Myoclonic-Astatic epilepsy (MAE), Children, Cannabidiol (CBD), GWP42003-P
Medical subject headings
Epilepsy, Seizures, Epilepsies, Myoclonic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • GWP42003-PDrug

    Also called EPIDIOLEX, Cannabidiol, Cannabidiol oral solution (CBD-OS)

    oral solution

  • PlaceboDrug

    oral solution

Study groups in NCT05288283
Study groupRoleWhat they receive
GWP42003-PExperimentalParticipants will be initiated on a dose of GWP42003-P 2.5 milligrams per kilogram (mg/kg) twice a day (BID) (5 mg/kg/day); after 1 week, the dose will be increased to 5 mg/kg BID (10 mg/kg/day). Dose escalation up to a maximum daily dosage of 20 mg/kg/day (in increments of 5 mg/kg/day [2.5 mg/kg BID] no more rapidly than every 7 days) may occur after Day 15 based on the investigator's assessment of efficacy, safety and tolerability.
Receives: Drug: GWP42003-P
PlaceboPlacebo comparatorParticipants will receive the matching placebo.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Part A: Percent Change From Baseline in Epilepsy With Myoclonic-atonic Seizures (EMAS) Associated Seizure Frequency (Myoclonic-atonic, Atonic, Tonic, Clonic, or Tonic-clonic) Over the 14-week Treatment Period

    Measured: Baseline; up to 14 weeks

  2. Part B: Number of Participants With Treatment-emergent Adverse Events

    Measured: up to Week 54

  3. Part B: Number of Participants With Clinically Significant Vital Sign Values

    Measured: up to Week 50

  4. Part B: Number of Participants With Clinically Significant Physical Examination Values

    Measured: up to Week 48

  5. Part B: Number of Participants With Clinically Significant 12-lead Electrocardiogram (ECG) Values

    Measured: up to Week 48

  6. Part B: Number of Participants With Clinically Significant Laboratory Test Values

    Measured: up to Week 48

  7. Part B: Number of Participants With Changes in Tanner Staging

    Measured: up to Week 48

  8. Part B: Number of Participants With a Change in Columbia-Suicide Severity Rating Scale (C-SSRS) Ideation Scores

    Measured: up to Week 54

  9. Part B: Number of Participants With a Change in the Number of Suicide Attempts Per C-SSRS Scores

    Measured: up to Week 54

Secondary outcomes (24)

  1. Part A: Number of Participants Who Achieve ≥ 50% Reduction From Baseline in EMAS-associated Seizures Over the 14-week Treatment Period

    Measured: Baseline; up to 14 weeks

  2. Part A: Total Seizure Frequency Over the 14-week Treatment Period

    Measured: Baseline; up to 14 weeks

  3. Part A: Caregiver Global Impression of Change (CGIC) Score at Week 14

    Measured: Week 14

  4. Part A: Physician Global Impression of Change (PGIC) Score at Week 14

    Measured: Week 14

  5. Part A: Number of Participants Who Achieve ≥ 25%, ≥ 50%, ≥ 75%, and 100% Reduction From Baseline in Total Seizures Over the 14-week Treatment Period

    Measured: Baseline; up to 14 weeks

  6. Part A: Change From Baseline in the Number of EMAS-associated Seizure-free Days Over the 14-week Treatment Period

    Measured: Baseline; up to 14 weeks

  7. Part A: Number of Participants With at Least 25% and 50% Reduction From Baseline in the Number of Days Per Week With Myoclonic Seizures During the 14-week Treatment Period

    Measured: Baseline; up to 14 weeks

  8. Part A: Time to Baseline Seizure Frequency

    Measured: up to 14 weeks

  9. Part A: Number of Participants With Treatment-emergent Adverse Events

    A TEAE is an adverse event that started or worsened in severity or seriousness following the first dose of the investigational medicinal product.

    Measured: From the time of informed consent signing up to 27 weeks.

  10. Part A: Number of Participants With Clinically Significant Laboratory Test Values

    Measured: up to 27 weeks

  11. Part A: Number of Participants With Clinically Significant Vital Sign Values

    Measured: up to 27 weeks

  12. Part A: Number of Participants With Clinically Significant Physical Examination Values

    Measured: up to 27 weeks

  13. Part A: Number of Participants With Clinically Significant 12-lead ECG Values

    Measured: up to 27 weeks

  14. Part A: Number of Participants With Changes in Tanner Staging

    Measured: up to Day 99

  15. Part A: Number of Participants With a Change in C-SSRS Ideation Scores

    Measured: up to 27 weeks

  16. Part A: Number of Participants With a Change in the Number of Suicide Attempts Per C-SSRS Scores

    Measured: up to 27 weeks

  17. Part B: Percent Change From Baseline in EMAS-associated Seizure Frequency (Myoclonic-atonic, Atonic, Tonic, Clonic, or Tonic-clonic) Over the 48-week Open-label Treatment Period

    Measured: Baseline; up to 48 weeks

  18. Part B: Number of Participants Achieving ≥50% Reduction From Baseline in EMAS-associated Seizures Over the 48-week Open-label Treatment Period

    Measured: Baseline; up to 48 weeks

  19. Part B: Total Seizure Frequency Over the 48-week Open-label Treatment Period

    Measured: up to Week 48

  20. Part B: CGIC Score at Weeks 14, 24, and 48

    Measured: Weeks 14, 24, and 48

  21. Part B: PGIC Score at Weeks 14, 24, and 48

    Measured: Weeks 14, 24, and 48

  22. Part B: Number of Participants Who Achieve ≥ 25%, ≥ 50%, ≥ 75%, and 100% Reduction From Baseline in Total Seizures Over the 48-week Open-label Treatment Period

    Measured: Baseline; up to 48 weeks

  23. Part B: Change From Baseline in the Number of EMAS-associated Seizure-free Days Over the 48-week Open-label Treatment Period

    Measured: Baseline; up to 48 weeks

  24. Part B: Number of Participants With at Least 25% and 50% Reduction From Baseline in the Number of Days Per Week With Myoclonic Seizures During the 48-week Open-label Treatment Period

    Measured: Baseline; up to 48 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Mar 2022
  2. Study start31 Oct 2022
  3. Primary completion28 Sep 2023
  4. Study completion28 Sep 2023

Why it stopped: The study was terminated due to a business decision.

Resources

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
3 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05288283
Sponsor's protocol ID
GWEP20238
Status last verified
Jan 2025
First submitted
11 Mar 2022
Last updated
3 Feb 2025
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing GWP42003-P in people with Seizures Associated With EMAS, run by Jazz Pharmaceuticals at 14 sites in 2 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 17 inclusion and 44 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: stopped early, as of the sponsor's last update on 3 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 14 sites in United States, Italy. 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 3 Feb 2025). 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?

Part A: Percent Change From Baseline in Epilepsy With Myoclonic-atonic Seizures (EMAS) Associated Seizure Frequency (Myoclonic-atonic, Atonic, Tonic, Clonic, or Tonic-clonic) Over the 14-week Treatment Period (time frame: Baseline; up to 14 weeks). The study lists 9 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 NCT05288283.

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 3 Feb 2025.

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