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

NCT05288283 | Terminated Phase 3 Results FDA Drug

• 1 other identifier: GWEP20238
• Study Type: interventional
• Target: 3
• Locations: 2 countries
• Sites: 14

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

Conditions

Seizures Associated With EMAS

Keywords

Epilepsy; Seizures; Epilepsy with Myoclonic-Atonic Seizures (EMAS); Myoclonic-Atonic Epilepsy; Doose syndrome; Myoclonic-Astatic epilepsy (MAE); Children; Cannabidiol (CBD); GWP42003-P

Outcome Measures

Primary Outcomes (9)

• 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

  Baseline; up to 14 weeks

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

  up to Week 54

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

  up to Week 50

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

  up to Week 48

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

  up to Week 48

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

  up to Week 48

• Part B: Number of Participants With Changes in Tanner Staging

  up to Week 48

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

  up to Week 54

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

  up to Week 54

Secondary Outcomes (24)

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

  Baseline; up to 14 weeks

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

  Baseline; up to 14 weeks

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

  Week 14

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

  Week 14

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

  Baseline; up to 14 weeks

Study Arms (2)

GWP42003-P

EXPERIMENTAL

Participants 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.

Drug: GWP42003-P

Placebo

PLACEBO COMPARATOR

Participants will receive the matching placebo.

Drug: Placebo

Interventions

GWP42003-P DRUG

oral solution

Also known as: EPIDIOLEX, Cannabidiol, Cannabidiol oral solution (CBD-OS)

GWP42003-P

Placebo DRUG

oral solution

Placebo

Eligibility Criteria

• Age: 1 Year - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.
• 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:

You may not qualify if:

• 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
• 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);
• 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.

Sponsors & Collaborators

• Jazz Pharmaceuticals: lead

Study Sites (14)

Children's Hospital of Alabama

Birmingham, Alabama, 35233, United States

Location

University of California Davis Health

Sacramento, California, 95817, United States

Location

Healthcare of Atlanta

Atlanta, Georgia, 30329, United States

Location

Ann & Robert H. Lurie Children's Hospital

Chicago, Illinois, 60611, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Wake Forest Baptist Health Sciences, Department of Neurology

Winston-Salem, North Carolina, 27157, United States

Location

Cincinnati Children's Hospital Medical Center - TS Clinic

Cincinnati, Ohio, 45229, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Dell's Children's Hospital

Austin, Texas, 78723, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

Azienda Ospedaliero Universitaria Ospedale Pediatrico Meyer

Florence, 50139, Italy

Location

Istituto Giannina Gaslini-Ospedale Pediatrico IRCCS

Genova, 16147, Italy

Location

IRCCS Fondazione Istituto Neurologico Nazionale D. Mondino Pavia

Pavia, 27100, Italy

Location

UOC Neuropsichiatria Infantile AOUI Verona

Verona, 37126, Italy

Location

MeSH Terms

Conditions

Epilepsy; Seizures; Epilepsies, Myoclonic

Interventions

Cannabidiol

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Epilepsy, Generalized; Epileptic Syndromes

Intervention Hierarchy (Ancestors)

Cannabinoids; Terpenes; Hydrocarbons; Organic Chemicals

Results Point of Contact

• Title: Clinical Trial Disclosure & Transparency
• Organization: Jazz Pharmaceuticals

ClinicalTrialDisclosure@JazzPharma.com

215-832-3750

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 11, 2022
• First Posted: March 21, 2022
• Study Start: October 31, 2022
• Primary Completion: September 28, 2023
• Study Completion: September 28, 2023
• Last Updated: February 3, 2025
• Results First Posted: February 3, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

IT (4); US (10)