Assessment of Adjunctive Cannabidiol Oral Solution (GWP42003-P) in Children With Tuberous Sclerosis Complex (TSC), Dravet Syndrome (DS), or Lennox-Gastaut Syndrome (LGS) Who Experience Inadequately-controlled Seizures

Jazz Pharmaceuticals

Status and phase: Terminated; Phase 3

Conditions: Seizure in Participants With Lennox-Gastaut Syndrome; Seizure in Participants With Tuberous Sclerosis Complex; Seizure in Participants With Dravet Syndrome

Treatments: Drug: GWP42003-P

Study type: Interventional

Funder types: Industry

Identifiers

NCT04485104

2020-002132-67 (EudraCT Number)

GWEP17005

Details and patient eligibility

About

This study will be conducted to evaluate the safety, pharmacokinetics (PK), and efficacy of adjunctive GWP42003-P in participants < 2 years of age with tuberous sclerosis complex (TSC), Lennox-Gastaut syndrome (LGS), or Dravet syndrome (DS).

Full description

The study duration will be up to approximately 62 weeks, including a 4-week screening/baseline period, a 52-week dose optimization treatment period (which includes a fixed 2-week titration period followed by flexible dose optimization), a 10-day taper period, and a safety follow-up period (4 weeks after the end-of-taper visit).

Enrollment: 3 patients

Sex: All

Ages: 1 to 23 months old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• Participants with TSC (1 month to < 2 years of age), or DS (1 year to < 2 years of age), or LGS (1 year to < 2 years of age) within the specified age range at the time of initial informed consent.
• Parent(s)/legal representative is/are willing and able to give informed consent for participation in the study.
• Parent(s)/legal representative is/are willing and able (in the investigator's opinion) to comply with all study requirements (including accurate electronic participant-reported outcome [ePRO] diary completion).
• Participants with TSC must have a diagnosis per the 2012 International Tuberous Sclerosis Complex Consensus Conference. Participants with LGS or DS must have a diagnosis that is consistent with International League Against Epilepsy (ILAE) guidelines and confirmed by the Epilepsy Study Consortium (ESCI).
• Participants who have uncontrolled seizures, and who are currently receiving 1 or more antiseizure medication (ASMs).
• A suitable VEEG, as available in the medical record, within 1 year of Visit 1. When a historical VEEG is not available, and if clinically indicated and appropriate (due to uncertainties or new seizures), a VEEG will be completed and read to confirm diagnosis prior to Visit 3. All VEEGs are to be read at baseline by the investigator and by an independent reviewer.
• Has seizures which are not adequately controlled through their current ASMs, defined as ≥ 1 seizure reported on the seizure diary during the screening/baseline period

Key Exclusion Criteria:

• Has tumor growth which, in the opinion of the investigator, could affect participant safety.

• Has clinically significant abnormal laboratory values, in the investigator's opinion, at screening/baseline.

• Has clinically significant abnormalities in the electrocardiogram (ECG) measured at screening/baseline.

• Has any concurrent cardiovascular conditions, that will, in the investigator's opinion, interfere with the ability to assess their ECGs.

• Has any known or suspected hypersensitivity to cannabinoids or any of the excipients of the study intervention such as sesame seed oil.

• Has significantly impaired hepatic function prior to Visit 3, defined as:

  • Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 3 × upper limit of normal (ULN) and (total bilirubin [TBL] > 2 × ULN or international normalized ratio [INR] > 1.5).
  • Serum ALT or AST > 5 × 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 should be discussed with the medical monitor prior to Visit 3; the medical monitor may allow for a confirmatory re-draw prior to Visit 3.

• Has received another study intervention within 4 weeks prior to Visit 1 or plans to take another study intervention during the study.

• 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.

• Any clinically significant abnormalities identified following a physical examination of the participant that, in the opinion of the investigator, would jeopardize the safety of the participant if they took part in the study.

• Has previously been enrolled into this study.

• Has plans to travel outside their country of residence during the study, unless the participant has confirmation that the study intervention is permitted in the destination country.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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3 participants in 1 patient group

GWP42003-P

Experimental group

Description:

The 52-week treatment period includes a fixed 2-week titration schedule followed by flexible dose optimization. Day 1: 5 mg/kg/day (2.5 mg/kg twice daily (b.i.d.)) Day 8: 10 mg/kg/day (5 mg/kg b.i.d.) Day 15 to Week 52: Flexible dosing based on the participant's observed efficacy, safety, and tolerability per the investigator's clinical judgement. Up to a maximum of 20 mg/kg/day (10 mg/kg b.i.d.) for LGS and DS or 25 mg/kg/day (12.5 mg/kg b.i.d.) for TSC, in maximum weekly increments of 5 mg/kg/day (≤ 2.5 mg/kg b.i.d.).

Treatment:

Drug: GWP42003-P