An Open-label, Single-arm Study to Assess the Safety, Pharmacokinetics, and Efficacy of Adjunctive Cannabidiol Oral Solution (GWP42003‑P) in Participants with Tuberous Sclerosis Complex (Age 1 Month to < 2 Years of Age), Dravet Syndrome (1 Year to < 2 Years of Age), or Lennox-Gastaut Syndrome (1 Year to < 2 Years of Age) who Experience Inadequately‑controlled Seizures

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Gw Research Limited, Jazz Pharmaceuticals Research UK Limited

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

29 Jul 2024 → 28 Jan 2025

Decision date (initial)

2023-11-29

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

External identifiers

EU CT number

2023-505851-33-00

ClinicalTrials.gov

NCT04485104

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Pharmacokinetic, Efficacy

To evaluate the safety and tolerability of adjunctive GWP42003-P assessed during the 52-week treatment period
To investigate the exposure of GWP42003-P and its major metabolites following multiple doses of GWP42003-P
To evaluate the efficacy of GWP42003-P in reducing the frequency of indication-specific countable seizures.

Secondary objectives 5

1. To evaluate the efficacy of GWP42003-P in reducing the frequency of total countable seizures
2. To assess the retention of participants receiving GWP42003-P
3. Exploratory: To evaluate the efficacy of GWP42003-P based on video electroencephalogram (VEEG)
4. Exploratory: To evaluate the effects of GWP42003-P on quality of life (QoL)
5. Exploratory: To evaluate time of dosing relative to food intake time

Conditions and MedDRA coding

Dravet Syndrome

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-001964-PIP01-16

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. 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
2. 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)
3. Participants who have uncontrolled seizures, and who are currently receiving 1 or more ASMs.
4. Parent(s)/LAR is/are willing and able to give informed consent for participation in the study
5. Parent(s)/LAR is/are willing and able (in the investigator’s opinion) to comply with all study requirements (including accurate electronic patient-reported outcome [ePRO] diary completion)
6. Caregiver completes at least 75% of ePRO and paper seizure diary entries during the 28 days of the baseline period (≥ 21 days of entries)
7. 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 an independent reviewer. • A suitable VEEG meets all the following criteria: i. Multichannel (minimum 8-channel) ii. Prolonged continuous recording up to 24 hours iii. Completed within 1 year of Visit 1 iv. Consistent with the participant’s current seizures (in the investigator’s opinion) v. Can be reviewed by the investigator and an independent reviewer prior to Visit 3 vi. Consistent with a diagnosis of inadequately-controlled seizures
8. Currently taking ≥ 1 ASMs at a dose that remains stable 2 weeks prior to Visit 3 and during the treatment period. Where required for participant safety, adjustments of concomitant ASMs or addition of new ASM may be permitted following discussion with the medical monitor. • Adrenocorticotropic hormone (ACTH) or high dose corticosteroids for the treatment of IS/ES are counted as ASMs.
9. Has seizures that are not adequately controlled through their current ASMs, defined as ≥ 1 seizure reported on the seizure diary during the screening/baseline period.
10. Parent(s)/LAR is/are willing to allow the responsible authorities to be notified of participation in the study, if mandated by local law
11. Parent(s)/LAR is/are willing to allow the participant’s primary care practitioner (if they have one) and consultant (if they have one) to be notified of participation in the study if the primary care practitioner/consultant is different from the investigator

Exclusion criteria 19

1. Has clinically significant unstable medical condition other than epilepsy
2. Has had clinically significant symptoms or a clinically significant illness within the 4 weeks prior to Visit 1, other than epilepsy, which in the opinion of the investigator could affect seizure frequency
3. Has undergone general anesthesia within 4 weeks prior to Visit 1
4. Has undergone surgery for epilepsy within 6 months prior to Visit 1 or has plans to undergo surgery for epilepsy during the study
5. Has taken felbamate < 1 year prior to Visit 1
6. Is < 1 year of age and taking valproic acid
7. Has tumour growth which, in the opinion of the investigator, could affect participant safety
8. Has clinically significant abnormal laboratory values, in the investigator’s opinion, at screening/baseline
9. Has clinically significant abnormalities in the ECG measured at screening/baseline
10. Has any concurrent cardiovascular conditions that will, in the investigator’s opinion, interfere with the ability to assess their ECGs
11. Has any known or suspected hypersensitivity to cannabinoids or any of the excipients of the study intervention such as sesame seed oil
12. 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.
13. Has received another study intervention within 4 weeks prior to Visit 1 or plans to take another study intervention during the study
14. Caregiver is currently giving or has given recreational or medicinal cannabis, cannabinoid-based medications (including Sativex) or CBD (including Epidiolex/ Epidyolex [GWP42003-P]) to the participant within the 4 weeks prior to Visit 1 or is unwilling to abstain from doing so for the duration of the study
15. Mother (if breastfeeding) is currently using or has used recreational or medicinal cannabis, cannabinoid-based medications (including Sativex) or CBD (including Epidiolex/Epidyolex [GWP42003-P]) within the 4 weeks prior to Visit 1 or is unwilling to abstain from doing so for the duration of the study
16. 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
17. 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
18. Has previously been enrolled into this study
19. 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 and all stops along the way

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. Adverse events (frequency,type and severity). Vital signs. Physical examination. 12-lead electrocardiogram(ECG). Clinically significant changes in laboratory parameters. Emergence of new seizure types as recorded by AE reporting. Comphrensive neuredevelopmental assessment.
2. 3-hour and 6-hour postdose plasma concentrations of GWP42003-P and its major metabolites following multiple doses of GWP42003-P.
3. Percentage change from baseline in indication-specific countable seizures (average per 28 days) as recorded by caregivers on seizure diaries at Week 12, every 4 weeks thereafter, and during the 4-week period prior to end of treatment (EOT).
4. Comprhensive neuredevelopmental assessment

Secondary endpoints 5

1. Total countable seizures(average per28days)as recorded by caregivers on seizure diaries at W12,every 4W thereafter,and during the 4W period prior to EOT will be used to determine the following endpoints: N. and percentage of participants considered treatment responders,defined as those with a ≥50% reduction from baseline in tot countable seizures.Categorical percentage change from baseline to EOT in tot countable seizures.Seizure freedom,defined as 100% reduction from baseline
2. Percentage of participants still taking GWP42003-P at Week 12 and every 4 weeks thereafter
3. Exploratory: Percent change in seizure frequency from baseline to EOT as captured by prolonged multichannel (minimum of 8 channels) VEEG of up to 24 hours of recording. Change in VEEG seizure burden (e.g., seizure type (s) and frequency recorded during VEEGs) from baseline to EOT. Where possible, correlation of multichannel VEEG-recorded seizures with seizure frequency recorded by investigators and caregivers.
4. Exploratory: Percent change from baseline in scores of ITQOL-SF47 caregiver questionnaire at EOT
5. Exploratory: Correlation between time of food intake and time of dosing obtained from diaries completed during the 24 hours before pharmacokinetic (PK) collection visits

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Gw Research Limited

Sponsor organisation

Gw Research Limited

Address

Sovereign House, Vision Park, Chivers Way, Histon Vision Park Chivers Way

City

Cambridge

Postcode

CB24 9BZ

Country

United Kingdom

Scientific contact point

Organisation

Gw Research Limited

Contact name

Clinical Trial Disclosure & Transparency

Public contact point

Organisation

Gw Research Limited

Contact name

Clinical Trial Disclosure & Transparency

Third parties 8

Jazz Pharmaceuticals Research UK Limited

Sponsor organisation

Jazz Pharmaceuticals Research UK Limited

Address

Building 730, Kent Science Park Kent Science Park

City

Sittingbourne

Postcode

ME9 8AG

Country

United Kingdom

Scientific contact point

Organisation

Jazz Pharmaceuticals Research UK Limited

Contact name

Clinical Trial Disclosure & Transparency

Public contact point

Organisation

Jazz Pharmaceuticals Research UK Limited

Contact name

Clinical Trial Disclosure & Transparency

Third parties 8

Locations

2 EU/EEA countries · 5 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 4 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications