A study to investigate behavioral and other co-occurring outcomes with Epid(i/y)olex as add-on therapy in participants aged 1 to 65 years of age with tuberous sclerosis complex.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Jazz Pharmaceuticals Research UK Limited, Jazz Pharmaceuticals Research UK Limited, Jazz Pharmaceuticals Research UK Limited

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

12 Nov 2024 → 6 Apr 2026

Decision date (initial)

2024-05-06

Transition trial

No

Low-intervention

Yes

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Jazz Pharmaceuticals, Inc.

External identifiers

EU CT number

2023-507426-17-00

ClinicalTrials.gov

NCT05864846

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety

Primary effectiveness - To evaluate the changes in the most problematic behavior as identified by caregivers in participants with TSC who experience seizures

Secondary objectives 7

1. To evaluate the changes in TAND in participants with TSC who experience seizures.
2. To evaluate the changes in behaviors and neuropsychiatric symptoms in participants with TSC who experience seizures
3. To assess the changes in other nonseizure outcomes, including executive function and sleep, in participants with TSC who experience seizures
4. To evaluate reported changes on QOL and family functioning in participants with TSC who experience seizures.
5. To assess any changes in participants with TSC who experience seizures on the following additional measures: • Overall symptom severity • Treatment retention • Seizure response • Seizure-free days
6. To assess any changes in behavioral outcomes in participants with TSC whose seizures do not respond to CBD-OS treatment.
7. To evaluate the safety and tolerability of CBD-OS in participants with TSC who experience seizures.

Conditions and MedDRA coding

Tuberous Scerlosis Complex

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Is within the required age range at the time of signing (or at the time of the participant’s parent(s)/LAR signing) the informed consent or providing assent (as applicable): • Participants based in the US: 1 to 65 years of age, inclusive. • Participants based outside the US: 2 to 65 years of age, inclusive.
2. Has a confirmed clinical diagnosis of TSC with a history of seizures in accordance with the 2012 International Tuberous Sclerosis Complex Consensus Conference criteria.
3. Has behaviors (eg, aggression, impulsivity, temper tantrum, self-injury, hyperactivity, extreme shyness, mood swings, poor eye contact, repetitive behaviors, restlessness, difficulty getting along with peers, rigid/inflexible to procedure and/or change) that are considered moderate or severe per the CareGI-S at Screening. • At Baseline, participants must have a most problematic behavior score of ≥ 6 to remain eligible.
4. Has behaviors (eg, aggression, impulsivity, temper tantrum, self-injury, hyperactivity, extreme shyness, mood swings, poor eye contact, repetitive behaviors, restlessness, difficulty getting along with peers, rigid/inflexible to procedure and/or change) that are considered moderate or severe per the CareGI-S at Screening. • At Baseline, participants must have a most problematic behavior score of ≥ 6 to remain eligible.
5. Is naïve to CBD-OS treatment or has been off CBD-OS treatment for at least 3 months prior to Screening.
6. Is willing to maintain any factors expected to affect seizures stable (eg, alcohol consumption, smoking, concomitant medication usage).
7. Is male or female a. Male participants: • Male participants are eligible to participate if they agree to the following during the intervention period and for at least 2 weeks, corresponding to the time needed to eliminate the study intervention (eg, 5 terminal half-lives) after the last dose of study intervention: − Refrain from donating fresh unwashed semen. PLUS − Use a male condom in addition to a second method of acceptable contraception used by their female partners when having sexual intercourse with a WOCBP who is not currently pregnant. b. Female participants: • A female participant is eligible to participate if she is not pregnant or breastfeeding and one of the following conditions applies: − Is a woman of nonchildbearing potential. OR − Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of < 1% per year), preferably with low user dependency, as described in (Appendix 4 Contraceptive and Barrier Guidance), during the study intervention period and for at least 3 months after the last dose of study intervention. The investigator should evaluate the potential for contraceptive method failure (eg, noncompliance, recently initiated) in relationship to the first dose of study intervention.
8. Participant or the participant’s parent(s)/LAR is capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol. • In cases where the participant’s parent(s)/LAR representative signs the ICF and the participant possesses adequate understanding, assent should also be taken according to local regulations.
9. Participant and their caregiver are willing and able (in the investigator’s opinion) to comply with all study requirements.
10. Participant’s parent(s)/ or LAR is willing to allow the responsible authorities to be notified of the participant’s involvement in the study, if mandated by local law.
11. Participant’s parent(s)/LAR is willing to allow his or her 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 to the investigator.
12. Participant (including adults lacking capacity) has a dedicated caregiver to participate in the study.

Exclusion criteria 14

1. Has a clinically significant unstable medical condition other than epilepsy.
2. Has an illness during the 4 weeks prior to screening other than epilepsy which, in the investigator’s opinion, could affect study outcomes.
3. Has TSC-specific tumor growth which, in the investigator’s opinion, could affect the effectiveness endpoints.
4. Has any other significant disease or disorder which, in the investigator’s opinion, 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.
5. Has previously undergone significant surgery for epilepsy that, in the investigator’s opinion, may impact the assessment of outcomes.
6. Has initiated felbamate within the last 12 months prior to Screening.
7. Is currently using or has in the past used recreational or medicinal cannabis or synthetic cannabinoid-based medications within the 3 months prior to Screening and is not willing to undergo a 1-month washout period before being rescreened.
8. Has received an investigational medicinal product within the 3 months prior to the Screening Visit.
9. Has previously been assigned study intervention for this study or is currently enrolled in any other interventional study (including behavioral intervention studies).
10. Has laboratory values at the Baseline Visit that are abnormal and of clinical significance in the investigator’s opinion.
11. Participant has significantly impaired hepatic function at the Baseline Visit, defined as any of the following: a. Serum ALT or AST > 5 × ULN b. Serum ALT or AST > 3 × ULN and TBL > 2 × ULN or INR > 1.5 c. Serum ALT or AST > 3 × ULN with the presence of fatigue, nausea, vomiting, right upper quadrant pain or tenderness, jaundice, fever, rash, and/or eosinophilia (> 5%) Note: This criterion can only be confirmed once the laboratory results are available; participants enrolled into the study who are later found to meet this criterion must be withdrawn from the study.
12. Has any history of suicidal behavior or any suicidal ideation of type 4 or 5 as evaluated with C-SSRS or Children’s C-SSRS at the Screening Visit (for participants ≥ 4 years of age).
13. Has any known or suspected hypersensitivity to cannabinoids or any of the excipients of CBD-OS.
14. Has a known or suspected history of alcohol or substance abuse.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from baseline in the most problematic behavior NRS score within the TAND-SQ at Weeks 13, 26, and 52

Secondary endpoints 19

1. Change from baseline in TAND-SQ at Weeks 13, 26, and 52.
2. Change from baseline in ABC at Weeks 13, 26, and 52
3. Change from baseline in CBCL/ABCL/ASR at Weeks 26, and 52
4. Change from baseline to Weeks 26 and 52 in PROMIS domains
5. Change from baseline in sleep characteristics in CSHQ/PSQI at Week 26
6. Change from baseline in executive function using the BRIEF at Week 26
7. Change from baseline in caregiver-reported assessment of QOL and family functioning using PedsQL FIM to Week 26
8. Change from baseline in assessment of QOL using PedsQL to Week 26
9. Change from baseline in caregiver/participant and clinician impression of overall severity of symptoms (behavior and seizure control) utilizing CareGI-S/PGI-S and CGI-S at Weeks 4, 13, 26, and 52
10. Retention at Weeks 13, 26, and 52 following initiation of treatment
11. Number of participants considered treatment responders from baseline to each evaluable visit
12. Number of participants experiencing a worsening, no change, or improvement in seizure frequency from baseline to each evaluable visit
13. Change in number of seizure-free days from baseline at Weeks 4, 13, 26, and 52
14. Change from baseline in the following measures at Weeks 4, 13, 26, and 52 (where available): most problematic behavior NRS (within TAND-SQ), TAND-SQ, ABC, CBCL/ABCL/ASR, BRIEF, PROMIS, CGI-S, and PGI-S/CareGI-S
15. Incidence and/or severity of TEAEs
16. Changes from baseline to each evaluable visit in clinical laboratory parameters and incidence of abnormal values
17. Change from baseline to each evaluable visit in ideation score and number of suicide attempts per the C-SSRS or Children’s C-SSRS (where applicable)
18. Number of participant inpatient hospitalizations due to epilepsy
19. Number of withdrawals due to TEAEs

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

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

Lisa Moore-Ramdin

Public contact point

Organisation

Jazz Pharmaceuticals Research UK Limited

Contact name

Aislinn Doody

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

Lisa Moore-Ramdin

Public contact point

Organisation

Jazz Pharmaceuticals Research UK Limited

Contact name

Aislinn Doody

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

Lisa Moore-Ramdin

Public contact point

Organisation

Jazz Pharmaceuticals Research UK Limited

Contact name

Aislinn Doody

Third parties 10

Sponsor responsibilities

Article 77 compliance

Jazz Pharmaceuticals Research UK Limited

Contact point sponsor

Jazz Pharmaceuticals Research UK Limited

Article 77 implementation

Jazz Pharmaceuticals Research UK Limited

Locations

1 EU/EEA country · 3 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

Documents 79 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