Placebo controlled study to assess the efficacy and safety of rapamycin in drug resistant epilepsy associated with tuberous sclerosis complex

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Instytut Pomnik Centrum Zdrowia Dziecka

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

7 Feb 2023 → ongoing

Decision date (initial)

2024-12-20

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Medical Reserach Agency

External identifiers

EU CT number

2024-515937-13-00

EudraCT number

2021-004548-64

ClinicalTrials.gov

NCT05534672

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Therapy, Safety, Efficacy

The primary objective of the RaRE-TS study is to determine safety,
tolerability and efficacy of rapamycin versus placebo in a drug resistant
epilepsy associated with tuberous sclerosis complex

Secondary objectives 1

1. The secondary aim of the study is to ascertain the impact of rapamycin on the TSC- Associated Neuropsychiatric Disorders (TAND) and TSCassociated tumors (brain, kidney, retina and skin lesions) in comparison to placebo.

Conditions and MedDRA coding

tuberous sclerosis complex, epilepsy, organ tumors associated with tuberous sclerosis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Parents/caregivers are willing to and able to give informed consent form for the participation in the study
2. Parents/caregivers are willing to and able to comply with all study requirements
3. Definite diagnosis of TSC according to the Consensus criteria (Northrup, 2013)
4. drug-resistant epilepsy associated with TSC with at least 8 seizures during 4 weeks
5. male or female aged from 3 months up to 55 years at the day of randomization
6. body weight of at least 6 kg and proper nutritional status (assessed by investigator)

Exclusion criteria 10

1. history of treatment with mTOR inhibitor in the three months prior to screening
2. history of pseudo-epileptic seizures
3. history of progressive CNS disease other than TSC
4. recent surgery within 2 weeks prior to the screening
5. severe infection within 2 weeks prior to the screening
6. contraindications for MRI or general anesthesia
7. occurrence of the serious comorbidities which, in the opinion of the investigator, may either put a patient at significant risk associated with the participation in the study or may influence the results of the study the investigator
8. pregnancy
9. hypersensitivity to the active substance or to any of the excipients of IMP / placebo
10. Allergy to peanuts or soy

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. comparison of the number of patients with at least 50% reduction of seizures per week in the last month of the core blinded phase in comparison to screening phase in the rapamycin vs placebo group (
2. number of adverse events (according to CTCAE classification) in the rapamycin vs placebo group during the double-blind core phase

Secondary endpoints 2

1. comparison of the number of seizures per week and the number of days free of seizures in the rapamycin vs placebo group, during 12-week treatment in double-blind core phase
2. severity of adverse events (according to CTCAE) and the number of patients withdrawn from the study due to adverse events in the rapamycin vs placebo group

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Instytut Pomnik Centrum Zdrowia Dziecka

Sponsor organisation

Instytut Pomnik Centrum Zdrowia Dziecka

Address

Aleja Dzieci Polskich 20

City

Warsaw

Postcode

04-730

Country

Poland

Scientific contact point

Organisation

Instytut Pomnik Centrum Zdrowia Dziecka

Contact name

Katarzyna Kotulska-Jóźwiak

Public contact point

Organisation

Instytut Pomnik Centrum Zdrowia Dziecka

Contact name

Katarzyna Kotulska-Jóźwiak

Third parties 3

Locations

1 EU/EEA country · 4 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 35 files

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

Application history

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