Open-label study to assess safety and efficacy of rapamycin in drugresistant epilepsy associated with mTOR pathway pathologies

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Instytut Pomnik Centrum Zdrowia Dziecka

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

27 Jun 2023 → 3 Dec 2025

Decision date (initial)

2025-01-11

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Medical Research Agency

External identifiers

EU CT number

2024-515950-25-00

EudraCT number

2021-006702-78

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic, Therapy, Efficacy

The primary objective of the study is to determine safety and tolerability of rapamycin in a drug resistant epilepsy associated with rare and ultrarare diseases of the central nervous system associated with the activation of the mTOR pathway.

Secondary objectives 1

1. The secondary aim of the study is to ascertain the antiseizure efficacy of rapamycin in a drug resistant epilepsy associated with rare and ultrarare diseases of the central nervous system associated with the activation of the mTOR pathway

Conditions and MedDRA coding

epilepsy, mTORopathies, focal cortical dysplasia, LEATS

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Age at inclusin from 4 months to 18 years.
2. Diagnosis of drug-resistant epilepsy as defined by ILAE (Kwan 2010), with focal onset (ICD-10: G40.2), with confirmed coexistence or suspicion of mTORopathy in MRI, including: FCD, hemimegalencephaly, LEATs; active epilepsy at study entry, at least 8 seizures in the prior 4 weeks prior to study entry
3. Informed consent to the participation in the study by the patient's legal caregivers and the patient himself, if he is 13 years of age or older.
4. Negative result of the pregnancy test performed within 2 weeks prior to the start of the study in patients of reproductive age.
5. Written consent to the use of effective contraception in sexually active patients or an obligation to abstaining from sexual activity during and for 3 months after its treatment.

Exclusion criteria 18

1. Severe coexisting diseases, e.g. renal failure, immunodeficiency
2. Clinically significant disease of the cardiovascular system, e.g. arrhythmia
3. Earlier diagnosis of neoplasm <5 years requiring antitumor treatment
4. Active infection requiring general treatment
5. Contraindications to use, including the inability to take or known hypersensitivity to the drug used in the study
6. Simultaneous administration of drugs that are strong inhibitors of CYP3A or PgP
7. Radiological features of active CNS bleeding except for asymptomatic resolving changes after biopsy or point bleeding in the tumor
8. Major surgery, open biopsy <28 days prior to treatment initiation
9. Minor surgical procedures <2 days before the start of treatment, e.g. implantation of a vascular port
10. Non-healing wound, unhealed fracture
11. Radiation therapy of the CNS <28 days
12. Pregnancy, breastfeeding
13. Active participation in another research program or completed <30 days
14. Systemic treatment with an mTOR inhibitor from other indications in the 3 months preceding study enrollment
15. Use of marijuana or its derivatives
16. Live vaccine intake <6 weeks prior to study inclusion
17. Receipt of inactivated vaccine or mRNA vaccine <4 weeks prior to study inclusion
18. Tuberous sclerosis

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary safety endpoint of rapamycin will be the assessment of the incidence of adverse reactions (according to the CTCAE classification) during the treatment phase and follow-up of patients with drug-resistant epilepsy. The primary efficacy endpoint will be the proportion of patients achieving a ≥50% reduction in seizures.

Secondary endpoints 1

1. A secondary safety endpoint will be the CTCAE severity of adverse reactions and the number of patients experiencing adverse reactions requiring exclusion from the study or premature termination of participation during the therapeutic dose period. The effect of treatment on the results of laboratory tests will also be analyzed. The secondary endpoint of the trial will be maintenance of short-term effects, improvement of quality of life in ≥50% of patients / families

Investigational products

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

Test 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

dr n. med. Julita Borkowska

Public contact point

Organisation

Instytut Pomnik Centrum Zdrowia Dziecka

Contact name

Anna Drużdżel

Third parties 2

Locations

1 EU/EEA country · 1 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 17 files

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

Application history

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