RaRE-TS: Placebo Controlled Study to Assess the Efficacy and Safety of Rapamycin in Drug Resistant Epilepsy Associated With Tuberous Sclerosis Complex

• Sponsor: Katarzyna Kotulska (Other)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT05534672
• Collaborator: (none)
• Enrollment: 200
• Locations: 2
• Arms: 2
• Anticipated Duration (Months): 57
• Patients Per Site: 100
• Patients Per Site Per Month: 1.8

Study Details

Study Description

Brief Summary

The purpose 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 (TSC).

Condition or Disease	Intervention/Treatment	Phase
Tuberous Sclerosis Complex	Other: Rapamycin; Other: Placebo	Phase 3

Detailed Description

This is a two-arm, randomized, double-blind, placebo controlled study to evaluate the efficacy, tolerability, and safety of rapamycin versus placebo in a drug resistant epilepsy associated with TSC. The study consists of 3 phases for each patient: screening, dose adjustment blinded phase, core blinded phase, followed by open-label observation. Patients who meet the eligibility criteria will be randomized to receive rapamycin or placebo. The randomization ratio is 1:1. Randomization will be stratified by age, sex and and the number of antiepileptic drugs ever used in the patient's history (up to 3 drugs / more than 3 drugs).

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 200 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Multicenter, Randomized, Double-blind, Placebo Controlled Study to Assess the Efficacy and Safety of Rapamycin in Drug Resistant Epilepsy Associated With TSC
• Anticipated Study Start Date: Sep 1, 2022
• Anticipated Primary Completion Date: Jun 1, 2027
• Anticipated Study Completion Date: Jun 1, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Rapamycin arm Each patient randomized to the rapamycin arm will receive rapamycin in liquid. The rapamycin will be administered in individually calculated doses depending on the body surface of participants	Other: Rapamycin; Rapamycin in liquid administered orally
Placebo Comparator: Placebo arm The patients assigned to the placebo arm will receive placebo in liquid, analogically to the rapamycin group.	Other: Placebo; Placebo in liquid administered orally

Outcome Measures

Primary Outcome Measures

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 [final analyses after the formal final database lock, planned within one month after the last patient last visit in the study]

2. number of adverse events (according to CTCAE classification) in the rapamycin vs placebo group during the double-blind core phase [final analyses after the formal final database lock, planned within one month after the last patient last visit in the study]

Secondary Outcome Measures

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 [final analyses after the formal final database lock, planned within one month after the last patient last visit in the study]

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 [final analyses after the formal final database lock, planned within one month after the last patient last visit in the study]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 3 Months to 50 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• male or female aged from 3 months up to 50 years at the day of randomization

• patients/parents/caregivers are willing to and able to give informed consent form for the participation in the study

• patients/parents/caregivers are willing to and able to comply with all study requirements

• definite diagnosis of TSC according to the Consensus criteria (Northrup, 2013)

• drug-resistant epilepsy associated with TSC with at least 8 seizures during 4 weeks

Exclusion Criteria:

• history of treatment with mTOR inhibitor in the three months prior to screening,

• history of pseudo-epileptic seizures,

• history of progressive CNS disease other than TSC

• recent surgery within 2 weeks prior to the screening

• severe infection within 2 weeks prior to the screening

• use of the cannabis derivatives

• contraindications for MRI or general anesthesia

• 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

• pregnancy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Medical University of Lodz	Lodz		Poland	90-419
2	Children's Memorial Health Institute, Neurology and Epileptology	Warsaw		Poland	04-730

Sponsors and Collaborators

• Katarzyna Kotulska

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Katarzyna Kotulska, Head of the Department of Neurology and Epileptology at The Children's Memorial Health Institute, Children's Memorial Health Institute, Poland
• ClinicalTrials.gov Identifier: NCT05534672
• Other Study ID Numbers: RaRE-TS
• First Posted: Sep 9, 2022
• Last Update Posted: Sep 9, 2022
• Last Verified: Sep 1, 2022

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Katarzyna Kotulska, Head of the Department of Neurology and Epileptology at The Children's Memorial Health Institute, Children's Memorial Health Institute, Poland: tuberous sclerosis complex, epilepsy, rapamycin, drug resistant epilepsy
• Additional relevant MeSH terms: Tuberous Sclerosis; Epilepsy; Drug Resistant Epilepsy; Sclerosis; Sirolimus

Study Results

No Results Posted as of Sep 9, 2022