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Efficacy and Safety of Rapamycin Versus Vigabatrin in the Prevention of Tuberous Sclerosis Complex Symptoms in Infants (ViRap)

Primary Purpose

Tuberous Sclerosis Complex

Status

Recruiting

Phase

Phase 2

Locations

Poland

Study Type

Interventional

Intervention

Vigabatrin

Rapamycin

Placebo

About this trial

This is an interventional prevention trial for Tuberous Sclerosis Complex focused on measuring tuberous sclerosis complex, epilepsy, rapamycin, vigabatrin, tumors, prevention

Eligibility Criteria

4 Weeks - 16 Weeks (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Male or female aged from 4 up to 16 weeks (44-56 weeks of gestational age) at the day of randomization
Parents/caregivers are willing to and able to give informed consent form for the participation in the study
Parents/caregivers are willing to and able to comply with all study requirements
Definite diagnosis of TSC according to the Consensus criteria (Northrup,2013)
At least 1 focus of cortical dysplasia disclosed on brain MRI

Exclusion Criteria:

history of seizures prior to randomization,
history of antiepileptic treatment,
history of treatment with mTOR (mammalian Target of Rapamycin) inhibitor,
gestational age below 44 weeks at the day of randomization,
body weight lower than 3 kg at the day of randomization,
SEGA (Subependymal Giant Cell Astrocytoma) or other TSC-associated lesion requiring urgent surgical intervention
recent surgery within 1 month prior to the randomization
intercurrent infection at the date of randomization
known history of HIV seropositivity
live vaccination within 1 month prior to randomization*
lack of first TBC and hepatitis B vaccinations
Any significant clinical, laboratory , ECG or other abnormalities, comorbidity or concomitant treatment 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.
Use of an investigational drug within 1 month prior to randomization.

Sites / Locations

Medical University of Warsaw, Department of Pediatric Neurology
Children's Memorial Health Institute, Neurology and EpileptologyRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Vigabatrin arm

Rapamycin arm

Arm Description

Vigabatrin in capsules co-administered with placebo in liquid.

Rapamycin in liquid co-administered with placebo in capsules.

Outcomes

Primary Outcome Measures

Occurrence of clinical seizures in the blinded phase of the study,

Summarized volume of TSC-associated tumors ≥ 125% of initial value within the blinded phase of the study

Secondary Outcome Measures

Total volume of TSC-associated tumors within the blinded phase and the whole study

The risk for high risk of autism assessed with psychological test at 6, 12, 18, 24 months

The risk for low developmental quotient (< 70 points in Bayley Scales of Infant Development, measured at the end of the blinded phase and at the end of the entire study) at the end of the study

The risk of drug-resistant epilepsy at any point of the study

Occurrence of adverse events within the blinded phase of the study

Number of adverse events across the whole study

Parameters of physical development (weight gain history) across the whole study

Parameters of physical development (height gain history) across the whole study

Full Information

NCT ID

NCT04987463

First Posted

May 28, 2021

Last Updated

September 6, 2022

Sponsor

Katarzyna Kotulska

1. Study Identification

Unique Protocol Identification Number

NCT04987463

Brief Title

Efficacy and Safety of Rapamycin Versus Vigabatrin in the Prevention of Tuberous Sclerosis Complex Symptoms in Infants

Acronym

ViRap

Official Title

Randomized, Placebo-controlled, Double-blind and Double-dummy Clinical Trial Comparing the Safety, Tolerability, and Efficacy of Vigabatrin and Rapamycin in a Preventive Treatment of Infants With Tuberous Sclerosis Complex

Study Type

Interventional

2. Study Status

Record Verification Date

September 2022

Overall Recruitment Status

Recruiting

Study Start Date

May 7, 2021 (Actual)

Primary Completion Date

March 2026 (Anticipated)

Study Completion Date

March 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Katarzyna Kotulska

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

The purpose of the study is to evaluate the efficacy, tolerability, and safety of vigabatrin versus rapamycin as a preventive treatment in infants with Tuberous Sclerosis Complex (TSC).

Detailed Description

This is a two-arm, randomized, double-blind and double-dummy, placebo controlled study to evaluate the efficacy, tolerability, and safety of vigabatrin versus rapamycin as a preventive treatment in infants with TSC. The study consists of 3 phases for each patient: screening, core blinded phase, and open-label follow-up phase. Patients who meet the eligibility criteria will be randomized to receive vigabatrin or rapamycin. The randomization ratio is 1:1. Randomization will be stratified by the sex and the presence of epileptiform activity on baseline videoEEG (video electroencephalography) recording (yes versus no). Approximately 60 infants are planned to be enrolled in the study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Tuberous Sclerosis Complex

Keywords

tuberous sclerosis complex, epilepsy, rapamycin, vigabatrin, tumors, prevention

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 2, Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Masking Description

Triple

Allocation

Randomized

Enrollment

60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Vigabatrin arm

Arm Type

Experimental

Arm Description

Vigabatrin in capsules co-administered with placebo in liquid.

Arm Title

Rapamycin arm

Arm Type

Experimental

Arm Description

Rapamycin in liquid co-administered with placebo in capsules.

Intervention Type

Drug

Intervention Name(s)

Vigabatrin

Intervention Description

Vigabatrin in capsules administered orally, initially (between V1 and V2) once daily in the evening,and starting from V2 administered two times daily.

Intervention Type

Drug

Intervention Name(s)

Rapamycin

Intervention Description

Rapamycin in liquid administered orally, in the morning, every other day or daily depending on the patient's body weight. The starting dose of rapamycin will be calculated according to the body weight of the patient measured at V1.

Intervention Type

Drug

Intervention Name(s)

Placebo

Other Intervention Name(s)

Placebo in liquid

Intervention Description

Placebo in liquid administered orally, once daily, in the morning. The starting dose of placebo in liquid will be calculated according to the body weight of the patient measured at V1.

Intervention Type

Drug

Intervention Name(s)

Placebo

Other Intervention Name(s)

Placebo in granules

Intervention Description

Placebo in granules administered orally, initially once daily in the evening,and after reaching the targeted dose administered two times daily.

Primary Outcome Measure Information:

Title

Occurrence of clinical seizures in the blinded phase of the study,

Time Frame

730 days

Title

Summarized volume of TSC-associated tumors ≥ 125% of initial value within the blinded phase of the study

Time Frame

730 days

Secondary Outcome Measure Information:

Title

Total volume of TSC-associated tumors within the blinded phase and the whole study

Time Frame

730 days

Title

The risk for high risk of autism assessed with psychological test at 6, 12, 18, 24 months

Time Frame

6, 12, 18, 24 months

Title

The risk for low developmental quotient (< 70 points in Bayley Scales of Infant Development, measured at the end of the blinded phase and at the end of the entire study) at the end of the study

Time Frame

730 days

Title

The risk of drug-resistant epilepsy at any point of the study

Time Frame

730 days

Title

Occurrence of adverse events within the blinded phase of the study

Time Frame

730 days

Title

Number of adverse events across the whole study

Time Frame

730 days

Title

Parameters of physical development (weight gain history) across the whole study

Time Frame

730 days

Title

Parameters of physical development (height gain history) across the whole study

Time Frame

730 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

4 Weeks

Maximum Age & Unit of Time

16 Weeks

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Male or female aged from 4 up to 16 weeks (44-56 weeks of gestational age) at the day of randomization Parents/caregivers are willing to and able to give informed consent form for the participation in the study Parents/caregivers are willing to and able to comply with all study requirements Definite diagnosis of TSC according to the Consensus criteria (Northrup,2013) At least 1 focus of cortical dysplasia disclosed on brain MRI Exclusion Criteria: history of seizures prior to randomization, history of antiepileptic treatment, history of treatment with mTOR (mammalian Target of Rapamycin) inhibitor, gestational age below 44 weeks at the day of randomization, body weight lower than 3 kg at the day of randomization, SEGA (Subependymal Giant Cell Astrocytoma) or other TSC-associated lesion requiring urgent surgical intervention recent surgery within 1 month prior to the randomization intercurrent infection at the date of randomization known history of HIV seropositivity live vaccination within 1 month prior to randomization* lack of first TBC and hepatitis B vaccinations Any significant clinical, laboratory , ECG or other abnormalities, comorbidity or concomitant treatment 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. Use of an investigational drug within 1 month prior to randomization.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Katarzyna Kotulska-Jozwiak

Phone

+48 22 8157404

k.kotulska@ipczd.pl

First Name & Middle Initial & Last Name or Official Title & Degree

Monika Szkop

Phone

+48 22 815 74 04

m.szkop@ipczd.pl

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Katarzyna Kotulska-Jozwiak

Organizational Affiliation

The Children's Memorial Health Institute

Official's Role

Principal Investigator

Facility Information:

Facility Name

Medical University of Warsaw, Department of Pediatric Neurology

City

Warsaw

ZIP/Postal Code

02-091

Country

Poland

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Sergiusz Jozwiak

Phone

48 22 3179681

sergiusz.jozwiak@wum.edu.pl

Facility Name

Children's Memorial Health Institute, Neurology and Epileptology

City

Warsaw

ZIP/Postal Code

04-730

Country

Poland

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Katarzyna Kotulska-Jozwiak

Phone

+48 22 8157404

k.kotulska@ipczd.pl

12. IPD Sharing Statement

Learn more about this trial

Efficacy and Safety of Rapamycin Versus Vigabatrin in the Prevention of Tuberous Sclerosis Complex Symptoms in Infants

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