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

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

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).

Study Overview

• Status: Recruiting
• Conditions: Tuberous Sclerosis Complex
• Intervention / Treatment: Drug: Vigabatrin; Drug: Placebo; Drug: Placebo; Drug: Rapamycin

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.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Katarzyna Kotulska-Jozwiak; Phone Number: +48 22 8157404; Email: k.kotulska@ipczd.pl
• Study Contact Backup: Name: Monika Szkop; Phone Number: +48 22 815 74 04; Email: m.szkop@ipczd.pl

Study Locations

• Poland
  • Warsaw, Poland, 02-091
    • Not yet recruiting
    • Medical University of Warsaw, Department of Pediatric Neurology
    • Contact: Sergiusz Jozwiak; Phone Number: 48 22 3179681; Email: sergiusz.jozwiak@wum.edu.pl
  • Warsaw, Poland, 04-730
    • Recruiting
    • Children's Memorial Health Institute, Neurology and Epileptology
    • Contact: Katarzyna Kotulska-Jozwiak; Phone Number: +48 22 8157404; Email: k.kotulska@ipczd.pl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 weeks to 3 months (Child)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vigabatrin arm; Vigabatrin in capsules co-administered with placebo in liquid.	Drug: Vigabatrin; Vigabatrin in capsules administered orally, initially (between V1 and V2) once daily in the evening,and starting from V2 administered two times daily.; Drug: Placebo; 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.; Other Names: Placebo in liquid; Drug: Placebo; Placebo in granules administered orally, initially once daily in the evening,and after reaching the targeted dose administered two times daily.; Other Names: Placebo in granules
Experimental: Rapamycin arm; Rapamycin in liquid co-administered with placebo in capsules.	Drug: Placebo; 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.; Other Names: Placebo in liquid; Drug: Placebo; Placebo in granules administered orally, initially once daily in the evening,and after reaching the targeted dose administered two times daily.; Other Names: Placebo in granules; Drug: Rapamycin; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Occurrence of clinical seizures in the blinded phase of the study,	730 days
Summarized volume of TSC-associated tumors ≥ 125% of initial value within the blinded phase of the study	730 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Total volume of TSC-associated tumors within the blinded phase and the whole study	730 days
The risk for high risk of autism assessed with psychological test at 6, 12, 18, 24 months	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	730 days
The risk of drug-resistant epilepsy at any point of the study	730 days
Occurrence of adverse events within the blinded phase of the study	730 days
Number of adverse events across the whole study	730 days
Parameters of physical development (weight gain history) across the whole study	730 days
Parameters of physical development (height gain history) across the whole study	730 days

Collaborators and Investigators

• Sponsor: Katarzyna Kotulska
• Investigators: Principal Investigator: Katarzyna Kotulska-Jozwiak, The Children's Memorial Health Institute

Study record dates

Study Major Dates

• Study Start (Actual): May 7, 2021
• Primary Completion (Estimated): March 1, 2026
• Study Completion (Estimated): March 1, 2026

Study Registration Dates

• First Submitted: May 28, 2021
• First Submitted That Met QC Criteria: July 23, 2021
• First Posted (Actual): August 3, 2021

Study Record Updates

• Last Update Posted (Actual): February 8, 2024
• Last Update Submitted That Met QC Criteria: February 7, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: tuberous sclerosis complex, epilepsy, rapamycin, vigabatrin, tumors, prevention
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Neoplasms; Congenital Abnormalities; Genetic Diseases, Inborn; Neurodegenerative Diseases; Heredodegenerative Disorders, Nervous System; Neoplastic Syndromes, Hereditary; Malformations of Cortical Development, Group I; Malformations of Cortical Development; Nervous System Malformations; Neurocutaneous Syndromes; Hamartoma; Neoplasms, Multiple Primary; Sclerosis; Tuberous Sclerosis; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Anti-Bacterial Agents; GABA Agents; Anticonvulsants; Antibiotics, Antineoplastic; Antifungal Agents; Sirolimus; Vigabatrin
• Other Study ID Numbers: ViRap

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No