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

NCT04987463 | Recruiting Phase 2

• 1 other identifier: ViRap
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 2

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).

Conditions

Tuberous Sclerosis Complex

Keywords

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

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (8)

• 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

Study Arms (2)

Vigabatrin arm

EXPERIMENTAL

Vigabatrin in capsules co-administered with placebo in liquid.

Drug: Vigabatrin; Drug: Placebo

Rapamycin arm

EXPERIMENTAL

Rapamycin in liquid co-administered with placebo in capsules.

Drug: Rapamycin; Drug: Placebo

Interventions

Vigabatrin DRUG

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

Vigabatrin arm

Rapamycin DRUG

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.

Rapamycin arm

Placebo DRUG

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.

Also known as: Placebo in liquid

Vigabatrin arm

Eligibility Criteria

• Age: 4 Weeks - 16 Weeks
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Katarzyna Kotulska: lead

Study Sites (2)

Medical University of Warsaw, Department of Pediatric Neurology

Warsaw, 02-091, Poland

NOT YET RECRUITING

Children's Memorial Health Institute, Neurology and Epileptology

Warsaw, 04-730, Poland

RECRUITING

MeSH Terms

Conditions

Tuberous Sclerosis; Epilepsy; Neoplasms

Interventions

Vigabatrin; Sirolimus; Fluid Therapy

Condition Hierarchy (Ancestors)

Hamartoma; Neoplasms, Multiple Primary; Neoplastic Syndromes, Hereditary; Malformations of Cortical Development, Group I; Malformations of Cortical Development; Nervous System Malformations; Nervous System Diseases; Neurocutaneous Syndromes; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Brain Diseases; Central Nervous System Diseases

Intervention Hierarchy (Ancestors)

gamma-Aminobutyric Acid; Aminobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins; Macrolides; Lactones; Drug Therapy; Therapeutics

Study Officials

• Katarzyna Kotulska-Jozwiak

  The Children's Memorial Health Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Katarzyna Kotulska-Jozwiak

CONTACT

+48 22 8157404; k.kotulska@ipczd.pl

Monika Szkop

CONTACT

+48 22 815 74 04; m.szkop@ipczd.pl

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Triple
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Head of the Department of Neurology and Epileptology at The Children's Memorial Health Institute

Study Record Dates

• First Submitted: May 28, 2021
• First Posted: August 3, 2021
• Study Start: May 7, 2021
• Primary Completion: March 1, 2026
• Study Completion: March 1, 2026
• Last Updated: February 8, 2024

Record last verified: 2024-02

Locations

PL (2)