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

Tuberous Sclerosis Complex Clinical Trial

— 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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04987463
• Other study ID #: ViRap
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: May 7, 2021
• Est. completion date: March 2026

Study information

• Verified date: February 2024
• Source: Children's Memorial Health Institute, Poland
• Contact: Katarzyna Kotulska-Jozwiak
• Phone: +48 22 8157404
• Email: k.kotulska[@]ipczd.pl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: March 2026
• Est. primary completion date: March 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 4 Weeks to 16 Weeks

Eligibility

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.

Related Conditions & MeSH terms

• Sclerosis
• Tuberous Sclerosis
• Tuberous Sclerosis Complex

Intervention

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

Locations

Country	Name	City	State
Poland	Children's Memorial Health Institute, Neurology and Epileptology	Warsaw
Poland	Medical University of Warsaw, Department of Pediatric Neurology	Warsaw

Sponsors (1)

Lead Sponsor	Collaborator
Katarzyna Kotulska

Country where clinical trial is conducted

Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Occurrence of clinical seizures in the blinded phase of the study,		730 days
Primary	Summarized volume of TSC-associated tumors = 125% of initial value within the blinded phase of the study		730 days
Secondary	Total volume of TSC-associated tumors within the blinded phase and the whole study		730 days
Secondary	The risk for high risk of autism assessed with psychological test at 6, 12, 18, 24 months		6, 12, 18, 24 months
Secondary	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
Secondary	The risk of drug-resistant epilepsy at any point of the study		730 days
Secondary	Occurrence of adverse events within the blinded phase of the study		730 days
Secondary	Number of adverse events across the whole study		730 days
Secondary	Parameters of physical development (weight gain history) across the whole study		730 days
Secondary	Parameters of physical development (height gain history) across the whole study		730 days