Comparison of the efficacy and safety of rapamycin versus vigabatrin in the prevention of Tuberous Sclerosis Complex symptoms in infants in the randomized clinical trial

2024-513068-25-00 Protocol ViRap Phase II and Phase III (Integrated) Ongoing, recruiting

Start 20 May 2021 · Status Ongoing, recruiting · 1 EU/EEA countries · 2 sites · Protocol ViRap

Overview

Sponsor-declared trial summary

Phase Phase II and Phase III (Integrated)
Status Ongoing, recruiting
Participants planned 60
Countries 1
Sites 2

Tuberous Sclerosis Complex, Epilepsy, Tumors associated with Tuberous Sclerosis Complex

The objective of the ViRap study is to investigate safety and efficacy of rapamycin versus vigabatrin in the preventive treatment of infants with TSC.

Key facts

Sponsor
Instytut Pomnik Centrum Zdrowia Dziecka
Participant type
Pediatric, Patients
Age range
0-17 years
Gender
Male and Female
Therapeutic area
Diseases [C] - Nervous System Diseases [C10]
Trial duration
20 May 2021 → ongoing
Decision date (initial)
2024-12-18
Transition trial
Yes
Low-intervention
No
Rare-disease indication
Yes
Vulnerable population
Yes
Funding sources
Medical Reserach Agency

External identifiers

EU CT number
2024-513068-25-00
EudraCT number
2020-003231-19
ClinicalTrials.gov
NCT04987463

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Efficacy, Safety, Others, Therapy

The objective of the ViRap study is to investigate safety and efficacy of
rapamycin versus vigabatrin in the preventive treatment of infants with
TSC.

Secondary objectives 1

  1. The secondary objective of the Virap study is to compare the safety profile of vigabatrin and rapamycin in infants with TSC and thecomparison of severity of epilepsy and its neuropsychiatric comorbidities, as well as changes in the size of TSC-associated tumors in patients receiving rapamycin and vigabatrin. Additionally, the impact of treatment on the quality of life of patients receiving rapamycin or vigabatrin will be compared.

Conditions and MedDRA coding

Tuberous Sclerosis Complex, Epilepsy, Tumors associated with Tuberous Sclerosis Complex

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

  1. Male or female aged up to 16 weeks (41-56 weeks of gestational age) at the day of randomization
  2. Parents/caregivers are willing to and able to give informed consent form for the participation in the study
  3. Parents/caregivers are willing to and able to comply with all study requirements
  4. Definite diagnosis of TSC according to the Consensus criteria (Northrup,2013)
  5. At least 1 focus of cortical dysplasia disclosed on brain MRI

Exclusion criteria 13

  1. history of seizures prior to randomization
  2. history of antiepileptic treatment
  3. history of treatment with mTOR inhibitor
  4. gestational age below 41 weeks at the day of randomization
  5. body weight lower than 3 kg at the day of randomization
  6. SEGA or other TSC- associated lesion requiring urgent surgical intervention
  7. recent surgery within 1 month prior to the randomization
  8. intercurrent infection at the date of randomization
  9. known history of HIV seropositivity
  10. live vaccination within 4 weeks prior to randomization
  11. lack of first hepatitis B vaccination
  12. 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.
  13. Use of an investigational drug within 1 month prior to randomization

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

  1. occurrence of clinical seizures in the blinded phase of the study
  2. increase in summarized volume of TSC-associated tumors ≥ 25% of initial value within the blinded phase of the study.

Secondary endpoints 9

  1. time from birth to onset of first clinical epileptic seizure
  2. total volume of TSC-associated tumors within the blinded phase and the whole study
  3. the risk for high risk of autism assessed with psychological test (ADOS) at the end of the study
  4. the risk for low developmental quotient (< 70 points in Bayley Scales of Infant Development,) at the end of the study,
  5. the risk of drug-resistant epilepsy at any point of the study
  6. occurrence of adverse events within the blinded phase of the study,
  7. number of adverse events across the whole study
  8. parameters of physical development (weight and height gain history) across the whole study.
  9. Parameters of vital signs (body temperature, pulse rate, respiraton rate and blood pressure)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Rapamune 1 mg/mL oral solution

PRD505741 · Product

Active substance
Sirolimus
Substance synonyms
SEL-110.36, RAPAMYCIN, NPG-12G, (3S,6R,7E,9R,10R,12R,14S,15E,17E,19E,21S,23S,26R,27R,34aS)-9,10,12,13,14,21,22,23,24,25,26,27,32,33,34,34a-Hexadecahydro-9,27-dihydroxy-3-[(1R)-2-[(1S,3R,4R)-4-hydroxy-3-methoxycyclohexyl]-1-methylethyl]-10,21-dimethoxy-6,8,12,14,20,26-hexamethyl-23,27-epoxy-3H-pyrido[2,1-c][1,4]oxaazacyclohentriacontine-1,5,11,28,29(4H,6H,31H)-pentone
Pharmaceutical form
ORAL SOLUTION
Route of administration
ORAL
Max daily dose
40 mg milligram(s)
Max total dose
0.7 mg/kg milligram(s)/kilogram
Max treatment duration
730 Day(s)
Authorisation status
Authorised
ATC code
L04AH01 — -
Marketing authorisation
EU/1/01/171/001
MA holder
PFIZER EUROPE MA EEIG
MA country
EU
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
Yes
Modification description
product will be overflowed to the pharmacy bottles in validated aseptic conditions

Comparator 1

SABRIL, 500 mg, granulat do sporządzania roztworu doustnego

PRD435615 · Product

Active substance
Vigabatrin
Pharmaceutical form
ORAL SOLUTION
Route of administration
ORAL
Max daily dose
3 g gram(s)
Max total dose
150 mg/kg milligram(s)/kilogram
Max treatment duration
730 Day(s)
Authorisation status
Authorised
ATC code
N03AG04 — VIGABATRIN
Marketing authorisation
8327
MA holder
SANOFI WINTHROP INDUSTRIE
MA country
Poland
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
Yes
Modification description
capsulated with addition of lactose as supplementary substance

Placebo 2

linseed oil

N/A · Product

Other product name
N/A
Pharmaceutical form
N/A
ATC code
N/A — N/A
Marketing authorisation
N/A
MA holder
N/A
MA country
Iceland
Paediatric formulation
No

lactose

N/A · Product

Other product name
N/A
Pharmaceutical form
N/A
ATC code
N/A — N/A
Marketing authorisation
N/A
MA holder
N/A
MA country
Iceland
Paediatric formulation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Instytut Pomnik Centrum Zdrowia Dziecka

8 Total trials 4 Recruiting 3 Ended
Academic / Non-commercial
Sponsor organisation
Instytut Pomnik Centrum Zdrowia Dziecka
Address
Aleja Dzieci Polskich 20
City
Warsaw
Postcode
04-730
Country
Poland

Scientific contact point

Organisation
Instytut Pomnik Centrum Zdrowia Dziecka
Contact name
Katarzyna Kotulska-Jóźwiak

Public contact point

Organisation
Instytut Pomnik Centrum Zdrowia Dziecka
Contact name
Magdalena Krawiec

Third parties 3

OrganisationCity, countryDuties
Instytut Pomnik Centrum Zdrowia Dziecka
ORG-100012689
 Warsaw, Poland Other
Uniwersytet Medyczny W Lodzi
ORG-100038568
 Lodz, Poland Other
Transition Technologies Science
ORL-000011639
 Warszawa, Poland Code 10, Data management

Locations

1 EU/EEA country · 2 investigational sites

By country

CountryMS statusPlanned subjectsSites
Poland Ongoing, recruiting 60 2
Rest of world — 0 —

Investigational sites

Poland

2 sites · Ongoing, recruiting
Institute Of Polish Mother's Health Center
Department of Developmental Neurology and Epileptology, Ul. Rzgowska 281/289, 93-338, Lodz
Instytut Pomnik Centrum Zdrowia Dziecka
Neurology and Epileptology Department, Aleja Dzieci Polskich 20, 04-730, Warsaw

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Country Trial startTrial end Recruitment startRecruitment end Early termination
Poland 2021-05-20 2021-05-20

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 9 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

TypeTitleVersion
Protocol (for publication) D1_Protocol_2024-513068-25-00_for publication_redacted 5
Recruitment arrangements (for publication) Placeholder_ViRap 1
Subject information and informed consent form (for publication) L1_SIS and ICF_blood biomarkers 3
Subject information and informed consent form (for publication) L1_SIS and ICF_cerebrospinal fluid 3
Subject information and informed consent form (for publication) L1_SIS and ICF_Data protection 3
Subject information and informed consent form (for publication) L1_SIS and ICF_Information clause 3
Subject information and informed consent form (for publication) L1_SIS and ICF_MRI 4
Subject information and informed consent form (for publication) L1_SIS and ICF_NGS 3
Subject information and informed consent form (for publication) L1_SIS and ICF_Parents 6

Application history

2 submissions — initial application plus substantial / non-substantial modifications

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2024-10-16 Poland Acceptable
2024-12-13
 2024-12-18
2 NON SUBSTANTIAL MODIFICATION NSM-2 2025-02-25 Poland Acceptable
2024-12-13
 2025-02-25

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