Clinical trial • Phase III • Neurology | Cardiology | Rare Disease

Methylprednisolone (methylprednisolone hydrogen succinate / hemisuccinate / sodium succinate depending on product) for Focal cerebral arteriopathy | Ischemic stroke (childhood)

Phase III trial of Methylprednisolone (methylprednisolone hydrogen succinate / hemisuccinate / sodium succinate depending on product) for Focal cerebral a…

Overview

Trial Therapeutic Area
Neurology | Cardiology | Rare Disease
Trial Disease
Focal cerebral arteriopathy | Ischemic stroke (childhood)
Trial Stage
Phase III
Drug Modality
Small molecule
Paediatric Trial
Yes

Key dates

Initial CTIS Submission Date
10-05-2024
First CTIS Authorization Date
05-07-2024

Trial design

Randomised, open-label, control arm: standard of care (including antithrombotic therapy). before inclusion antithrombotic therapy may be: aspirin 3-5 mg/kg/day (max 150 mg/day) or intravenous unfractioned heparin (ufh, dose adjusted per institutional protocols) or intravenous/subcutaneous low molecular weight heparin (lmwh, dose adjusted per institutional protocols). after inclusion antithrombotic therapy: aspirin 3-5 mg/kg/day (max 150 mg/day); ufh/lmwh must be changed to oral aspirin. experimental arm: high-dose steroid regimen in addition to standard of care — 3 days iv methylprednisolone 30 mg/kg bw/day (max. 1000 mg/dose) once daily, immediately followed by oral prednisolone 1 mg/kg/day (max 40 mg/day) for 2 weeks, then oral prednisolone 0.5 mg/kg/day (max 20 mg/day) for 2 weeks. Phase III trial in Austria, France, Germany and others.

Randomised
Yes
Open Label
Yes
Comparator
Control arm: Standard of care (including antithrombotic therapy). Before inclusion antithrombotic therapy may be: aspirin 3-5 mg/kg/day (max 150 mg/day) OR intravenous unfractioned heparin (UFH, dose adjusted per institutional protocols) OR intravenous/subcutaneous low molecular weight heparin (LMWH, dose adjusted per institutional protocols). After inclusion antithrombotic therapy: aspirin 3-5 mg/kg/day (max 150 mg/day); UFH/LMWH must be changed to oral aspirin. Experimental arm: High-dose steroid regimen in addition to standard of care — 3 days IV methylprednisolone 30 mg/kg BW/day (max. 1000 mg/dose) once daily, immediately followed by oral prednisolone 1 mg/kg/day (max 40 mg/day) for 2 weeks, then oral prednisolone 0.5 mg/kg/day (max 20 mg/day) for 2 weeks.
Target Sample Size
35
Trial Duration For Participant
365

Stratification factors

  • Age stratification: 6 months to 5 years; 6 years to 11 years; 12 years to 17 years
  • pedNIH stratification: < 7; 7 to 12; > 12

Eligibility

Recruits 35 paediatric patients.

Pregnancy Exclusion
Unless otherwise defined in the national addendum: Female participants age ≥ 13: Negative pregnancy test (blood or urine)
Vulnerable Population
The trial enrols children (age > 6 months and < 18 years). Informed consent must be provided by the legal representative of the trial participant and documented by signature. Age-specific information and consent/assent documents are prepared (multiple subject information and informed consent form documents for children, teens and parents across participating countries are listed in the documentation).

Inclusion criteria

  • {"criterion_text":"- Informed consent of the legal representative of the trial participant documented by signature\n- Age > 6 months & < 18 years at time of stroke\n- Randomisation possible within 48 hours of diagnosis and maximum 96 hours after stroke onset\n- Unilateral arteriopathy according to the following criteria: •\tNewly acquired neurologic deficits •\tSpecific neuroimaging (MRA) features of either -\tunilateral stenosis, or -\tunilateral vessel irregularities within the CNS\n- Unless otherwise defined in the national addendum: Female participants age ≥ 13: Negative pregnancy test (blood or urine)"}

Exclusion criteria

  • {"criterion_text":"- Previous stroke\n- Progressive large to medium childhood primary angiitis of the CNS (cPACNS ) with 2 of the following 3 criteria: a.\tpre-existing progressive neurocognitive dysfunction b.\tbilateral MRI lesions/vessel involvement c.\tsmall vessel arterial stenosis\n- On steroid treatment at disease onset\n- Contraindication to steroid treatment as e.g. a congenital or acquired immunodeficiency\n- Inability to follow the procedures of the study, e.g. due to language problems\n- Participation in another interventional study within the 30 days preceding the indication stroke and during the present study\n- Known syndromal disorders, as e.g. Trisomy 21, Neurofibromatosis type 1\n- Known genetic vasculopathies as e.g. PHACES syndrome, ACTA II\n- Moyamoya or sickle cell disease\n- Small vessel cerebral vasculitis (primary CNS vasculitis)\n- Bilateral arteriopathy\n- Arterial dissection(s)\n- Evidence of underlying systemic disorders, as e.g. lupus, rheumatoid problems\n- Secondary CNS angiitis due to infections (meningitis, endocarditis, borreliosis), or generalised angiitis due to rheumatic or other autoimmune problems"}

Endpoints

Primary endpoints

  • {"endpoint_text":"- The primary outcome is change in FCA Severity Score (FCASS) from baseline to 1 month","definition_or_measurement_approach":"Change in FCA Severity Score (FCASS) measured from baseline to 1 month (assessment by blinded central neuroradiologists reading MR imaging)."}

Secondary endpoints

  • {"endpoint_text":"- Neurological deficits over time as determined by PSOM, RRQ, modified Rankin scale (mRS) and Vineland Adaptive Behaviour Scale (VABS) at 6 and 12 months","definition_or_measurement_approach":"Neurological deficits measured using Paediatric Stroke Outcome Measure (PSOM), Recurrence and Recovery Questionnaire (RRQ), modified Rankin Scale (mRS) and Vineland Adaptive Behaviour Scale (VABS) at 6 and 12 months; assessments are blinded and performed centrally (telephone interviews where applicable)."}
  • {"endpoint_text":"- Neurocognitive outcome at 12 months","definition_or_measurement_approach":"Neurocognitive outcomes assessed at 12 months (specific neurocognitive instruments not detailed in the CTIS summary)."}
  • {"endpoint_text":"- Recurrence-free survival","definition_or_measurement_approach":"Time to stroke recurrence (recurrence-free survival)."}
  • {"endpoint_text":"- Change in FCASS at (3) and 6 months","definition_or_measurement_approach":"Change in FCASS measured at 3 months and 6 months compared to baseline."}
  • {"endpoint_text":"- Residual vasculopathy at 6 months","definition_or_measurement_approach":"Assessment of residual vasculopathy at 6 months (imaging-based evaluation)."}

Recruitment

Planned Sample Size
35
Recruitment Window Months
49
Consent Approach
Consent is obtained from the legal representative of the child and must be documented by signature. Age-specific information and consent/assent forms are prepared for different pediatric age groups (multiple ICF documents and country-specific ICFs listed for Denmark, Sweden, Germany, Austria, France). Outcome assessments (RRQ, mRS, VABS) will be performed centrally and blinded, including telephone interviews with participants, parents and/or legal representatives where applicable.

Geography

Total Number Of Sites
16
Total Number Of Participants
45

Austria

Earliest CTIS Part Ii Submission Date
29-05-2024
Latest Decision Or Authorization Date
07-07-2025
Processing Time Days
404
Number Of Sites
3
Number Of Participants
5

Sites

Site Name
Universitaet Wien
Department Name
Universitätsklinik für Kinder und Jugendheilkunde
Contact Person Name
Rainer Seidl
Contact Person Email
rainer.seidl@meduniwien.ac.at
Number Of Participants
5
Site Name
Johannes Kepler University Linz
Department Name
Universitätsklinik für Kinder und Jugendheilkunde
Contact Person Name
Ariane Biebl
Site Name
Tirol Kliniken GmbH
Department Name
Neuropediatric fellow at the Department of Pediatrics, Medical University Innsbruck, Austria
Contact Person Name
Christian Lechner
Contact Person Email
ch.lechner@i-med.ac.at

France

Earliest CTIS Part Ii Submission Date
26-06-2024
Latest Decision Or Authorization Date
14-11-2025
Processing Time Days
506
Number Of Sites
6
Number Of Participants
15

Sites

Site Name
CEREDIH Groupe Hospitalier Necker-Enfants Malades
Department Name
French Centre for Paediatric Stroke
Contact Person Name
Manoëlle Kossorotoff
Contact Person Email
manoelle.kossorotoff@aphp.fr
Site Name
Centre Hospitalier Regional De Marseille
Department Name
Service de Neurologie Pédiatrique, CHU, Timone-Enfants
Contact Person Name
Beatrice Desnous
Contact Person Email
beatrice.desnous@ap-hm.fr
Site Name
Bicetre Hospital
Department Name
Department of Neurology
Contact Person Name
Kumaran Deiva
Contact Person Email
kumaran.deiva@aphp.fr
Site Name
Hopital de Hautepierre Strasbourg
Department Name
Pediatric Neurology
Contact Person Name
Vincent Laugel
Site Name
Hospital Femme Mere Enfant
Department Name
Department of Pediatric Neurology
Contact Person Name
Maryline Carneiro
Contact Person Email
maryline.carneiro@chu-lyon.fr
Site Name
Hôpital Roger Salengro, CHRU de Lille
Department Name
Neurologie pédiatrique
Contact Person Name
Sylvie Joriot
Contact Person Email
Sylvie.JORIOT@chu-lille.fr
Number Of Participants
15

Germany

Earliest CTIS Part Ii Submission Date
29-05-2024
Latest Decision Or Authorization Date
15-05-2025
Processing Time Days
351
Number Of Sites
5
Number Of Participants
15

Sites

Site Name
Universitätsklinikum Freiburg
Department Name
Zentrum für Kinder- und Jugendmedizin Klinik für Neuropädiatrie und Muskelerkrankungen
Contact Person Name
Matthias Eckenweiler
Site Name
Medizinische Hochschule Hannover
Department Name
Klinik für pädiatrische Nieren-, Leber- und Stoffwechselerkrankungen und Neuropädiatrie
Contact Person Name
Christian Menke
Contact Person Email
Menke.Christian@mh-hannover.de
Site Name
Universitaetsklinikum Muenster AöR
Department Name
Klinik für Kinder- und Jugendmedizin, Neuropädiatrie
Contact Person Name
Timo Deba
Contact Person Email
timo.deba@ukmuenster.de
Site Name
Ludwig Maximilian University Of Munich
Department Name
Kinderklinik und Kinderpoliklinik im Dr. von Haunerschen Kinderspital
Contact Person Name
Lucia Gerstl
Site Name
Charite Universitaetsmedizin Berlin KöR
Department Name
Klinik für Pädiatrie m.S. Neurologie und Sozialpädiatrisches Zentrum
Contact Person Name
Ellen Knierim
Contact Person Email
ellen.knierim@charite.de
Number Of Participants
15

Denmark

Earliest CTIS Part Ii Submission Date
23-05-2025
Latest Decision Or Authorization Date
03-06-2025
Processing Time Days
11
Number Of Sites
1
Number Of Participants
5

Sites

Site Name
Rigshospitalet
Department Name
Afdelingen for Børn og Unge
Contact Person Name
Malene Landbo Børresen
Number Of Participants
5

Sweden

Earliest CTIS Part Ii Submission Date
09-05-2025
Latest Decision Or Authorization Date
26-05-2025
Processing Time Days
17
Number Of Sites
1
Number Of Participants
5

Sites

Site Name
Karolinska University Hospital
Department Name
Neuropediatriken Astrid Lindgrens barnsjukhus
Contact Person Name
Helena Marell Hesla
Number Of Participants
5

Sponsor

Primary sponsor

Full Name
Insel Gruppe AG
Organisation Type
Hospital/Clinic/Other health care facility
Country Of Registered Address
Switzerland

Third parties

  • {"country":"","full_name":"Swiss National Science Fondation (Schweizerischer Nationalfonds)","duties_or_roles":"Monetary support / source of funding","organisation_type":""}

Investigational products

Investigational Product Name
Methylprednisolone (IV)
Active Substance
Methylprednisolone (methylprednisolone hydrogen succinate / hemisuccinate / sodium succinate depending on product)
Modality
Small molecule
Routes Of Administration
Intravenous
Route
Intravenous
Authorisation Status
Authorised (marketing authorisation exists for listed methylprednisolone products)
Starting Dose
30 mg/kg BW/day (max. 1000 mg/dose) for 3 days IV
Dose Levels
30 mg/kg/day (single IV dose each day for 3 days); maximum 1000 mg/dose
Frequency
Once daily for 3 days
Maximum Dose
1000 mg per dose
Investigational Product Name
Prednisolone (oral)
Active Substance
Prednisolone
Modality
Small molecule
Routes Of Administration
Oral
Route
Oral
Authorisation Status
Authorised (marketing authorisation exists for listed prednisolone products)
Starting Dose
1 mg/kg/day (max 40 mg/day) for 2 weeks, then 0.5 mg/kg/day (max 20 mg/day) for 2 weeks
Dose Levels
1 mg/kg/day (weeks 1-2) then 0.5 mg/kg/day (weeks 3-4); max 40 mg then max 20 mg
Frequency
Daily (oral) according to schedule
Maximum Dose
40 mg/day (weeks 1-2), 20 mg/day (weeks 3-4)
Combination Treatment
Yes

Related trials

Other published trials that may interest you.