Stroke in childhood due to inflammatory narrowing of blood vessels: Treatment with steroids

2022-500631-36-00 Therapeutic confirmatory (Phase III) Authorised, recruitment pending

Status Authorised, recruitment pending · 5 EU/EEA countries · 17 sites

Overview

Sponsor-declared trial summary

Phase Therapeutic confirmatory (Phase III)
Status Authorised, recruitment pending
Participants planned 80
Countries 5
Sites 17

Focal cerebral arteriopathy and childhood stroke Focal cerebral arteriopathy (FCA) is an inflammatory vessel wall disease provoked by infection.

The purpose of this study is to evaluate if additional early anti-inflammatory treatment may influence the course of arteriopathy and improve clinical outcome and may prevent stroke recurrence in children with stroke and unilateral focal arteriopathy. The primary objective of this study is to determine if a high dose c…

Key facts

Sponsor
Insel Gruppe AG
Participant type
Pediatric, Patients
Age range
0-17 years
Gender
Male and Female
Therapeutic area
Diseases [C] - Cardiovascular Diseases [C14]
Decision date (initial)
2024-07-09
Transition trial
Yes
Low-intervention
No
Rare-disease indication
Yes
Vulnerable population
Yes
Funding sources
Swiss National Science Fondation (Schweizerischer Nationalfonds)

External identifiers

EU CT number
2022-500631-36-00
EudraCT number
2021-005571-39
ClinicalTrials.gov
NCT04873583

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy

The purpose of this study is to evaluate if additional early anti-inflammatory treatment may influence the course of arteriopathy and improve clinical outcome and may prevent stroke recurrence in children with stroke and unilateral focal arteriopathy.
The primary objective of this study is to determine if a high dose course of methylprednisolone/prednisolone in addition to standard of care including antithrombotic treatment results in better improvement of focal arteriopathy in children with acute ischemic stroke and focal arteriopathy compared to standard of care alone.

Secondary objectives 1

  1. The secondary objectives are to determine if a high dose course of methylprednisolone/prednisolone in addition to standard of care including antithrombotic treatment: • Improves functional clinical outcomes (measured by Recurrence and Recovery Questionnaire (RRQ), modified Rankin Scale (mRS), Paediatric Stroke Outcome measure (PSOM), and Vineland Adaptive Behaviour Scale (VABS)) The Recurrence and Recovery Questionnaire (RRQ) and the Paediatric Stroke Outcome measure (PSOM), although not identical, assess closely related aspects of recovery • Improves neurocognitive outcome • Reduces residual stenotic arteriopathy measured by FCASS (Focal Cerebral Arteriopathy Scaling System) • Decreases the final infarct volume measured by the modASPECTS (modified paediatric ASPECTS, Alberta stroke program early CT score) • Decreases recurrence risk of stroke

Conditions and MedDRA coding

Focal cerebral arteriopathy and childhood stroke Focal cerebral arteriopathy (FCA) is an inflammatory vessel wall disease provoked by infection.

VersionLevelCodeTermSystem organ class
20.0 LLT 10003209 Arteriopathy 10047065
22.1 LLT 10055221 Ischemic stroke 10029205

Study design 1 period

#TitleAllocationBlindingRoles blindedArms
1 Phase 3 prospective randomized controlled open label study
This study is a prospective multicentre, parallel group, two-arm, randomized controlled, open-label clinical trial with blinded outcome assessment, comparing a high dose course of methylprednisolone/ prednisolone plus standard of care with standard of care alone in children with unilateral arteriopathy and acute ischemic stroke. Randomization: Minimization is a dynamic randomization algorithm designed to minimize imbalance between treatments taking stratification factors into account and is a suitable randomisation method in studies with a small sample size. Randomization with minimization will be used to assign the patients into the two different study arms taking two stratification factors, age and pedNIH, into account. • Stratification groups, age: o 6 months to 5 years o 6 years to 11 years o 12 years to 17 years • Stratification groups, pedNIH: o < 7 o 7 to 12 o >12 Randomization is performed centrally using a computer system, which assures concealment of allocation.
 Randomised Controlled Single [{"id":145849,"code":4,"name":"Analyst"}] Control Intervention: Standard of Care: The control group will receive standard of care, as described in Appendix C (Acute management and standard of care). As antithrombotic therapy is an integral part of the standard of care, it is defined in more detail here: Before inclusion in the study, antithrombotic therapy is possible as follows: • Either aspirin, 3-5 mg/kg/day (max 150 mg/day, as appropriate) • Or intravenous unfractioned heparin (UFH, dose adjusted according to institutional protocols) • Or intravenous/subcutaneous Low Molecular Weight Heparin (LMWH, e.g. Clexane, dose adjusted according to institutional protocols) After inclusion in the study, antithrombotic therapy must be administered as follows: • Aspirin, 3-5 mg/kg/day (max 150 mg/day, as appropriate) • UFH and LMWH must be changed to oral aspirin
Experimental Intervention: Steroid Treatment and Standard of Care: The investigational treatment consists of • 3 days intravenous methylprednisolone at inclusion (i.e. starting on V2, day 0) Dose: 30 mg/kg BW/day (max. 1000 mg/dose) – one dose each day Immediately followed by • 2 weeks (week 1 and 2) oral prednisolone Dose: 1 mg/kg/day (max 40 mg/day) • 2 weeks (week 3 and 4) oral prednisolone Dose: 0.5 mg/kg/day (max 20 mg/day) The steroid dose regimen used in this study is standard for many immunotherapy treatment protocols in children 67, 68, and it is aligned with the planned FOCAS trial in Northern America 69. The duration of steroid treatment is determined by the disease course. In this study, unilateral arteriopathy is a monophasic non-relapsing disease and the target of the intervention is the early inflammatory phase. Therefore, a 31-day course has been chosen. All patients in the experimental arm will in addition receive standard of care, including antithrombotic treatment, as described in Appendix C, SOP Acute management and standard of care.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

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

Exclusion criteria 14

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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1. The primary outcome is change in FCA Severity Score (FCASS) from baseline to 1 month

Secondary endpoints 5

  1. Neurological deficits over time as determined by PSOM, RRQ, modified Rankin scale (mRS) and Vineland Adaptive Behaviour Scale (VABS) at 6 and 12 months
  2. Neurocognitive outcome at 12 months
  3. Recurrence-free survival
  4. Change in FCASS at (3) and 6 months
  5. Residual vasculopathy at 6 months

Investigational products

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

Test 19

SOLUPRED 5 mg, comprimé effervescent

PRD10488622 · Product

Active substance
Prednisolone Metasulfobenzoate Sodium
Pharmaceutical form
EFFERVESCENT TABLET
Route of administration
ORAL
Max daily dose
40 mg milligram(s)
Max total dose
840 mg milligram(s)
Max treatment duration
4 Week(s)
Authorisation status
Authorised
ATC code
H02AB06 — PREDNISOLONE
Marketing authorisation
34009 309 752 0 6
MA holder
CHEPLAPHARM ARZNEIMITTEL GMBH
MA country
France
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Prednisolon 5 mg JENAPHARM

PRD1752711 · Product

Active substance
Prednisolone
Pharmaceutical form
TABLET
Route of administration
ORAL
Max daily dose
40 mg milligram(s)
Max total dose
840 mg milligram(s)
Max treatment duration
4 Week(s)
Authorisation status
Authorised
ATC code
H02AB06 — PREDNISOLONE
Marketing authorisation
40631.01.00
MA holder
MIBE GMBH ARZNEIMITTEL
MA country
Germany
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Prednisolon 20 mg JENAPHARM

PRD1752710 · Product

Active substance
Prednisolone
Pharmaceutical form
TABLET
Route of administration
ORAL
Max daily dose
40 mg milligram(s)
Max total dose
840 mg milligram(s)
Max treatment duration
4 Week(s)
Authorisation status
Authorised
ATC code
H02AB — GLUCOCORTICOIDS
Marketing authorisation
40467.00.00
MA holder
MIBE GMBH ARZNEIMITTEL
MA country
Germany
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Prednisolon 1 mg JENAPHARM

PRD1752708 · Product

Active substance
Prednisolone
Pharmaceutical form
TABLET
Route of administration
ORAL
Max daily dose
40 mg milligram(s)
Max total dose
840 mg milligram(s)
Max treatment duration
4 Week(s)
Authorisation status
Authorised
ATC code
H02AB06 — PREDNISOLONE
Marketing authorisation
40631.00.00
MA holder
MIBE GMBH ARZNEIMITTEL
MA country
Germany
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Prednisolon 10 mg JENAPHARM

PRD1752709 · Product

Active substance
Prednisolone
Pharmaceutical form
TABLET
Route of administration
ORAL
Max daily dose
40 mg milligram(s)
Max total dose
840 mg milligram(s)
Max treatment duration
4 Week(s)
Authorisation status
Authorised
ATC code
H02AB06 — PREDNISOLONE
Marketing authorisation
55204.01.00
MA holder
MIBE GMBH ARZNEIMITTEL
MA country
Germany
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Aprednislon 25 mg Tabletten

PRD10276753 · Product

Active substance
Prednisolone
Pharmaceutical form
TABLET
Route of administration
ORAL
Max daily dose
40 mg milligram(s)
Max total dose
840 mg milligram(s)
Max treatment duration
4 Week(s)
Authorisation status
Authorised
ATC code
H02AB06 — PREDNISOLONE
Marketing authorisation
12.106
MA holder
MERCK GESELLSCHAFT MBH
MA country
Austria
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Prednisolon 50 mg JENAPHARM

PRD1752712 · Product

Active substance
Prednisolone
Pharmaceutical form
TABLET
Route of administration
ORAL
Max daily dose
40 mg milligram(s)
Max total dose
840 mg milligram(s)
Max treatment duration
4 Week(s)
Authorisation status
Authorised
ATC code
H02AB06 — PREDNISOLONE
Marketing authorisation
40467.01.00
MA holder
MIBE GMBH ARZNEIMITTEL
MA country
Germany
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Betamethasone Sodium Phosphate

SCP1158234 · ATC

Active substance
Betamethasone Sodium Phosphate
Substance synonyms
BETAMETHASONE DISODIUM PHOSPHATE
Route of administration
ORAL
Max daily dose
40 mg milligram(s)
Max total dose
840 mg milligram(s)
Max treatment duration
4 Week(s)
Authorisation status
Authorised
ATC code
H02AB06 — PREDNISOLONE
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Aprednislon 5 mg Tabletten

PRD10276681 · Product

Active substance
Prednisolone
Pharmaceutical form
TABLET
Route of administration
ORAL
Max daily dose
40 mg milligram(s)
Max total dose
840 mg milligram(s)
Max treatment duration
4 Week(s)
Authorisation status
Authorised
ATC code
H02AB06 — PREDNISOLONE
Marketing authorisation
11.258
MA holder
MERCK GESELLSCHAFT MBH
MA country
Austria
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Aprednislon 1 mg Tabletten

PRD10567874 · Product

Active substance
Prednisolone
Pharmaceutical form
TABLET
Route of administration
ORAL
Max daily dose
40 mg milligram(s)
Max total dose
840 mg milligram(s)
Max treatment duration
4 Week(s)
Authorisation status
Authorised
ATC code
H02AB06 — PREDNISOLONE
Marketing authorisation
1-24819
MA holder
MERCK GESELLSCHAFT MBH
MA country
Austria
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Lidocaine Hydrochloride Monohydrate

SCP101878658 · ATC

Active substance
Lidocaine Hydrochloride Monohydrate
Route of administration
INTRAVENOUS
Max daily dose
1000 mg milligram(s)
Max total dose
3000 mg milligram(s)
Max treatment duration
3 Day(s)
Authorisation status
Authorised
ATC code
H02AB04 — METHYLPREDNISOLONE
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Methylprednisolut 16 mg

PRD5290594 · Product

Active substance
Methylprednisolone Hydrogen Succinate
Pharmaceutical form
SOLUTION FOR INJECTION/INFUSION
Route of administration
INTRAVENOUS
Max daily dose
1000 mg milligram(s)
Max total dose
3000 mg milligram(s)
Max treatment duration
3 Day(s)
Authorisation status
Authorised
ATC code
H02AB04 — METHYLPREDNISOLONE
Marketing authorisation
94866.00.00
MA holder
MIBE GMBH ARZNEIMITTEL
MA country
Germany
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

SOLUMEDROL 500 mg, poudre pour solution injectable

PRD457223 · Product

Active substance
Methylprednisolone Hemisuccinate
Pharmaceutical form
SOLUTION FOR INJECTION
Route of administration
INTRAVENOUS
Max daily dose
1000 mg milligram(s)
Max total dose
3000 mg milligram(s)
Max treatment duration
3 Day(s)
Authorisation status
Authorised
ATC code
H02AB04 — METHYLPREDNISOLONE
Marketing authorisation
34009 386 777 4 4
MA holder
PFIZER HOLDING FRANCE
MA country
France
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Methylprednisolut 250 mg

PRD1753261 · Product

Active substance
Methylprednisolone Hydrogen Succinate
Pharmaceutical form
SOLUTION FOR INJECTION/INFUSION
Route of administration
INTRAVENOUS
Max daily dose
1000 mg milligram(s)
Max total dose
3000 mg milligram(s)
Max treatment duration
3 Day(s)
Authorisation status
Authorised
ATC code
H02AB04 — METHYLPREDNISOLONE
Marketing authorisation
81075.00.00
MA holder
MIBE GMBH ARZNEIMITTEL
MA country
Germany
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

SOLUMEDROL 500 mg, poudre pour solution injectable

PRD8721252 · Product

Active substance
Methylprednisolone Hemisuccinate
Pharmaceutical form
SOLUTION FOR INJECTION
Route of administration
INTRAVENOUS
Max daily dose
1000 mg milligram(s)
Max total dose
3000 mg milligram(s)
Max treatment duration
3 Day(s)
Authorisation status
Authorised
ATC code
H02AB04 — METHYLPREDNISOLONE
Marketing authorisation
34009 302 223 9 3
MA holder
PFIZER HOLDING FRANCE
MA country
France
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Methylprednisolut 32 mg

PRD5290595 · Product

Active substance
Methylprednisolone Hydrogen Succinate
Pharmaceutical form
SOLUTION FOR INJECTION/INFUSION
Route of administration
INTRAVENOUS
Max daily dose
1000 mg milligram(s)
Max total dose
3000 mg milligram(s)
Max treatment duration
3 Day(s)
Authorisation status
Authorised
ATC code
H02AB04 — METHYLPREDNISOLONE
Marketing authorisation
94867.00.00
MA holder
MIBE GMBH ARZNEIMITTEL
MA country
Germany
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Methylprednisolut 1000 mg

PRD1753260 · Product

Active substance
Methylprednisolone Hydrogen Succinate
Pharmaceutical form
SOLUTION FOR INJECTION/INFUSION
Route of administration
INTRAVENOUS
Max daily dose
1000 mg milligram(s)
Max total dose
3000 mg milligram(s)
Max treatment duration
3 Day(s)
Authorisation status
Authorised
ATC code
H02AB04 — METHYLPREDNISOLONE
Marketing authorisation
81076.00.00
MA holder
MIBE GMBH ARZNEIMITTEL
MA country
Germany
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Solu-Medrol® 1000 mg – Trockenstechampulle mit Lösungsmittel

PRD468045 · Product

Active substance
Methylprednisolone Sodium Succinate
Pharmaceutical form
SOLUTION FOR INJECTION/INFUSION
Route of administration
INTRAVENOUS
Max daily dose
1000 mg milligram(s)
Max total dose
3000 mg milligram(s)
Max treatment duration
3 Day(s)
Authorisation status
Authorised
ATC code
H02AB04 — METHYLPREDNISOLONE
Marketing authorisation
16.218
MA holder
PFIZER CORPORATION AUSTRIA GES.M.B.H.
MA country
Austria
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Solu-Medrol® 500 mg – Trockenstechampulle mit Lösungsmittel

PRD411368 · Product

Active substance
Methylprednisolone Sodium Succinate
Pharmaceutical form
SOLUTION FOR INJECTION/INFUSION
Route of administration
INTRAVENOUS
Max daily dose
1000 mg milligram(s)
Max total dose
3000 mg milligram(s)
Max treatment duration
3 Day(s)
Authorisation status
Authorised
ATC code
H02AB04 — METHYLPREDNISOLONE
Marketing authorisation
16.217
MA holder
PFIZER CORPORATION AUSTRIA GES.M.B.H.
MA country
Austria
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Insel Gruppe AG

5 Total trials 3 Recruiting 1 Ended
Academic / Non-commercial
Sponsor organisation
Insel Gruppe AG
Address
Freiburgstrasse 18
City
Bern
Postcode
3010
Country
Switzerland

Scientific contact point

Organisation
Insel Gruppe AG
Contact name
Prof.em.Dr.med Maja Steinlin

Public contact point

Organisation
Insel Gruppe AG
Contact name
Prof.em.Dr.med Maja Steinlin

Locations

5 EU/EEA countries · 17 investigational sites

By country

CountryMS statusPlanned subjectsSites
Austria Authorised, recruitment pending 5 3
Denmark Authorised, recruitment pending 5 1
France Authorised, recruitment pending 15 6
Germany Authorised, recruitment pending 15 6
Sweden Authorised, recruitment pending 5 1
Rest of world
Australia, United Kingdom, Switzerland
 — 35 —

Investigational sites

Austria

3 sites · Authorised, recruitment pending
Universitaet Wien
Universitätsklinik für Kinder und Jugendheilkunde, Waehringer Guertel 18-20, Alsergrund, Vienna
Tirol Kliniken GmbH
Neuropediatric fellow at the Department of Pediatrics, Medical University Innsbruck, Austria, Anichstrasse 35, 6020, Innsbruck
Johannes Kepler University Linz
Universitätsklinik für Kinder- und Jugendheilkunde, Altenberger Strasse 69, 4040, Linz

Denmark

1 site · Authorised, recruitment pending
Rigshospitalet
Afdelingen for Børn og Unge, Blegdamsvej 9, 2100, Copenhagen Oe

France

6 sites · Authorised, recruitment pending
Centre Hospitalier Regional De Marseille
Service de Neurologie Pédiatrique, CHU, Timone-Enfants, 264 Rue Saint Pierre, 13005, Marseille
Hospital Femme Mere Enfant
Department of Pediatric Neurology, 52 Boulevard Pinel, 69500, Bron
Bicetre Hospital
Department of Neurology, 78 Rue Du General Leclerc, 94275, Le Kremlin Bicetre Cedex
Hopital de Hautepierre Strasbourg
Pediatric Neurology, Avenue Moliere, 67098, Strasbourg
CEREDIH Groupe Hospitalier Necker-Enfants Malades
French Centre for Paediatric Stroke, 149 Rue De Sevres, 75743, Paris Cedex 15
Hôpital Roger Salengro, CHRU de Lille
Neurologie pédiatrique, Rue Emilie Laine, 59037, Lille

Germany

6 sites · Authorised, recruitment pending
Universitaetsklinikum Duesseldorf AöR
Klinik für Allgemeine Pädiatrie, Neonatologie und Kinderkardiologie, Moorenstrasse 5, Bilk, Duesseldorf
Universitaetsklinikum Muenster AöR
Klinik für Kinder- und Jugendmedizin, Neuropädiatrie, Albert-Schweitzer-Campus 1, Sentrup, Muenster
Charite Universitaetsmedizin Berlin KöR
Klinik für Pädiatrie m.S. Neurologie und Sozialpädiatrisches Zentrum, Augustenburger Platz 1, Wedding, Berlin
Ludwig Maximilian University Of Munich
Kinderklinik und Kinderpoliklinik im Dr. von Haunerschen Kinderspital, Lindwurmstrasse 4, Ludwigsvorstadt-Isarvorstadt, Munich
Universitätsklinikum Freiburg
Zentrum für Kinder- und Jugendmedizin Klinik für Neuropädiatrie und Muskelerkrankungen, Mathildenstraße 1, 79106, Freiburg
Medizinische Hochschule Hannover
Klinik für pädiatrische Nieren-, Leber- und Stoffwechselerkrankungen und Neuropädiatrie, Carl-Neuberg-Strasse 1, Gross Buchholz, Hanover

Sweden

1 site · Authorised, recruitment pending
Karolinska University Hospital
Neuropediatriken Astrid Lindgrens barnsjukhus, Karolinska Vagen 37a, 171 64, Solna

Results and documents

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

Documents 59 files

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

TypeTitleVersion
Protocol (for publication) D1_Protocol 2022-500631-36 6
Protocol (for publication) D1_Protocol 2022-500631-36_Addendum AT 3
Protocol (for publication) D1_Protocol 2022-500631-36_Addendum DE 4.0
Protocol (for publication) D1_Protocol 2022-500631-36_Addendum FR 3.0
Protocol (for publication) D1_Protocol 2022-500631-36_Appendix A_Contact List 10
Protocol (for publication) D1_Protocol 2022-500631-36_Appendix B_List of Study Sites 2.1
Protocol (for publication) D1_Protocol 2022-500631-36_Appendix C_Standard of Care 3
Protocol (for publication) D1_Protocol 2022-500631-36_Appendix D_Risk Profile Investigation 3
Protocol (for publication) D1_Protocol 2022-500631-36_Appendix E_MRI Protocol 5
Protocol (for publication) D1_Protocol 2022-500631-36_Appendix F_Biomarker Satallite Study_Biobanking Sponsor Responsibilities 3.0.0
Protocol (for publication) D1_Protocol 2022-500631-36_Appendix F_Biomarker Satallite Study_Sample Handling 3.0.0
Protocol (for publication) D1_Protocol 2022-500631-36-00_TC 6
Recruitment arrangements (for publication) K1_Recruitment arrangements_PASTA_AT_en 1
Recruitment arrangements (for publication) K1_Recruitment arrangements_PASTA_DE_en 1
Recruitment arrangements (for publication) K1_Recruitment arrangements_PASTA_FR_en 1
Recruitment arrangements (for publication) Recruitment Arrangments and Informed Consent_Denmark 2
Recruitment arrangements (for publication) Recruitment Arrangments and Informed Consent_Denmark_tc 2
Recruitment arrangements (for publication) Recruitment Arrangments and Informed Consent_Sweden_SWE 1
Subject information and informed consent form (for publication) IC 15-17years 1
Subject information and informed consent form (for publication) IC Forldremyndighedsindehavere 1
Subject information and informed consent form (for publication) IC Habile personer 1
Subject information and informed consent form (for publication) L1_SIS and ICF_Adolescents_PASTA_FR_fr 3.0.1
Subject information and informed consent form (for publication) L1_SIS and ICF_Adults_PASTA_DE_de 2
Subject information and informed consent form (for publication) L1_SIS and ICF_Children 3 to 5 yrs_PASTA_FR_fr 2.0.1
Subject information and informed consent form (for publication) L1_SIS and ICF_Children 6 to 12 yrs_PASTA_FR_fr 2.0.1
Subject information and informed consent form (for publication) L1_SIS and ICF_Children_PASTA_AT_de 5
Subject information and informed consent form (for publication) L1_SIS and ICF_Children_PASTA_DE_de 1
Subject information and informed consent form (for publication) L1_SIS and ICF_Parents_PASTA_AT_de 5
Subject information and informed consent form (for publication) L1_SIS and ICF_Parents_PASTA_FR_fr 2.0.1
Subject information and informed consent form (for publication) L1_SIS and ICF_Youth_PASTA_AT_de 5
Subject information and informed consent form (for publication) L1_SIS and ICF_Youth_PASTA_DE_de 1
Subject information and informed consent form (for publication) PASTA_DE_Muenster_ICF_Eltern_V3_20240909_tc 1
Subject information and informed consent form (for publication) PASTA_DEN_COPE_ICF_Children 12-14_draft_22052025_clean 2
Subject information and informed consent form (for publication) PASTA_DEN_COPE_ICF_Children 12-14_draft_22052025_tc 2
Subject information and informed consent form (for publication) PASTA_DEN_COPE_ICF_Children 2-5_draft_22052025_clean 2
Subject information and informed consent form (for publication) PASTA_DEN_COPE_ICF_Children 2-5_draft_22052025_tc 2
Subject information and informed consent form (for publication) PASTA_DEN_COPE_ICF_Children 6-11_draft_22052025_tc 2
Subject information and informed consent form (for publication) PASTA_DEN_COPE_ICF_Children_draft_22052025_clean 2
Subject information and informed consent form (for publication) PASTA_DEN_COPE_ICF_Parents_draft_22052025_clean 2
Subject information and informed consent form (for publication) PASTA_DEN_COPE_ICF_Parents_draft_22052025_tc 2
Subject information and informed consent form (for publication) PASTA_DEN_COPE_ICF_Teens 15-17_draft_22052025_tc 2
Subject information and informed consent form (for publication) PASTA_DEN_COPE_ICF_Teens_draft_22052025_clean 2
Subject information and informed consent form (for publication) PASTA_SWE_COPE_ICF_Children_20250429_clean 1
Subject information and informed consent form (for publication) PASTA_SWE_COPE_ICF_Children_draft_12-14_20250429 1
Subject information and informed consent form (for publication) PASTA_SWE_COPE_ICF_Children_draft_20250429_tc 1
Subject information and informed consent form (for publication) PASTA_SWE_COPE_ICF_Parents_20250429_clean 1
Subject information and informed consent form (for publication) PASTA_SWE_COPE_ICF_Parents_draft_20250429_tc 1
Subject information and informed consent form (for publication) PASTA_SWE_COPE_ICF_Teens_20250429_clean 1
Subject information and informed consent form (for publication) PASTA_SWE_COPE_ICF_Teens_draft_20250429_tc 1
Subject information and informed consent form (for publication) Site overview 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC methylprednisolone_de 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC methylprednisolone_FR_fr 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC prednisolone_de 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC prednisolone_FR_fr 1
Synopsis of the protocol (for publication) D1_Protocol synopsis 2022-500631-36-00_de 2
Synopsis of the protocol (for publication) D1_Protocol synopsis 2022-500631-36-00_de_TC 2
Synopsis of the protocol (for publication) D1_Protocol synopsis 2022-500631-36-00_en 1
Synopsis of the protocol (for publication) D1_Protocol synopsis 2022-500631-36-00_FR_fr 3
Synopsis of the protocol (for publication) D1_Protocol synopsis 2022-500631-36-00_FR_fr_TC V3_TC

Application history

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

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2024-05-10 Austria Acceptable with conditions
2024-07-05
 2024-07-05
2 SUBSTANTIAL MODIFICATION SM-1 2024-09-24 Austria Acceptable
2025-01-15
 2025-01-17
3 SUBSEQUENT ADDITION OF MSC APP-3 2025-03-14 2025-06-03
4 SUBSEQUENT ADDITION OF MSC APP-4 2025-03-14 2025-05-26
5 SUBSTANTIAL MODIFICATION SM-5 2025-04-11 Acceptable 2025-05-15
6 SUBSTANTIAL MODIFICATION SM-6 2025-05-04 Austria Acceptable 2025-07-07
7 SUBSTANTIAL MODIFICATION SM-7 2025-09-16 Acceptable 2025-11-14