Overview
Sponsor-declared trial summary
Phase
Therapeutic confirmatory (Phase III)
Status
Ongoing, recruiting
Participants planned
91
Countries
6
Sites
23
Moderately to severely active Crohn's disease (CD)
To evaluate the efficacy of 2 different dose regimens of vedolizumab IV in pediatric subjects with moderately to severely active CD during maintenance therapy, based on clinical and endoscopic assessments at Week 54.
Key facts
- Sponsor
- Takeda Development Center Americas Inc.
- Participant type
- Pediatric, Patients
- Age range
- 0-17 years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Digestive System Diseases [C06]
- Trial duration
- 28 Feb 2022 → ongoing
- Decision date (initial)
- 2024-08-21
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- Yes
- Funding sources
- Takeda Development Center Americas, Inc.
External identifiers
- EU CT number
- 2023-509045-13-00
- EudraCT number
- 2020-004301-31
- ClinicalTrials.gov
- NCT04779320
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Efficacy, Others, Safety
To evaluate the efficacy of 2 different dose regimens of vedolizumab IV
in pediatric subjects with moderately to severely active CD during
maintenance therapy, based on clinical and endoscopic assessments at
Week 54.
Secondary objectives 11
- To evaluate the efficacy of high and low doses of vedolizumab IV as measured by clinical and endoscopic remission at W14 and W54
- To evaluate the efficacy of high and low doses of vedolizumab IV as measured by sustained clinical and endoscopic remission at W54
- To evaluate the efficacy of high and low doses of vedolizumab IV as measured by sustained clinical response at W54
- To evaluate the efficacy of high and low doses of vedolizumab IV as measured by sustained endoscopic remission at W54
- To evaluate the efficacy of high and low doses of vedolizumab IV as measured by clinical remission at W54
- To evaluate the effect of high and low doses of vedolizumab IV on achieving corticosteroid-free remission at W54
- To evaluate the effect of high and low doses of vedolizumab IV on clinical response and clinical remission over time up to W54
- To evaluate vedolizumab PK in pediatric subjects with moderately to severely active CD after IV administration
- To evaluate safety in pediatric subjects on maintenance therapy up to W54
- To evaluate the immunogenicity of vedolizumab in pediatric subjects with moderately to severely active CD treated with vedolizumab IV
- To evaluate the effect of vedolizumab on patterns of growth and pubertal development in pediatric subjects with moderately to severely active CD during their participation in the study
Conditions and MedDRA coding
Moderately to severely active Crohn's disease (CD)
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 20.1 | LLT | 10058815 | Crohn's disease acute episode | 10017947 |
Study design 2 periods
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | 14-week, open–label induction period On Day 1 the PCDAI score should be verified and documented before
infusion. During the induction period, subjects ≥30 kg will receive open–label vedolizumab,
300 mg IV at Day 1, Week 2, and Week 6; subjects who weigh >15 to <30 kg will receive an
open–label dose of vedolizumab 200 mg IV at Day 1, Week 2, and Week 6; and subjects who
weigh 10 to 15 kg will receive an open–label dose of vedolizumab 150 mg IV at Day 1, Week 2,
and Week 6. These doses were determined using an established population PK model, developed using data from adult phase 3 studies and the pediatric phase 2 study (MLN0002-2003) for ≥30 kg and <30 kg cohort, to match the vedolizumab exposure seen in the adult populations during the induction phase. Approximately 120 subjects will be enrolled in the induction period with around three-fourths of subjects weighing ≥30 kg and around one-fourth of subjects weighing 10 to <30 kg at the time of enrollment into the study.
|
Not Applicable | None | "On Day 1 the PCDAI score should be verified and documented before infusion. During the induction p: subjects ≥30 kg will receive open–label vedolizumab 300 mg IV open–label induction period: subjects who weigh >15 to <30 kg will receive an open–label dose of vedolizumab 200 mg IV open–label induction period: subjects who weigh 10 to 15 kg will receive an open–label dose of vedolizumab 150 mg IV |
|
| 2 | 40-week, 2-dose arm, randomized, double-blind maintenance period Subjects will initiate blinded IV doses of vedolizumab once every 8 weeks (Q8W) as maintenance dose through Week 46. The maintenance doses for the 3 weight groups were chosen similar to the way induction doses were chosen. A population PK model was used to match the vedolizumab exposure seen in phase 3 studies for the adult population during the maintenance phase. The high and low doses were selected to maximize the dose difference between the two arms while maintaining the exposure within the adult population range. Based on the chosen induction dose, a high and low maintenance dose of 300 mg and 150 mg was chosen for ≥30 kg weight group, 200 mg and 100 mg was chosen for >15 to <30 kg weight group, and 150 mg and 100 mg was chosen for the 10 to 15 kg weight group. A 150 mg high maintenance dose in the 10 to 15 kg weight group was predicted to result in an exposure closer to, but not exceeding, the upper limit of the adult exposure in the maintenance phase. Similarly, a 100 mg low maintenance dose was predicted to result in an exposure closer to, but not below, the lower limit of adult exposure in the maintenance phase. A 100 mg low maintenance dose was predicted to result in similar and consistent exposure among the entire <30 kg weight groups. A dose of 75 mg was considered for the low maintenance dose in the 10 to 15 kg weight cohort; however, this would have resulted in an exposure less than adult phase 3 exposure.
|
Randomised Controlled | Double | [{"id":140572,"code":3,"name":"Monitor"},{"id":140568,"code":4,"name":"Analyst"},{"id":140571,"code":2,"name":"Investigator"},{"id":140570,"code":1,"name":"Subject"},{"id":140569,"code":5,"name":"Carer"}] | High dose: Based on the chosen induction dose, a high maintenance dose of 300 mg was chosen for ≥ 30 kg weight group, 200 mg was chosen for the >15 to <30 kg weight group, and 150 mg was chosen for the 10 to 15 kg weight group. Low dose: Based on the chosen induction dose, a low maintenance dose of 150 mg was chosen for ≥ 30 kg weight group, 100 mg was chosen for the >15 to <30 kg weight group, and 100 mg was chosen for the 10 to 15 kg weight group. |
Regulatory references
- EMA paediatric investigation plan (PIP)
- EMEA-000645-PIP01-09
- Plan to share IPD
- Yes
- IPD plan description
- Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
| EU CT number | Title | Sponsor |
|---|---|---|
| 2023-509018-12-00 | A Randomized, Double-Blind, Phase 3 Study to Evaluate the Efficacy and Safety of Vedolizumab Intravenous as Maintenance Therapy in Pediatric Subjects with Moderately to Severely Active Ulcerative Colitis Who Achieved Clinical Response Following Open-Label Vedolizumab Intravenous Therapy | Takeda Development Center Americas Inc. |
| 2020-004300-34 | A Randomized, Double-Blind, Phase 3 Study to Evaluate the Efficacy and Safety of Vedolizumab Intravenous as Maintenance Therapy in Pediatric Subjects with Moderately to Severely Active Ulcerative Colitis Who Achieved Clinical Response Following Open–Label Vedolizumab Intravenous Therapy, Randomizované, dvojitě zaslepené klinické hodnocení fáze 3 k posouzení účinnosti a bezpečnosti vedolizumabu podávaného nitrožilně jako udržovací léčba u pediatrických pacientů se středně až závažně aktivní ulcerózní kolitidou, kteří dosáhli klinické odpovědi po otevřené nitrožilní léčbě vedolizumabem, Randomizované, dvojitě zaslepené klinické hodnocení fáze 3 k posouzení účinnosti a bezpečnosti vedolizumabu podávaného nitrožilně jako udržovací léčba u pediatrických pacientů se středně až závažně aktivní ulcerózní kolitidou, kteří dosáhli klinické odpovědi po otevřené nitrožilní léčbě vedolizumabem, Randomizované, dvojitě zaslepené klinické hodnocení fáze 3 k posouzení účinnosti a bezpečnosti vedolizumabu podávaného nitrožilně jako udržovací léčba u pediatrických pacientů se středně až závažně aktivní ulcerózní kolitidou, kteří dosáhli klinické odpovědi po otevřené nitrožilní léčbě vedolizumabem, Randomizované, dvojito zaslepené klinické skúšanie vo fáze 3 na hodnotenie účinnosti a bezpečnosti intravenózne podávaného vedolizumabu ako udržiavacej liečby u pediatrických pacientov so stredne ťažkou až ťažkou formou aktívnej ulceróznej kolitídy, ktorí dosiahli klinickú odpoveď po nezaslepenej intravenóznej liečbe vedolizumabom, Randomizované, dvojito zaslepené klinické skúšanie vo fáze 3 na hodnotenie účinnosti a bezpečnosti intravenózne podávaného vedolizumabu ako udržiavacej liečby u pediatrických pacientov so stredne ťažkou až ťažkou formou aktívnej ulceróznej kolitídy, ktorí dosiahli klinickú odpoveď po nezaslepenej intravenóznej liečbe vedolizumabom, Randomizované, dvojito zaslepené klinické skúšanie vo fáze 3 na hodnotenie účinnosti a bezpečnosti intravenózne podávaného vedolizumabu ako udržiavacej liečby u pediatrických pacientov so stredne ťažkou až ťažkou formou aktívnej ulceróznej kolitídy, ktorí dosiahli klinickú odpoveď po nezaslepenej intravenóznej liečbe vedolizumabom, Randomizované, dvojito zaslepené klinické skúšanie vo fáze 3 na hodnotenie účinnosti a bezpečnosti intravenózne podávaného vedolizumabu ako udržiavacej liečby u pediatrických pacientov so stredne ťažkou až ťažkou formou aktívnej ulceróznej kolitídy, ktorí dosiahli klinickú odpoveď po nezaslepenej intravenóznej liečbe vedolizumabom, Randomizované, dvojito zaslepené klinické skúšanie vo fáze 3 na hodnotenie účinnosti a bezpečnosti intravenózne podávaného vedolizumabu ako udržiavacej liečby u pediatrických pacientov so stredne ťažkou až ťažkou formou aktívnej ulceróznej kolitídy, ktorí dosiahli klinickú odpoveď po nezaslepenej intravenóznej liečbe vedolizumabom, Studio di fase 3 randomizzato, in doppio cieco volto a valutare l’efficacia e la sicurezza di vedolizumab per via endovenosa come terapia di mantenimento in soggetti pediatrici con colite ulcerosa da moderatamente a gravemente attiva che hanno ottenuto una risposta clinica dopo una terapia endovenosa in aperto con vedolizumab, Estudio de fase III, aleatorizado y doble ciego para evaluar la eficacia y la seguridad de vedolizumab intravenoso como tratamiento de mantenimiento en pacientes pediátricos con colitis ulcerosa activa moderada a grave que lograron una respuesta clínica después del tratamiento intravenoso abierto con vedolizumab | |
| 2021-000630-34 | A Phase 3b Extension Study to Evaluate the Long-term Safety of Vedolizumab Intravenous in Pediatric Patients With Ulcerative Colitis or Crohn’s Disease, Prodloužené klinické hodnocení fáze 3b k posouzení dlouhodobé bezpečnosti přípravku vedolizumab podávaného nitrožilně u pediatrických pacientů s ulcerózní kolitidou nebo Crohnovou chorobou., Prodloužené klinické hodnocení fáze 3b k posouzení dlouhodobé bezpečnosti přípravku vedolizumab podávaného nitrožilně u pediatrických pacientů s ulcerózní kolitidou nebo Crohnovou chorobou., Estudio de extensión de fase 3b para evaluar la seguridad a largo plazo de vedolizumab intravenoso en pacientes pediátricos con colitis ulcerosa o enfermedad de Crohn, Predĺženie klinického skúšania fázy 3b s cieľom posúdiť dlhodobú bezpečnosť intravenózne podávaného vedolizumabu u pediatrických pacientov s ulceróznou kolitídou alebo Crohnovou chorobou, Predĺženie klinického skúšania fázy 3b s cieľom posúdiť dlhodobú bezpečnosť intravenózne podávaného vedolizumabu u pediatrických pacientov s ulceróznou kolitídou alebo Crohnovou chorobou, Predĺženie klinického skúšania fázy 3b s cieľom posúdiť dlhodobú bezpečnosť intravenózne podávaného vedolizumabu u pediatrických pacientov s ulceróznou kolitídou alebo Crohnovou chorobou, Produžetak ispitivanja faze 3b za procjenu dugoročne sigurnosti vedolizumaba za intravensku primjenu u pedijatrijskih ispitanika s ulceroznim kolitisom ili Crohnovom bolešću, Studio di estensione di fase 3b volto a valutare la sicurezza a lungo termine di vedolizumab per via endovenosa in pazienti pediatrici affetti da colite ulcerosa o malattia di Crohn | |
| 2023-509046-36-00 | A Phase 3b Extension Study to Evaluate the Long-term Safety of Vedolizumab Intravenous in Pediatric Patients With Ulcerative Colitis or Crohn's Disease | Takeda Development Center Americas Inc. |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 5
- Subjects aged 2 to 17 years, inclusive, who weigh ≥10 kg at the time of screening and enrollment into the maintenance phase of the study.
- Subjects with CD diagnosed at least 1 month before screening. Subjects with moderately to severely active CD defined by a PCDAI >30 and an SES-CD >6 (or an SES-CD ≥4 if disease is confined to terminal ileum) at screening endoscopy.
- Subjects who have failed, lost response to, or been intolerant to treatment with at least 1 of the following agents: corticosteroids, immunomodulators (eg, AZA, 6-mercaptopurine, methotrexate), and/or TNF-α antagonist therapy (eg, infliximab, adalimumab). This includes subjects who are dependent on corticosteroids or exclusive or partial enteral nutrition to control symptoms and who are experiencing worsening of disease in the moderate-to-severe range when attempting to wean off corticosteroids or discontinue exclusive enteral nutrition.
- Subjects with extensive colitis or pancolitis of >8 years' duration or left-sided colitis of >12 years' duration must have documented evidence of a negative surveillance colonoscopy within 12 months before screening.
- Subjects with vaccinations that are up-to-date based on the countrywide accepted schedule of childhood vaccines.
Exclusion criteria 10
- Subjects who have had previous exposure to approved or investigational anti-integrins, including but not limited to natalizumab, efalizumab, etrolizumab, or AMG 181, or mucosal addressin cell adhesion molecule-1 (MAdCAM-1) antagonists or rituximab.
- Subjects who have had prior exposure to vedolizumab.
- Subjects with hypersensitivity or allergies to vedolizumab or any of its excipients.
- Subjects who have received either (1) an investigational biologic (other than those listed in Exclusion Criterion #1) within 60 days or 5 half-lives before screening (whichever is longer); or (2) an approved biologic or biosimilar agent within 2 weeks before the first dose of study drug or at any time during the screening period.
- Subjects with active cerebral/meningeal disease, signs/symptoms or history of progressive multifocal leukoencephalopathy (PML) or any other major neurological disorders including stroke, multiple sclerosis, brain tumor or neurodegenerative disease.
- Subjects who currently require surgical intervention or are anticipated to require surgical intervention for CD during this study.
- Subjects who have had subtotal or total colectomy or have a jejunostomy, ileostomy, colostomy, ileo-anal pouch, known fixed stenosis of the intestine, short bowel syndrome, or >3 small intestine resections.
- Subjects with a current diagnosis of indeterminate colitis.
- Subjects with clinical features suggesting monogenic very early-onset inflammatory bowel disease.
- The subject has other serious comorbidities that will limit his or her ability to complete the study.
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 2
- Co-primary 1 (based on PCDAI): Clinical remission defined as a PCDAI ≤10 at Week 54.
- Co-primary 2 (based on SES-CD): Endoscopic response at Week 54, where a subject achieves endoscopic response if he or she has at least a 50% reduction in SES-CD score from baseline.
Secondary endpoints 14
- Clinical and endoscopic remission at Week 14, where a subject achieves both clinical and endoscopic remission if he or she meets the following definition: PCDAI ≤10 and SES-CD ≤4 with at least a 2-point reduction from baseline and no subscore >1.
- Clinical and endoscopic remission at Week 54, where a subject achieves both clinical and endoscopic remission if he or she meets the following definition: PCDAI ≤10 and SES-CD ≤4 with at least a 2-point reduction from baseline and no subscore >1.
- Sustained clinical and endoscopic remission at Week 54, where a subject achieves sustained clinical and endoscopic remission if he or she achieved clinical and endoscopic remission (based on PCDAI and SESCD) at Week 14 and at Week 54.
- Corticosteroid-free remission at Week 54, where a subject achieves corticosteroid-free clinical remission based on PCDAI at Week 54 and he or she has been off corticosteroids at least 12 weeks before Week 54.
- Sustained endoscopic remission, where a subject achieves sustained endoscopic remission if he or she meets the following definition: SES-CD ≤4 with at least a 2 point reduction from baseline and no subscore >1, achieved at both Weeks 14 and 54.
- Sustained clinical remission at Week 54, where a subject achieves sustained clinical remission if he or she achieved clinical remission (based on PCDAI) at Week 14 and at Week 54.
- Serum trough concentrations of vedolizumab over time.
- Positive antivedolizumab antibody (AVA) and positive neutralizing AVA titers during the study.
- Sustained clinical response of subjects at Weeks 14 and 54, where a subject meets clinical response of if he or she has a PCDAI score ≤30 and reduction of the PCDAI by ≥15 points from baseline.
- Clinical remission at Weeks 2, 6, 10, 14, 22, 30, 38, 46, and 54 where a subject achieves clinical remission if he or she meets the following definition: PCDAI ≤10
- Clinical response at Weeks 2, 6, 10, 14, 22, 30, 38, 46, and 54 where a subject achieves clinical response if he or she meets the following definition: PCDAI ≤30 with reduction in the PCDAI of ≥15 points from baseline.
- Safety assessments: Descriptions of adverse events (AEs); serious adverse events (SAEs) and AEs of special interest (AESIs), including evaluation of opportunistic infection, such as PML, and liver injury, malignancies, infusion-related reactions, and hypersensitivity
- Change from baseline in weight and linear growth z-score during the course of dosing with vedolizumab.
- Change in Tanner stage at Week 54, compared with baseline, each domain separately
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
Entyvio 300 mg powder for concentrate for solution for infusion
PRD1598541 · Product
- Active substance
- Vedolizumab
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 300 mg milligram(s)
- Max total dose
- 113.4 g gram(s)
- Max treatment duration
- 54 Week(s)
- Authorisation status
- Authorised
- ATC code
- L04AG05 — -
- Marketing authorisation
- EU/1/14/923/001
- MA holder
- TAKEDA PHARMA A/S
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Auxiliary 2
SUB10020MIG · Substance
- Active substance
- Prednisone
- Pharmaceutical form
- TABLETS
- Route of administration
- ORAL
- Max daily dose
- 40 mg milligram(s)
- Max total dose
- 5075 mg milligram(s)
- Max treatment duration
- 26 Week(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- Yes
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB05955MIG · Substance
- Active substance
- Budesonide
- Pharmaceutical form
- CAPSULE
- Route of administration
- ORAL
- Max daily dose
- 9 mg milligram(s)
- Max total dose
- 504 mg milligram(s)
- Max treatment duration
- 8 Week(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Takeda Development Center Americas Inc.
- Sponsor organisation
- Takeda Development Center Americas Inc.
- Address
- 500 Kendall Street
- City
- Cambridge
- Postcode
- 02142-1108
- Country
- United States
Scientific contact point
- Organisation
- Takeda Development Center Americas Inc.
- Contact name
- Director, Clinical Operations
Public contact point
- Organisation
- Takeda Development Center Americas Inc.
- Contact name
- Director, Clinical Operations
Third parties 9
| Organisation | City, country | Duties |
|---|---|---|
| Bioclinica Inc. ORG-100033079
|
Princeton, United States | Other |
| QPS LLC ORG-100012847
|
Newark, United States | Other |
| PPD International Holdings LLC ORG-100007655
|
Zaventem, Belgium | Other |
| PPD Development LP ORG-100011560
|
Wilmington, United States | On site monitoring, Code 10, Code 11, Code 12, Code 2, Interactive response technologies (IRT), Data management, E-data capture, Code 8, Code 9 |
| Q Squared Solutions Limited ORG-100042527
|
Reading, United Kingdom | Other |
| PPD Global Ltd. ORG-100007531
|
Marousi, Greece | On site monitoring, Code 10, Code 11, Code 12, Code 2, Interactive response technologies (IRT), Data management, E-data capture, Code 8, Code 9 |
| Medidata Solutions Inc. ORG-100016256
|
New York, United States | E-data capture |
| Q Squared Solutions LLC ORG-100043195
|
Durham, United States | Other |
| Scout Clinical ORG-100042228
|
Dallas, United States | Other |
Locations
6 EU/EEA countries · 23 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Belgium | Ongoing, recruiting | 6 | 3 |
| Croatia | Ongoing, recruiting | 4 | 1 |
| Greece | Ongoing, recruiting | 4 | 3 |
| Hungary | Ongoing, recruiting | 3 | 3 |
| Italy | Ongoing, recruiting | 6 | 5 |
| Poland | Ongoing, recruiting | 28 | 8 |
| Rest of world
Israel, Japan, United States, United Kingdom, Canada, China, Australia, Korea, Republic of
|
— | 40 | — |
Investigational sites
Antwerp University Hospital
Pediatric Gastoenterology, Drie Eikenstraat 655, 2650, Edegem
UZ Brussel
Pediatric Gastoenterology, Laarbeeklaan 101, 1090, Jette
UZ Leuven
Pediatric Gastoenterology, Herestraat 49, 3000, Leuven
Klinika Za Djecje Bolesti Zagreb
Department of Pediatric Gastroenterology, Hepatology and Eating Disorders, Ulica Vjekoslava Klaica 16, Zagreb, Grad Zagreb
University General Hospital Attikon
3rd Pediatric Department of the University of Athens, Paidogastroenterology unit, Rimini Street 1, 124 62, Athens
Ippokratio General Hospital Of Thessaloniki
3rd ’ Pediatric Clinic AUTΗ, Konstadinoupoleos 49, 546 42, Thessaloniki
Nosokomeio Paidon I Agia Sofia
1st Department of Pediatrics , University of Athens and of Gastroenterology Department, Thivon, Papadiamantopoulou, Athens
Borsod-Abauj-Zemplen Varmegyei Koezponti Korhaz Es Egyetemi Oktatokorhaz
Velkey Lászlo Gyermek Egészségügyi Központ, Szentpeteri Kapu 72-76, 3526, Miskolc
Semmelweis University
I. Sz. Gyermekgyógyászati Klinika, Bokay Janos Utca 53, 1083, Budapest VIII
Clinexpert Kft.
N/A, Kaszasdulo Utca 5, 1033, Budapest III
Azienda Ospedaliero-Universitaria Policlinico Umberto I
UOC Gastroenterologia ed Epatologia Pediatrica, Viale Del Policlinico 155, 00161, Rome
Azienda Unita Sanitaria Locale Di Bologna
UOC Pediatria – Gastroenterologia Pediatrica, Largo Bartolo Nigrisoli 2, 40133, Bologna
Azienda Ospedaliera Universitaria Meyer IRCCS
SOC Gastroenterologia e Nutrizione, Viale Gaetano Pieraccini 24, 50139, Florence
Azienda Ospedaliera Universitaria Universita' Degli Studi Della Campania Luigi Vanvitelli
UO Pediatria Dipartimento della Donna e del Bambino - Chirurgia Generale Specialistica, Piazza Luigi Miraglia 2, 80138, Naples
Azienda Ospedaliera Universitaria Federico II Di Napoli
Unità di Endoscopia e Motilità Digestiva Pediatrica, Via Sergio Pansini 5, 80131, Naples
Instytut Pomnik Centrum Zdrowia Dziecka
Klinika Gastroenterologii, Hepatologii, Zaburzeń Odżywiania i Pediatrii, Aleja Dzieci Polskich 20, 04-730, Warsaw
Instytut Centrum Zdrowia Matki Polki
Klinika Gastroenterologii, Alergologii, Ul. Rzgowska 281/289, 93-338, Lodz
WIP Warsaw IBD Point Profesor Kierkus
WIP Warsaw IBD Point Profesor Kierkus, ul. Płowiecka 103, 04-501, Warszawa
Uniwersytecki Szpital Dzieciecy W Krakowie
Klinika Pediatrii, Gastroenterologii i Żywienia, Ul. Wielicka 265, 30-663, Cracow
Gornoslaskie Centrum Zdrowia Dziecka Im. Sw. Jana Pawla II Samodzielny Publiczny Szpital Kliniczny Nr 6 Slaskiego Uniwersytetu Medycznego W Katowicach
Oddział Gastroenterologiczny, Ul. Medykow 16, 40-752, Katowice
Twoja Przychodnia Szczecinskie Centrum Medyczne Sp. z o.o.
Twoja Przychodnia – Szczecińskie Centrum Medyczne, Ul. Juliusza Slowackiego 19, 71-434, Szczecin
Samodzielny Publiczny Zaklad Opieki Zdrowotnej Centralny Szpital Kliniczny Uniwersytetu Medycznego W Lodzi
Klinika Alergologii, Gastroenterologii i Żywienia Dzieci, Ul Sporna 36/50, 91-738, Lodz
Korczowski Bartosz, Gabinet Lekarski
Korczowski Bartosz, Gabinet Lekarski, ul Litewska 4a/7, 35-302, Rzeszów
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Belgium | 2022-10-12 | 2022-11-22 | |||
| Croatia | 2022-03-24 | 2022-04-28 | |||
| Greece | 2022-02-28 | 2022-04-08 | |||
| Hungary | 2022-03-23 | 2022-04-20 | |||
| Italy | 2022-03-30 | 2022-07-11 | |||
| Poland | 2022-03-14 | 2022-03-23 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 150 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Takeda_MLN0002-3025_Protocol_2023-509045-13-00_ELL_Public | 7.0 |
| Protocol (for publication) | D1_Takeda_MLN0002-3025_Protocol_2023-509045-13-00_Public | 7.0 |
| Protocol (for publication) | D4_Takeda_MLN0002-3025_Patient-Facing Material_Placeholder_Public | N/A |
| Recruitment arrangements (for publication) | K1_MLN0002-3025_Patient_Materials_IT_placeholder_Public | n/a |
| Recruitment arrangements (for publication) | K1_MLN0002-3025_Recruitment_Informed_Consent_Procedure_HU_Public | 1 |
| Recruitment arrangements (for publication) | K1_MLN0002-3025_Recruitment-and-Informed-consent-procedure_PL_Polish_Public | 1 |
| Recruitment arrangements (for publication) | K1_MLN0002-3025_Recruitment-Arrangements_BE_Public | 1.0 |
| Recruitment arrangements (for publication) | K1_MLN0002-3025_Recruitment-Arrangements_GRC_Public | n/a |
| Recruitment arrangements (for publication) | K1_MLN0002-3025_Recruitment-Arrangements_HR_Public | 1 |
| Recruitment arrangements (for publication) | K1_MLN0002-3025_Recruitment-Arrangements_IT_Public | n/a |
| Recruitment arrangements (for publication) | K2_MLN0002-3025_ j-elita_ogloszenie_badania_PL_Polish_Public | 1.0 |
| Recruitment arrangements (for publication) | K2_MLN0002-3025_ PFM Placeholder Document_Public | n/a |
| Recruitment arrangements (for publication) | K2_MLN0002-3025_Ad_Copy_PL_Polish_Public | 1.1 |
| Recruitment arrangements (for publication) | K2_MLN0002-3025_Banner-Ads_PL_Polish_Public | 1.0 |
| Recruitment arrangements (for publication) | K2_MLN0002-3025_Crohns Brochure_BE_Dutch_Public | 1.1 |
| Recruitment arrangements (for publication) | K2_MLN0002-3025_Crohns Brochure_BE_English_Public | 1.1 |
| Recruitment arrangements (for publication) | K2_MLN0002-3025_Crohns Brochure_BE_French_Public | 1.1 |
| Recruitment arrangements (for publication) | K2_MLN0002-3025_Crohns Brochure_CD_HU_Hungarian_Public | 1.1 |
| Recruitment arrangements (for publication) | K2_MLN0002-3025_Crohns_Brochure_CD_PL_Polish_Public | 1.2 |
| Recruitment arrangements (for publication) | K2_MLN0002-3025_Crohns-Brochure_HR_Croatian_Public | 1.2 |
| Recruitment arrangements (for publication) | K2_MLN0002-3025_Crohns-Brochure-CD_GRC_Greek_Public | 1.1 |
| Recruitment arrangements (for publication) | K2_MLN0002-3025_Digital_Announcement_PL_Polish_Public | 1.0 |
| Recruitment arrangements (for publication) | K2_MLN0002-3025_Facebook_Post_PL_Polish_Public | 1.0 |
| Recruitment arrangements (for publication) | K2_MLN0002-3025_Facebook_Whitelisting_Settings_PL_English_Public | 1.0 |
| Recruitment arrangements (for publication) | K2_MLN0002-3025_Facebook-Copy_PL_Polish_Public | 2.0 |
| Recruitment arrangements (for publication) | K2_MLN0002-3025_IC-Flip-Chart_BE_Dutch_Public | 2.0 |
| Recruitment arrangements (for publication) | K2_MLN0002-3025_IC-Flip-Chart_BE_English_Public | 2.0 |
| Recruitment arrangements (for publication) | K2_MLN0002-3025_IC-Flip-Chart_BE_French_Public | 2.0 |
| Recruitment arrangements (for publication) | K2_MLN0002-3025_Images_PL_Polish_Public | 1.0 |
| Recruitment arrangements (for publication) | K2_MLN0002-3025_Informed Consent Flip Chart_HU_Hungarian_Public | 2.0 |
| Recruitment arrangements (for publication) | K2_MLN0002-3025_Informed_Consent_Flip_Chart_PL_Polish_Public | 2.0 |
| Recruitment arrangements (for publication) | K2_MLN0002-3025_Informed-Consent-Flip-Chart_GRC_Greek_Public | 2.0 |
| Recruitment arrangements (for publication) | K2_MLN0002-3025_Informed-Consent-Flip-Chart_HR_Croatian_Public | 2.0 |
| Recruitment arrangements (for publication) | K2_MLN0002-3025_Instagram_Copy_PL_Polish_Public | 1.1 |
| Recruitment arrangements (for publication) | K2_MLN0002-3025_Instagram_Management_PL_English_Public | 1.0 |
| Recruitment arrangements (for publication) | K2_MLN0002-3025_NTF about recruitment materials in track change_HU_Bilingual_Public | n/a |
| Recruitment arrangements (for publication) | K2_MLN0002-3025_PAG_Email_PL_Polish_Public | 2.0 |
| Recruitment arrangements (for publication) | K2_MLN0002-3025_PFM Placeholder_GRC_English_Public | n/a |
| Recruitment arrangements (for publication) | K2_MLN0002-3025_PFM_Placeholder_Document_HR_English_Public | N/A |
| Recruitment arrangements (for publication) | K2_MLN0002-3025_PFM_Placeholder_Document_Public | n/a |
| Recruitment arrangements (for publication) | K2_MLN0002-3025_Placeholder-Document_BE_Public | n/a |
| Recruitment arrangements (for publication) | K2_MLN0002-3025_Site_Internet_Ad_PL_Polish_Public | 1.0 |
| Recruitment arrangements (for publication) | K2_MLN0002-3025_Site-Dig-Kit-Site-In-Ad_GRC_Greek_Public | 1.0 |
| Recruitment arrangements (for publication) | K2_MLN0002-3025_Site-Digital-Kit-Digital-An_GRC_Greek_Public | 1.0 |
| Recruitment arrangements (for publication) | K2_MLN0002-3025_Study_Site_Banner_Ads_PL_Polish_Public | 1.1 |
| Recruitment arrangements (for publication) | K2_MLN0002-3025_Study_Welcome_Organizer_PL_Polish_Public | 1.0 |
| Recruitment arrangements (for publication) | K2_MLN0002-3025_Study-Site-Banner-Ads_GRC_Greek_Public | 1.1 |
| Recruitment arrangements (for publication) | K2_MLN0002-3025_Study-Welc-Org-Pat_Car_GRC_Public | 1.0 |
| Recruitment arrangements (for publication) | K2_MLN0002-3025_Study-Welcome-Organizer-for Patient_Caregiver_BE_Public | 1.0 |
| Recruitment arrangements (for publication) | K2_MLN0002-3025_Study-Welcome-Organizer-for-Patient-Caregiver_HR_Croatian_Public | 1.0 |
| Recruitment arrangements (for publication) | K2_MLN0002-3025_Und-Cli-Trials-Brochure_GRC_Greek_Public | 1.1 |
| Recruitment arrangements (for publication) | K2_MLN0002-3025_Understanding Clinical Trials Brochure_HU_Hungarian_Public | 1.2 |
| Recruitment arrangements (for publication) | K2_MLN0002-3025_Understanding_Clinical_Trials_PL_Polish_Public | 1.2 |
| Recruitment arrangements (for publication) | K2_MLN0002-3025_Understanding-Clinical-Trials-Brochure_BE_Dutch_Public | 1.2 |
| Recruitment arrangements (for publication) | K2_MLN0002-3025_Understanding-Clinical-Trials-Brochure_BE_English_Public | 1.2 |
| Recruitment arrangements (for publication) | K2_MLN0002-3025_Understanding-Clinical-Trials-Brochure_BE_French_Public | 1.2 |
| Recruitment arrangements (for publication) | K2_MLN0002-3025_Understanding-Clinical-Trials-Brochure_HR_Croatian_Public | 1.2 |
| Recruitment arrangements (for publication) | K2_MLN0002-3025_Web_Homepage_Screenshot_PL_Polish_Public | 1.1 |
| Recruitment arrangements (for publication) | K2_MLN0002-3025_Webb_Mobile_Screenshot_PL_Polish_Public | 1.1 |
| Recruitment arrangements (for publication) | K2_MLN0002-3025_Website_Copy_PL_Polish_Public | 2.0 |
| Subject information and informed consent form (for publication) | L1_ MLN0002-3025_Parental ICF_PL_Polish_Public | 4.1 |
| Subject information and informed consent form (for publication) | L1_MLN0002-3025_Adult ICF_Annex 1_IT_Italian_Public | 3.1 |
| Subject information and informed consent form (for publication) | L1_MLN0002-3025_Adult ICF_BE_Dutch_Public | 5.0 |
| Subject information and informed consent form (for publication) | L1_MLN0002-3025_Adult ICF_BE_English_Public | 5.0 |
| Subject information and informed consent form (for publication) | L1_MLN0002-3025_Adult ICF_BE_French_Public | 5.0 |
| Subject information and informed consent form (for publication) | L1_MLN0002-3025_Adult ICF_IT_Italian_Public | 4.1 |
| Subject information and informed consent form (for publication) | L1_MLN0002-3025_Adult ICF_PL_Polish_Public | 4.1 |
| Subject information and informed consent form (for publication) | L1_MLN0002-3025_Adult_ICF_GRC_Greek_Public | 4.1 |
| Subject information and informed consent form (for publication) | L1_MLN0002-3025_Adult-Future-ICF_HR_Croatian_Public | 4.0 |
| Subject information and informed consent form (for publication) | L1_MLN0002-3025_Adult-ICF_HR_Croatian_Public | 4.0 |
| Subject information and informed consent form (for publication) | L1_MLN0002-3025_Age 10-12_ICF_GRC_Greek_Public | 5.1 |
| Subject information and informed consent form (for publication) | L1_MLN0002-3025_Age 13-15_ICF_GRC_Greek_Public | 4.1 |
| Subject information and informed consent form (for publication) | L1_MLN0002-3025_Age 16-18_ICF_GRC_Greek_Public | 4.1 |
| Subject information and informed consent form (for publication) | L1_MLN0002-3025_Age 6-9_ICF_GRC_Greek_Public | 3.2 |
| Subject information and informed consent form (for publication) | L1_MLN0002-3025_Assent 6-11y_IT_Italian_Public | 3.1 |
| Subject information and informed consent form (for publication) | L1_MLN0002-3025_Assent Age 6-12_PL_Polish_Public | 3.1 |
| Subject information and informed consent form (for publication) | L1_MLN0002-3025_Assent form_12-15y_HU_Hungarian_Public | 4.1 |
| Subject information and informed consent form (for publication) | L1_MLN0002-3025_Assent form_16-17y_HU_Hungarian_Public | 4.1 |
| Subject information and informed consent form (for publication) | L1_MLN0002-3025_Assent form_6-11y_HU_Hungarian_Public | 3.1 |
| Subject information and informed consent form (for publication) | L1_MLN0002-3025_Assent Form_Ages 12-15_BE_Dutch_Public | 4.0 |
| Subject information and informed consent form (for publication) | L1_MLN0002-3025_Assent Form_Ages 12-15_BE_English_Public | 4.0 |
| Subject information and informed consent form (for publication) | L1_MLN0002-3025_Assent Form_Ages 12-15_BE_French_Public | 4.0 |
| Subject information and informed consent form (for publication) | L1_MLN0002-3025_Assent Form_Ages 16-17_BE_Dutch_Public | 5.0 |
| Subject information and informed consent form (for publication) | L1_MLN0002-3025_Assent Form_Ages 16-17_BE_English_Public | 5.0 |
| Subject information and informed consent form (for publication) | L1_MLN0002-3025_Assent Form_Ages 16-17_BE_French_Public | 5.0 |
| Subject information and informed consent form (for publication) | L1_MLN0002-3025_Assent Form_Ages 6-11_BE_Dutch_Public | 4.0 |
| Subject information and informed consent form (for publication) | L1_MLN0002-3025_Assent Form_Ages 6-11_BE_English_Public | 4.0 |
| Subject information and informed consent form (for publication) | L1_MLN0002-3025_Assent Form_Ages 6-11_BE_French_Public | 4.0 |
| Subject information and informed consent form (for publication) | L1_MLN0002-3025_Assent Form_Under 6 yrs_BE_Dutch_Public | 4.0 |
| Subject information and informed consent form (for publication) | L1_MLN0002-3025_Assent Form_Under 6 yrs_BE_English_Public | 4.0 |
| Subject information and informed consent form (for publication) | L1_MLN0002-3025_Assent Form_Under 6 yrs_BE_French_Public | 4.0 |
| Subject information and informed consent form (for publication) | L1_MLN0002-3025_Assent form_Under 6_HU_Hungarian_Public | 3.1 |
| Subject information and informed consent form (for publication) | L1_MLN0002-3025_Assent_ Age 16-17_PL_Polish_Public | 4.1 |
| Subject information and informed consent form (for publication) | L1_MLN0002-3025_Assent_12-17y_IT_Italian_Public | 4.1 |
| Subject information and informed consent form (for publication) | L1_MLN0002-3025_Assent_Age 13-15_PL_Polish_Public | 4.1 |
| Subject information and informed consent form (for publication) | L1_MLN0002-3025_Assent_Under 6y_IT_Italian_Public | 3.1 |
| Subject information and informed consent form (for publication) | L1_MLN0002-3025_Assent-12-14_HR_Croatian_Public | 4.0 |
| Subject information and informed consent form (for publication) | L1_MLN0002-3025_Assent-15-17_HR_Croatian_Public | 4.0 |
| Subject information and informed consent form (for publication) | L1_MLN0002-3025_Assent-6-8_HR_Croatian_Public | 3.0 |
| Subject information and informed consent form (for publication) | L1_MLN0002-3025_Assent-9-11_HR_Croatian_Public | 3.0 |
| Subject information and informed consent form (for publication) | L1_MLN0002-3025_Assent-Under-6_HR_Croatian_Public | 3.0 |
| Subject information and informed consent form (for publication) | L1_MLN0002-3025_ICF_Adult_HU_Hungarian_Public | 4.1 |
| Subject information and informed consent form (for publication) | L1_MLN0002-3025_ICF_Parental_HU_Hungarian_Public | 4.1 |
| Subject information and informed consent form (for publication) | L1_MLN0002-3025_ICF_Pregnant Partner_HU_Hungarian_Public | 1.1 |
| Subject information and informed consent form (for publication) | L1_MLN0002-3025_ICFs_Placeholder_PL_Polish_Public | n/a |
| Subject information and informed consent form (for publication) | L1_MLN0002-3025_Minor-PP-Assent_HR_Croatian_Public | 2.0 |
| Subject information and informed consent form (for publication) | L1_MLN0002-3025_Minor-PS-Assent_HR_Croatian_Public | 2.0 |
| Subject information and informed consent form (for publication) | L1_MLN0002-3025_Parent-Future-ICF_HR_Croatian_Public | 4.0 |
| Subject information and informed consent form (for publication) | L1_MLN0002-3025_Parent-ICF_HR_Croatian_Public | 4.0 |
| Subject information and informed consent form (for publication) | L1_MLN0002-3025_Parent-Minor-PP-Assent_HR_Croatian_Public | 2.0 |
| Subject information and informed consent form (for publication) | L1_MLN0002-3025_Parent-Minor-PS-Assent_HR_Croatian_Public | 2.0 |
| Subject information and informed consent form (for publication) | L1_MLN0002-3025_Parental ICF_Annex 1_IT_Italian_Public | 3.1 |
| Subject information and informed consent form (for publication) | L1_MLN0002-3025_Parental ICF_BE_Dutch_Public | 5.0 |
| Subject information and informed consent form (for publication) | L1_MLN0002-3025_Parental ICF_BE_English_Public | 5.0 |
| Subject information and informed consent form (for publication) | L1_MLN0002-3025_Parental ICF_BE_French_Public | 5.0 |
| Subject information and informed consent form (for publication) | L1_MLN0002-3025_Parental ICF_IT_Italian_Public | 4.1 |
| Subject information and informed consent form (for publication) | L1_MLN0002-3025_Parental_ICF_GRC_Greek_Public | 4.1 |
| Subject information and informed consent form (for publication) | L1_MLN0002-3025_PP-ICF_HR_Croatian_Public | 2.0 |
| Subject information and informed consent form (for publication) | L1_MLN0002-3025_Pre-Screening Assent 10-12_ICF_GRC_Greek_Public | 1.1 |
| Subject information and informed consent form (for publication) | L1_MLN0002-3025_Pre-Screening Assent 13-15_ICF_GRC_Greek_Public | 1.1 |
| Subject information and informed consent form (for publication) | L1_MLN0002-3025_Pre-Screening Assent 16-18_ICF_GRC_Greek_Public | 1.1 |
| Subject information and informed consent form (for publication) | L1_MLN0002-3025_Pre-Screening Assent 6-9_ICF_GRC_Greek_Public | 1.1 |
| Subject information and informed consent form (for publication) | L1_MLN0002-3025_Pre-Screening Parental_ICF_GRC_Greek_Public | 1.2 |
| Subject information and informed consent form (for publication) | L1_MLN0002-3025_Pregnant Partner Authorization_Annex 1_IT_Italian_Public | 2.1 |
| Subject information and informed consent form (for publication) | L1_MLN0002-3025_Pregnant Partner Authorization_IT_Italian_Public | 2.1 |
| Subject information and informed consent form (for publication) | L1_MLN0002-3025_Pregnant Partner ICF_BE_Dutch_Public | 2.0 |
| Subject information and informed consent form (for publication) | L1_MLN0002-3025_Pregnant Partner ICF_BE_English_Public | 2.0 |
| Subject information and informed consent form (for publication) | L1_MLN0002-3025_Pregnant Partner ICF_BE_French_Public | 2.0 |
| Subject information and informed consent form (for publication) | L1_MLN0002-3025_Pregnant Partner ICF_PL_Polish_Public | 2.1 |
| Subject information and informed consent form (for publication) | L1_MLN0002-3025_PS-ICF_HR_Croatian_Public | 2.0 |
| Subject information and informed consent form (for publication) | L2_MLN0002-3025_Patient card_HU_Hungarian_Clean_Public | 3.0.0 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_Takeda_MLN0002-3025_SmPC_Entyvio IV_Public | N/A |
| Synopsis of the protocol (for publication) | D1_Takeda_MLN0002-3025_Plain Language Prot Synopsis_2023-509045-13-00_BE-DE_Public | 7.0 |
| Synopsis of the protocol (for publication) | D1_Takeda_MLN0002-3025_Plain Language Prot Synopsis_2023-509045-13-00_BE-FR_Public | 7.0 |
| Synopsis of the protocol (for publication) | D1_Takeda_MLN0002-3025_Plain Language Prot Synopsis_2023-509045-13-00_BE-NL_Public | 7.0 |
| Synopsis of the protocol (for publication) | D1_Takeda_MLN0002-3025_Plain Language Prot Synopsis_2023-509045-13-00_ENG_Public | 7.0 |
| Synopsis of the protocol (for publication) | D1_Takeda_MLN0002-3025_Plain Language Prot Synopsis_2023-509045-13-00_GR_EL_Public | 7.0 |
| Synopsis of the protocol (for publication) | D1_Takeda_MLN0002-3025_Plain Language Prot Synopsis_2023-509045-13-00_HR_HRV_Public | 7.0 |
| Synopsis of the protocol (for publication) | D1_Takeda_MLN0002-3025_Plain Language Prot Synopsis_2023-509045-13-00_HU_HUN_Public | 7.0 |
| Synopsis of the protocol (for publication) | D1_Takeda_MLN0002-3025_Plain Language Prot Synopsis_2023-509045-13-00_IT_ITA_Public | 7.0 |
| Synopsis of the protocol (for publication) | D1_Takeda_MLN0002-3025_Plain Language Prot Synopsis_2023-509045-13-00_PO_PO_Public | 7.0 |
| Synopsis of the protocol (for publication) | D1_Takeda_MLN0002-3025_Protocol Synopsis_2023-509045-13-00_BE_DEU_Public | 7.0 |
| Synopsis of the protocol (for publication) | D1_Takeda_MLN0002-3025_Protocol Synopsis_2023-509045-13-00_BE_FRA_Public | 7.0 |
| Synopsis of the protocol (for publication) | D1_Takeda_MLN0002-3025_Protocol Synopsis_2023-509045-13-00_BE_NLD_Public | 7.0 |
| Synopsis of the protocol (for publication) | D1_Takeda_MLN0002-3025_Protocol Synopsis_2023-509045-13-00_ENG_Public | 7.0 |
| Synopsis of the protocol (for publication) | D1_Takeda_MLN0002-3025_Protocol Synopsis_2023-509045-13-00_GR_ELL_Public | 7.0 |
| Synopsis of the protocol (for publication) | D1_Takeda_MLN0002-3025_Protocol Synopsis_2023-509045-13-00_HR_HRV_Public | 5.0 |
| Synopsis of the protocol (for publication) | D1_Takeda_MLN0002-3025_Protocol Synopsis_2023-509045-13-00_HU_HUN_Public | 7.0 |
| Synopsis of the protocol (for publication) | D1_Takeda_MLN0002-3025_Protocol Synopsis_2023-509045-13-00_IT_ITA_Public | 5.0 |
| Synopsis of the protocol (for publication) | D1_Takeda_MLN0002-3025_Protocol Synopsis_2023-509045-13-00_PL_POL_Public | 5.0 |
Application history
4 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-07-12 | Italy | Acceptable 2024-08-21
|
2024-08-21 |
| 2 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2024-10-18 | Italy | Acceptable 2024-08-21
|
2024-10-18 |
| 3 | SUBSTANTIAL MODIFICATION | SM-1 | 2024-12-17 | Italy | Acceptable 2025-04-08
|
2025-04-09 |
| 4 | NON SUBSTANTIAL MODIFICATION | NSM-2 | 2025-08-14 | Italy | Acceptable 2025-04-08
|
2025-08-14 |