Clinical trial • Phase III • Gastroenterology

Vedolizumab for Crohn's disease | Moderately to severely active Crohn's disease

Phase III trial of Vedolizumab for Crohn's disease | Moderately to severely active Crohn's disease.

Overview

Trial Therapeutic Area
Gastroenterology
Trial Disease
Crohn's disease | Moderately to severely active Crohn's disease
Trial Stage
Phase III
Drug Modality
Monoclonal antibody | Small molecule
Paediatric Trial
Yes

Key dates

Initial CTIS Submission Date
12-07-2024
First CTIS Authorization Date
21-08-2024

Trial design

Randomised, open-label, two blinded maintenance comparator arms (high dose vs low dose vedolizumab). maintenance doses by weight group: high dose: ≥30 kg = 300 mg iv q8w; >15 to <30 kg = 200 mg iv q8w; 10–15 kg = 150 mg iv q8w. low dose: ≥30 kg = 150 mg iv q8w; >15 to <30 kg = 100 mg iv q8w; 10–15 kg = 100 mg iv q8w. induction (open-label) dosing: subjects ≥30 kg receive 300 mg iv at day 1, week 2, week 6; >15 to <30 kg receive 200 mg iv at day 1, week 2, week 6; 10–15 kg receive 150 mg iv at day 1, week 2, week 6.-controlled Phase III trial across 23 sites in Greece, Hungary, Belgium and others.

Randomised
Yes
Open Label
Yes
Comparator
Two blinded maintenance comparator arms (high dose vs low dose vedolizumab). Maintenance doses by weight group: High dose: ≥30 kg = 300 mg IV Q8W; >15 to <30 kg = 200 mg IV Q8W; 10–15 kg = 150 mg IV Q8W. Low dose: ≥30 kg = 150 mg IV Q8W; >15 to <30 kg = 100 mg IV Q8W; 10–15 kg = 100 mg IV Q8W. Induction (open-label) dosing: subjects ≥30 kg receive 300 mg IV at Day 1, Week 2, Week 6; >15 to <30 kg receive 200 mg IV at Day 1, Week 2, Week 6; 10–15 kg receive 150 mg IV at Day 1, Week 2, Week 6.
Target Sample Size
120
Trial Duration For Participant
378

Eligibility

Recruits 120 paediatric patients.

Vulnerable Population
Pediatric subjects (children and adolescents) aged 2–17 years are included. The trial uses age-specific assent and consent processes: parental/legal guardian informed consent (Parental ICF) and age-appropriate subject information/assent forms (examples: Pre-Screening Assent and Assent forms for age bands such as under 6, 6–9, 10–12, 13–15, 16–18). Subject information and ICF documents are provided for local application and are available in local languages for participating countries (examples in the dossier: Greek, Hungarian, Italian, Polish, Dutch/French/English for Belgium, Croatian).

Inclusion criteria

  • {"criterion_text":"- 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."}
  • {"criterion_text":"- 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."}
  • {"criterion_text":"- 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."}
  • {"criterion_text":"- 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."}
  • {"criterion_text":"- Subjects with vaccinations that are up-to-date based on the countrywide accepted schedule of childhood vaccines."}

Exclusion criteria

  • {"criterion_text":"- 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."}
  • {"criterion_text":"- The subject has other serious comorbidities that will limit his or her ability to complete the study."}
  • {"criterion_text":"- Subjects who have had prior exposure to vedolizumab."}
  • {"criterion_text":"- Subjects with hypersensitivity or allergies to vedolizumab or any of its excipients."}
  • {"criterion_text":"- 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."}
  • {"criterion_text":"- 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."}
  • {"criterion_text":"- Subjects who currently require surgical intervention or are anticipated to require surgical intervention for CD during this study."}
  • {"criterion_text":"- 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."}
  • {"criterion_text":"- Subjects with a current diagnosis of indeterminate colitis."}
  • {"criterion_text":"- Subjects with clinical features suggesting monogenic very early-onset inflammatory bowel disease."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Co-primary 1 (based on PCDAI): Clinical remission defined as a PCDAI ≤10 at Week 54.","definition_or_measurement_approach":"Clinical remission defined as a PCDAI ≤10 at Week 54; PCDAI (Pediatric Crohn's Disease Activity Index) score assessed at Week 54."}
  • {"endpoint_text":"- 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.","definition_or_measurement_approach":"Endoscopic response defined as ≥50% reduction in SES-CD score from baseline measured at Week 54."}

Secondary endpoints

  • {"endpoint_text":"- 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.","definition_or_measurement_approach":"Clinical remission: PCDAI ≤10; Endoscopic remission: SES-CD ≤4 with ≥2-point reduction from baseline and no subscore >1, assessed at Week 14."}
  • {"endpoint_text":"- 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.","definition_or_measurement_approach":"Clinical remission: PCDAI ≤10; Endoscopic remission: SES-CD ≤4 with ≥2-point reduction from baseline and no subscore >1, assessed at Week 54."}
  • {"endpoint_text":"- 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.","definition_or_measurement_approach":"Sustained remission = meeting the clinical and endoscopic remission definitions at both Week 14 and Week 54 (PCDAI and SES-CD criteria as defined)."}
  • {"endpoint_text":"- 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.","definition_or_measurement_approach":"Clinical remission (PCDAI ≤10) at Week 54 with no corticosteroid use for at least 12 weeks prior to Week 54."}
  • {"endpoint_text":"- 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.","definition_or_measurement_approach":"SES-CD ≤4 with ≥2-point reduction from baseline and no subscore >1, achieved at both Weeks 14 and 54."}
  • {"endpoint_text":"- 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.","definition_or_measurement_approach":"Clinical remission (PCDAI ≤10) at both Week 14 and Week 54."}
  • {"endpoint_text":"- Serum trough concentrations of vedolizumab over time.","definition_or_measurement_approach":"Pharmacokinetic measurement of vedolizumab serum trough concentrations at scheduled timepoints."}
  • {"endpoint_text":"- Positive antivedolizumab antibody (AVA) and positive neutralizing AVA titers during the study.","definition_or_measurement_approach":"Immunogenicity assays for anti-vedolizumab antibodies and neutralizing antibody titers during study treatment."}
  • {"endpoint_text":"- 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.","definition_or_measurement_approach":"Clinical response defined as PCDAI ≤30 and reduction ≥15 points from baseline, assessed at Weeks 14 and 54."}
  • {"endpoint_text":"- 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","definition_or_measurement_approach":"Clinical remission (PCDAI ≤10) assessed at multiple timepoints (Weeks 2, 6, 10, 14, 22, 30, 38, 46, 54)."}
  • {"endpoint_text":"- 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.","definition_or_measurement_approach":"Clinical response (PCDAI ≤30 and reduction ≥15 points from baseline) assessed at multiple timepoints."}
  • {"endpoint_text":"- 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","definition_or_measurement_approach":"Collection and characterization of AEs, SAEs, and AESIs including predefined categories (PML, liver injury, malignancies, infusion reactions, hypersensitivity)."}
  • {"endpoint_text":"- Change from baseline in weight and linear growth z-score during the course of dosing with vedolizumab.","definition_or_measurement_approach":"Change from baseline in weight and linear growth z-score measured during treatment."}
  • {"endpoint_text":"- Change in Tanner stage at Week 54, compared with baseline, each domain separately","definition_or_measurement_approach":"Change in Tanner stage domains at Week 54 versus baseline assessed separately."}

Recruitment

Digital Remote Recruitment
Yes
Planned Sample Size
120
Recruitment Window Months
57
Consent Approach
Informed consent obtained from parent/legal guardian (Parental ICF). Age-appropriate assent is obtained from pediatric participants using specific assent forms for defined age bands (examples in documents: Pre-Screening Assent and Assent/ICF sets for under 6, 6–9, 10–12, 13–15, 16–18). Site materials include subject information and ICFs in local languages for participating countries; separate parental and subject documents (and Pregnant Partner ICF where applicable) are provided.

Methods

  • Site-based recruitment at participating hospitals/clinics using study teams and local site contact details (site lists and contact persons provided for Greece, Hungary, Belgium, Italy, Poland, Croatia).
  • Printed patient-facing materials and brochures (e.g., Crohn's Brochure, Understanding Clinical Trials Brochure) distributed at sites and to caregivers/patients.
  • Digital recruitment: social media posts and advertisements (Facebook, Instagram), site banner ads, website homepage copy and internet ads tailored per country (documents specifically reference digital assets for Poland, Belgium and other countries).
  • Patient/caregiver outreach materials: Study Welcome Organizer and Patient-Facing Materials provided to caregivers and patients at sites.
  • Email outreach and engagement materials (e.g., PAG_Email_PL indicating targeted email outreach in Poland).
  • On-site information tools: Informed-Consent Flip Chart and site digital kits to support discussion with families and assent process.

Geography

Total Number Of Sites
23
Total Number Of Participants
51

Greece

Latest Decision Or Authorization Date
22-08-2024
Number Of Sites
3
Number Of Participants
4

Sites

Site Name
University General Hospital Attikon
Department Name
3rd Pediatric Department of the University of Athens, Paidogastroenterology unit
Contact Person Name
Smaragdi Fessatou
Contact Person Email
sfessatou@yahoo.gr
Site Name
Ippokratio General Hospital Of Thessaloniki
Department Name
3rd ’ Pediatric Clinic AUTΗ
Contact Person Name
Ioannis Xinias
Contact Person Email
xinias@auth.gr
Site Name
Nosokomeio Paidon I Agia Sofia
Department Name
1st Department of Pediatrics , University of Athens and of Gastroenterology Department
Contact Person Name
Alexandra Papadopoulou

Hungary

Latest Decision Or Authorization Date
22-08-2024
Number Of Sites
3
Number Of Participants
3

Sites

Site Name
Clinexpert Kft.
Contact Person Name
Natália Lásztity
Contact Person Email
laszity.clinexpert@gmail.com
Site Name
Borsod-Abauj-Zemplen Varmegyei Koezponti Korhaz Es Egyetemi Oktatokorhaz
Department Name
Velkey Lászlo Gyermek Egészségügyi Központ
Contact Person Name
Erzsébet Szakos
Contact Person Email
szakos.iiigyek@bazmkorhaz.hu
Site Name
Semmelweis University
Department Name
I. Sz. Gyermekgyógyászati Klinika
Contact Person Name
Aron Cseh
Contact Person Email
cseharon@gmail.com

Belgium

Latest Decision Or Authorization Date
21-08-2024
Number Of Sites
3
Number Of Participants
6

Sites

Site Name
UZ Leuven
Department Name
Pediatric Gastoenterology
Contact Person Name
Ilse Hoffman
Contact Person Email
ilse.hoffman@uzleuven.be
Site Name
Antwerp University Hospital
Department Name
Pediatric Gastoenterology
Contact Person Name
Els Van de Vijver
Contact Person Email
Els.vandevijver@uza.be
Site Name
UZ Brussel
Department Name
Pediatric Gastoenterology
Contact Person Name
Elisabeth De Greef
Contact Person Email
Elisabeth.degreef@uzbrussel.be

Italy

Latest Decision Or Authorization Date
17-09-2024
Number Of Sites
5
Number Of Participants
6

Sites

Site Name
Azienda Ospedaliera Universitaria Meyer IRCCS
Department Name
SOC Gastroenterologia e Nutrizione
Contact Person Name
PAOLO LIONETTI
Contact Person Email
paolo.lionetti@unifi.it
Site Name
Azienda Ospedaliero-Universitaria Policlinico Umberto I
Department Name
UOC Gastroenterologia ed Epatologia Pediatrica
Contact Person Name
SALVATORE OLIVA
Contact Person Email
salvatore.oliva@uniroma1.it
Site Name
Azienda Ospedaliera Universitaria Federico II Di Napoli
Department Name
Unità di Endoscopia e Motilità Digestiva Pediatrica
Contact Person Name
ERASMO MIELE
Contact Person Email
erasmo.miele@unina.it
Site Name
Azienda Ospedaliera Universitaria Universita' Degli Studi Della Campania Luigi Vanvitelli
Department Name
UO Pediatria Dipartimento della Donna e del Bambino - Chirurgia Generale Specialistica
Contact Person Name
CATERINA STRISCIUGLIO
Site Name
Azienda Unita Sanitaria Locale Di Bologna
Department Name
UOC Pediatria – Gastroenterologia Pediatrica
Contact Person Name
PATRIZIA ALVISI

Poland

Latest Decision Or Authorization Date
29-08-2024
Number Of Sites
8
Number Of Participants
28

Sites

Site Name
WIP Warsaw IBD Point Profesor Kierkus
Department Name
WIP Warsaw IBD Point Profesor Kierkus
Contact Person Name
Monika Meglicka
Contact Person Email
wip@wip.waw.pl
Site Name
Samodzielny Publiczny Zaklad Opieki Zdrowotnej Centralny Szpital Kliniczny Uniwersytetu Medycznego W Lodzi
Department Name
Klinika Alergologii, Gastroenterologii i Żywienia Dzieci
Contact Person Name
Ewa Toporowska-Kowalska
Contact Person Email
etka@op.pl
Site Name
Twoja Przychodnia Szczecinskie Centrum Medyczne Sp. z o.o.
Department Name
Twoja Przychodnia – Szczecińskie Centrum Medyczne
Contact Person Name
Beata Gawdis - Wojnarska
Contact Person Email
gawdis@twojaprzychodnia.com
Site Name
Gornoslaskie Centrum Zdrowia Dziecka Im. Sw. Jana Pawla II Samodzielny Publiczny Szpital Kliniczny Nr 6 Slaskiego Uniwersytetu Medycznego W Katowicach
Department Name
Oddział Gastroenterologiczny
Contact Person Name
Urszula Grzybowska-Chlebowczyk
Contact Person Email
urszulachlebowczyk@wp.pl
Site Name
Uniwersytecki Szpital Dzieciecy W Krakowie
Department Name
Klinika Pediatrii, Gastroenterologii i Żywienia
Contact Person Name
Kinga Kowalska – Duplag
Contact Person Email
kingakd@mp.pl
Site Name
Instytut Pomnik Centrum Zdrowia Dziecka
Department Name
Klinika Gastroenterologii, Hepatologii, Zaburzeń Odżywiania i Pediatrii
Contact Person Name
Piotr Kierkuś
Contact Person Email
j.kierkus@med-net.pl
Site Name
Korczowski Bartosz, Gabinet Lekarski
Department Name
Korczowski Bartosz, Gabinet Lekarski
Contact Person Name
Bartosz Korczowski
Site Name
Instytut Centrum Zdrowia Matki Polki
Department Name
Klinika Gastroenterologii, Alergologii
Contact Person Name
Elżbieta Czkwianianc
Contact Person Email
kpg@iczmp.edu.pl

Croatia

Latest Decision Or Authorization Date
22-08-2024
Number Of Sites
1
Number Of Participants
4

Sites

Site Name
Klinika Za Djecje Bolesti Zagreb
Department Name
Department of Pediatric Gastroenterology, Hepatology and Eating Disorders
Contact Person Name
Iva Hojsak
Contact Person Email
gastro.dijagnostika@kdb.hr

Sponsor

Primary sponsor

Full Name
Takeda Development Center Americas Inc.
Organisation Type
Pharmaceutical company
Country Of Registered Address
United States

Contract research organisations

Name
Bioclinica Inc.
Responsibilities
Endoscopy - Central Imaging
Name
QPS LLC
Responsibilities
PK, AVA
Name
PPD International Holdings LLC
Responsibilities
Specialty testing (Bulhmann Calprotectin)
Name
PPD Development LP
Name
PPD Global Ltd.
Name
Q Squared Solutions LLC
Responsibilities
Micro - C Difficle PCR (fecal sample), Ova and parasites (fecal sample)

Third parties

  • {"country":"United States","full_name":"Bioclinica Inc.","duties_or_roles":"Endoscopy - Central Imaging","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"United States","full_name":"QPS LLC","duties_or_roles":"PK, AVA","organisation_type":"Pharmaceutical company"}
  • {"country":"Belgium","full_name":"PPD International Holdings LLC","duties_or_roles":"Specialty testing (Bulhmann Calprotectin)","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"PPD Development LP","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
  • {"country":"United Kingdom","full_name":"Q Squared Solutions Limited","duties_or_roles":"Safety (Haematology/Chemistry), C Difficle (fecal sample), TB","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"Greece","full_name":"PPD Global Ltd.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"Electronic data capture / data services (code: 7)","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United States","full_name":"Q Squared Solutions LLC","duties_or_roles":"Micro - C Difficle PCR (fecal sample), Ova and parasites (fecal sample)","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"United States","full_name":"Scout Clinical","duties_or_roles":"Expense Management","organisation_type":"Hospital/Clinic/Other health care facility"}

Investigational products

Investigational Product Name
Entyvio 300 mg powder for concentrate for solution for infusion
Active Substance
Vedolizumab
Modality
Monoclonal antibody
Routes Of Administration
Intravenous
Route
Intravenous
Authorisation Status
Authorised (EU marketing authorisation: EU/1/14/923/001)
Starting Dose
Induction: subjects ≥30 kg: 300 mg IV at Day 1, Week 2, Week 6; >15 to <30 kg: 200 mg IV at Day 1, Week 2, Week 6; 10–15 kg: 150 mg IV at Day 1, Week 2, Week 6.
Dose Levels
Maintenance high vs low by weight group: High = ≥30 kg: 300 mg Q8W; >15–<30 kg: 200 mg Q8W; 10–15 kg: 150 mg Q8W. Low = ≥30 kg: 150 mg Q8W; >15–<30 kg: 100 mg Q8W; 10–15 kg: 100 mg Q8W.
Frequency
Induction: Day 1, Week 2, Week 6; Maintenance: every 8 weeks (Q8W) through Week 46.
Maximum Dose
300 mg
Investigational Product Name
PREDNISONE
Active Substance
Prednisone
Modality
Small molecule
Routes Of Administration
Oral
Route
Oral
Maximum Dose
40 mg (maxDailyDoseAmount as recorded)
Investigational Product Name
BUDESONIDE
Active Substance
Budesonide
Modality
Small molecule
Routes Of Administration
Oral
Route
Oral
Maximum Dose
9 mg (maxDailyDoseAmount as recorded)

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