A Study of Vedolizumab in Children and Teenagers With Ulcerative Colitis or Crohn's Disease

Official title

An Open-Label, Phase 3 Study to Evaluate the Pharmacokinetics, Safety, and Immunogenicity of Vedolizumab Subcutaneous in Pediatric Subjects With Moderately to Severely Active Ulcerative Colitis or Crohn's Disease Who Achieved Clinical Response Following Open-Label Vedolizumab Intravenous Therapy

Overview

The main aim of this study is to learn how the body of a child or teenager with moderately to severely active ulcerative colitis (UC) or Crohn's disease (CD) processes vedolizumab (pharmacokinetics) given just under the skin subcutaneously (SC). The participants will be treated with vedolizumab for up to 34 weeks. During the study, participants will visit their study clinic several times.

Detailed description

The drug being tested in this study is vedolizumab. Vedolizumab is being tested to treat pediatric participants with moderate to severe active UC or CD who achieved clinical response following open-label vedolizumab intravenous (IV) therapy. The study will look at the pharmacokinetics, safety, and immunogenicity of vedolizumab.

The study will enroll approximately 70 patients. During the Induction Period participants will receive 3 doses of vedolizumab IV infusion at Day 1, Week 2, and Week 6 based on their weight at Baseline as:

* Participants ≥30 kilograms (kg), Vedolizumab (High Dose) * Participants \>15 to \<30 kg, Vedolizumab (Medium Dose) * Participants ≥10 to ≤15 kg, Vedolizumab (Low Dose)

At Week 14, participants who achieve clinical response will be assigned to one of the following groups, stratified by weight to receive vedolizumab 108 mg SC injection during the 20-week Maintenance Period:

* Participants ≥30 kg, Vedolizumab 108 mg once every 2 weeks (Q2W) * Participants ≥10 to \<30 kg, Vedolizumab 108 mg once every 4 weeks (Q4W)

This multi-center trial will be conducted globally. After the Week 34 end of treatment (EOT) visit assessments have been completed, participants may be eligible to receive continued treatment with vedolizumab SC in an extension study, whereas participants who do not qualify to receive continued treatment in the extension study or participants who discontinue from the study for any reason will complete the EOT visit, and the follow-up safety visit (18 weeks after last dose).

Interventions

• Drug Vedolizumab IV
  Vedolizumab IV injection.
• Drug Vedolizumab SC
  Vedolizumab SC injection.

Primary outcome measures

• Ctrough,ss: Steady-state Median Observed Plasma Concentration at the End of a Dosing Interval for Vedolizumab at Week 34 [Time frame: Predose at Week 34]
• Cavg,ss: Average Serum Concentration at Steady-state for Vedolizumab at Week 34 [Time frame: Multiple time points prior to Week 34; pre-dose at Week 34]

Secondary outcome measures (2)

• Percentage of Participants with Positive Antivedolizumab Antibody (AVA) [Time frame: Baseline up to 18 weeks after last dose of study drug (up to Week 50)]
• Percentage of Participants with Positive Neutralizing AVA [Time frame: Baseline up to 18 weeks after last dose of study drug (up to Week 50)]

Eligibility criteria

Inclusion criteria

• The participant weighs ≥10 kg at the time of screening and enrollment into the study.
• Participants with UC or CD diagnosed at least 1 month before screening. Participants with moderately to severely active disease defined as:

• Participants with UC: a modified Mayo score of 5 to 9 (sum of Mayo endoscopic subscore, stool frequency subscore, and rectal bleeding subscore) with a Mayo endoscopic subscore of ≥2 (with the presence of mucosal friability excluding an endoscopic subscore of 1 and mandating a score of at least 2). (The results of screening endoscopy should be applied.)
• Participants with CD: a pediatric Crohn's disease activity index (PCDAI) >30 and a simple endoscopic score for Crohn's disease (SES-CD) >6 (or an SES-CD ≥4 if disease is confined to terminal ileum) at screening endoscopy.
• Participants who have failed, lost response to, or been intolerant to treatment with at least 1 of the following agents: corticosteroids, immunomodulators (for example, azathioprine \[AZA\], 6-mercaptopurine \[6-MP\], methotrexate \[MTX\]), and/or tumor necrosis factor (TNF)-α antagonist therapy (for example, infliximab, adalimumab).
• Participants with evidence of UC extending proximal to the rectum (that is, not limited to proctitis), at a minimum.
• Participants 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.
• Participants with vaccinations that are up-to-date based on the countrywide accepted schedule of childhood vaccines.

Exclusion criteria

• Participants who have had previous exposure to approved or investigational anti-integrins, including but not limited to, natalizumab, efalizumab, etrolizumab, or abrilumab (AMG 181); or mucosal addressin cell adhesion molecule-1 (MAdCAM-1) antagonists (ontamalimab), or rituximab.
• Participants who have had prior exposure to vedolizumab.
• Participants with hypersensitivity or allergies to vedolizumab or any of its excipients.
• Participants with active cerebral/meningeal disease, signs/symptoms or history of progressive multifocal leukoencephalopathy (PML) or any other major neurological disorders.
• The participant has received any live vaccinations within 30 days before first dose of study drug.
• Participants who currently require surgical intervention or are anticipated to require surgical intervention for UC or CD during this study.
• Participants 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.
• Participants with a current diagnosis of indeterminate colitis.
• Participants with clinical features suggesting monogenic very early-onset inflammatory bowel disease (IBD).
• Participants with active or latent tuberculosis (TB).
• Participants with evidence of positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb). Hepatitis B virus (HBV) immune subjects (that is, HBsAg negative and hepatitis B surface antibody \[anti-HBs\]-positive) may, however, be included.
• The participant has any identified congenital or acquired immunodeficiency (for example, common variable immunodeficiency, human immunodeficiency virus \[HIV\] infection, organ transplantation).
• Participants with positive stool studies for ova and/or parasites or stool culture at screening visit.
• Participants with positive Clostridioides difficile (C difficile) stool test at screening visit.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 14 centers

• Phoenix Children's Hospital — Phoenix
• Loma Linda University School of Medicine — Loma Linda
• Children's Hospital Of Orange County — Orange
• Stanford Children's Health — Palo Alto
• Advocate Children's Hospital — Park Ridge
• Children's Hospital of Michigan — Detroit
• Atlantic Health System — Morristown
• New York Presbyterian Hospital, Weill Cornell Medical College — New York
• … and 6 more centers

Italy · 4 centers

• Azienda Ospedaliera Universitaria Gaetano Martino Messina — Messina
• V. Buzzi Hospital — Milan
• Unita Operativa Complessa Di Pediatria Medica — Pescara
• IRCCS Ospedale Pediatrico Bambino Gesu — Rome

Poland · 4 centers

• Instytut Pomnik - Centrum Zdrowia Dziecka — Warsaw
• Korczowski Bartosz, Gabinet Lekarski — Rzeszów
• Medical Network Sp. Z.o.o. WIP Warsaw IBD Point Profesor Kierkus — Warsaw
• SPSK Nr 1 im. Prof. S. Szyszko SUM w Katowicach — Zabrze

South Korea · 4 centers

• Kyungpook National University Chilgok Hospital (KNUCH) — Daegu
• Seoul National University Hospital — Seoul
• Severance Hospital, Yonsei University Health System — Seoul
• Samsung Medical Center — Seoul

Spain · 4 centers

• Complejo Hospitalario Universitario de Ferrol — Ferrol
• Hospital Universitario 12 de Octubre — Madrid
• Hospital U. Virgen Macarena — Seville
• Hospital Univesritario y Politecnico La Fe. Av Fernando abril Martorell106. Valencia 46026 — Valencia

Japan · 3 centers

• Kurume University Hospital — Kurume
• Juntendo University Hospital — Bunkyo-ku
• National Center for Child Health and Development (NCCHD) — Setagaya-Ku

Portugal · 3 centers

• Hospital Pediatrico - Unidade Local de Saude de Coimbra — Coimbra
• Hospital St Maria- Centro Hospitalar de Lisboa, Norte EPE — Lisbon
• Centro Materno Infantil do Norte - Unidade Local de Saude de Santo Antonio — Porto

Romania · 3 centers

• "Emergency County Clinical Hospital ""Pius Brinzeu""" — Timișoara
• Dr Victor Gomoiu Clinical Children Hospital — Bucharest
• Spitalul Clinic de Urgenta Pentru Copii ,,Grigore Alexandrescu, — Bucharest

Serbia · 3 centers

• University Children's Hospital — Belgrade
• Mother and child helath care Institute of Serbia dr Vukan Cupic — Belgrade
• Institute for Childand YouthHealth Care of Vojvodina — Novi Sad

Switzerland · 3 centers

• Centre Hospitalier Universitaire Vaudois (CHUV) — Lausanne
• Inselspital, Universitatsspital Bern, Kinderklinik, Julie-von-Jenner-Haus — Bern
• Universitats-Kinderspital — Zurich

Taiwan · 3 centers

• National Taiwan University Children's Hospital — Taipei
• Changhua Christian Hospital — Changhua
• Kaohsiung Medical University Chung-Ho Memorial Hospital — Kaohsiung City

Belgium · 2 centers

• Cliniques Universitaires Saint-Luc — Brussels
• Centre Hospitalier Chretien MontLegia — Liège

Bulgaria · 1 center

• University Hospital "Saint George" — Plovdiv

Denmark · 1 center

• Hvidovre University Hospital — Hvidovre

Ireland · 1 center

• Childrens Health Ireland — Dublin

Netherlands · 1 center

• Radboud University Medical Center — Nijmegen

Identifiers

NCT: NCT06100289 · VedolizumabSC-3003 · 2023-503188-40-00 · jRCT2071240072

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗