Clinical trial NCT06100289: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Ulcerative Colitis
Crohn's Disease
Keywords: Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2023-10-25
Enrollment: 70
Sex: ALL
Minimum age (years): 2
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).

Eligibility criteria: Inclusion Criteria:

1. The participant weighs ≥10 kg at the time of screening and enrollment into the study.
2. 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.
3. 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).
4. Participants with evidence of UC extending proximal to the rectum (that is, not limited to proctitis), at a minimum.
5. 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.
6. Participants with vaccinations that are up-to-date based on the countrywide accepted schedule of childhood vaccines.

Exclusion Criteria:

1. 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.
2. Participants who have had prior exposure to vedolizumab.
3. Participants with hypersensitivity or allergies to vedolizumab or any of its excipients.
4. Participants with active cerebral/meningeal disease, signs/symptoms or history of progressive multifocal leukoencephalopathy (PML) or any other major neurological disorders.
5. The participant has received any live vaccinations within 30 days before first dose of study drug.
6. Participants who currently require surgical intervention or are anticipated to require surgical intervention for UC or CD during this study.
7. 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.
8. Participants with a current diagnosis of indeterminate colitis.
9. Participants with clinical features suggesting monogenic very early-onset inflammatory bowel disease (IBD).
10. Participants with active or latent tuberculosis (TB).
11. 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.
12. The participant has any identified congenital or acquired immunodeficiency (for example, common variable immunodeficiency, human immunodeficiency virus \[HIV\] infection, organ transplantation).
13. Participants with positive stool studies for ova and/or parasites or stool culture at screening visit.
14. Participants with positive Clostridioides difficile (C difficile) stool test at screening visit.

Primary outcomes:
measure: Ctrough,ss: Steady-state Median Observed Plasma Concentration at the End of a Dosing Interval for Vedolizumab at Week 34
timeFrame: Predose at Week 34
measure: Cavg,ss: Average Serum Concentration at Steady-state for Vedolizumab at Week 34
timeFrame: Multiple time points prior to Week 34; pre-dose at Week 34
Secondary outcomes:
measure: Percentage of Participants with Positive Antivedolizumab Antibody (AVA)
timeFrame: Baseline up to 18 weeks after last dose of study drug (up to Week 50)
measure: Percentage of Participants with Positive Neutralizing AVA
timeFrame: Baseline up to 18 weeks after last dose of study drug (up to Week 50)
Other outcomes:
Locations:
city: Garden Grove
country: United States
facility: VVCRD Clinical Research
state: California
city: Loma Linda
country: United States
facility: Loma Linda University School of Medicine
state: California
city: Orange
country: United States
facility: Children's Hospital Of Orange County
state: California
city: Palo Alto
country: United States
facility: Stanford Children's Health
state: California
city: Park Ridge
country: United States
facility: Advocate Children's Hospital
state: Illinois
city: Detroit
country: United States
facility: Children's Hospital of Michigan
state: Michigan
city: Morristown
country: United States
facility: Morristown Medical Center
state: New Jersey
city: New York
country: United States
facility: The New York Presbyterian Hospital, Weill Cornell Medical College
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Oklahoma City
country: United States
facility: The University of Oklahoma Health Sciences Center
state: Oklahoma
city: North Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Brussels
country: Belgium
facility: Hospital UCL Saint Luc
city: Liege
country: Belgium
facility: Centre Hospitalier Chretien MontLegia
city: Plovdiv
country: Bulgaria
facility: UMHAT Sveti Georgi EAD
city: Sofia
country: Bulgaria
facility: Specialized Hospital for Active Treatment of Children's diseases Prof Ivan Mitev
city: Hvidovre
country: Denmark
facility: Hvidovre University Hospital
state: Hovedstaden
city: Dublin
country: Ireland
facility: Childrens Health Ireland
city: Messina
country: Italy
facility: Azienda Ospedaliera Universitaria Gaetano Martino Messina
city: Milan
country: Italy
facility: Ospedale dei Bambini Vittore Buzzi
city: Pescara
country: Italy
facility: Unita Operativa Complessa Di Pediatria Medica
city: Rome
country: Italy
facility: IRCCS Ospedale Pediatrico Bambino Gesu
city: Kurume
country: Japan
facility: Kurume University Hospital
state: Fukuoka
city: Setagaya-Ku Tokyo
country: Japan
facility: National Center for Child Health and Development (NCCHD)
state: Tokyo-to
city: Bunkyo-ku
country: Japan
facility: Juntendo University Hospital
state: Tokyo
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Chilgok Hospital (KNUCH)
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Nijmegen
country: Netherlands
facility: Radboud University Medical Center
state: Gelderland
city: Warsaw
country: Poland
facility: Instytut Pomnik - Centrum Zdrowia Dziecka
state: Mazowieckie
city: Zabrze
country: Poland
facility: SPSK Nr 1 im. Prof. S. Szyszko SUM w Katowicach
state: Slaskie
city: Krakow
country: Poland
facility: Uniwersytecki Szpital Dzieciecy W Krakowie
city: Rzeszow
country: Poland
facility: Korczowski Bartosz, Gabinet Lekarski
city: Warsaw
country: Poland
facility: WIP Warsaw IBD Point Profesor Kierkus
city: Coimbra
country: Portugal
facility: Hospitais da Universidade de Coimbra
city: Lisboa
country: Portugal
facility: Hospital St Maria- Centro Hospitalar de Lisboa, Norte EPE
city: Porto
country: Portugal
facility: Centro Hospitalar Universitario do Porto - Hospital de Santo Antonio
city: Timisoara
country: Romania
facility: Emergency County Clinical Hospital Pius Brinzeu
state: Timis
city: Bucharest
country: Romania
facility: Children's Clinical Hospital Dr. Victor Gomoiu
city: Bucharest
country: Romania
facility: Emergency Clinical Hospital for Children Grigore Alexandrescu
city: Belgrade
country: Serbia
facility: University Children's Clinic
city: Belgrade
country: Serbia
facility: Institut Za Zdravstvenu Zastitu Majke I Deteta Srbije Dr Vukan Cupic
city: Novi Sad
country: Serbia
facility: Institute for Childand YouthHealth Care of Vojvodina
city: Ferrol
country: Spain
facility: Hospital Arquitecto Marcide de Ferrol
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Sevilla
country: Spain
facility: Universidad de Sevilla - Hospital Universitario Virgen Macarena
city: Valencia
country: Spain
facility: Universitat de Valencia - Hospital Universitari i Politecnic La Fe de Valencia (Hospital La Fe Bulevar Sur)
city: Bern
country: Switzerland
facility: Inselspital - Universitatsspital Bern - Kinderklinik Bern
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois (CHUV)
city: Luzern 16
country: Switzerland
facility: Kantonsspital Luzern
city: Zurich
country: Switzerland
facility: Children's Hospital Zurich
city: Changhua
country: Taiwan
facility: Changhua Christian Medical Foundation - Changhua Christian Childrens Hospital
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Chung-Ho Memorial Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Istanbul
country: Turkey
facility: Koc University Hospital
state: Zeytinburnu
city: Istanbul
country: Turkey
facility: Istanbul University, Istanbul Medical Faculty
city: Izmir
country: Turkey
facility: Dokuz Eylul University Medical Faculty
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: