A Phase I Study of Etrolizumab Followed by Open-Label Extension and Safety Monitoring in Pediatric Patients With Moderate to Severe Ulcerative Colitis or Moderate to Severe Crohn's Disease

NCT ID: NCT03478956

Last Updated: 2024-12-27

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-03-27
• Study Completion Date: 2023-09-27

Brief Summary

This study will evaluate pharmacokinetics, pharmacodynamics and safety of etrolizumab in pediatric patients of 4 to <18 years of age with moderate to severe ulcerative colitis (UC) or with moderate to severe Crohn's disease (CD).

Conditions

Ulcerative Colitis; Crohn's Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Etrolizumab Q4W

Etrolizumab 1.5 milligrams per kilogram of body weight (mg/kg) was administered by subcutaneous (SC) injection once every 4 weeks (Q4W) for a total of 4 doses over the course of the 24-week randomized treatment phase (16-week treatment period plus 8-week safety follow-up). Participants were then given the option to participate in the 312-week open-label extension (OLE) treatment phase with etrolizumab 1.5 mg/kg SC Q4W followed by the 104-week safety surveillance phase (no etrolizumab treatment) to monitor for progressive multifocal leukoencephalopathy (PML). All participants who chose not to enter the OLE phase after the 24-week randomized treatment phase entered the 104-week PML monitoring phase.

Group Type: EXPERIMENTAL

Etrolizumab

Intervention Type: DRUG

Etrolizumab was administered by subcutaneous (SC) injection as described for each treatment arm.

Etrolizumab Q8W

Etrolizumab 3.0 mg/kg was administered by subcutaneous (SC) injection once every 8 weeks (Q8W) for a total of 2 doses over the course of the 24-week randomized treatment phase (16-week treatment period plus 8-week safety follow-up). Participants were then given the option to participate in the 312-week open-label extension (OLE) treatment phase with etrolizumab 1.5 mg/kg SC Q4W followed by the 104-week safety surveillance phase (no etrolizumab treatment) to monitor for progressive multifocal leukoencephalopathy (PML). All participants who chose not to enter the OLE phase after the 24-week randomized treatment phase entered the 104-week PML monitoring phase.

Group Type: EXPERIMENTAL

Etrolizumab

Intervention Type: DRUG

Etrolizumab was administered by subcutaneous (SC) injection as described for each treatment arm.

Interventions

Etrolizumab

Etrolizumab was administered by subcutaneous (SC) injection as described for each treatment arm.

Intervention Type: DRUG

Other Intervention Names

RG7413; RO5490261; PRO145223; rhuMAb Beta7

Eligibility Criteria

Inclusion Criteria

• Age of 4 years to <18 years at the time of signing the Informed Consent Form.
• Weight of 13 kilograms (kg) or more
• Diagnosis of ulcerative colitis (UC) or Crohn's Disease (CD) confirmed by biopsy and established for ≥3 months (i.e., after first diagnosis by a physician according to American College of Gastroenterology [ACG] guidelines) prior to screening
• Inadequate response, loss of response or intolerance to prior immunosuppressants and/or corticosteroid treatment and/or anti-tumor necrosis factor (TNF) therapy
• For postpubertal females of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use acceptable contraceptive methods during the treatment period and for at least 24 weeks after the last dose of etrolizumab.
• For male patients: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm

Exclusion Criteria

• Pregnant or lactating
• Lack of peripheral venous access
• Congenital or acquired immune deficiency
• Neurological conditions or diseases that may interfere with monitoring for progressive multifocal leukoencephalopathy (PML)
• History of demyelinating disease
• History of cancer, including hematologic malignancy, solid tumors, and carcinoma in situ, within 5 years before screening

• Prior extensive colonic resection, subtotal or total colectomy, or planned surgery
• Past or present ileostomy or colostomy
• Diagnosis of indeterminate colitis
• Suspicion of ischemic colitis, radiation colitis, or microscopic colitis
• Diagnosis of toxic megacolon within 12 months of initial screening visit
• Abdominal abscess
• A history or current evidence of colonic mucosal dysplasia
• Patients with fixed symptomatic stenosis of the intestine
• Patients with history or evidence of adenomatous colonic polyps that have not been removed

• Severe extensive colitis per investigator judgment that colectomy is imminent

• Sinus tract with evidence for infection (e.g., purulent discharge) in the clinical judgment of the investigator
• Short-bowel syndrome
• Evidence of abdominal or perianal abscess
• Expected to require surgery to manage CD-related complications during the study

• Any prior treatment with anti-integrin agents (including natalizumab, vedolizumab, and efalizumab), ustekinumab, anti-adhesion molecules (e.g., anti-MAdCAM-1), or rituximab
• Use of IV steroids within 30 days prior to screening with the exception of a single administration of IV steroid
• Use of agents that deplete B or T cells (e.g., alemtuzumab or visilizumab) within 12 months prior to Day 1, with the exception of AZA and 6-MP
• Use of cyclosporine, tacrolimus, sirolimus, or mycophenolate mofetil (MMF) within 4 weeks prior to Day 1
• Use of other biologics (e.g. anti-TNF) within 8 weeks before dosing (unless drug level is below detectability before completion of the 8-week interval)
• Chronic nonsteroidal anti-inflammatory drug (NSAID) use
• Patients who are currently using anticoagulants
• Apheresis (i.e., Adacolumn apheresis) within 2 weeks prior to Day 1
• Received any investigational treatment including investigational vaccines within 12 weeks prior to Day 1 of the study or 5 half-lives of the investigational product, whichever is greater
• History of moderate or severe allergic or anaphylactic/anaphylactoid reactions to chimeric, human, or humanized antibodies, fusion proteins, or murine proteins or hypersensitivity to etrolizumab (active drug substance) or any of the excipients (L-histidine, L-arginine, succinic acid, polysorbate 20)

• Minimum Eligible Age: 4 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

Hôpital Enfants Reine Fabiola

Brussels, , Belgium

Gabinet Lekarski, Bartosz Korczowski

Rzeszów, , Poland

Centrum Zdrowia MDM

Warsaw, , Poland

Hospital Niño Jesus; Servicio de Pediatria - Gastrenterologia y Nutricion

Madrid, , Spain

Royal Manchester Childrens Hospital

Manchester, , United Kingdom

Countries

Germany; United States; Belgium; Poland; Spain; United Kingdom

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2017-003649-10

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CA40192

Identifier Type: -

Identifier Source: org_study_id