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

A Phase I, Open-Label, Randomized, Pharmacokinetic, Pharmacodynamic, and Safety Study of Etrolizumab Followed by Open-Label Extension and Safety Monitoring in Pediatric Patients From 4 Years to Less Than 18 Years Of Age With Moderate to Severe Ulcerative Colitis or Moderate To Severe Crohn's Disease

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).

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

Exclusion Criteria Related to Inflammatory Bowel Disease:

• 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

Exclusion Criteria Related to Ulcerative Colitis:

• Severe extensive colitis per investigator judgment that colectomy is imminent

Exclusion Criteria Related to Crohn's Disease:

• 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

Exclusion Criteria Related to Prior or Concomitant Therapy:

• 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)