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

Conditions: Ulcerative Colitis; Crohn's Disease

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).


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 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)