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
Condition: Ulcerative Colitis; Crohn's Disease
MeSH terms: Crohn Disease; Colitis; Colitis, Ulcerative; Ulcer
Intervention: Etrolizumab
Intervention description: Etrolizumab was administered by subcutaneous (SC) injection as described for each treatment arm.
Intervention MeSH terms: Etrolizumab
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 24.0
Sex: All
Minimum age: 4 Years
Maximum age: 17 Years
Healthy volunteers: No

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)