A Phase 3 Randomized, Double-Blind, Placebo-Controlled Study, with a Vedolizumab IV Reference Arm, to Evaluate the Efficacy and Safety of Vedolizumab Subcutaneous as Maintenance Therapy in Subjects With Moderately to Severely Active Ulcerative Colitis Who Achieved Clinical Response Following Open-Label Vedolizumab Intravenous Therapy

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 5

Inclusion Criteria

1. The subject has a diagnosis of UC established at least 6 months prior to screening, by clinical and endoscopic evidence and corroborated by a histopathology report.;2. The subject has moderately to severely active UC as determined by a complete Mayo score of 6-12 with an endoscopic subscore *2 within 10 days prior to the first dose of study drug.;3. The subject has evidence of UC extending proximal to the rectum (*15 cm of involved colon).;4. The subject has demonstrated an inadequate response to, loss of response to, or intolerance of at least 1 of the following agents: immunomodulators, corticosteroids, or TNF-alpha antagonist.

Exclusion Criteria

1. The subject has evidence of abdominal abscess or toxic megacolon at the initial Screening Visit.;2. The subject has had extensive colonic resection, subtotal or total colectomy.;3. The subject has had ileostomy, colostomy, or known fixed symptomatic stenosis of the intestine.;4. The subject has received any of the investigational or approved non-biologic therapies (eg, cyclosporine, tacrolimus, thalidomide, methotrexate or tofacitinib, except for those specifically listed in the protocol) for the treatment of underlying disease within 30 days or 5 half-lives of screening (whichever is longer).;5. The subject has received any investigational or approved biologic or biosimilar agent within 60 days or 5 half-lives of screening (which ever is longer). ;6. The subject currently requires or is anticipated to require surgical intervention for UC during the study.;7. The subject has a history or evidence of adenomatous colonic polyps that have not been removed, or has a history or evidence of colonic mucosal dysplasia.;8. The subject has a suspected or confirmed diagnosis of Crohn*s entercolitis, indeterminate colitis, ischaemic colitis, radiation colitis, diverticular disease associated with colitis, or microscopic colitis.;9. The subject has evidence of an active infection during the Screening Period.;10. The subject has evidence of, or treatment for, C. difficile infection or other intestinal pathogen with 28 days prior to first dose of study drug. ;11. The subject has chronic hepatitis B virus (HBV) infection or chronic hepatitis C virus (HCV) infection. HBV immune subjects (ie, being hepatitis B surface antigen [HBsAg] negative and hepatitis B antibody positive) may, however, be included.;12. The subject has active or latent TB as evidenced by the following:
i. A positive diagnostic TB test within 30 days prior to screening or during the Screening Period, defined as:
1. A positive QuantiFERON test or 2 successive indeterminate QuantiFERON tests, (or, A positive T-SPOT TB test [Japan only]), OR,
2. A tuberculin skin test reaction *5 mm.
Note: if subjects have received BCG vaccine then a QuantiFERON TB Gold test should be performed instead of the tuberculin skin test.
OR
ii. Chest X-ray within 3 months prior to Week 0 which is suspicious for pulmonary TB, and a positive or 2 successive indeterminate QuantiFERON tests (or, A positive T-SPOT TB test [Japan only]) within 30 days prior to Screening or during the Screening Period.
Note: subjects with documented previously treated TB with a negative QuantiFERON test can be included in the study.;13. The subject has any identified congenital or acquired immunodeficiency (eg, common variable immunodeficiency, human immunodeficiency virus [HIV] infection, organ transplantation).;14. The subject has received any live vaccinations within 30 days prior to screening.;15. The subject had a clinically significant infection (eg, pneumonia, pyelonephritis) within 30 days prior to screening, or ongoing chronic infection.;16. The subject has used a topical (rectal) treatment with 5-aminosalicylic acid (5-ASA) or corticosteroid enemas/suppositories within 2 weeks of the administration of the first dose of study drug.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The primary endpoint for the study is the proportion of subjects with clinical<br /><br>remission, defined as a complete Mayo score of *2 points and no individual<br /><br>subscore >1 point, at Week 52.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Secondary endpoints for this study are:<br /><br>* Proportion of subjects with mucosal healing, defined as Mayo endoscopic<br /><br>subscore of 1 point, at Week 52.<br /><br> Proportion of subjects with durable clinical response, defined as clinical<br /><br>response at Weeks 6 and 52, where clinical response is defined as a reduction<br /><br>in complete Mayo score of 3 points and 30% from Baseline (Week 0) with an<br /><br>accompanying decrease in rectal bleeding subscore of 1 point or absolute<br /><br>rectal bleeding subscore of 1 point.<br /><br>* Proportion of subjects with durable clinical remission, defined as clinical<br /><br>remission at Weeks 6 and 52.</p><br>