An Efficacy and Safety Study of Vedolizumab Intravenous (IV) Compared to Adalimumab Subcutaneous (SC) in Participants With Ulcerative Colitis

Phase 3

Completed

• Conditions: Colitis, Ulcerative
• Interventions: Drug: Vedolizumab; Drug: Adalimumab; Drug: Vedolizumab placebo; Drug: Adalimumab placebo

• Registration Number: NCT02497469
• Lead Sponsor: Takeda

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of vedolizumab intravenous (IV) treatment compared to adalimumab subcutaneous (SC) treatment over a 52-week treatment period.

Detailed Description

The drug being tested in this study is called vedolizumab. Vedolizumab is being tested to treat people who have ulcerative colitis. This study will look at the stool frequency, rectal bleeding and findings on endoscopy of people who take vedolizumab compared to those who take adalimumab.

The study will enroll approximately 658 participants. Participants will be randomly assigned (by chance, like flipping a coin) to one of the two treatment groups-which will remain undisclosed to the patient and study doctor during the study (unless there is an urgent medical need):

* Vedolizumab 300 mg IV

* Adalimumab 160 mg on Day 1 followed by 80 mg on Week 2 then 40 mg every 2 weeks SC

All participants will receive 1 intravenous infusion on Day 1 and Weeks 2, 6, 14, 22, 30, 38, and 46. All participants will also receive 4 SC injections on Day 1 or 2 SC injections each on Days 1 and 2, followed by 2 SC injections in 1 day on Week 2 and then 1 SC injection every 2 weeks for up to Week 50. All participants will be asked to record the symptoms of ulcerative colitis in a daily diary.

This multi-center trial will be conducted worldwide. The overall time to participate in this study is 79 weeks. Participants will make approximately 11 visits to the clinic, and will be contacted by telephone 6 months after last dose of study drug for a follow-up assessment.

Study Timeline

• Study Start: 2015-06-29
• Study First Submitted: 2015-07-10
• Study First Submitted QC: 2015-07-10
• Study First Posted: 2015-07-14
• Primary Completion: 2018-09-26
• Study Completion: 2019-01-18
• Results First Submitted: 2019-09-17
• Results First Submitted QC: 2019-09-17
• Results First Posted: 2019-10-10
• Status Verified: 2020-01
• Last Update Submitted: 2020-01-14
• Last Update Posted: 2020-01-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 771

Inclusion Criteria

1. Has a diagnosis of ulcerative colitis established at least 3 months prior to screening by clinical and endoscopic evidence and corroborated by a histopathology report.

2. Has moderately to severely active ulcerative colitis as determined by a Mayo score of 6 to 12 with an endoscopic subscore greater than or equal to >=2 within 14 days prior to the randomization.

3. Has evidence of ulcerative colitis proximal to the rectum (>=15 centimeter [cm] of involved colon).

4. With extensive colitis (up to the hepatic flexure) or pancolitis of >8 years duration or left-sided colitis of >12 years duration must have documented evidence that a surveillance colonoscopy was performed within 12 months of the initial screening visit (may be performed during the Screening Period).

5. The participant:

   1. Has had previous treatment with tumor necrosis factor- alpha (TNF-alpha) antagonists without documented clinical response to treatment (example, due to lack of response [primary nonresponders], loss of response, or intolerance [secondary nonresponders]), or
   2. Has previously used a TNF-alpha antagonists (except adalimumab), and discontinued its use due to reasons other than safety, or
   3. Is naïve to TNF-alpha antagonist therapy but is failing current treatment (example, corticosteroids, 5-aminosalicylate [5-ASA], or immunomodulators).

Exclusion Criteria

1. Clinical evidence of abdominal abscess or toxic megacolon at Screening.

2. Has had an extensive colonic resection, subtotal or total colectomy.

3. Has had ileostomy, colostomy, or known fixed symptomatic stenosis of the intestine.

4. Has a diagnosis of Crohn's colitis or indeterminate colitis, ischemic colitis, radiation colitis, diverticular disease associated with colitis, or microscopic colitis.

5. Has received any of the following for the treatment of underlying disease within 30 days of randomization:

   1. Non-biologic therapies (example, cyclosporine, tacrolimus, thalidomide) other than those specifically listed in Section Permitted Medications For Treatment of UC.
   2. An approved non-biologic therapy in an investigational protocol.

6. Has received any investigational or approved biologic or biosimilar agent within 60 days or 5 half lives prior to the screening (whichever is longer).

7. Has previously received natalizumab, efalizumab, adalimumab, AMG-181, anti-mucosal addressin cell adhesion molecule-1 antibodies, or rituximab.

8. Has previously received vedolizumab.

9. Has history or evidence of adenomatous colonic polyps that have not been removed, or colonic mucosal dysplasia.

10. Evidence of an active infection during Screening.

11. Evidence of, or treatment for, Clostridium difficile (C. difficile) or other intestinal pathogen within 28 days prior to the 1st dose of study drug.

12. Has chronic hepatitis B virus (HBV) infection* or chronic hepatitis C virus (HCV) infection (* HBV immune participants, ie, being hepatitis B surface antigen [HBsAg], may participate).

13. Has active or latent TB, regardless of treatment history.

14. Has used a topical (rectal) treatment with (5-ASA) or corticosteroid enemas/suppositories within 2 weeks of the administration of the 1st dose of study drug.

15. Has a positive progressive multifocal leukoencephalopathy (PML) subjective symptom checklist prior to the administration of the first dose of study drug.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Adalimumab SC 160/80/40 mg	Vedolizumab placebo	Adalimumab 160 mg, injection, subcutaneously on Day 1, adalimumab 80 mg, injection, subcutaneously at Week 2, then adalimumab 40 mg, injection, subcutaneously every 2 weeks thereafter up to Week 50. Vedolizumab placebo-matching infusion, intravenously on Day 1 and Weeks 2, 6, 14, 22, 30, 38, and 46.
Vedolizumab IV 300 mg	Adalimumab placebo	Vedolizumab 300 milligram (mg), infusion, intravenously over 30 minutes on Day 1 and Weeks 2, 6, 14, 22, 30, 38, and 46. Adalimumab placebo-matching injection, subcutaneously on Day 1, Week 2, and every 2 weeks thereafter up to Week 50.
Vedolizumab IV 300 mg	Vedolizumab	Vedolizumab 300 milligram (mg), infusion, intravenously over 30 minutes on Day 1 and Weeks 2, 6, 14, 22, 30, 38, and 46. Adalimumab placebo-matching injection, subcutaneously on Day 1, Week 2, and every 2 weeks thereafter up to Week 50.
Adalimumab SC 160/80/40 mg	Adalimumab	Adalimumab 160 mg, injection, subcutaneously on Day 1, adalimumab 80 mg, injection, subcutaneously at Week 2, then adalimumab 40 mg, injection, subcutaneously every 2 weeks thereafter up to Week 50. Vedolizumab placebo-matching infusion, intravenously on Day 1 and Weeks 2, 6, 14, 22, 30, 38, and 46.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Who Achieved Clinical Remission	Week 52	Clinical remission was defined as a complete Mayo score of ≤2 points and no individual subscore \>1 point. The Mayo score was a standard assessment tool to measure ulcerative colitis disease activity in clinical trials. The index consisted of 4 subscores: rectal bleeding, stool frequency, findings on endoscopy, and physician's global assessment. Each subscore was scored on a scale from 0 to 3 and the complete Mayo score ranges from 0 to 12 (higher scores indicate greater disease activity).

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants Who Achieved Mucosal Healing	Week 52	Mucosal healing was defined as a Mayo score endoscopic subscore of \<= 1 point. The Mayo score was a standard assessment tool to measure ulcerative colitis disease activity in clinical trials. The index consisted of 4 subscores: rectal bleeding, stool frequency, findings on endoscopy, and physician's global assessment. Each subscore was scored on a scale from 0 to 3 and the complete Mayo score ranges from 0 to 12 (higher scores indicate greater disease activity).
Percentage of Participants Who Used Oral Corticosteroids at Baseline Who Discontinued Corticosteroids and Were in Clinical Remission	Week 52	Corticosteroid-free remission was defined as participants using oral corticosteroids at Baseline (Week 0) who had discontinued oral corticosteroids and were in clinical remission at Week 52. Clinical remission was defined as a complete Mayo score of ≤ 2 points and no individual subscore \> 1 point. The Mayo score was a standard assessment tool to measure ulcerative colitis disease activity in clinical trials. The index consisted of 4 subscores: rectal bleeding, stool frequency, findings on endoscopy, and physician's global assessment. Each subscore was scored on a scale from 0 to 3 and the complete Mayo score ranges from 0 to 12 (higher scores indicate greater disease activity).

Trial Locations

Locations (329)

IMC - Diagnostic and Medical Clinic; 🇺🇸 Mobile, Alabama, United States

Arizona Arthritis & Rheumatology Research, PLLC; 🇺🇸 Phoenix, Arizona, United States

Arkansas Primary Care Clinic, PA; 🇺🇸 Little Rock, Arkansas, United States

WCCT Global (PH 1 Unit); 🇺🇸 Costa Mesa, California, United States

California Medical Research Associates Inc.; 🇺🇸 Northridge, California, United States

Sutter Institute for Medical Research; 🇺🇸 Sacramento, California, United States

Rocky Mountain Gastroenterology; 🇺🇸 Lakewood, Colorado, United States

Medical Research Center of Connecticut, LLC; 🇺🇸 Hamden, Connecticut, United States

Innovative Medical Research of South Florida, Inc.; 🇺🇸 Aventura, Florida, United States

Advanced Clinical Research of Miami; 🇺🇸 Doral, Florida, United States

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