Primary:* To determine the effect of vedolizumab IV compared to adalimumab SC on clinical remission at Week 52.Secondary:* To evaluate the effect of vedolizumab IV compared to adalimumab SC on mucosal healing at Week 52.* To evaluate the effect of…
ID
Source
Brief title
Condition
- Gastrointestinal inflammatory conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint for the study is proportion of subjects achieving clinical
remission (defined as a complete Mayo score of *2 points and no individual
subscore >1 point) at Week 52.
Secondary outcome
Secondary endpoints for this study are:
* Proportion of subjects achieving mucosal healing (defined as Mayo endoscopic
subscore *1 point) at Week 52.
* Proportion of subjects using oral corticosteroids at Baseline who have
discontinued corticosteroids and are in clinical remission at Week 52.
Background summary
Current treatments have been effective for many patients with UC but have
numerous limitations for patients with moderately to severely active disease.
These limitations indicate that there is a significant need for safer and more
effective therapies. Vedolizumab (also called MLN0002) is a humanized
immunoglobulin (Ig) G1 mAb developed as a treatment for UC and CD that acts as
a gut-selective immunomodulator. The aim of the current study is to evaluate
the efficacy and safety of vedolizumab IV compared with adalimumab SC in the
treatment of subjects with moderately to severely active UC.
Study objective
Primary:
* To determine the effect of vedolizumab IV compared to adalimumab SC on
clinical remission at Week 52.
Secondary:
* To evaluate the effect of vedolizumab IV compared to adalimumab SC on mucosal
healing at Week 52.
* To evaluate the effect of vedolizumab IV compared to adalimumab SC on
corticosteroid-free remission at Week 52.
Study design
This is a phase 3b randomized, double-blind, double-dummy, multicenter,
active-controlled study to evaluate the efficacy and safety of vedolizumab
compared to adalimumab over a 52 week Treatment Period followed by 18-week
Follow-up Period. The study will be conducted globally and will include 658
subjects with moderately to severely active ulcerative colitis (UC).
Intervention
On Day 1, subjects who meet the inclusion criteria and who meet none of the
exclusion criteria will be randomly assigned in a 1:1 ratio to double-blind
medication for 50 weeks.
Subjects in the vedolizumab treatment group will receive a 300 mg intravenous
(IV) infusion on Day 1 and Weeks 2, 6, 14, 22, 30, 38, and 46, as well as
placebo subcutaneous (SC) injection on Day 1, Week 2, and once every 2 weeks
(Q2W) thereafter until Week 50.
Subjects in the adalimumab treatment group will receive a 160 mg SC injection
on Day 1 (4 40 mg injections in 1 day or 2 40 mg injections per day for 2
consecutive days), 80 mg at Week 2 (2 40 mg injections in 1 day), then 40 mg
Q2W thereafter until Week 50, as well as a placebo IV infusion at Day 1 and
Weeks 2, 6, 14, 22, 30, 38, and 46.
Study burden and risks
Including screening and follow-up the study will consist of 29 visits (12 at
the hospital, the remaining at home) over a period of 72 weeks. Additionally,
subjects will be required to participate in a long-term follow-up (LTFU) safety
survey by telephone 6 months after the last dose of study drug.
During the treatment period subjects will receive 8 infusions and 26 injections
over a period of 50 weeks. Subjects will need to maintain a daily electronic
diary throughout the study up until week 52 and complete an IBDQ questionnaire
at 3 study visits. Procedures will among others include 3 flexible
sigmoidoscopies (with biopsy), 2 ECGs and collection of blood (10x), stool (5x)
and urine (2x) samples. As part of the study screening subjects will be tested
for TB, HIV and Hepatitis B/C and be informed of any positive result.
The most common side effects of the study drug, reported in more than 10% of
patients, include common cold, headache, joint pains and worsening of Crohn*s
disease in patients with Crohn*s disease. To address the theoretical risk of
the development of PML in subjects treated with vedolizumab, a Risk
Minimization Action Plan for PML will be implemented.
Aldwich 61
London WC2B 4AE
GB
Aldwich 61
London WC2B 4AE
GB
Listed location countries
Age
Inclusion criteria
* The subject has a diagnosis of UC established at least 3 months prior to enrollment, by clinical and endoscopic evidence and corroborated by a histopathology report.;* The subject has moderately to severely active UC as determined by a complete Mayo score of 6-12 with an endoscopic subscore *2 within 14 days prior to randomization.;* The subject has evidence of UC extending proximal to the rectum (*15 cm of involved colon).;* a. The subject has had previous treatment with tumor necrosis factor*alpha (TNF-*) antagonists without documented clinical response to treatment (eg, due to lack of response [primary nonresponders], loss of response, or intolerance [secondary nonresponder], or
b. Has previously used a TNF-alpha antagonist (except adalimumab), and discontinued its use due to reasons other than safety.;* The subject is naïve to TNF-alpha antagonist therapy but is failing current treatment (ie, corticosteroids, 5-aminosalicylate, or immunomodulators).
Exclusion criteria
* The subject has had extensive colonic resection, subtotal or total colectomy.;* The subject has any evidence of an active infection during Screening. ;* The subject has a positive progressive multifocal leukoencephalopathy (PML) subjective symptom checklist at Screening or before the administration of study drug at Day 1. ;* The subject has received any investigational or approved biologic or biosimilar agent (other than those listed below) within 60 days or 5 half lives prior to screening (whichever is longer).;* The subject has had prior exposure to vedolizumab, natalizumab, efalizumab, adalimumab, etrolizumab, AMG-181, anti-mucosal addressin cell adhesion molecule-1 (MAdCAM-1)-antibodies or rituximab.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2015-000939-33-NL |
| ClinicalTrials.gov | NCT02497469 |
| CCMO | NL54690.056.15 |