Primary:* To assess the effect of vedolizumab SC maintenance treatment on clinical remission at Week 52 in subjects with moderately to severely active UC who achieved clinical response at Week 6 following administration of vedolizumab IV at Weeks 0…
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 the proportion of subjects with 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 with mucosal healing, defined as Mayo endoscopic
subscore of *1 point, at Week 52.
* Proportion of subjects with durable clinical response, defined as clinical
response at Weeks 6 and 52, where clinical response is defined as a reduction
in complete Mayo score of *3 points and *30% from Baseline (Week 0) with an
accompanying decrease in rectal bleeding subscore of *1 point or absolute
rectal bleeding subscore of *1 point.
* Proportion of subjects with durable clinical remission, defined as clinical
remission at Weeks 6 and 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 maintenance treatment with vedolizumab SC in
subjects with moderately to severely active UC who achieved a clinical response
following open-label therapy with vedolizumab IV. The study includes a
vedolizumab IV reference arm to allow for within study descriptive comparisons
on efficacy, safety, and immunogenicity between the two vedolizumab
presentations.
Study objective
Primary:
* To assess the effect of vedolizumab SC maintenance treatment on clinical
remission at Week 52 in subjects with moderately to severely active UC who
achieved clinical response at Week 6 following administration of vedolizumab IV
at Weeks 0 and 2.
Secondary:
* To determine the effect of vedolizumab SC maintenance treatment on mucosal
healing at Week 52 in subjects who achieved clinical response at Week 6
following administration of vedolizumab IV at Weeks 0 and 2.
* To determine the effect of vedolizumab SC maintenance treatment on durable
clinical response at Week 52 in subjects who achieved clinical response at Week
6 following administration of vedolizumab IV at Weeks 0 and 2.
* To determine the effect of vedolizumab SC maintenance treatment on durable
clinical remission at Week 52 in subjects who achieved clinical response at
Week 6 following administration of vedolizumab IV at Weeks 0 and 2.
* To determine the effect of vedolizumab SC maintenance treatment on
corticosteroid free remission at Week 52 in subjects who achieved clinical
response at Week 6 following administration of vedolizumab IV at Weeks 0 and 2.
Exploratory objectives:
* To assess the PK of multiple doses of vedolizumab SC maintenance treatment in
subjects with moderately to severely active UC.
* To assess the immunogenicity of multiple doses of vedolizumab SC maintenance
treatment in subjects with moderately to severely active UC who achieve
clinical response at Week 6 following administration of vedolizumab IV at Weeks
0 and 2.
* To determine the effect of vedolizumab SC maintenance treatment on
patient-reported outcomes (PRO) from Baseline to Week 52 and from Week 6 to
Week 52 in subjects with moderately to severely active UC who achieved clinical
response at Week 6 following administration of vedolizumab IV at Weeks 0 and 2.
* To determine the effect of vedolizumab SC maintenance treatment on time to
major UC-related events (hospitalizations, colectomies, and procedures) at Week
52 in subjects with moderately to severely active UC who achieved clinical
response at Week 6 following administration of vedolizumab IV at Weeks 0 and 2.
* To determine the effect of vedolizumab SC maintenance treatment on Work
Productivity and Activity Impairment (WPAI-UC) from Baseline (Week 0) to Week
52 and from Week 6 to Week 52 in subjects with moderately to severely active UC
who achieved clinical response at Week 6 following administration of
vedolizumab IV at Weeks 0 and 2.
* To descriptively compare the efficacy, safety, and immunogenicity of the
vedolizumab IV and vedolizumab SC presentations.
* To correlate UC-associated genetic polymorphisms and inflammation biomarkers
with therapeutic response to vedolizumab SC maintenance treatment, if indicated.
* To determine the effect of vedolizumab SC maintenance treatment on
histological remission at Week 52 in subjects who achieved clinical response at
Week 6 following administration of vedolizumab IV at Weeks 0 and 2.
* To determine the effect of vedolizumab SC maintenance treatment on clinical
remission at Week 52 in subjects who achieved clinical response at Week 6
following administration of vedolizumab IV at Weeks 0 and 2 using an alternate
definition on clinical remission.
* To determine the effect of vedolizumab SC maintenance treatment on achieving
corticosteroid free status for 90 days and 180 days, respectively, at Week 52
in subjects who achieved clinical response at Week 6 following administration
of vedolizumab IV at Weeks 0 and 2.
* To determine the effect of vedolizumab SC maintenance treatment on durable
clinical remission at Week 52, where durable clinical remission is defined as
clinical remission at Weeks 6 and 52 in subjects who achieved remission at Week
6.
Study design
This is a pivotal, phase 3, multicenter, multinational, randomized,
double-blind, double-dummy, placebo-controlled trial, including a vedolizumab
IV reference arm, designed to evaluate the efficacy and safety of maintenance
treatment with vedolizumab SC in adult subjects with moderately to severely
active UC who achieved a clinical response at Week 6 following open-label
therapy with 300 mg vedolizumab IV administered at Weeks 0 and 2. The study
includes a vedolizumab IV reference arm to allow for within study descriptive
comparisons on efficacy, safety, and immunogenicity between the two vedolizumab
presentations.
Moderately to severely active UC is defined as a complete Mayo score of 6 to 12
points with endoscopic subscore of *2. Subjects that are tumor necrosis
factor-alpha (TNF-*) antagonist naïve or with TNF-* antagonist failure will be
included, ensuring that no more than 50% of subjects with TNF-* antagonist
failure are enrolled.
Intervention
Following screening, all subjects that meet the entry criteria for the study
will enter a 6-week induction phase during which they will receive 300 mg open
label vedolizumab IV at weeks 0 and 2.
If at week 6 a clinical response is achieved, subjects will be randomized over
3 groups for the maintenance phase. 50% will receive vedolizumab SC injections
and placebo infusions (group 1). 25% will receive placebo injections and
vedolizumab IV infusions (group 2). 25% will receive placebo injections and
placebo infusions (group 3).
During maintenance, subjects will receive 300 mg vedolizumab IV/placebo
infusions at weeks 6, 14, 22, 30, 38 and 46. Including the induction phase, in
total 8 infusions will be given during the course of the study.
During maintenance, subjects will receive 108 mg vedolizumab SC/placebo
injections every 2 weeks from week 6 till week 50. In total, 23 injections will
be given during the course of the study. Subjects will be trained to administer
these injections themselves.
Study burden and risks
Including screening and follow-up the study will consist of 30 visits over a
period of 68 weeks. These visits will partly be in the hospital and partly take
place at home. The hospital will need to be visited at least 15 times. During
the treatment period subjects will receive 8 infusions and 23 injections over a
period of 50 weeks. The injections will largely be administered by subjects
themselves. Subjects will need to maintain a daily electronic diary throughout
the study up until week 52 and complete 3 questionnaires at 5 study visits.
Procedures will among others include 3 flexible sigmoidoscopies, 2 ECGs and
collection of blood (15x), stool (4x) and urine (4x) samples. As part of the
study screening subjects will be tested for 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
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.
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 | EUCTR2015-000480-14-NL |
| ClinicalTrials.gov | NCT02611830 |
| CCMO | NL55501.056.15 |