A Phase 3b Open-label Study to Determine the Long-term Safety and Efficacy of Vedolizumab Subcutaneous in Subjects with Ulcerative Colitis and Crohn*s Disease

Current treatments have been effective for many patients with inflammatory
bowel disease 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. Vedolizumab SC is a new liquid
presentation that has been developed for subcutaneous administration to enable
self-injection by patients or their caregivers. The aim of the current study is
to gather data on the long-term safety and efficacy of vedolizumab SC in
subjects with ulcerative colitis (UC) or Crohn*s disease (CD).

Primary:
* To obtain data on long term safety and tolerability on vedolizumab SC in
subjects with Ulcerative Colitis (UC) or Crohn's Disease (CD).

Secondary:
* To obtain data on adverse events of special interest (AESIs; serious
infections including opportunistic infection such as PML, liver injury,
malignancies, injection site reactions or systemic reactions and
hypersensitivity) in UC and CD subjects receiving long-term vedolizumab SC
treatment.
* To obtain data on maintaining clinical response and clinical remission in UC
and CD subjects receiving long-term vedolizumab SC treatment
* To obtain data on patient reported outcomes (PROs) including quality of life
and work productivity and activity, in UC and CD subjects receiving long-term
vedolizumab SC treatment
* To obtain data on time to major UC and CD-related events (hospitalizations,
bowel surgeries, and procedures) in UC and CD subjects receiving long-term
vedolizumab SC treatment

This is a phase 3b open-label extension (OLE) study to gather the long-term
safety and efficacy of vedolizumab subcutaneous (vedolizumab SC) in subjects
with ulcerative colitis (UC) or Crohn*s disease (CD). All enrolled subjects
will receive vedolizumab SC 108 mg. From this OLE study of vedolizumab SC
therapy, data regarding the occurrence of important clinical events resulting
from chronic vedolizumab SC administration will be obtained. Important clinical
events including those related to safety and adverse events of special interest
(AESIs; serious infections including opportunistic infection such as PML, liver
injury, malignancies, injection site reactions or systemic reactions and
hypersensitivity) as well as efficacy (eg, maintenance of clinical remission/
clinical response, quality of life, and various other patient-reported outcome
[PRO] measures) will be collected. This study will provide long-term safety
data for vedolizumab SC dosing to complement the safety data gathered from
Study MLN0002SC-3027 in UC subjects and Study MLN0002SC-3031 in CD subjects.

The first dose of vedolizumab SC in this OLE study will be timed according to
the last
dose of study drug in the MLN0002SC-3027 or MLN0002SC-3031 studies, to maintain
the trough serum concentration above the level associated with clinical
efficacy of
vedolizumab IV in UC and CD subjects.

Subjects with UC or CD who completed the Maintenance Period (Week 52
assessment) will receive vedolizumab SC 108 mg Q2W.

Subjects with UC or CD who withdrew early from the Maintenance Period due to
disease worsening or need for rescue medications will receive vedolizumab SC
108 mg QW.

Subjects with UC and CD who did not achieve a clinical response at Week 6 but
who did achieve a clinical response at Week 14 after having received a 3rd
vedolizumab IV infusion at Week 6 will receive vedolizumab SC 108 mg Q2W.

Subjects will need to visit the hospital 3 times during the first 8 weeks and
then once every 8 weeks. The total study duration will vary by subject
depending on continued benefit. During the treatment period subjects will
self-inject the study drug every week or every 2 weeks, depending on their
response in the prior study. Subjects will need to maintain a daily electronic
diary throughout the study and complete 3 questionnaires every 24 weeks.
Procedures will include physical exams, ECGs and collection of blood, stool and
urine samples.
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.