Effectiveness and Safety of Vedolizumab SC as Maintenance Therapy in Ulcerative Colitis

INTERVENTION:

Trade Name: Entyvio Product Name: Vedolizumab IV Product Code: MLN0002 Pharmaceutical Form: Powder for concentrate for solution for infusion INN or Proposed

INN:

Vedolizumab CAS Number: 943609‐66‐3 Other descriptive name: VEDOLIZUMAB Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 300‐ Pharmaceutical form of the placebo: Solution for injection/infusion Route of administration of the placebo: Intravenous use Product Name: Vedolizumab SC Product Code: MLN0002 SC Pharmaceutical Form: Solution for injection in pre‐filled syringe INN or Proposed

INN:

Vedolizumab SC CAS Number: 943609‐66‐3 Current Sponsor code: MLN0002 SC Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 108‐ Pharmaceutical form of the placebo: Solution for injection in pre‐filled syringe Route of administration of the placebo: Subcutaneous use

CONDITION:

Therapeutic area: Diseases [C] ‐ Immune System Diseases [C20] Ulcerative Colitis ; MedDRA version: 20.1 Level: LLT Classification code 10045365 Term: Ulcerative colitis System Organ Class: 100000004856

PRIMARY OUTCOME:

Main Objective: • 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. Primary end point(s): • 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 Objective: • 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.; Timepoint(s) of evaluation of this end point: Week 52

SECONDARY OUTCOME:

Secondary end point(s): • 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.; • Proportion of subjects with corticosteroid‐free remission, defined as subjects using oral corticosteroids at Baseline (Week 0) who have discontinued oral corticosteroids and are in clinical remission at Week 52.; Timepoint(s) of evaluation of this end point: Week 52: Mucosal healing and corticosteroid‐free remission.; Week 6 and Week 52: Durable clinical response and durable clinical remission.

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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age range 388 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 12