The purpose of this study is to assess the effect of vedolizumab subcutaneous (vedolizumab SC) maintenance treatment on clinical remission at Week 52 in participants with moderately to severely active ulcerative colitis (UC) who achieved clinical response following administration of vedolizumab intravenous (vedolizumab IV) induction therapy.
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
BACKGROUND & AIMS: Maintenance treatment with vedolizumab, a monoclonal antibody that inhibits the gut-selective α4β7 integrin, is administered intravenously. Some patients might prefer a subcutaneous formulation of vedolizumab for maintenance treatment. Subcutaneous vedolizumab was investigated as maintenance treatment in patients with moderately to severely active ulcerative colitis.
METHODS: We performed a phase 3, double-blind, double-dummy trial at 141 sites in 29 countries from December 18, 2015 through August 21, 2018. Patients with moderately to severely active ulcerative colitis received open-label treatment with intravenous vedolizumab 300 mg at weeks 0 and 2. At week 6, patients with clinical response were randomly assigned maintenance treatment with subcutaneous vedolizumab 108 mg every 2 weeks, intravenous vedolizumab 300 mg every 8 weeks, or placebo. The primary end point was clinical remission at week 52, which was defined as a total Mayo score of ≤2 and no subscore >1.
RESULTS: Among the randomized 216 patients, clinical remission at week 52 was achieved by 46.2%, 42.6%, and 14.3% of patients in the subcutaneous vedolizumab, intravenous vedolizumab, and placebo groups, respectively (subcutaneous vedolizumab vs placebo: Δ32.3%; 95% confidence interval, 19.7%-45.0%; P < .001). The subcutaneous vedolizumab group also had greater endoscopic improvement and durable clinical response at week 52 compared with placebo (both P < .001). The incidence of injection-site reactions was more frequent in patients given subcutaneous vedolizumab (10.4%) than intravenous vedolizumab (1.9%) or placebo (0%); these were not treatment limiting, most were mild, and none resulted in discontinuation. Subcutaneous and intravenous vedolizumab safety profiles were otherwise similar.
CONCLUSIONS: Subcutaneous vedolizumab is effective as maintenance therapy in patients with moderately to severely active ulcerative colitis who had a clinical response to intravenous vedolizumab induction therapy. It has a favorable safety and tolerability profile. ClinicalTrials.gov ID: NCT02611830; EudraCT 2015-000480-14.
The purpose of this study is to assess the effect of vedolizumab subcutaneous (vedolizumab SC) maintenance treatment on clinical remission at Week 52 in participants with moderately to severely active ulcerative colitis (UC) who achieved clinical response following administration of vedolizumab intravenous (vedolizumab IV) induction therapy.
