• Compare proportion of subjects in response (reduction from baseline in Mayo score ≥ 3 pts and ≥ 30%, also with decrease from baseline in rectal bleeding subscore ≥ 1 pt or absolute rectal bleeding subscore ≤ 1 pt) at Wk 12 between abatacept and placebo [ Time Frame: after 12 weeks of Induction therapy ] [ Designated as safety issue: No ]
• Compare proportion of subjects in response (reduction from baseline in Mayo score ≥3 pts and ≥30%, also with decrease from baseline in rectal bleeding subscore ≥1 pt or absolute rectal bleeding subscore of ≤1) at Month 12 between abatacept and placebo [ Time Frame: after 12 weeks of Induction therapy and a subsequent 12 months of maintenance therapy ] [ Designated as safety issue: No ]
• Assess the long-term clinical safety and tolerability of abatacept treatment during the Open-Label Extension Phase [ Time Frame: during the open-label treatment period ] [ Designated as safety issue: Yes ]

• Compare the proportion of subjects in clinical remission (defined as Mayo score ≤ 2 points and no individual subscore exceeding 1 point) at Week 12 between the abatacept and placebo treatment regimens [ Time Frame: after 12 weeks of Induction therapy ] [ Designated as safety issue: No ]
• Compare the proportion of subjects with mucosal healing (defined as endoscopic subscore ≤ 1 point) at Week 12 between the abatacept and placebo treatment regimens [ Time Frame: after 12 weeks of Induction therapy ] [ Designated as safety issue: No ]
• Evaluate the dose-response relationship by comparing the proportions of subjects in clinical response at Week 12 induced by placebo and abatacept in increasing doses (3 mg/kg, ~10 mg/kg, 30/~10 mg/kg) [ Time Frame: after 12 weeks of Induction therapy ] [ Designated as safety issue: No ]
• Assess in abatacept vs placebo treated subjects improvements in quality of life as measured by the Inflammatory Bowel Disease Questionnaire (IBDQ) score at Week 12 [ Time Frame: after 12 weeks of Induction therapy ] [ Designated as safety issue: No ]
• Assess the proportion of abatacept vs placebo treated subjects with Mayo subscores (rectal bleeding, stool frequency, physician's global assessment) indicative of mild disease (individual subscore ≤ 1) at Week 12 [ Time Frame: after 12 weeks of Induction therapy ] [ Designated as safety issue: No ]
• Evaluate in subjects with inadequate response and/or intolerance to anti TNFs, the dose-response relationship by comparing the proportions of subjects in clinical response at Wk 12 induced by placebo and abatacept in increasing doses (3,~10, 30/~10mg/kg) [ Time Frame: after 12 weeks of Induction therapy ] [ Designated as safety issue: No ]
• Assess in abatacept vs placebo treated subjects who have had an inadequate response and/or intolerance to anti-TNF therapy, a) the proportion in clinical response, b) the proportion in remission, and c) the proportion with mucosal healing at Weeks 12 [ Time Frame: after 12 weeks of Induction therapy ] [ Designated as safety issue: No ]
• Assess the immunogenicity of abatacept in subjects with UC [ Time Frame: after 12 weeks of Induction therapy ] [ Designated as safety issue: No ]
• Assess the tolerability and safety of abatacept in subjects with UC [ Time Frame: after 12 weeks of Induction therapy ] [ Designated as safety issue: Yes ]
• Compare the proportion of subjects who are in clinical remission (defined as a Mayo score ≤ 2 points and no individual subscore exceeding 1 point) at Month 12 between the abatacept and placebo treatment regimens [ Time Frame: after 12 weeks of Induction therapy and a subsequent 12 months of maintenance therapy ] [ Designated as safety issue: No ]
• Compare the proportion of subjects with mucosal healing (defined as endoscopic subscore ≤ 1) at Month 12 between the abatacept and placebo treatment regimens [ Time Frame: after 12 weeks of Induction therapy and a subsequent 12 months of maintenance therapy ] [ Designated as safety issue: No ]
• Compare the proportion of subjects who are in clinical remission at both Month 6 (Day MP-169) and Month 12 between the abatacept and placebo treatment regimens [ Time Frame: after 12 weeks of Induction therapy and a subsequent 6 months and 12 months of maintenance therapy ] [ Designated as safety issue: No ]
• Compare the proportion of subjects using oral corticosteroids at baseline who have discontinued corticosteroids and are in remission at Month 12 between the abatacept and placebo treatment regimens [ Time Frame: after 12 weeks of Induction therapy and a subsequent 12 months of maintenance therapy ] [ Designated as safety issue: No ]
• Assess in abatacept vs placebo treated subjects improvements in quality of life as measured by a) the IBDQ score and b) the Short Form-36 (SF-36) at Month 12 [ Time Frame: after 12 weeks of Induction therapy and a subsequent 12 months of maintenance therapy ] [ Designated as safety issue: No ]
• Assess the proportion of abatacept versus placebo treated subjects using oral corticosteroids at baseline who have discontinued corticosteroids for at least 90 consecutive days and are in remission at Month 12 [ Time Frame: after 12 weeks of Induction therapy and a subsequent 12 months of maintenance therapy ] [ Designated as safety issue: No ]
• Assess the proportion of abatacept versus placebo treated subjects with Mayo subscores (rectal bleeding, stool frequency, physician's global assessment) indicative of mild disease (individual subscore ≤ 1) at Month 12 [ Time Frame: after 12 weeks of Induction therapy and a subsequent 12 months of maintenance therapy ] [ Designated as safety issue: No ]
• Assess in abatacept versus placebo treated-subjects who have had an inadequate response and/or intolerance to anti-TNF therapy a) the proportion in clinical response, b) the proportion in remission, and c) the proportion with mucosal healing at Month 12 [ Time Frame: after 12 weeks of Induction therapy and a subsequent 12 months of maintenance therapy ] [ Designated as safety issue: No ]
• Assess the immunogenicity of abatacept in subjects with UC [ Time Frame: during the 12 week double-blind induction treatment period and during the subsequent 12 month double-blind maintenance treatment period ] [ Designated as safety issue: No ]
• Assess the tolerability and safety of abatacept in subjects with UC [ Time Frame: during the 12 week double-blind induction treatment period and during the subsequent 12 month double-blind maintenance treatment period ] [ Designated as safety issue: Yes ]
• Assess durability of clinical efficacy (clinical response and remission), clinical efficacy upon retreatment, immunogenicity, and corticosteroid use [ Time Frame: during the open-label treatment period ] [ Designated as safety issue: No ]

• Remission
• Mucosal Healing at time point and with scoring system noted in Mayo score

The purpose of this clinical research study is to learn if abatacept can improve signs and symptoms of active ulcerative colitis in patients who have not had an adequate response to other therapies. The safety of this treatment will also be studied

• Drug: abatacept
• Drug: placebo

• Experimental:

  4 arms for induction period

  2 arms for maintenance period

• Placebo Comparator:

  4 arms for induction period

  2 arms for maintenance period

• Other: 1 arm for open-label extension phase

Inclusion Criteria:

• Men or women 18 years or older
• Ulcerative colitis for at lease 3 months
• Moderate to severe active ulcerative colitis
• Inadequate response or intolerance to standard ulcerative colitis treatment