Clinical Trial: A Study of Adalimumab in Japanese Subjects With Moderately to Severely Active Ulcerative Colitis

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Multi-Center, Randomized, Double-Blind, Placebo-controlled Study of Adalimumab in Japanese Subjects With Moderately to Severely Active Ulcerative Colitis.

Brief Summary: The purpose of this study is to assess the efficacy and safety of adalimumab in Japanese subjects with moderately to severely active ulcerative colitis (UC).

Detailed Summary: Patients who meet all of the inclusion criteria and none of the exclusion criteria are randomized 1:1:1 to receive subcutaneous injections of adalimumab at either 160/80 mg at Week 0/2 and 40 mg every other week (eow) starting at Week 4 to Week 50, 80/40 mg at Week 0/2 and 40 mg eow starting at Week 4 to Week 50, or placebo eow starting at Week 0 to Week 50 under the double-blind condition. At or after Week 8, participants who have inadequate response during the double-blind period can switch to the rescue arm, where participants from the placebo group initially receive adalimumab 160 mg and 80 mg 2 weeks later and those from the adalimumab group receive adalimumab 40 mg initially and 2 weeks later under double-blind conditions. All participants in the rescue arm then receive 40 mg adalimumab eow until Week 50. Participants who complete the 52-week double-blind period receive open-label adalimumab 40 mg eow starting at Week 52 and continuing until the end of the study. Participants who have an inadequate response or disease flare can dose escalate to 80 mg eow at or after Week 60. Participants who dose escalate to 80 mg eow and continue to have an inadequate response or disease flare are withdrawn from the study.
Sponsor: AbbVie (prior sponsor, Abbott)

Current Primary Outcome:

  • Percentage of Participants With Clinical Remission at 8 Weeks [ Time Frame: Week 8 ]

    Clinical remission was defined as a Mayo score ≤ 2 with no individual subscore > 1. The Mayo score is a composite score of ulcerative colitis disease activity calculated as the sum of four subscores:

    • Stool Frequency Subscore (SFS), based on the participant's diary and scored from zero (normal number of stools) to three (5 or more stools than normal);
    • Rectal Bleeding Subscore (RBS), based on the participant's diary and scored from zero (no blood) to three (blood only passed);
    • Endoscopy Subscore (ESS), based on colonoscopy or sigmoidoscopy and scored from zero (normal or inactive disease) to three (severe disease, spontaneous bleeding, ulceration);
    • Physician's Global Assessment (PGA) subscore, based on the physician's overall assessment, and scored from zero (normal) to three (severe disease).

    The total Mayo score ranges from 0 to 12 points, with higher scores representing more severe disease.

  • Percentage of Participants With Clinical Remission at 52 Weeks [ Time Frame: Week 52 ]

    Clinical remission was defined as a Mayo score ≤ 2 with no individual subscore > 1. The Mayo score is a composite score of ulcerative colitis disease activity calculated as the sum of four subscores:

    • Stool Frequency Subsc

      Original Primary Outcome:

      • Mayo Score [ Time Frame: Week 8 ]
      • Mayo Score [ Time Frame: Week 52 ]


      Current Secondary Outcome:

      • Percentage of Participants With Clinical Remission at 8, 32, and 52 Weeks [ Time Frame: Weeks 8, 32, and 52 ]

        Clinical remission was defined as a Mayo score ≤ 2 with no individual subscore > 1. The Mayo score is a composite score of ulcerative colitis disease activity calculated as the sum of four subscores:

        • Stool Frequency Subscore (SFS), based on the participant's diary and scored from zero (normal number of stools) to three (5 or more stools than normal);
        • Rectal Bleeding Subscore (RBS), based on the participant's diary and scored from zero (no blood) to three (blood only passed);
        • Endoscopy Subscore (ESS), based on colonoscopy or sigmoidoscopy and scores from zero (normal or inactive disease) to three (severe disease, spontaneous bleeding, ulceration);
        • Physician's Global Assessment (PGA) subscore, based on the physician's overall assessment, and scored from zero (normal) to three (severe disease).

        The total Mayo score ranges from 0 to 12 points, with higher scores representing more severe disease.

      • Percentage of Participants With a Clinical Response [ Time Frame: Baseline and Weeks 8, 32, and 52 ]

        A clinical response was defined as a decrease in Mayo score of ≥ 3 points and ≥ 30% from Baseline PLUS a decrease in the Rectal Bleeding Subscore (RBS) ≥ 1 or an absolute RBS of 0 or 1.

        The Mayo score is a composite score of ulcerative colitis disease activity calculated as the sum of four subscores:

        • Stool Frequency Subscore, based on the participant's diary and scored from zero (normal number of stools) to three (5 or more stools than normal);
        • Rectal Bleeding Subscore, based on the participant's diary and scored from zero (no blood) to three (blood only passed);
        • Endoscopy Subscore, based on colonoscopy or sigmoidoscopy and scored from zero (normal or inactive disease) to three (severe disease, spontaneous bleeding, ulceration);
        • Physician's Global Assessment subscore, based on the physician's overall assessment, and scored from zero (normal) to three (severe disease).

        The total Mayo score ranges from 0 to 12 points, with higher scores representing more severe disease.

      • Percentage of Participants With Mucosal Healing [ Time Frame: Weeks 8, 32, and 52 ]

        Mucosal healing was defined as an endoscopy subscore of ≤ 1 and was assessed using flexible sigmoidoscopy performed at Weeks 8, 32, and 52.

        The endoscopy subscore ranges from zero to three as follows:

        0 = Normal or inactive disease, 1 = Mild disease (erythema, decreased vascular pattern, mild friability), 2 = Moderate disease (marked erythema, absent vascular pattern, friability, erosions), 3 = Severe disease (spontaneous bleeding, ulceration).

      • Percentage of Participants With Rectal Bleeding Subscore Indicative of Mild Disease (≤ 1) [ Time Frame: Weeks 8, 32, and 52 ]

        Rectal bleeding was assessed from the participant's diary, taking the worst score from the 3 days prior to each study visit. The rectal bleeding subscore ranges from zero to three, according to the following scale:

        0 = no blood seen, 1 = streaks of blood with stool less than half the time, 2 = obvious blood with stool most of the time, 3 = blood alone passed.

      • Percentage of Participants With Physician's Global Assessment Subscore Indicative of Mild Disease (≤ 1) [ Time Frame: Weeks 8, 32, and 52 ]

        The Physician's Global Assessment Subscore acknowledges the three other subscores (Stool Frequency, Rectal Bleeding, and Endoscopy), the participant's daily record of abdominal discomfort and functional assessment, and other observations such as physical findings and the participant's performance status. Possible scores range from zero to three as follows:

        0 = Normal (other subscores are 0), 1 = Mild disease (other subscores are mostly 1), 2 = Moderate disease (other subscores are 1 to 2), 3 = Severe disease (other subscores are 2 to 3).

      • Percentage of Participants With Stool Frequency Subscore Indicative of Mild Disease (≤ 1) [ Time Frame: Weeks 8, 32, and 52 ]

        Stool frequency was assessed from the participant's diary, taking the worst score from the 3 days prior to each study visit. The stool frequency subscore ranges from zero to three, according to the following scale:

      • Mayo Score [ Time Frame: Week 32 ]
      • Inflammatory Bowel Disease Questionnaire (IBDQ) [ Time Frame: Week 52 ]
      • Adverse Events [ Time Frame: Week 8 ]
      • Adverse Events [ Time Frame: Week 52 ]


      Information By: AbbVie

      Dates:
      Date Received: February 27, 2009
      Date Started: February 2009
      Date Completion:
      Last Updated: September 3, 2014
      Last Verified: September 2014