Efficacy and Safety of Adalimumab in Subjects With Moderately to Severely Acute Ulcerative Colitis
Condition: Ulcerative Colitis
MeSH terms: Colitis; Colitis, Ulcerative; Ulcer
Intervention: adalimumab; adalimumab; placebo
Intervention description: Prefilled syringe, 40 mg (loading dose then every other week dosing). 80 mg at Week 0, 40 mg at Week 2, and 40 mg every other week starting at Week 4.; Prefilled syringe, 40 mg (loading dose then every other week dosing). 160 mg at Week 0, 80 mg at Week 2, and 40 mg every other week starting at Week 4.; Placebo for 40 mg syringe. Matching placebo for loading dose and every other week dosing. Subjects received placebo at Weeks 0, 2, 4, and 6, followed by 160 mg adalimumab at Week 8, 80 mg adalimumab at Week 10, and 40 mg adalimumab eow thereafter (prior to Amendment 3) or 40 mg adalimumab eow starting at Week 8 (after Amendment 3).
Intervention MeSH terms: Adalimumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 576.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Moderate to Severe Ulcerative Colitis; Double-blind; Adalimumab; Induction of Clinical Remission

Summary:

      The objective of this study is to assess the efficacy and safety of adalimumab for the
      induction of clinical remission in subjects with moderately to severely active ulcerative
      colitis.
    

Eligibility criteria:

        The following eligibility criteria applied to participants enrolled following Amendment 3
        to the study protocol.

        Inclusion Criteria:

          1. Male and female participants >= 18 years of age

          2. Diagnosis of ulcerative colitis for greater than 90 days prior to Baseline

          3. Diagnosis of active ulcerative colitis confirmed by colonoscopy with biopsy or
             flexible sigmoidoscopy with biopsy during the Screening Period, with exclusion of
             infection

          4. Active UC with a Mayo score of 6 to 12 points and endoscopy subscore of 2 to 3 points,
             despite concurrent treatment with at least 1 of the following (oral corticosteroids or
             immunosuppressants or both as defined below):

               -  Stable oral corticosteroid dose (prednisone dose of >= 20 mg/day or equivalent)
                  for at least 14 days prior to Baseline or stable oral corticosteroid dose
                  (prednisone of < 20 mg/day) for at least 40 days prior to Baseline.

             and/or

               -  At least a consecutive 90 day course of azathioprine or 6-mercaptopurine (6 MP)
                  prior to Baseline, with a dose of azathioprine >= 1.5 mg/kg/day or 6 MP >= 1
                  mg/kg/day (rounded to the nearest available tablet formulation), or a dose that
                  is the highest tolerated by the participant (e.g., due to leukopenia, elevated
                  liver enzymes, nausea) during that time. Participant was to be on a stable dose
                  for at least 28 days prior to Baseline.

             Concurrent therapy was not required for participants who were previously treated with
             corticosteroids or immunosuppressants (azathioprine or 6-MP) during the previous 5
             years and, in the judgment of the investigator, have failed to respond to or could not
             tolerate their treatment.

          5. Had to be able to self-administer or has caregiver who can reliably administer
             subcutaneous injections.

          6. Had to be able and willing to give written informed consent and to comply with the
             requirements of this study protocol.

          7. Female had to be either not of childbearing potential, defined as postmenopausal for
             at least 1 year or surgically sterile (bilateral tubal ligation, bilateral
             oophorectomy or hysterectomy), or of childbearing potential and practicing an approved
             method of birth control throughout the study and for 150 days after last dose of study
             drug. Examples of approved methods of birth control included the following:

               -  Condoms, sponge, foams, jellies, diaphragm or intrauterine device

               -  Oral, parenteral or intravaginal contraceptives for 90 days prior to study drug
                  administration

               -  A vasectomized partner

          8. The results of the serum pregnancy test performed at the Screening Visit and urine
             pregnancy test performed at the Baseline Visit had to be negative.

          9. Judged to be in generally good health as determined by the principal investigator

        Exclusion Criteria:

          1. History of subtotal colectomy with ileorectostomy or colectomy with ileoanal pouch,
             Koch pouch, or ileostomy for ulcerative colitis or is planning bowel surgery.

          2. Received infliximab or any other anti-TNF agent or any biological therapy in the past.

          3. Received previous treatment with adalimumab or previous participation in an adalimumab
             clinical study.

          4. Received cyclosporine, tacrolimus, or mycophenolate mofetil within 30 days prior to
             Baseline.

          5. Received intravenous corticosteroids within 14 days prior to Screening or during the
             Screening Period.

          6. Received therapeutic enema or suppository, other than required for endoscopy, within
             14 days prior to the Screening endoscopy and during the remainder of the Screening
             Period.

          7. Current diagnosis of fulminant colitis and/or toxic megacolon.

          8. Participants with disease limited to the rectum (ulcerative proctitis).

          9. Current diagnosis of indeterminate colitis.

         10. Current diagnosis and/or history of Crohn's disease.

         11. Currently receiving total parenteral nutrition.

         12. Discontinued use of azathioprine or 6-MP within 28 days of Baseline.

         13. Discontinued use of corticosteroid within 14 days of Baseline.

         14. Participants using aminosalicylates for less than 90 days prior to Baseline, not on a
             stable dose for at least 28 days prior to Baseline, or discontinued use within 28 days
             of Baseline.

         15. Participants with positive Clostridium difficile stool assay.

         16. Infections requiring treatment with intravenous (IV) antibiotics, IV antivirals, or IV
             antifungals within 30 days prior to Baseline or oral antibiotics, oral antivirals, or
             oral antifungals within 14 days prior to Baseline.

         17. History of malignancy other than a successfully treated non-metastatic cutaneous
             squamous cell or basal cell carcinoma and/or localized carcinoma in situ of the
             cervix. If the Screening colonoscopy/flexible sigmoidoscopy showed evidence of
             dysplasia or a malignancy, the participant was not to be enrolled in the study.

         18. History of listeria, histoplasmosis, chronic or active hepatitis B infection, human
             immunodeficiency virus, immunodeficiency syndrome, central nervous system
             demyelinating disease, or untreated tuberculosis (TB).

         19. Female participants who was pregnant or breast-feeding or considering becoming
             pregnant during the study. There should be at least a 150-day period between the last
             dose of study drug and either conception or initiation of breast-feeding in women of
             childbearing potential.

         20. Poorly controlled medical condition(s), such as uncontrolled diabetes, unstable
             ischemic heart disease, moderate to severe congestive heart failure, recent
             cerebrovascular accident and any other condition, which in the opinion of the
             investigator, would put the participant at risk by participation in the protocol.

         21. Received any investigational agent within 30 days or 5 half lives prior to Baseline
             (whichever is longer).

         22. History of clinically significant drug or alcohol abuse during the previous year.

         23. Participants with known hypersensitivity to the excipients of adalimumab as stated in
             the label.

         24. Participants with any prior exposure to Tysabri® (natalizumab).

         25. Participants currently taking both budesonide and prednisone (or equivalent)
             simultaneously.