Efficacy and Safety of Adalimumab in Subjects With Moderately to Severely Active Ulcerative Colitis
Condition: Ulcerative Colitis
MeSH terms: Colitis; Colitis, Ulcerative; Ulcer
Intervention: adalimumab; placebo
Intervention description: Prefilled syringe, 40 mg, 160 mg at Week 0, 80 mg at Week 2, and 40 mg every other week between Weeks 4 and 50.; Matching Placebo for prefilled syringe, 40 mg,
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: 518.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Ulcerative Colitis; Adalimumab; TNF Antagonist; Mayo Score

Summary:

      This was a Phase 3, multicenter, randomized, double-blind, placebo-controlled trial designed
      to evaluate the efficacy and safety of the human anti-tumor necrosis factor (TNF) monoclonal
      antibody adalimumab (ADA) in patients with moderately to severely active ulcerative colitis
      (UC).
    

Eligibility criteria:

        Inclusion Criteria:

          1. Participants >=18 years of age and in good health (Investigator discretion) with a
             recent stable medical history

          2. Diagnosis of UC for greater than 90 days prior to Baseline

          3. Diagnosis of active UC 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 >= 20 mg/day or equivalent) for at
                  least 14 days prior to Baseline or maintenance, corticosteroid dose (prednisone <
                  20 mg/day or equivalent) for at least 40 days prior to Baseline

             and/or

               -  At least a 90 day course of azathioprine (AZA) or 6-mercaptopurine (6-MP) prior
                  to Baseline, with a dose of AZA >= 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 must 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 (AZA or 6-MP) during the past 5 years and in the
             judgment of the Investigator have failed to respond to, or could not tolerate, their
             treatment.

          5. Participants may have been included if they had previously used an anti-tumor necrosis
             factor (TNF) agent (except ADA) and discontinued its use due to a loss of response or
             intolerance to the agent.

          6. Had to be able to self-administer or had caregiver who could reliably administer
             subcutaneous (SC) injections.

          7. Had to be able and willing to give written informed consent and to comply with the
             requirements of the study protocol.

          8. 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 the 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, intravaginal contraceptives for 90 days prior to study drug
                  administration

               -  A vasectomized partner The results of the serum pregnancy test performed at the
                  Screening Visit and urine pregnancy test performed at the Baseline Visit must
                  have been negative.

          9. Judged to be in generally good health as determined by the Investigator

        Exclusion Criteria:

          1. History of subtotal colectomy with ileorectostomy or colectomy with ileoanal pouch,
             Koch pouch, or ileostomy for UC, or planned bowel surgery.

          2. Received previous treatment with ADA or previous participation in an ADA clinical
             study.

          3. Received cyclosporine, tacrolimus, or mycophenolate mofetil within 30 days of
             Baseline.

          4. Received intravenous (IV) corticosteroids within 14 days of Screening or during the
             Screening Period.

          5. Received therapeutic enema or suppository, other than required for endoscopy, within
             14 days of the Screening endoscopy and during the remainder of the Screening Period.

          6. Current diagnosis of fulminant colitis and/or toxic megacolon.

          7. Disease limited to the rectum (ulcerative proctitis).

          8. Current diagnosis of indeterminate colitis.

          9. Current diagnosis and/or history of Crohns disease (CD).

         10. Currently receiving total parenteral nutrition.

         11. Used aminosalicylates for < 90 days before Baseline or not on a stable dose for at
             least 28 days before Baseline or discontinued use within 28 days of Baseline.

         12. Positive Clostridium difficile stool assay.

         13. Previously used infliximab or any anti-TNF agent within 56 days of Baseline.

         14. Previously used infliximab or any anti-TNF agent without clinical response at any time
             ("primary non-responder") unless subject experienced a treatment-limiting reaction.

         15. Infections requiring treatment with IV antibiotics, antivirals, or antifungals within
             30 days of Baseline or oral antibiotics, antivirals, or antifungals within 14 days of
             Baseline.

         16. 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, subject was not to be enrolled in the study.

         17. History of listeria, histoplasmosis, chronic or active hepatitis B infection, human
             immunodeficiency virus (HIV), immunodeficiency syndrome, central nervous system
             demyelinating disease, or untreated tuberculosis (TB).

         18. Female subject who was pregnant or breast-feeding or considering becoming pregnant
             during the study (there should be at least 150 days between the last dose of study
             drug and either conception or initiation of breast-feeding in women of childbearing
             potential).

         19. Poorly controlled medical condition(s), such as uncontrolled diabetes, unstable
             ischemic heart disease, moderate to severe congestive heart failure (CHF), recent
             cerebrovascular accident, and any other condition, which in the opinion of the
             investigator, put the subject at risk by participation in the protocol.

         20. Received any investigational agent within 30 days or 5 half lives prior to Baseline
             (whichever was longer).

         21. History of clinically significant drug or alcohol abuse during the past year.

         22. Known hypersensitivity to the excipients of ADA as stated in the label.

         23. Any prior exposure to Tysabri® (natalizumab), or Orencia® (abatacept) or any other
             biological therapy [other than Kineret® (anakinra) and anti-TNF agents].

         24. Currently taking both budesonide and prednisone (or equivalent) simultaneously.