Efficacy and Safety of Adalimumab in Subjects With Moderately to Severely Acute Ulcerative Colitis

Launched by ABBOTT · Oct 9, 2006

Keywords

ClinConnect Summary

This was a Phase 3, multicenter, randomized, double-blind (DB), placebo-controlled trial designed to evaluate the efficacy and safety of the human anti-TNF monoclonal antibody adalimumab for the induction of clinical remission in participants with moderately to severely active ulcerative colitis (UC).

Adult participants with moderate to severe UC (Mayo score of 6 to 12 points with endoscopy subscore of 2 to 3 points), confirmed by colonoscopy with biopsy or by flexible sigmoidoscopy with biopsy, were enrolled at 80 sites worldwide. The study enrolled 576 participants, including 186 partici...

Gender

ALL

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.