A Multicenter, Randomized, Double-blind, Placebo controlled Study of the Human Anti-TNF Monoclonal Antibody Adalimumab for the Induction and Maintenance of Clinical Remission in Subjects with Moderately to Severely Active Ulcerative Colitis.
- Conditions
- Moderately to severely active ulcerative colitis.MedDRA version: 8.1Level: LLTClassification code 10045365Term: Ulcerative colitis
- Registration Number
- EUCTR2006-002782-40-BE
- Lead Sponsor
- Abbott GmbH & Co. KG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 500
1. Male or female 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 ulcerative colitis with a Mayo Score of 6-12 points and endoscopy subscore
of 2-3 despite concurrent treatment with at least one 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 stable oral corticosteroid dose (prednisone
< 20 mg/day) for at least 40 days prior to Baseline.
And/or
? At least a consecutive 90 day course of azathioprine or 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 subject (e.g., due to leukopenia, elevated liver
enzymes, nausea) during that time. Subject must be on a stable dose for at
least 28 days prior to Baseline.
Note: If subjects are on both oral corticosteroid and immunosuppressants, only
one of the drugs needs to meet the above criteria
Concurrent therapy will not be required for subjects who were previously treated
with corticosteroids or immunosuppressants (azathioprine 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. Subjects may be included if they have previously used an anti-TNF agent (except adalimumab) and discontinued its used due to a loss of response or intolerance to the agent.
6. Must be able to self-administer or has caregiver who can reliably administer subcutaneous injections.
7. Must be able and willing to give written informed consent and to comply with the requirements of this study protocol.
8. Female subjects must 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 is 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 include the following:
? Condoms, sponge, foams, jellies, diaphragm or intrauterine device (IUD)
? Oral or parenteral or 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 be negative.
9. Judged to be in generally good health by the investigator.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
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 previous treatment with adalimumab or previous participation in an adalimumab clinical study.
3. Received cyclosporine, tacrolimus, or mycophenolate mofetil, within 30 days prior
to Baseline.
4. Received intravenous corticosteroids within 14 days prior to Screening or during the Screening Period.
5. 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.
6. Current diagnosis of fulminant colitis and/or toxic megacolon.
7. Subject with disease limited to the rectum (ulcerative proctitis).
8. Current diagnosis of indeterminate colitis.
9. Current diagnosis and/or history of Crohn's disease.
10. Currently receiving total parenteral nutrition (TPN).
11. Subject using aminosalicylates for less than 90 days prior to Baseline or not on a stable dose for at least 28 days prior to Baseline or discontinued use within 28 days of Baseline.
12. Subject with positive Clostridium difficlie (C. difficile) stool assay.
13. Subject who has previously used infliximab or any anti-TNF agent within 56 days of Baseline.
14. Subject who has previously used infliximab or any anti-TNF agent and has not clinically responded at any time ('primary non-responded') unless subject experienced a treatment limiting reaction.
15. Infections requiring treatment with intravenous (iv) antibiotics, antivirals, or
antifungals within 30 days prior to Baseline or oral antibiotics, antivirals, or
antifungals within 14 days prior to 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 shows evidence of dysplasia or a malignancy, subject may not 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 (CNS) demyelinating disease, or untreated tuberculosis (TB).
18. Female subject who is 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.
19. Infections requiring treatment with intravenous (iv) antibiotics, antivirals, or
antifungals within 30 days prior to Baseline or oral antibiotics, antivirals, or
antifungals within 14 days prior to Baseline.
20. Received any investigational agent within 30 days or 5 half lives prior to Baseline (whichever is longer).
21. History of clinically significant drug or alcohol abuse during the past year.
22. Subjects with known hypersensitivity to the excipients of adalimumab as stated in the label.
23. Subject with any prior exposure to Tysabri® (natalizumab), or Orencia®
(abatacept) or any other biological therapy [other than Kineret® (anakinra) and
anti-TNF agents].
24. Subject currently taking both budesonide and prednisone (or equivalent) simultaneously.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To assess the efficacy and safety of adalimumab for the induction and maintenance of clinical remission in subjects with moderately to severely active ulcerative colitis.;Secondary Objective: To assess the pharmacokinetics (PK) of adalimumab following subcutaneous administration. ;Primary end point(s): The co-primary efficacy endpoint is the proportion of subjects who achieve remission at Week 8 and proportion of subjects who achieve remission at Week 52.
- Secondary Outcome Measures
Name Time Method