To assess the efficacy and safety of adalimumab for the induction of clinical remission in subjects with moderately to severely active ulcerative colitis.
ID
Source
Brief title
Condition
- Gastrointestinal conditions NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary efficacy endpoint of this study is the proportion of subjects with
remission at Week 8.
Secondary outcome
Ranked secondary efficacy variables assessed at Week 8 include (in the order at
which statistical test will be conducted):
1. Proportion of subjects with response per Mayo Score (defined as a decrease
in Mayo score >= 30% from Baseline and >= 3 points PLUS a decrease in the rectal
bleeding subscore [RBS] >= 1 or an absolute RBS of 0 or 1).
2. Proportion of subjects with mucosal healing (defined as an endoscopic
subscore of 0 or 1).
3. Proportion of subjects with Rectal Bleeding subscore indicative of mild
disease (<= 1).
4. Proportion of subjects with Physician's Global Assessment subscore
indicative of mild disease (<= 1).
5. Proportion of subjects with Stool Frequency subscore indicative of mild
disease (<= 1).
6. Proportion of IBDQ responders (defined as subjects with at least a 16 point
increase from Baseline in total IBDQ score).
Non-ranked secondary efficacy variables:
* Proportion of subjects with response per Partial Mayo Score at Week 2, 4, and
6
* Proportion of subjects with Rectal Bleeding subscore indicative of mild
disease (<= 1) at Weeks 2, 4, and 6
* Proportion of subjects with Physician's Global Assessment subscore indicative
of mild disease (<= 1) at Weeks 2, 4, and 6
* Proportion of subjects with Stool Frequency subscore indicative of mild
disease (<= 1) at Weeks 2, 4, and 6
* Change from Baseline in total Inflammatory Bowel Disease Questionnaire (IBDQ)
score at Week 8
* Change from Baseline in Short Form-36 Questionnaire (SF-36) at Week 8
* Change from Baseline in Partial Mayo Score at Weeks 2, 4, 6, and 8
* Change from Baseline in Mayo Score at Week 8
* Time to clinical response per Partial Mayo Score (up to Week 8)
Background summary
The aim of medical treatment in UC is to induce and maintain remission.
Conventional pharmaceutical therapies do not completely abate the inflammatory
process and have significant side effects.
It is postulated that UC results from unregulated and exaggerated local immune
response to environmental triggers. TNF is a naturally occurring
proinflammatory cytokine that appears to be critical to the amplification of
mucosal inflammation in UC. TNF-α is found in increased concentrations in the
blood, colonic tissue, and stools of patients with UC.
Adalimumab is a recombinant human immunoglobulin monoclonal antibody
exclusively containing human peptide sequences. It binds specifically with high
affinity to the soluble and transmembrane forms of TNFα and inhibits the
binding of TNFα with its receptors. This decreases the immune reaction.
Study objective
To assess the efficacy and safety of adalimumab for the induction of clinical
remission in subjects with moderately to severely active ulcerative colitis.
Study design
This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled
trial
designed to evaluate the efficacy and safety of the human anti-TNF monoclonal
antibody adalimumab in subjects with moderately to severely active ulcerative
colitis (UC).
Study drug will be administered by subcutaneous injection. Subjects will
receive blinded therapy from Baseline until Week 12. Subjects will receive
open-label therapy from Week 12 until the end of the study. Subjects will
receive four injections of adalimumab 40 mg (160 mg) or four injections of
placebo
at Baseline (Week 0) followed by two injections of adalimumab 40 mg (80 mg) or
two injections of placebo at Week 2 and one injection of adalimumab 40 mg or
placebo at Weeks 4 and 6. At Week 8 subjects randomized to placebo will receive
four injections of adalimumab 40 mg (160 mg) followed by two injections of
adalimumab 40 mg (80 mg) at Week 10. Subjects randomized to adalimumab will
receive three injections of placebo and one injection of adalimumab 40 mg at
Week 8 and one injection of placebo and one injection of adalimumab 40 mg at
Week 10. All subjects will continue to receive one injection of open-label
adalimumab 40 mg every other week (eow) beginning at Week 12 up to
Week 52/Early Termination.
Intervention
Vena punction for bloodsampling, subcutanious injections (administration of
study medication), a biopsy and 3 times an endoscopy.
Study burden and risks
The burden and risk to the patient are limited.
Venapunction, biopsy and endoscopy will be done by qualified people,
subcutaneous injections will be adminstred in the hospital by qualified people
for the first 12 weeks: During the first 3 visits the person that will
adminstrate the injection at home in a later stadium will be trained on the
administration, during the other 6 visits the administration will be done under
supervision by the patient self or by the person who will administrate the
injection at home in a later stadium.
During the treatment with TNF antagonists patients are at higher risk for
death, serious infections, tuberculosis, sepsis, malignancy, demyelating
disease ans serious allergic reactions.
Riscs will be limited by selecting patients by the in- and exclusion criteria.
Also patients with UC are so ill that a higher risc is accepted. Patients will
be followed thorougly by visits and examinations.
Siriusdreef 51
2132 WT Hoofddorp
NL
Siriusdreef 51
2132 WT Hoofddorp
NL
Listed location countries
Age
Inclusion criteria
* Diagnosis of ulcerative colitis for greater than 90 days prior to Baseline
*Diagnosis of ulcerative colitis confirmed by colonoscopy with biopsy (< 6 months old), or colonoscopy with biopsy (>6 months old) followed by flexible sigmoidoscopy for confirmation during screening
*Active ulcerative colitis with Mayo Score of 6-12 points plus an endoscopic sub-score of 2-3 points, despite concurrent treatment with oral corticosteroids and or immunosuppressants
*Patient should be able to self administer or has a caregiver who can reliably administer subcutaneous injections
*Patient must be able and willing togive written informed consent and comply to study requirements of this study protocol
*Female who are of child bearing potential must use an acceptable method of birth control
*Negative pregnancy test in serum
*Judged to be in general good health by the 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 in the past.
3. Received previous treatment with adalimumab or previous participation in an adalimumab clinical study.
4. Received cyclosporine, tacrolimus, mycophenolate mofetil, or methotrexate within 60 days prior to Baseline.
5. Received intravenous corticosteroids within 14 days prior to Screening and during the Screening Period.
6. Received therapeutic enema or suppository, other than required for endoscopy, within 14 days prior to the Screening Visit and during the Screening Period.
7. Current diagnosis of fulminant colitis and/or toxic megacolon.
8. Subjects 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 (TPN).
12. Discontinued use of azathioprine, or 6-MP within 28 days of Baseline.
13. Discontinued use of corticosteroid within 14 days of Baseline.
14. Subjects 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.
15. Subjects with positive Clostridium difficile (C. difficile) stool assay.
16. Persistent chronic or active non-UC related 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 shows evidence of dysplasia or a malignancy, subject may not be enrolled in the study.
18. 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).
19. 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.
20. Poorly controlled medical condition, such as uncontrolled diabetes with documented history of recurrent infections, unstable ischemic heart disease, congestive heart failure, recent cerebrovascular accident and any other condition, which in the opinion of the investigator, would put the subject 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 past year.
23. Subjects with known hypersensitivity to the excipients of adalimumab as stated in the label.
24. Subjects with any prior exposure to Tysabri® (natalizumab).
25. Subjects currently taking both budesonide and prednisone (or equivalent) simultaneously.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2006-002781-20-NL |
| ClinicalTrials.gov | NCT00385736 |
| CCMO | NL15615.060.07 |