A Multi-Center, Randomized, Double-Blind, Placebo - Controlled Study of the Human Anti-TNF Monoclonal Antibody Adalimumab Endoscopy Trial to Evaluate the Effects on Mucosal Healing in Subjects with Crohn's Disease Involving the Colon.

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2005-005291-32-NL
• Date of registration: 28/06/2006
• Prospective Registration: Yes
• Primary sponsor: Abbott GmbH & Co. KG
• Public title: A Multi-Center, Randomized, Double-Blind, Placebo - Controlled Study of the Human Anti-TNF Monoclonal Antibody Adalimumab Endoscopy Trial to Evaluate the Effects on Mucosal Healing in Subjects with Crohn's Disease Involving the Colon.
• Scientific title: A Multi-Center, Randomized, Double-Blind, Placebo - Controlled Study of the Human Anti-TNF Monoclonal Antibody Adalimumab Endoscopy Trial to Evaluate the Effects on Mucosal Healing in Subjects with Crohn's Disease Involving the Colon.
• Date of first enrolment: 23/08/2006
• Target sample size: 130
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2005-005291-32
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Austria, Belgium, Germany, Italy, Netherlands, Sweden

Key inclusion & exclusion criteria

Inclusion criteria:
A subject will be eligible for study participation if he/she meets the following criteria:
1. Diagnosis of Crohn's Disease for greater than 4 months.
2. A diagnosis of ileocolonic Crohn's Disease confirmed by endoscopy or radiologic evaluation within 3 years of Baseline.
3. For subjects that have had operations in the ileocolonic region of the intestine after documented diagnosis of ileocolonic disease, postoperative recurrence of the disease must be documented.
4. Endoscopic documentation of ulceration at Screening corresponding to a score of 2 or 3 on the Ulcerated Surface subscore of the SES-CD.
5. Crohn's Disease Activity Index (CDAI) score of greater than or equal to 220 and less than or equal to 450.
6. Males and females older than or equal to 18 and younger than or equal to 75 years of age at the Baseline visit.
7. If female, subject is either not of child bearing potential, defined as post menopausal for at least (1) year, surgically sterile (bilateral tubal ligation, bilateral oophorectomy or hysterectomy), or is of childbearing potential and practicing one of the following methods of birth control during the study and for 150 days after the last dose:
? Condoms, sponge, foam, jellies, diaphragm or intrauterine device
? Oral or parenteral contraceptives for three months prior to study drug administration
? A vasectomized partner
8. If female, subject is not breast-feeding throughout the study and for 150 days after the last dose.
9. Subject or his/her legal representative has voluntarily signed and dated an informed consent approved by and compliant with the requirements of this study protocol which has been approved by an Institutional Review Board (IRB)/Independent Ethics Committee (IEC).
10. Adequate cardiac, renal and hepatic function as determined by the principal investigator and demonstrated by Screening laboratory evaluations, questionnaires, and physical examination results that are within normal limits.
11. Subjects must be able to self-inject study medication or have a designee or healthcare professional who can inject the study medication.
12. Subjects must agree to undergo up to 4 endoscopies.
13. Subjects may be included if they used infliximab or any anti-TNF agent (except adalimumab) and a) responded and then stopped the agent, b) responded and lost their response, c) responded and became intolerant, or d) did not tolerate the anti-TNF agent.

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

Exclusion criteria:
A subject will be excluded from the study if he/she meets any of the following criteria:
1. History of cancer or lymphoproliferative disease other than a successfully and completely treated cutaneous squamous cell or basal cell carcinoma or carcinoma - in-situ of the cervix.
2. History of listeria, human immunodeficiency virus (HIV), Hepatitis B, an immunodeficiency syndrome, central nervous system (CNS) demyelinating disease or untreated TB.
3. Subject with a current diagnosis of ulcerative colitis or indeterminate colitis as determined by the investigator and Abbott Medical Monitor.
4. Subject with symptomatic known obstructive strictures.
5. Subject who has had surgical bowel resections within the past 6 months or is planning any resection at any time point while enrolled in the study.
6. Subject with an ostomy or ileoanal pouch. (Subjects with a previous ileo-rectal anastomosis are not excluded).
7. Subject who has short bowel syndrome as determined by the investigator.
8. Subject who is currently receiving total parenteral nutrition (TPN).
9. Females who are pregnant or will not discontinue breast-feeding.
10. Subject who has received any investigational chemical agent in the past 30 days or 5 half-lives prior to Baseline (whichever is longer).
11. Subject who has received any investigational biological agent in the past 3 months or 5 half-lives prior to Baseline (whichever is longer).
12. Subject who has had systemic antibiotic, antiviral or antifungal treatment(s) within 3 weeks prior to Baseline for all non-Crohn's related infections.
13. Subject with a history of clinically significant drug or alcohol abuse in the last year.
14. Subjects with a poorly controlled medical condition such as: uncontrolled diabetes with documented history of recurrent infections, unstable ischemic heart disease, congestive heart failure, recent cerebrovascular accidents and any other condition which, in the opinion of the investigator or the sponsor, would put the subject at risk by participation in the protocol.
15. Subjects with positive C. difficile stool assay.
16. Subject who has previously used infliximab or any anti-TNF within 8 weeks of Baseline.
17. Subject who has previously used infliximab or any anti-TNF agent and has not clinically responded.
18. Previous treatment with adalimumab or previous participation in an adalimumab clinical study.
19. Screening laboratory and other analyses show any of the following abnormal results:
? Electrocardiogram (ECG) - with clinically significant abnormalities;
? Aspartate transaminase (AST) or alanine transaminase (ALT) >1.75 x the upper limit of the reference range;
? Total bilirubin ³3 mg/dL;
? Serum creatinine >1.6 mg/dL;
20. Subjects on Imuran® (azathioprine), 6 MP, or MTX who have not been on stable doses of these medications for at least 4 weeks prior to Baseline. For subjects on those medications, doses are to remain stable during the entire course of the study. Additionally, for subjects on those medications, subjects must have been on azathioprine, 6 MP, or MTX for at least 12 weeks prior to Baseline. Moreover, subjects who have been on azathioprine, 6 MP, or MTX who have discontinued these medications within 12 weeks of Baseline are excluded.
21. Subjects on aminosalicylates, mesalamine, sulfasalazine, or Crohn's related antibiotics who have not been on stable doses of these medications for at least 4 weeks prior to Baseline. In addition, subjects on aminosalicylates, sulfasalazine or C

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Crohn's Disease
MedDRA version: 8.1 Level: LLT Classification code 10057035

Intervention(s)

Product Name: Humira
Pharmaceutical Form: Injection*
INN or Proposed INN: Adalimumab
Concentration unit: mg milligram(s)
Concentration type: range
Concentration number: 40-160
Pharmaceutical form of the placebo: Injection*
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Secondary Objective: Secondary efficacy variables will be Crohn's Disease Endoscopic Index of Severity (CDEIS) scores, the Simple Endoscopic Score for Crohn's Disease (SES-CD) and ulcer counts, CDAI score, number of subjects discontinued from steroids, total IBDQ scores, WPAI scores, SF - 36 dimension scores, and Unscheduled Outpatient Visits, Emergency Room Visits and Hospitalizations Questionnaire. For detailed secondary endpoints which will be assessed please see section 5.3.4.2. of the protocol.

Main Objective: To demonstrate the efficacy of therapy with adalimumab 40mg eow, starting at Week 4 after a 160mg/80mg loading dose, on mucosal healing in subjects with moderate to severe ileocolonic Crohn's Disease and to delineate the safety of adalimumab when administered to subjects with Crohn's Disease.

Primary end point(s): The primary efficacy variable is the presence or absence of mucosal ulceration by endoscopy. The primary outcome analysis will be a comparison of the proportions of subjects without mucosal ulceration on endoscopy in the adalimumab and placebo groups at Week 12.

Secondary ID(s)

M05-769

2005-005291-32-BE