A Phase 2B, Multi-center, Randomized, Double- blind, Parallel Group, Placebo-controlled, Dose Ranging Study Comparing the Efficacy, Safety, and Pharmacokinetics of Intravenous Infusions of ABT - 874 vs. Placebo in Subjects with Moderately to Severely Active Crohn's Disease

• Conditions: MedDRA version: 9.1Level: LLTClassification code 10011401Term: Crohn's disease; Crohn's disease

• Registration Number: EUCTR2008-004919-36-SE
• Lead Sponsor: Abbott

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-12-11
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 225

Inclusion Criteria

1. Diagnosis of Crohn's disease for greater than 4 months confirmed by endoscopy or
radiologic evaluation.
2. CDAI score of greater than or equal to 220 and less than or equal to 450 at Week 0.
3. Males and females greater than or equal to 18 years and less than 75 years of age at the Screening visit.
4. Females are eligible to participate in the study if the result of the serum pregnancy
performed during the Screening period is negative and the woman meets one of the
following criteria:
? Females of childbearing potential must undergo monthly pregnancy testing
during the study and agree to use two methods of
contraception throughout the study and for 60 days after the last dose of study
drug.
? Females who are postmenopausal (for at least one year), sterile, or
hysterectomized;
? Females who have undergone tubal ligation will be required to undergo
monthly pregnancy testing during the duration of the study and agree to use a
second form of contraception.
5. Judged to be in generally good health as determined by the Investigator based
upon the results of medical history, laboratory profile, physical examination, chest
X-ray (CXR), and 12-lead electrocardiogram (ECG) performed during the
Screening period.
6. Able and willing to give written informed consent and to comply with the
requirements of this study protocol.
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

1. Current diagnosis of colitis other than Crohn's disease.
2. Symptomatic known strictures.
3. Surgical bowel resections within the past 6 months or is planning any resection at
any time point while enrolled in the study.
4. Ostomy or ileoanal pouch.
5. Short bowel syndrome as determined by the investigator.
6. Evidence of dysplasia or a history of malignancy other than a successfully treated
non-metastatic cutaneous squamous cell, basal cell carcinoma or localized
carcinoma in situ of the cervix.
7. History of moderate to severe congestive heart failure (NYHA class III or IV),
recent cerebrovascular accident and any other condition that, in the opinion of the
investigator, would put the subject at risk by participating in the study.
8. Infection or risk factors for severe infections.
9. Abscess or suspicion of abscess.
10. Diagnosed with dysplasia of the gastrointestinal tract.
11. History of clinically significant drug or alcohol abuse in the last 12 months.
12. Females who are pregnant or considering becoming pregnant during the study, or breast-feeding.
13. Screening laboratory analysis shows any abnormal results as specified in the protocol.
14. Positive C. difficile stool assay at the Screening visit.
15. Received total parenteral nutrition within 2 weeks prior to the Week 0 visit.
16. Not on stable amounts of enteral nutrition for at least 4 weeks prior to Week 0
visit.
17. Previous exposure to systemic or biologic anti-IL-12 therapy, including ABT-874.
18. History of an allergic reaction or significant sensitivity to constituents of study
drug.
19. Received any investigational agent within 30 days or 5 half-lives prior to the
Week 0 visit (whichever is longer) or within a duration of its known
pharmacological activity.
20. Subjects who have initiated or discontinued Imuran® (azathioprine), 6-MP, or
MTX therapy within 12 weeks of the Week 0 visit. Subjects taking these
medications who have undergone a change in dosage within 4 weeks prior to the
Week 0 visit.
21. Subjects who have initiated or discontinued aminosalicylates, mesalamine,
sulfasalazine, or Crohn's-related antibiotics within 4 weeks of the Week 0 visit. In
addition, subjects taking these medications who have undergone a change in
dosage within 4 weeks prior to the Week 0 visit.
22. Undergone therapeutic enemas within 14 days prior to the Week 0 visit.
23. On prednisolone > 40 mg/day (or equivalent) and subjects who were not on stable
doses for 2 weeks prior to Week 0. In addition, subjects who discontinued
prednisolone (or equivalent) within 2 weeks of the Week 0 visit.
24. On cyclosporine (IV, oral), tacrolimus (any form) or Mycophenolate mofetil
within 8 weeks of the Week 0 visit.
25. On budesonide > 9 mg/day and subjects who are not on stable doses of budesonide
for at least 2 weeks prior to the Week 0 visit. In addition, subjects who
discontinue budesonide within 2 weeks of the Week 0 visit.
26. Received Tysabri within 4 months of the Week 0 visit.
27. Received Kineret® (anakinra) within two days of the Week 0 visit.
28. Received an anti-TNF therapy within 8 weeks of the Week 0 visit.
29. Received an anti-TNF therapy that is currently investigational.
30. Received a transfusion of any blood product or has lost 550 mL or more of blood
due to a hemorrhage within an interval of time judged by the investigator to be
unacceptable for study participation.
31. The Investigator considers the subject, for any reason, to be unacceptable for study participation.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The objective of this study is to compare the efficacy, safety, and pharmacokinetics of<br>200, 400 or 700 mg IV dosing every four weeks of ABT-874 to placebo in<br>subjects who have moderately to severely active Crohn's disease.;Secondary Objective: Additionally, an optional exploratory substudy will evaluate the correlation between the response to ABT-874 and pharmacogenomic and pharmacogenetic analysis.;Primary end point(s): Proportion of subjects achieving clinical remission, defined as CDAI score of < 150 points, at Week 6.