A Multicenter, Double-Blind Study to Evaluate the Safety, Efficacy and Pharmacokinetics of the Human Anti-TNF Monoclonal Antibody Adalimumab in Pediatric Subjects with Moderate to Severe Crohn's Disease

• Conditions: Moderate to Severe Crohn's Disease; MedDRA version: 8.1Level: LLTClassification code 10011401Term: Crohn's disease

• Registration Number: EUCTR2006-004814-41-NL
• Lead Sponsor: Abbott GmbH & Co. KG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-01-22
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 184

Inclusion Criteria

1. Subjects between the ages of 6 and 17, inclusive prior to Baseline dosing.
2. Subjects with a diagnosis of CD for greater than 12 weeks prior to Screening, confirmed by endoscopy or radiologic evaluation.
3. PCDAI score of > 30 despite concurrent treatment with an oral corticosteroid, and/or azathioprine or 6-mercaptopurine (6-MP) or methotrexate (MTX) as defined on page 27 of the study protocol.
4. If female, subjects who are sexually active and are of child-bearing potential should be practicing an approved method of birth control throughout the study and for 150 days after study completion. Examples of approved methods of birth control include the following:
? Condoms, sponge, foam, jellies, diaphragm or intrauterine device (IUD)
? Oral, parenteral or intravaginal contraceptives for 12 weeks prior to study drug
administration
? A vasectomized partner
5. Parent or legal guardian as required has voluntarily signed and dated an informed consent form, approved by an Institutional Review Board (IRB)/Independent Ethics Committee (IEC), after the nature of the study has been explained and the subject's parent or legal guardian has had the opportunity to ask questions. Subjects will be included in all discussions in order to obtain their signature on an assent form.
6. Adequate cardiac, renal and hepatic function as determined by the principal investigator and demonstrated by Screening laboratory evaluations and physical examination results that are within normal limits.
7. Parent or legal guardian must be willing to actively supervise storage and administration of study drug and to ensure that the time of each dose is accurately recorded in the subject's diary.
8. For subjects that have previously received infliximab, the subjects must have had an initial response and then discontinued use due to a loss of response or must have discontinued use due to intolerance to the medication (see Appendix A for definitions).
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion 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, histoplasmosis, chronic or active hepatitis B infection, human immunodeficiency virus (HIV) infection, any immunodeficiency syndrome, central nervous system (CNS) demyelinating disease or active TB (receiving treatment or not receiving treatment), severe infections such as sepsis and opportunistic infections.
3. Subject with a current diagnosis of ulcerative colitis or indeterminate colitis as determined by the investigator and Medical Monitor.
4. Subject with symptomatic known obstructive strictures.
5. Subject who has had surgical bowel resections within the past 24 weeks of the Baseline visit or is planning any resection at any timepoint 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 are currently 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 16 weeks 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, recurrent infections, unstable ischemic heart disease, moderate to severe 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 within 8 weeks of Baseline.
17. Subject who has previously used infliximab and has not clinically responded at any time (primary non-responder) unless subject experienced a treatment limiting reaction to infliximab.
18. Previous treatment with any other anti-TNF agent except infliximab.
19. Received previous treatment with adalimumab or previous participation in an adalimumab clinical study.
20. Screening laboratory and other analyses show abnormal results. (Please see page 31 of the study protocol for details).
21. Subjects on azathioprine, 6 MP, or MTX who have not been on these medications for at least 8 weeks prior to Baseline and on stable doses of these medications for at least 4 weeks prior to Baseline. Subjects who have been on azathioprine, 6 MP, or MTX who have discontinued these medications within 8 weeks of Baseline.
22. Subjects on aminosalicylates, or Crohn's-related antibiotics (fluoroquinolones such as ciprofloxacin or nitroimidazole derivatives such as metronidazole) who have not been on stable doses of these medications for at least 4 weeks prior to Baseline. In addition, subjects on aminosalicylates or Crohn's-related antibiotic treatments who have discontinued these medications within 4 weeks of Baseline.
23. Subjects on prednison

Study & Design

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

Primary Outcome Measures

Name	Time	Method
Main Objective: To demonstrate the safety and efficacy of adalimumab and to assess the pharmacokinetics (PK) of adalimumab administered by SC injection in pediatric subjects with moderate to severe CD. ;Secondary Objective: ;Primary end point(s): The primary analysis will be the comparison of the proportion of subjects in the two adalimumab dosing groups [40 mg/20 mg eow vs. 20 mg/10 mg. eow] who achieved clinical remission at Week 26 (irrespective of whether they were clinical responders or non-responders at Week 4).