A phase IIIb, multinational, randomized, double-blind, placebo-controlled trial to assess the efficacy and safety of certolizumab pegol, a pegylated Fab' fragment of a humanized anti-TNF-alpha monoclonal antibody, administered subcutaneously at weeks 0, 2 and 4 in subjects with moderately to severely active Crohn?s disease - ND

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

Registration Number: EUCTR2007-001913-41-IT

Lead Sponsor: CB Celletech

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 500

Inclusion Criteria

1.Diagnosis of Crohn?s disease confirmed (at least 3 months prior to screening visit) by either radiological or endoscopic evidence.
2.Moderately to severely active Crohn?s disease (CDAI ≥ 220 ≤ 450) scored over the 7 days prior to the Baseline visit
3.No previous treatment with an anti-TNF agent
4.Male or female aged 18-75 years old
5.Are considered eligible according to the following TB screening criteria:
Have no history of latent or active TB prior to screening
Have no signs or symptoms suggestive of active TB
Have a negative PPD (TST) skin test as defined by induration less than 5 mm
Subjects who have a positive PPD test defined as induration equal or greater than 5mm are required to commit to have prophylactic treatment with for example isonicotinic acid hydrazide (INH therapy) with vitamin B6 to prevent neuropathy, for a minimum duration of 9 months. Additional prophylactic treatment and follow-up of subjects is at the discretion of the investigator. Subjects who do not initiate prophylactic treatment for latent TB per sponsor requirement are not eligible to enter the trial. Subjects are eligible to enter the study once 30-day period on TB prophylaxis has elapsed
All subjects should take a TB survey at visit 1 of the study (Appendix 17.4). Subjects deemed to have a high risk of latent TB are required to have TB prophylaxis initiated irrespective of PPD test result
Have a chest x-ray taken within 3 months prior to the Baseline visit that was read by a qualified radiologist or pulmonary physician, with no evidence of current active TB or old inactive TB
6.Have screening laboratory results as follows:
Serum Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) levels not exceeding 2 times the upper limit of normal for the central laboratory conducting the test.
Serum creatinine not exceeding 1.7 mg/dl ( SI: ≤ 150 mol/L)
Platelets ≥ 100 x 103 cells/L (SI: ≥ 100 x 109 cells/L)
Neutrophils ≥ 1.5 x 103cells/L (SI: ≥ 1.5 x 109 cells/L)
7.Have met all the concomitant medication criteria in the following table. For all drugs taken at screening, the subject must remain on a stable dose throughout the duration of the study.
8.Are capable of providing informed consent, which must be obtained prior to any study related procedures
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.Subject with Crohn?s disease who has perianal disease and/or any known fistulae
2.Subject with abscess or suspicion of abscess
3.Subject with symptomatic known obstructive strictures or bowel perforation in last 6 months
4.Subject with short bowel syndrome
5.Subject who has had a surgical bowel resection within the past 6 months or is planning any resection at time while enrolled in the study
6.Subject with current diagnosis of Ulcerative Colitis (UC) or Indeterminant Colitis as determined by investigator or Sponsor
7.Subject with ostomy or ileoanal pouch
8.Subject who is currently receiving total parenteral nutrition
9.Subject with positive stool cultures for enteric pathogens during screening (e.g. C. difficile)
10.Previous participation in a certolizumab pegol study
11.Subject who has received any investigational agent within 5 half-lives prior to study drug administration
12.Subject who has received any biologic product within 12 weeks prior to screening
13.Subject with any prior exposure to natalizumab (Tysabri)
14.Subject with a history of drug or alcohol abuse
15.Females who are pregnant or breast feeding
16.Females of child bearing age not practicing effective birth control
17.History of malignancy within last 5 years (except carcinoma ?in situ of cervix or basal cell carcinoma that was successfully treated)
18.History or symptoms suggestive of lymphoproliferative disease as defined by unexplained lymphadenopathy and/or unexplained increase of white blood count of >20 x 109 cells/L
19.History of Human Immunodeficiency Virus (HIV), chronic or active Hepatitis B or Hepatitis C
20.History of Congestive Heart Failure (CHF), including medically controlled asymptomatic CHF
21.Has had a opportunistic infection (e.g. cytomegalovirus, pneumoncystis carii, aspergillosis, histoplasmosis, coccidioidomycosis) within 6 months prior to screening
22.Has had a serious infection, (e.g. pneumonia, sepsis, pyelonephritis), has been hospitalized for an infection, or has been treated with IV antibiotics for an infection within 3 months prior to screening. Less severe infections (acute upper respiratory tract infections, urinary tract infections) occurring in this timeframe need not be considered exclusionary at the discretion of the investigator and approval of the study physician. However subjects should not be enrolled when acutely ill with an intercurrent infection
23.Has a transplanted organ (except corneal transplant)
24.Has had a chest x-ray within 3 months prior to the first administration of study treatment that shows an abnormality suggestive of a malignancy or active infection, including TB
25.Has received or is expecting to receive, any live virus or bacterial vaccination within 3 months of first study drug administration, during the trial or 3 months after last dose of study drug
26.History of known demyelinating disease such as optic neuritis or multiple sclerosis
27.Has signs or symptoms of severe, progressive, or uncontrolled renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, cardiac, neurologic, psychiatric or cerebral disease