A Phase 2b, Multicenter, Randomized, Double-blind,Placebo-controlled, Parallel-group Study to Evaluate the Efficacyand Safety of Ustekinumab Therapy in Subjects with Moderatelyto Severely Active Crohn’s Disease Previously Treated with TNFAntagonist Therapy - CERTIFI
- Conditions
- Moderately to Severely Active Crohn’s DiseaseMedDRA version: 9.1Level: LLTClassification code 10011401Term: Crohn's disease
- Registration Number
- EUCTR2008-000649-77-NL
- Lead Sponsor
- Centocor BV
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 500
- Have Crohn’s disease or fistulizing Crohn’s disease of at least 3 months’ duration,
with colitis, ileitis, or ileocolitis, confirmed by radiography and/or endoscopy.
- Have active disease, defined as a baseline CDAI score of = 220 and = 450.
- Have received infliximab, adalimumab, or certolizumab pegol at a dose approved
for the treatment of Crohn’s disease and:
a. Did not respond initially (ie, primary nonresponders). or
b. Responded initially but then lost response with continued therapy
(ie, secondary nonresponders). or
c. Were intolerant to the medication.
- Are men or women who are = 18 years of age at time of consent.
- Adhere to the following concomitant medication requirements relative to the first
study agent administration at baseline (Week 0).
a. 5-ASA compounds.
b. Oral corticosteroids (eg, prednisone, budesonide)
c. Crohn’s disease-specific antibiotics
d. Immunomodulators:
-Women of childbearing potential and all men must be using adequate birth control
measures
- Have the capacity to understand and sign an informed consent form.
- Be able to adhere to the study visit schedule and other protocol requirements.
- Have screening laboratory test results within the following parameters:
- Hemoglobin > 8.5 g/dL
- WBCs = 3.5 x 103/µL
- Neutrophils = 1.5 x 103/µL
- Platelets = 100 x 103/µL
- Serum creatinine < 1.5 mg/dL
- AST and ALT concentrations must be within 2 times the ULN range for the
laboratory conducting the test.
- Direct (conjugated) bilirubin < 2.0 mg/dL.
- Are considered eligible according to the following TB screening criteria:
a. Have no history of latent or active TB prior to screening.
b. Have no signs or symptoms suggestive of active TB upon medical history
and/or physical examination.
c. Have had no recent close contact with a person with active TB or, if there has
been such contact, will be referred to a physician specializing in TB to
undergo additional evaluation and, if warranted, receive appropriate
treatment for latent TB prior to or simultaneously with the first administration
of study agent.
d. Within 2 months prior to the first administration of study agent, either have
negative diagnostic TB test results (defined as a negative QuantiFERON-TB
Gold In-Tube test), or have a newly identified positive diagnostic TB test
result (defined as a positive QuantiFERON-TB Gold In-Tube test) during
screening in which active TB has been ruled out and for which appropriate
treatment for latent TB has been initiated either prior to or simultaneously
with the first administration of study agent.
e. Have a chest radiograph (both posterior-anterior and lateral views), taken
within 3 months prior to the first administration of study agent and read by a
qualified radiologist, with no evidence of current active TB or old inactive
TB.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years)
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years)
F.1.3.1 Number of subjects for this age range
- Have complications of Crohn’s disease such as strictures, stenoses, short gut
syndrome, or any other manifestation that might require surgery, could preclude the
use of the CDAI to assess response to therapy, or would possibly confound the
evaluation of benefit from treatment with ustekinumab.
- Have any current or prior abscesses, unless they have been drained and treated at
least 6 weeks prior to baseline and are not anticipated to require surgery. Subjects
with active fistulas may be included if there is no anticipation of a need for surgery
and there are currently no abscesses present.
- Have had any kind of bowel resection, diversion, or placement of a stoma within
months or any other intra-abdominal surgery within 3 months prior to screening.
- Have received treatment with total parenteral nutrition (TPN) within 2 weeks of
screening.
- Have a stool culture or other examination positive for an enteric pathogen,
including Clostridium difficile toxin, in the last 4 months unless a repeat
examination is negative and there are no signs of ongoing infection with that
pathogen.
- Are pregnant, nursing, or planning pregnancy (both men and women) while
enrolled in the study, or within 20 weeks after receiving the last dose of study agent.
- Have used any therapeutic agent targeted at reducing IL-12 or IL-23, including but
not limited to, ustekinumab (CNTO 1275) and ABT-874.
- Have used any investigational drug within the previous 4 weeks or 5 times the
half-life of the investigational agent prior to the first administration of study agent,
whichever is longer.
- Have used any TNF antagonist = 8 weeks prior to the first administration of study
agent or any other biologic = 12 weeks prior to the first administration of study
agent or within 5 times the half-life of the biologic prior to the first administration
of study agent, whichever is longer.
- Have received natalizumab, efalizumab, or agents that deplete B or T cells within 12 months of screening, or, if after receiving these agents, evidence is available at screening of persistent depletion of the targeted lymphocyte population.
- Have used apheresis (eg, Ada column apheresis) = 2 weeks prior to screening.
- Have received any live bacterial or viral vaccination = 12 weeks prior to Week 0.
Subjects must agree not to receive a live virus or bacterial vaccination during the
study or up to 12 months after the last administration of study agent.
- Have had a Bacille Calmette-Guérin (BCG) vaccination within 12 months of
screening. Subject must agree not to receive a BCG vaccination during the study or
up to 12 months after the last study agent administration.
- Have a history of, or ongoing, chronic or recurrent infectious disease.
- Have current signs or symptoms of infection or history of serious infection.
- Have evidence of a herpes zoster infection = 8 weeks of screening.
- Have a history of latent or active granulomatous infection.
- Have evidence of current active infection.
- Have or ever have had a nontuberculous mycobacterial infection or serious
opportunistic infection.
- Are known to be infected with human immunodeficiency virus, hepatitis B, or
hepatitis C.
- Have severe, progressive, or uncontrolled renal, hepatic, hematological, endocrine,
pulmonary, cardiac, neurologic, cerebral, or psychiatric disease, or signs and
symptoms thereof.
- Have a transplanted organ (with exception of a corneal transplant > 12 weeks prior
to screening) or have ever received stem cell therapy
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method