A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter Study to Evaluate the Safety and Efficacy of Ustekinumab Induction Therapy in Subjects with Moderately to Severely Active Crohn's Disease Who Have Failed or Are Intolerant to TNF Antagonist Therapy
- Conditions
- Crohn's Disease10017969
- Registration Number
- NL-OMON38117
- Lead Sponsor
- Janssen-Cilag
- Brief Summary
Trial is onging in other countries
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 32
Each potential subject must satisfy all of the following criteria to be enrolled in the study. Each
subject must:
1. Be a man or woman >= 18 years of age.;2. Have Crohn*s disease or fistulizing Crohn*s disease of at least 3 months* duration, with
colitis, ileitis, or ileocolitis, confirmed at any time in the past by radiography, histology,
and/or endoscopy.;3. Have active Crohn*s disease, defined as a baseline CDAI score of >= 220 and <= 450.;4. 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.;5. Adhere to the following requirements for concomitant medication for the treatment of
Crohn*s disease. The following medications are permitted provided doses meeting the
requirements below are stable for or have been discontinued at least 3 weeks prior to baseline
(Week 0), unless otherwise specified.
a. Oral 5-ASA compounds.
b. Oral corticosteroids (eg, prednisone, budesonide) at a prednisone-equivalent dose of
<= 40 mg/day or <= 9 mg/day of budesonide.
c. Antibiotics being used as a primary treatment of Crohn*s disease.
d. Subjects receiving conventional immunomodulators (ie, AZA, 6-MP, or MTX) must have
been taking them for >= 12 weeks, and on a stable dose for a least 4 weeks prior to
baseline.;6. Have screening laboratory test results within the following parameters:
a. Hemoglobin >= 8.5 g/dL
b. WBCs >= 3.5 x 103/uL
c. Neutrophils >= 1.5 x 103/uL
d. Platelets >= 100 x 103/uL
e. Serum creatinine < 1.7 mg/dL
f. AST and ALT concentrations must be within 2 times the ULN range for the laboratory
conducting the test.
g. Direct (conjugated) bilirubin < 1.0 mg/dL.;7. Are considered eligible according to the following TB screening criteria:
a. Have no history of latent or active TB prior to screening. Exceptions are made for
subjects currently receiving treatment for latent TB, if there is no evidence of active TB,
or who have a history of latent TB and documentation of having completed adequate
treatment for latent TB within 3 years prior to the first administration of study agent. It is
the responsibility of the investigator to verify the adequacy of previous TB treatment and
provide appropriate documentation.
Note: The exceptions outlined above exclude subjects in countries with high multidrugresistant
TB burden (eg, South Africa, Bulgaria, and the Russian Federation), due to
potential concerns for multi-drug resistant TB.
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
QuantiFERON-TB Gold test (Attachment 2), or have a newly identified positive
QuantiFERON-TB Gold test in which active TB has been ruled out, and for which
appropri
Any potential subject who meets any of the following criteria will be excluded from participating
in the study. The subject will be excluded if he or she:
1. Has complications of Crohn*s disease such as symptomatic strictures or stenoses, short gut
syndrome, or any other manifestation that might be anticipated to require surgery, could
preclude the use of the CDAI to assess response to therapy, or would possibly confound the
ability to assess the effect of treatment with ustekinumab.;2. Currently has or is suspected to have an abscess. Recent cutaneous and perianal abscesses
are not exclusionary if drained and adequately treated at least 3 weeks prior to baseline, or
8 weeks prior to baseline for intra-abdominal abscesses, provided that there is no anticipated
need for any further surgery. Subjects with active fistulas may be included if there is no
anticipation of a need for surgery and there are currently no abscesses identified.;3. Has had any kind of bowel resection within 6 months or any other intra-abdominal surgery
within 3 months prior to baseline.;4. Has a draining (ie, functioning) stoma or ostomy.;5. Has received any of the following prescribed medications or therapies within the specified
period:
a. IV corticosteroids < 3 weeks prior to baseline.
b. Other oral immunomodulatory agents (eg, 6-thioguanine [6-TG], cyclosporine,
tacrolimus, sirolimus, or mycophenolate mofetil) < 6 weeks prior to baseline.
c. Non-biologic experimental or investigational agents < 4 weeks or within 5 half-lives of
agent prior to baseline, whichever is longer.
d. Non-autologous stem cell therapy (eg, Prochymal), natalizumab, efalizumab, or biologic
agents that deplete B or T cells (eg, rituximab, alemtuzumab, or visilizumab)
< 12 months prior to baseline.
e. Anti-TNF biologic agents (eg, monoclonal antibody therapies) or other agents intended to
suppress or eliminate TNF < 8 weeks prior to baseline.
f. Other immunomodulatory biologic agents < 12 weeks or within 5 half-lives of agent prior
to baseline, whichever is longer.
g. Treatment with apheresis (eg, Adacolumn apheresis) or total parenteral nutrition (TPN)
as a treatment for Crohn*s disease < 3 weeks prior to baseline.;6. 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.;7. Has previously received a biologic agent targeting IL-12 or IL-23, including but not limited
to ustekinumab (CNTO 1275) or briakinumab (ABT-874).;8. Has received a Bacille Calmette-Guérin (BCG) vaccination within 12 months or any other
live bacterial or live viral vaccination within 12 weeks of baseline.;9. Has a history of, or ongoing, chronic or recurrent infectious disease, including but not limited
to, chronic renal infection, chronic chest infection, recurrent urinary tract infection (eg,
recurrent pyelonephritis or chronic nonremitting cystitis), or open, draining, or infected skin
wounds or ulcers.;10. Has current signs or symptoms of infection. Established nonserious infections (eg, acute
upper respiratory tract infection, simple urinary tract infection) need not be considered
exclusionary at the discretion of the investigator.;11. Has a history of serious infection (eg, sepsis, pneumonia, or pye
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The primary endpoint is clinical response at Week 6, defined as a reduction<br /><br>from baseline in the CDAI score of >= 100 points. Subjects with a baseline CDAI<br /><br>score of >= 220 to <= 248 points are considered to be in clinical response if a<br /><br>CDAI score of < 150 is attained.</p><br>
- Secondary Outcome Measures
Name Time Method <p>The major secondary endpoints, in order of importance, are:<br /><br>1. Clinical remission at Week 8, defined as a CDAI score of < 150 points.<br /><br>2. Clinical response at Week 8.<br /><br>3. 70-point response at Week 6, defined as a reduction from baseline in the<br /><br>CDAI score of >= 70 points.<br /><br>4. 70-point response at Week 3.</p><br>