Crohns disease
Conditions
Interventions
Group 1: Placebo, administered at the visit in week 0. Group 2: Ustekinumab 130
mg, administered at the visit in week 0. Group 3: Weight-range based
ustekinumab doses approximating ustekinumab 6 mg/
Sponsors
Janssen-Cilag
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 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. A baseline CDAI score of * 220 and * 450, AND b. At least one of the following: 1) An abnormal CRP (> 0.3 mg/L) at screening; OR 2) Calprotectin > 250 mg/kg at screening; OR 3) Endoscopy with evidence of active Crohn*s disease during the current disease flare (defined as ulcerations in the ileum and/or colon). The endoscopy must have occurred within 3 months prior to baseline.;4. Meet the following requirements for prior or current medications for Crohn*s disease: a. Has failed conventional therapy: 1) Is currently receiving corticosteroids and/or immunomodulators (ie, AZA, MTX, or 6-MP) at adequate therapeutic doses; OR 2) Has a history of failure to respond to or tolerate an adequate course of corticosteroids and/or immunomodulators (ie, AZA, MTX, or 6-MP); OR 3) Is corticosteroid dependent or has had a history of corticosteroid dependency; AND b. Has not previously demonstrated inadequate response or intolerance to 1 or more TNF antagonist therapies (ie, infliximab, adalimumab, or certolizumab pegol) as outlined in Attachment 1 in the protocol.;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 = 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 a
Exclusion criteria
Exclusion criteria: 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary endpoint is clinical response at Week 6, defined as a reduction from baseline in the CDAI score of >= 100 points. Subjects with a baseline CDAI score of >= 220 to | — |
Secondary
| Measure | Time frame |
|---|---|
| The major secondary endpoints, in order of importance, are: 1. Clinical remission at Week 8, defined as a CDAI score of = 70 points. 4. 70-point response at Week 3. | — |
Countries
Netherlands
Outcome results
None listed