A Study to Evaluate the Safety and Efficacy of Ustekinumab Induction Therapy in Patients with Moderately to Severely Active Crohn’s Disease
- Conditions
- Moderately to severely active Crohn's diseaseMedDRA version: 17.0Level: PTClassification code 10011401Term: Crohn's diseaseSystem Organ Class: 10017947 - Gastrointestinal disordersTherapeutic area: Diseases [C] - Immune System Diseases [C20]
- Registration Number
- EUCTR2010-022759-42-HU
- Lead Sponsor
- Janssen-Cilag International N.V.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 612
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/dL or > 3.0 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. 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 at adequate therapeutic doses;
OR
2) Has a history of failure to respond to or tolerate an adequate course of corticosteroids and/or immunomodulators;
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.
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 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 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 parameters mentioned in the protocol:
7. Are considered eligible according to the TB screening criteria mentioned in the protocol:
8. If a woman, before entry she must be:
a. Postmenopausal, defined as
1) > 45 years of age with amenorrhea for at least 18 months,
OR
2) > 45 years of age with amenorrhea for at least 6 months and a serum follicle stimulating hormone (FSH) level > 40 IU/mL
OR
b. Menstrual
1) Surgically sterile, or
2) If heterosexually active, practicing a highly effective method of birth control, including hormonal prescription oral contraceptives, contraceptive injections, contraceptive patch, intrauterine device, double-barrier method, or male partner sterilization, consistent with local regulations regarding use of birth control methods for subjects participating in clinical trials, for the duration of their participation in the study and for 20 weeks after receiving study agent, or
3) Not heterosexually active.
9. If a woman of childbearing potential, she must have a negative serum ß-human chorionic gonadotropin (ß-hCG) pregnancy test at screening; and a negative urine pregnancy test at Week 0.
10. If a man and heterosexually active with a woman of childbearing potential, and not surgically sterile, he must agree to use a double barrier method of birth control and to not donate sperm during the study and for 20 weeks after receiving study agent.
11. Be willing and able to adhere to the prohibitions and restrictions specified in this protocol.
12. Sign an informed consent document indicating that they understand the purpose of and procedures required for the stud
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 stoma or ostomy.
5. Has received any of the prescribed medications or therapies within the specified period (mentioned in the protocol).
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, or open, draining, or infected skin wounds or ulcers.
10. Has current signs or symptoms of infection. Established nonserious infections need not be considered exclusionary at the discretion of the investigator.
11. Has a history of serious infection, including any infection requiring hospitalization or IV antibiotics, for 8 weeks prior to baseline.
12. Has evidence of a herpes zoster infection = 8 weeks prior to baseline.
13. Has a history of latent or active granulomatous infection, including histoplasmosis or coccidioidomycosis, prior to screening. Refer to inclusion criteria for information regarding eligibility with a history of latent TB.
14. Has evidence of current active infection, including but not limited to TB (exceptions see protocol).
15. Has or ever has had a nontuberculous mycobacterial infection or serious opportunistic infection.
16. Is known to be infected with HIV, hepatitis B, or hepatitis C.
17. Has severe, progressive, or uncontrolled renal, hepatic, hematological, endocrine, pulmonary, cardiac, neurologic, cerebral, or psychiatric disease, or signs and symptoms thereof.
18. Has a transplanted organ.
19. Has a known history of lymphoproliferative disease, including lymphoma, or signs and symptoms suggestive of possible lymphoproliferative disease, such as lymphadenopathy and/or splenomegaly.
20. Has any known malignancy or has a history of malignancy.
21. Has previously undergone allergy immunotherapy for prevention of anaphylactic reactions.
22. Is unable or unwilling to undergo multiple venipunctures because of poor tolerability or lack of easy access to veins.
23. Is known to have had a substance abuse problem w
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