A double-blind, placebo-controlled Clinical Trial to evaluate the Safety and Efficacy of JNJ-64304500 in patients with Moderately to Severely Active Crohn’s Disease
- Conditions
- Active Crohn's DiseaseMedDRA version: 20.0Level: PTClassification code 10011401Term: Crohn's diseaseSystem Organ Class: 10017947 - Gastrointestinal disordersTherapeutic area: Diseases [C] - Immune System Diseases [C20]
- Registration Number
- EUCTR2016-000634-21-HU
- Lead Sponsor
- Janssen-Cilag International NV
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 693
- 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.
- Have active Crohn's disease, defined as a baseline CDAI score of =220
but =450.
Have at least one of the following at screening: An abnormal CRP (>0.3
mg/dL [>3.0 mg/L]) OR Calprotectin >250 mg/kg.
Study 1: Has previously demonstrated inadequate response, loss of
response, or intolerance to 1 or more approved biologic therapies
Study 2: Has failed conventional therapy (currently receiving
corticosteroids and/or immunomodulators OR has a history of failure to
respond to or tolerate an adequate course of corticosteroids and/or
immunomodulators OR is corticosteroid dependent or has had a history
of corticosteroid dependency).
Part II: Has previously demonstrated inadequate response, loss of
response, or intolerance to 1 or more approved biologic therapies or has failed conventional therapy.
All 3 Studies:
- Adhere to the following requirements for concomitant medication for
the treatment of Crohn's disease, which are permitted provided that
doses meeting these requirements are stable, or have been
discontinued, for at least 3 weeks before baseline (Week 0), unless
otherwise specified:
a. Oral 5-aminosalicylic acid (5-ASA) compounds.
b. Oral corticosteroids at a prednisone-equivalent dose at or below 40
mg/day, or 9 mg/day of budesonide, or 5 mg/day beclomethasone
dipropionate.
c. Antibiotics being used as a primary treatment of Crohn's disease.
d. Conventional immunomodulators (ie, AZA, 6-MP, or MTX): subjects
must have been taking them for at least 12 weeks and at a stable dose
for at least 4 weeks before baseline.
- A subject with a family history of colorectal cancer, personal history of
increased colorectal cancer risk, age >50 years, or other known risk
factor must be up-to-date on colorectal cancer surveillance
- A subject who has had extensive colitis for =8 years, or disease limited
to the left side of the colon for =12 years, must either have had a
colonoscopy to assess for the presence of dysplasia within 1 year before
the first administration of study agent or a colonoscopy to assess for the
presence of malignancy at the screening visit, with no evidence of
malignancy.
- Have screening laboratory test results within the following parameters:
a. Hemoglobin =8.0 g/dL.
b. White blood cell count (WBCs) =3.0 × 103/µL.
c. Neutrophils =1.5 × 103/µL.
d. Platelets =100 × 103/µL.
e. Serum creatinine <1.7 mg/dL.
f. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST)
concentrations must be within 2 times the upper limit of the normal
range (ULN) range for the laboratory conducting the test.
g. Direct (conjugated) bilirubin <1.0 mg/dL.
- Are considered eligible according to the following tuberculosis (TB)
screening criteria (see details in protocol):
a. Have no history of latent or active TB before 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 before or simultaneously with the
first administration of study agent.
d. Within 2 months before the first admini
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, or would possibly confound the ability to assess the effect of treatment with JNJ-64304500 or ustekinumab.
2. Currently has or is suspected to have an abscess (see details in protocol).
3. Has had any kind of bowel resection within 6 months or any other intra-abdominal surgery within 3 months before 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 before baseline.
b. Other oral immunomodulatory agents (eg, 6-thioguanine [6-TG], cyclosporine, tacrolimus, sirolimus, or mycophenolate mofetil, tofacitinib and other Janus kinase [JAK] inhibitors) <6 weeks or within 5 half-lives of agent before baseline, whichever is longer.
c. Nonbiologic experimental or investigational agents <4 weeks or within 5 half-lives of agent before baseline, whichever is longer.
d. Nonautologous stem cell therapy (eg, Prochymal), natalizumab, efalizumab, or biologic agents that deplete B or T cells (eg, rituximab, alemtuzumab, or visilizumab) <12 months before baseline.
e. TNFa-antagonist biologic agents (eg, mAb therapies) or other agents intended to suppress or eliminate TNFa <8 weeks before baseline.
f. Vedolizumab <16 weeks before baseline.
g. Other immunomodulatory biologic agents <12 weeks or within 5 half-lives of agent before baseline, whichever is longer.
h. Treatment with apheresis (eg, Adacolumn apheresis) or total parenteral nutrition as a treatment for Crohn’s disease <3 weeks before baseline.
6. Has a stool culture or other examination positive for an enteric pathogen 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.
8. Has previously received JNJ-64304500 or NNC0142-002.
9. Has received a Bacille Calmette-Guérin (BCG) vaccination within 12 months or any other live bacterial or live viral vaccination within 12 weeks before baseline.
10. Has a history of, or ongoing, chronic or recurrent infectious disease.
11. 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.
12. Has a history of serious infection (eg, sepsis, pneumonia, or pyelonephritis) for 8 weeks before baseline.
13. Has evidence of a Herpes zoster infection =8 weeks before baseline.
14. Has a history of latent or active granulomatous infection before screening.
15. Has evidence of current active infection, including TB, or a nodule suspicious for lung malignancy on screening or any other available chest radiograph.
16. Has or ever has had a nontuberculous mycobacterial infection or serious opportunistic infection.
17. Has a history of HIV antibody positivity, or tests positive for HIV at screening.
18. Are seropositive for antibodies to HCV without a history of successful treatment.
19. Subjects must undergo screening for HBV:
a. Subjects who test negative for all HBV screening tests (ie, HBsAg-, anti-HBc-, and anti-HBs-) are eligible for this study.
b. Subjects who test positive for surface an
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