A Phase IIa Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study of JNJ-38518168 in Subjects with Active Rheumatoid Arthritis Despite Methotrexate Therapy With Synovial Biopsy Substudy
- Conditions
- MedDRA version: 9.1Level: HLTClassification code 10039075Term: Rheumatoid arthritis and associated conditionsJNJ-38518168 is being developed for the treatment of Rheumatoid Arthritis.
- Registration Number
- EUCTR2009-012118-27-GB
- Lead Sponsor
- Janssen-Cilag International NV
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 95
1. Man or woman between 18 - 75 yrs, inclusive.
2.2 Have a diagnosis of RA according to the revised 1987 criteria of the ARA for at least 6 m at screening.
3.3 Have active RA defined for the purpose of this study as persistent disease activity with both of the following criteria:
a. Serum CRP =6 mg/L at screening only. Serum CRP between 5.5 and 6.0
mg/L can be rounded to 6 mg/L.
b. 66/68 Joint Count as follows:
• Primary study subjects: at least 6 swollen and 6 tender joints using a 66/68 joint count.
• Synovial biopsy substudy subjects: at least 4 swollen and 4 tender joints using a 66/68 joint count with a clinically inflamed knee, or ankle joint.
4. Have been treated with and tolerated MTX treatment at dosages between 7.5 to 25 mg/wk inclusive, for a minimum of 4 m prior to screening and must have a stable MTX dose for a minimum of 4 wks prior to the first study drug dose. In addition, based on the Investigator’s assessment, an adequate supply of MTX as needed
throughout the subject’s participation in the study.
5.1. If using NSAIDs or other analgesics regularly for RA, subjects must have been on a stable dose for at least 2 wks prior to the first dose of study medication. If not using NSAIDs or other analgesics for RA at study initiation, the patient must have not received NSAIDs or other analgesics for at least 2 wks prior to the first dose
of study medication.
6. If using oral corticosteroids, must be on a stable dose of =10 mg/day of prednisone or an equipotent dose of another oral corticosteroid for at least 4 weeks prior to the first dose of study medication, and continue with the same dose throughout the study. If not using corticosteroids at study initiation, the subject must have not received oral corticosteroids for at least 4 weeks prior to the first dose of study medication.
7. Currently treated with folic acid at a minimum dose of 5 mg/wk.
8.3. Are considered eligible according to the following TB screening criteria:
a. Have no history of latent or active TB at screening. An exception is made for
subjects who have a history of latent TB (defined for the purposes of this
study as having had a positive result from either the tuberculin skin test or the
QuantiFERON-TB Gold test prior to screening) and documentation of having
completed an adequate treatment regimen for latent TB prior to the first
administration of study agent under this protocol.
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, have been evaluated by a physician specializing in TB and found not to have evidence of, or require treatment for latent TB.
d. Within 6 wks prior to the first administration of study medication, have negative TB screening test results
e. Have a TB-negative chest X-ray, within 3 months prior to screening, and read by a qualified radiologist.
9.2 At screening, the results of the following laboratory tests performed at the central laboratory must be within the limits specified in Protocol.
10. Except for signs and symptoms of active RA, subjects should be free from any significant health condition on the basis of the physical examination, medical history, laboratory tests, vital signs, 12-lead ECG, and all other assessments performed at screening.
11. Women must be one of the following:
a)Postmenopausal;
b)Surgically sterile,
c)Sexually abstinent or If, se
1. Diagnosis of RA Functional Class IV according to the ACR criteria which has been ongoing for at least 6 m.
2. Inflammatory diseases other than RA. At the discretion of the Investigator, certain inflammatory may be acceptable after discussion with the Medical Monitor.
3. Current signs or symptoms of liver or renal insufficiency or cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, psychiatric, or metabolic disturbances that are severe, progressive or uncontrolled in the Investigator’s discretion.
4.2 Except for MTX, have been treated with the following approved or investigational non-biologic DMARDs:
a. Including, D-penicillamine, hydroxychloroquine, chloroquine, oral or parenteral gold salts, sulfasalazine, azathioprine, cyclosporine, tacrolimus, and mycophenolate mofetil within 4 w prior to randomization
b. Leflunomide within 4 w prior to randomization, or have received leflunomide from 4 to 12 w prior to randomization and have not undergone a drug elimination procedure.
c. Any investigational non-biologic disease-modifying antirheumatic drugs within 4 wks or 5 half-lives prior to randomization, whichever is longer.
5. Received intra-articular, IM, or IV corticosteroids, including adrenocorticotropic hormone, within 4 w prior to the first dose of study medication, or would be expected to need such therapy during the participation in the
study.
6.2 Received any approved or investigational antirheumatic agent targeted at inhibiting TNF including:
a. Infliximab, golimumab, or certolizumab pegol within 3 months prior to randomization
b. Etanercept, or adalimumab within 2 m prior to randomization
c. Any other investigational anti-TNFa biologic agent within 3 months or five half lives of the drug prior to randomization, whichever is longer
7.2 Treated with more than either the total of three biologic antirheumatic agents and/or the total of five DMARDs that proved ineffective anytime before the screening.
8.2 Treated with approved or investigational biologic anti-inflammatory or immunosuppressive agents other than anti-TNFa agents during the six months or five half-lives of the drug prior to the first dose of study medication,
whichever is longer.
9. Treated with Prosorba column apheresis within 3 m.
10. Treated with any other investigational drug or medical device within 4 wk or 5 half lives of the drug, whichever is longer.
11. Except for MTX, have been treated with a cytotoxic agent anytime before the first dose of study medication.
12. Undergone surgical treatments for RA including synoviectomy and arthroplasty within 3 m.
13.2 Undergone arthrocentesis or synovial biopsy (except the biopsy procedure performed in the substudy) within 1 m prior to the first dose of study medication.
14. Received drugs that potently inhibit or induce CYP450 3A4 isoform or any drug that potently inhibits or induces the PGP within 2 wk or within 5 half-lives of the drug, whichever is longer.
15. Received drugs with a risk of torsades de pointes within 1 wk or within 5 half-lives of the drug, whichever is longer.
16. Have a history of latent or active granulomatous infection, histoplasmosis, or coccidioidomycosis.
17. Have a QTcF interval >450 msec at screening or baseline, or have a history or current evidence of additional risk factors for torsades de pointes.
18. Have received, or are expected to receive, any live virus or bacterial vaccines within 1 m prior to the first dose of study medication, during
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To assess the safety, tolerability, and efficacy (in terms of change in DAS28 [using C-Reactive Protein (CRP)] from baseline) of JNJ-38518168 at a dose of 100 mg/day for up to 12 weeks compared to placebo in subjects with active Rheumatoid Arthritis (RA) despite methotrexate (MTX) therapy;Secondary Objective: To assess the efficacy of JNJ-38518168 as measured by ACR 20, 50, 70, 90 response rates at Week 12 and other efficacy assessments.<br>;Primary end point(s): Change from baseline in DAS28 (using CRP) score at Week 12
- Secondary Outcome Measures
Name Time Method