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: JNJ-38518168 is being developed for the treatment of Rheumatoid Arthritis.; MedDRA version: 9.1Level: HLTClassification code 10039075Term: Rheumatoid arthritis and associated conditions

• Registration Number: EUCTR2009-012118-27-NL
• Lead Sponsor: Janssen-Cilag International NV

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-05-27
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 90

Inclusion Criteria

1. Man or woman between 18 and 75 years of age, inclusive.
2. Have a diagnosis of RA at screening established as positive for either anti-CCP antibody or Rheumatoid Factors (RF) in serum at screening.
3. Have active RA at screening and at baseline (for joint count only). Active RA is defined for the purpose of this study as persistent disease activity with both of the following criteria:
a. Serum CRP > upper limit of normal at screening only.
b. 66/68 Joint Count as follows:
• Primary study subjects: at least 6 swollen and 6 tender joints using a 66/68 joint count at the time of screening and at baseline
• 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 at the time of screening and at baseline.
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 min 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. If using NSAIDs regularly for RA or other conditions, 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 at study initiation, the patient must have been off NSAIDs for at least 2 wks prior to the first dose of study medication.
6. If using oral corticosteroids (CS), must be on a stable dose of =10 mg/day of prednisone or an equipotent dose of another oral CS for at least 4 wks prior to the first dose of study medication, and continue with the same dose throughout the study. If not using CS at study initiation, the subject must have not received oral CS for at least 4 wks prior to the first dose of study medication.
7. Currently treated with folic acid at a minimum dose of 5 mg/wk.
8. Eligible according to the following TB screening criteria (see protocol for details)
9. The results of the following laboratory tests performed at the central laboratory must be within the limits specified in the 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. If there are abnormalities, they must be consistent with the underlying illness in the study population at Investigator’s discretion.
11. Women must be one of the following:
a. Postmenopausal,
b. Surgically sterile,
c. Sexually abstinent, or
d. If sexually active, be practicing a highly effective method of birth control and must agree to continue to use the same method of contraception throughout the study.
12. All women must have a negative beta human chorionic gonadotropin pregnancy test at screening and at baseline.
13. Male subjects must consent to utilize a medically acceptable method of contraception throughout the study and for three months after the last dose of study drug and to not donate sperm during the study and for 3 months after receiving the last dose of study drug.
14. Willing and able to adhere to all of the procedures, prohibitions and restrictions specified in this protocol.
15. Before any screening procedure is undertaken, subjects must have signed an informed consent document indicating that they under

Exclusion Criteria

1. Have a diagnosis of RA Functional Class IV according to the ACR criteria which has been ongoing for at least 6 m prior to the first dose of study medication.
2. Have inflammatory diseases other than RA. At the discretion of the Investigator, certain inflammatory diseases such as Sjogrens Syndromeor Chronic Thyroiditis may be acceptable after discussion with the Medical Monitor.
3. Have 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. RA subjects with chronic co-morbidities will not be excluded if the Investigator has determined that the co-morbid condition is not severe or progressive and is being controlled with stable therapy.
4. Except for MTX, have been treated with approved or investigational non-biologic DMARDs during the 4 wk or 5 half-lives prior to the first dose of study medication, whichever is longer.
5. Have received intra-articular, IM, or IV corticosteroids (CS), including adrenocorticotropic hormone, within 4 wk prior to the first dose of study medication, or would be expected to need such therapy during the participation in the study.
6. Have received any approved or investigational antirheumatic agent targeted at reducing TNF within 3 m or five half lives of the drug prior to the first dose of study medication, whichever is longer.
7. Have been treated with more than either the total of three biologic antirheumatic agents or the total of five DMARDs that proved ineffective anytime before the screening.
8. Have been treated with other approved or investigational biologic anti-inflammatory or immunosuppressive agents during the six m or five half-lives of the drug prior to the first dose of study medication, whichever is longer.
9. Have been treated with Prosorba column apheresis within 3 m prior to the first dose of study medication.
10. Have been treated with any other investigational drug or medical device within 4 wk or 5 half lives of the drug, whichever is longer prior to the first dose of study medication.
11. Except for MTX, have been treated with a cytotoxic agent anytime before the first dose of study medication.
12. Have undergone surgical treatments for RA including synoviectomy and arthroplasty within 3 m prior to the first dose of study medication.
13. Have undergone arthrocentesis or synovial biopsy within 1 m prior to the first dose of study medication.
14. Have 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, prior to the first dose of study medication.
15. Have received drugs with a risk of torsades de pointes within 1 wk or within 5 half-lives of the drug, whichever is longer, prior to the first dose of study medication. Use of drugs known to prolong the QT interval should be discussed with the Medical Monitor on a case by case basis.
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 the

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified