Safety and Effectiveness Study of RWJ-445380 Cathepsin-S Inhibitor in Patients With Active Rheumatoid Arthritis Despite Methotrexate Therapy

Johnson & Johnson (J&J)

Status and phase: Completed; Phase 2

Conditions: Rheumatoid Arthritis

Treatments: Drug: Placebo; Drug: RWJ-445380 200 mg; Drug: RWJ-445380 100 mg; Drug: RWJ-445380 300 mg

Study type: Interventional

Funder types: Industry

Identifiers

NCT00425321

C-2006-009 (Other Identifier)

CR012511

Details and patient eligibility

About

The primary objective of the study is to evaluate the safety and tolerability of 100, 200, and 300 mg/day doses of RWJ-445380 for up to 12 weeks in patients with active Rheumatoid Arthritis despite methotrexate therapy.

Full description

Trials with a new, first -in-class drug will be done to ascertain safety, tolerability, and to explore efficacy in the treatment of rheumatoid arthritis, including its effects on biomarkers. Approximately 240 adult patients with rheumatoid arthritis despite the use of methotrexate therapy will be recruited for the study. They will be randomly assigned to one of 4 treatment arms; each patient has an equal chance of receiving the placebo, or 100 mg, 200 mg, 300 mg dose of RWJ-445380. Patients will take the medication daily for up to 12 weeks. Patients will receive study medication in a blinded fashion, i.e. the patient, the doctor and the study sponsor will not know what group the patient is in until all patients complete the study. The investigator and the sponsor will monitor the study for the occurrence of possible side effects. In addition to a screening visit, patients will have visits every week for the first 2 weeks then every 2 weeks until 12 weeks of treatment. After 12 weeks, there will be a followup visit 4 weeks after the last dose of study drug is taken. Medical history, physical examination, blood pressure, heart rate, temperature, and ECGs are checked periodically. Joints will be assessed to explore whether the drug might affect tender and swollen joints. Blood samples will be taken for standard safety laboratory tests as well as special tests of the drug blood level, biomarkers to see whether the drug might be affecting the biological pathway of antigen presentation, and other markers for rheumatoid arthritis. Samples will also be taken to see whether certain types of immune cells are affected by taking the drug. Immunization with tetanus vaccine will be done to see if taking the drug might affect immune responses to this agent Patients will receive RWJ-445380, 100, 200, 300 mg, or placebo. Patients will receive oral capsules daily for up to 12 weeks.

Enrollment: 259 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patients diagnosed with rheumatoid arthritis for at least 6 months with at least 8 tender and 8 swollen joints
• methotrexate treatment for 6 months
• at least 10mg/wk and stable dose for at least 8 weeks
• negative TB screening

Exclusion criteria

• Use of other disease-modifying anti-rheumatic drugs (DMARDs) (other than Methotrexate MTX)
• previous use of more than 1 anti-TNF (tumor necrosis factor) agent
• previous use of cytotoxics, p38 MAPkinase inhibitor, anti-CD4 antibody
• receipt of live vaccine within 1 month of study drug
• serious infection in previous 2 months or history of chronic or recurrent infectious disease or history of opportunistic infection
• other clinically significant disease of other organ system

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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259 participants in 4 patient groups, including a placebo group

RWJ-445380 100 mg

Experimental group

Treatment:

Drug: RWJ-445380 100 mg

RWJ-445380 200 mg

Experimental group

Treatment:

Drug: RWJ-445380 200 mg

RWJ-445380 300 mg

Experimental group

Treatment:

Drug: RWJ-445380 300 mg

Placebo

Placebo Comparator group

Treatment:

Drug: Placebo