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

NCT ID: NCT00425321

Last Updated: 2014-05-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 259 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-12-31
• Study Completion Date: 2008-01-31

Brief Summary

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.

Detailed 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.

Conditions

Rheumatoid Arthritis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

RWJ-445380 100 mg

Group Type: EXPERIMENTAL

RWJ-445380 100 mg

Intervention Type: DRUG

RWJ-445380 100 mg once daily for up to 12 weeks

RWJ-445380 200 mg

Group Type: EXPERIMENTAL

RWJ-445380 200 mg

Intervention Type: DRUG

RWJ-445380 200 mg once daily for up to 12 weeks

RWJ-445380 300 mg

Group Type: EXPERIMENTAL

RWJ-445380 300 mg

Intervention Type: DRUG

RWJ-445380 300 mg once daily for up to 12 weeks

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo once daily for up to 12 weeks

Interventions

RWJ-445380 100 mg

RWJ-445380 100 mg once daily for up to 12 weeks

Intervention Type: DRUG

RWJ-445380 200 mg

RWJ-445380 200 mg once daily for up to 12 weeks

Intervention Type: DRUG

RWJ-445380 300 mg

RWJ-445380 300 mg once daily for up to 12 weeks

Intervention Type: DRUG

Placebo

Placebo once daily for up to 12 weeks

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial

Role: STUDY_DIRECTOR

Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Locations

Birmingham, Alabama, United States

Huntsville, Alabama, United States

Tucson, Arizona, United States

Fair Oaks, California, United States

Whittier, California, United States

Waterbury, Connecticut, United States

Sarasota, Florida, United States

Morton Grove, Illinois, United States

Springfield, Illinois, United States

Frederick, Maryland, United States

Duncansville, Pennsylvania, United States

Nashville, Tennessee, United States

Austin, Texas, United States

Buenos Aires, , Argentina

Federal, , Argentina

Luján, , Argentina

Curitiba, , Brazil

Porto Alegre, , Brazil

São Paulo, , Brazil

Brno, , Czechia

Plzeò 1, , Czechia

Prague, , Czechia

Uherské Hradiště, , Czechia

Zlín, , Czechia

Bad Abbach, , Germany

Bad Nauheim, , Germany

Dresden, , Germany

Essen, , Germany

Frankfurt, , Germany

Herne, , Germany

Leipzig, , Germany

Guadalajara, , Mexico

Mexico City, , Mexico

México, , Mexico

San Luis Potosí City, , Mexico

Bialystok, , Poland

Bydgoszcz, , Poland

Krakow, , Poland

Lublin, , Poland

Poznan, , Poland

Szczecin, , Poland

Warsaw, , Poland

Countries

United States; Argentina; Brazil; Czechia; Germany; Mexico; Poland

Other Identifiers

C-2006-009

Identifier Type: OTHER

Identifier Source: secondary_id

CR012511

Identifier Type: -

Identifier Source: org_study_id

NCT00766610

Identifier Type: -

Identifier Source: nct_alias