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

• ClinicalTrials.gov Identifier: NCT00425321
• Recruitment Status: Completed
• First Posted: January 22, 2007
• Last Update Posted: May 21, 2014
• Sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
• Information provided by (Responsible Party): Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Rheumatoid Arthritis	Drug: RWJ-445380 100 mg; Drug: RWJ-445380 200 mg; Drug: RWJ-445380 300 mg; Drug: Placebo	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 259 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase IIa Multicenter, Randomized, Double-Blind, Placebo -Controlled, Parallel Group Study of RWJ-445380 Cathepsin-S Inhibitor in Patients With Active Rheumatoid Arthritis Despite Methotrexate Therapy
• Study Start Date: December 2006
• Actual Primary Completion Date: January 2008
• Actual Study Completion Date: January 2008

Arms and Interventions

Arm	Intervention/treatment
Experimental: RWJ-445380 100 mg	Drug: RWJ-445380 100 mg; RWJ-445380 100 mg once daily for up to 12 weeks
Experimental: RWJ-445380 200 mg	Drug: RWJ-445380 200 mg; RWJ-445380 200 mg once daily for up to 12 weeks
Experimental: RWJ-445380 300 mg	Drug: RWJ-445380 300 mg; RWJ-445380 300 mg once daily for up to 12 weeks
Placebo Comparator: Placebo	Drug: Placebo; Placebo once daily for up to 12 weeks

Outcome Measures

Primary Outcome Measures :

1. Evaluate the safety of RWJ-445380 for up to 12 weeks; assessing adverse events, vital signs, laboratory and physical exam and ECGs in patients with rheumatoid arthritis [ Time Frame: up to 12 weeks ]

Secondary Outcome Measures :

1. Explore effectiveness of drug through accepted arthritis clinical measures and biomarkers [ Time Frame: 12 weeks, Explore effectiveness of drug through accepted clinical measures and biomarkers ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, Alabama

Birmingham, Alabama, United States

Huntsville, Alabama, United States

United States, Arizona

Tucson, Arizona, United States

United States, California

Fair Oaks, California, United States

Whittier, California, United States

United States, Connecticut

Waterbury, Connecticut, United States

United States, Florida

Sarasota, Florida, United States

United States, Illinois

Morton Grove, Illinois, United States

Springfield, Illinois, United States

United States, Maryland

Frederick, Maryland, United States

United States, Pennsylvania

Duncansville, Pennsylvania, United States

United States, Tennessee

Nashville, Tennessee, United States

United States, Texas

Austin, Texas, United States

Argentina

Buenos Aires, Argentina

Ciudad Autónoma De Buenos Aires, Argentina

Federal, Argentina

Lujan, Argentina

Brazil

Curitiba, Brazil

Porto Alegre, Brazil

Sao Paulo, Brazil

Czech Republic

Brno, Czech Republic

Plzeò 1, Czech Republic

Praha 1, Czech Republic

Praha 2, Czech Republic

Uherske Hradiste, Czech Republic

Zlin, Czech Republic

Germany

Bad Abbach, Germany

Bad Nauheim, Germany

Dresden, Germany

Essen, Germany

Frankfurt, Germany

Herne, Germany

Leipzig, Germany

Mexico

Ciudad De Mexico, Mexico

Guadalajara, Mexico

Mexico, Mexico

San Luis Potosi, Mexico

Poland

Bialystok, Poland

Bydgoszcz, Poland

Krakow, Poland

Lublin, Poland

Poznan, Poland

Szczecin, Poland

Warszawa, Poland

Sponsors and Collaborators

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

Investigators

• Study Director: Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial; Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

More Information

• Responsible Party: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
• ClinicalTrials.gov Identifier: NCT00425321
• Obsolete Identifiers: NCT00766610
• Other Study ID Numbers: CR012511; C-2006-009 ( Other Identifier: Johnson & Johnson Pharmaceutical Research and Development, L.L.C. )
• First Posted: January 22, 2007
• Last Update Posted: May 21, 2014
• Last Verified: May 2014

Keywords provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.:

Arthritis; Joints; Auto immune

Additional relevant MeSH terms:

Arthritis; Arthritis, Rheumatoid; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases