Clinical trial NCT00425321: Safety and Effectiveness Study of RWJ-445380 Cathepsin-S Inhibitor in Patients With Active Rheumatoid Arthritis Despite Methotrexate Therapy
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Rheumatoid Arthritis
Keywords: Arthritis
Joints
Auto immune
Lead sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Sponsor class: INDUSTRY
First posted: 2007-01-22
Enrollment: 259
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: 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
timeFrame: up to 12 weeks
Secondary outcomes:
measure: Explore effectiveness of drug through accepted arthritis clinical measures and biomarkers
timeFrame: 12 weeks, Explore effectiveness of drug through accepted clinical measures and biomarkers
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Huntsville
country: United States
state: Alabama
city: Tucson
country: United States
state: Arizona
city: Fair Oaks
country: United States
state: California
city: Whittier
country: United States
state: California
city: Waterbury
country: United States
state: Connecticut
city: Sarasota
country: United States
state: Florida
city: Morton Grove
country: United States
state: Illinois
city: Springfield
country: United States
state: Illinois
city: Frederick
country: United States
state: Maryland
city: Duncansville
country: United States
state: Pennsylvania
city: Nashville
country: United States
state: Tennessee
city: Austin
country: United States
state: Texas
city: Buenos Aires
country: Argentina
city: Ciudad Autónoma De Buenos Aires
country: Argentina
city: Federal
country: Argentina
city: Lujan
country: Argentina
city: Curitiba
country: Brazil
city: Porto Alegre
country: Brazil
city: Sao Paulo
country: Brazil
city: Brno
country: Czech Republic
city: Plzeò 1
country: Czech Republic
city: Praha 1
country: Czech Republic
city: Praha 2
country: Czech Republic
city: Uherske Hradiste
country: Czech Republic
city: Zlin
country: Czech Republic
city: Bad Abbach
country: Germany
city: Bad Nauheim
country: Germany
city: Dresden
country: Germany
city: Essen
country: Germany
city: Frankfurt
country: Germany
city: Herne
country: Germany
city: Leipzig
country: Germany
city: Ciudad De Mexico
country: Mexico
city: Guadalajara
country: Mexico
city: Mexico
country: Mexico
city: San Luis Potosi
country: Mexico
city: Bialystok
country: Poland
city: Bydgoszcz
country: Poland
city: Krakow
country: Poland
city: Lublin
country: Poland
city: Poznan
country: Poland
city: Szczecin
country: Poland
city: Warszawa
country: Poland
Study officials:
affiliation: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
name: Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial
role: STUDY_DIRECTOR
References: