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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
ClinicalTrials.gov Identifier:
NCT00425321
First received: January 19, 2007
Last updated: June 24, 2013
Last verified: June 2013
  Purpose

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 Intervention Phase
Rheumatoid Arthritis
Drug: RWJ-445380 100 mg
Drug: RWJ-445380 200 mg
Drug: RWJ-445380 300 mg
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, 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

Resource links provided by NLM:


Further study details as provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Enrollment: 259
Study Start Date: December 2006
Study Completion Date: January 2008
Primary Completion Date: January 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00425321

  Show 44 Study Locations
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

No publications provided

Responsible Party: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
ClinicalTrials.gov Identifier: NCT00425321     History of Changes
Obsolete Identifiers: NCT00766610
Other Study ID Numbers: CR012511, C-2006-009
Study First Received: January 19, 2007
Last Updated: June 24, 2013
Health Authority: United States: Food and Drug Administration

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
Methotrexate
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on April 20, 2014