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

• Register: EUCTR
• Last refreshed on: 1 May 2012
• Main ID: EUCTR2006-003983-73-CZ
• Date of registration: 22/11/2006
• Prospective Registration: Yes
• Primary sponsor: Janssen-Cilag International N.V.
• Public 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
• Scientific 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
• Date of first enrolment: 17/01/2007
• Target sample size: 240
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2006-003983-73
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Czech Republic, Germany

Key inclusion & exclusion criteria

Inclusion criteria:
1. Patients must have provided written consent to participate in the study prior to any study procedures and understand that they are free to withdraw from the study at any time.

2. Patients must be able to read and understand the consent form, complete the study-related procedures, and communicate with the study staff.

3. Patients may be men or women and must be 18 years or older. For potential patients > 70 years of age, the investigator must confer with the Medical Monitor during screening to determine the patient’s medical suitability prior to enrollment.

4. Patient must have a diagnosis of Rheumatoid Arthritis Functional Class I-III according to the American College of Rheumatology (ACR) criteria for at least 6 months prior to Screening. (See Appendix 3).

5. Patients must have active RA at the time of Screening and at baseline, as defined by eight or more swollen joints and eight or more tender joints.

6. Patients must have started oral or parenteral MTX treatment, at least 10 mg/week, for a minimum of 6 months prior to Screening and must have a stable MTX dose for a minimum of 8 weeks prior to the first study drug dose.

7. Patients must be on a stable dose of folate preparation (folic or folinic acid) for at least 4 weeks prior to the first study drug dose.

8. If using oral corticosteroids, patients must be on a stable dose equivalent to £ 10 mg of prednisone/day for at least 4 weeks prior to the first study dose. If currently not using corticosteroids, patients must have not received oral corticosteroids for at least 4 weeks prior to the first study dose.

9. If using non-steroidal anti-inflammatory drugs (NSAIDs), patients must be on a stable dose for at least 4 weeks prior to the first study dose. If currently not using NSAIDs, the patient must not have received NSAIDs for at least 4 weeks prior to the first study dose.

10. Patients must have Screening laboratory test result as follows:
· Hemoglobin ³ 9.0 g/dL (International System of Units [SI]: ³ 90 g/L)
· White blood cells (WBC) ³ 3.0 x 103 cells/µL (SI: ³ 3.0 x109 cells/L)
· Neutrophils ³ 1.5 x 103 cells/mL (SI: ³ 1.5 x109 cells/L)
· Platelets ³ 100 x 103 cells/mL (SI: ³ 100 x109 cells/L)
· Transaminase level not exceeding 1.5 times the upper limit of normal (ULN) for the central laboratory conducting the test
· Bilirubin level not exceeding 1.5 times the upper limit of normal (ULN) for the central laboratory conducting the test
· Serum creatinine not exceeding 1.5 mg/dL (SI: £ 125 mmol/L)

11. Patients must have a negative intradermal tuberculin skin test at Screening or within 1 month prior to study treatment initiation. Specific guidelines for administering and interpreting the TB skin test are provided in Appendix 10, along with provisions for enrolling patients with positive TB skin tests because of prior vaccination with BCG. For the purposes of this study, the criterion for PPD positivity generally applied for immunocompromised patients (induration >5 mm) will be used.

12. Patients must satisfy the following Screening criteria for TB:
· No history of active or latent TB prior to Screening
· Have no signs or symptoms suggestive of active TB upon medical history and/or physical examination
· Have had no recent close contact with a person with active TB (if contact has occurred, has been referred to a physician for evaluation; evaluation should be documented and discussed with sponsor medical monitor, as appropriate).

13. Patients must consent to utili
Exclusion criteria:
1. Patients who are pregnant, nursing, or planning a pregnancy (both men and women) within 6 months of enrollment.

2. Patients who have other inflammatory diseases that might confound the evaluations from RWJ-445380 therapy (including but not limited to ankylosing spondylitis, systemic lupus erythematosus, Lyme disease).

3. Patients who have received disease-modifying anti-rheumatic drugs ([DMARDs] other than MTX (e.g., D penicillamine, hydroxychloroquine, chloroquine, oral or parenteral gold, azathioprine or sulphasalazine) or interleukin [IL]-1 receptor antagonist [anakinra] within 4 weeks prior to the first study dose, or leflunomide within 3 months of the first study dose.

4. Patients who have been previously treated with more than one therapeutic agent targeted at reducing TNFa (including but not limited to infliximab, etanercept, adalimumab, CDP870 or thalidomide).

5. Patients who have received prior anti-TNF treatment within 4 weeks prior to first study dose or received the anti-TNF infliximab within 3 months prior to the first study dose.

6. Patients who have been treated with any p38 MAP kinase inhibitor, abatacept or rituximab.

7. Patient who have used cytotoxic drugs, including chlorambucil, cyclophos-phamide, nitrogen mustard, or other alkylating agents.

8. Patients who have previously received treatment with a Prosorba® column.

9. Patients who have been treated with any anti-CD4 antibody.

10. Patients who have received intra-articular, intramuscular, or IV cortico-steroids, including intramuscular adrenocorticotrophic hormone during the 4 weeks prior to the first study dose.

11. Patients who have taken any investigational drug within the previous 30 days or within a period of 5 half-lives, whichever is greater, prior to first study dose.

12. Patients who have received, or who are expected to receive, live virus or bacterial vaccinations within 1 month before first study drug dose, during the trial, or up to 1 month after the last study drug dose.

13. Patients who have a history of infected joint prosthesis or have received antibiotics for a suspected infection of a joint prosthesis if that prosthesis has not been removed or replaced.

14. Patients who have, or have had, a serious infection during the previous 2 months prior to first study treatment (including but not limited to hepatitis, pneumonia, or pyelonephritis, or have been hospitalized or received IV antibiotics for an infection.

15. Patients who have a history of, ongoing chronic, or recurrent infectious disease, including but not limited to, chronic renal infection, chronic chest infection (eg, bronchiectasis), sinusitis, recurrent urinary tract infection (recurrent pyelonephritis or chronic nonremitting cystitis), an open, draining, or infected skin wound, or ulcer.

16. Patients who have, or have history of an opportunistic infection (eg, herpes zoster [shingles], cytomegalovirus, Pneumocystis carinii, aspergillosis, histoplasmosis, mycobacteria other than TB, or granulomatous infection).

17.Patients with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C.

18.Patients with current signs or symptoms of clinically significant, progressive, or uncontrolled renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, cardiac, neurologic, psychiatric, or cerebral disease.

19. Patients with medical conditions associated with pruritus (dermatological or drug induced), current or within 6 months of screening.

20. Patie

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Rheumatoid arthritis
MedDRA version: 8.1 Level: LLT Classification code 10039073 Term: Rheumatoid arthritis

Intervention(s)

Product Name: RWJ-445380 Capsules 50 mg
Product Code: RWJ-445380-002
Pharmaceutical Form: Capsule*
CAS Number: 400797-45-7
Current Sponsor code: RWJ-445380-002
Other descriptive name: JNJ-16240159-AAC
Concentration unit: % (W/W) percent weight/weight
Concentration type: range
Concentration number: 45 mg-55 mg
Pharmaceutical form of the placebo: Capsule*
Route of administration of the placebo: Oral use

Product Name: RWJ-445380 capsule 100 mg
Product Code: RWJ-445380-002
Pharmaceutical Form: Capsule*
CAS Number: 400797-45-7
Current Sponsor code: RWJ-445380-002
Other descriptive name: JNJ-16240159-AAC
Concentration unit: % (W/W) percent weight/weight
Concentration type: range
Concentration number: 90 mg-110 mg
Pharmaceutical form of the placebo: Capsule*
Route of administration of the placebo: Oral use

Product Name: RWJ-445380 capsules 150 mg
Product Code: RWJ-445380-002
Pharmaceutical Form: Capsule*
CAS Number: 400797-45-7
Current Sponsor code: RWJ-445380-002
Other descriptive name: JNJ-16240159-AAC
Concentration unit: % (W/W) percent weight/weight
Concentration type: range
Concentration number: 135 mg-165 mg
Pharmaceutical form of the placebo: Capsule*
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: ·To evaluate the efficacy of RWJ-445380 in patients with active RA despite methotrexate therapy receiving doses of 100, 200, or 300 mg/day.

·To assess the effect of RWJ-445380 on various biomarkers associated with RA.

Main Objective: To assess the safety and tolerability of RWJ-445380 at doses of 100, 200, or 300 mg/day for up to 12 weeks in patients with active Rheumatoid Arthritis (RA) despite methotrexate (MTX) therapy.

Primary end point(s): Primary endpoint is response to ACR20, but responses to ACR50 and ACR70 will also be evaluated. ACR(%) is a composite efficacy measure comprised of: swollen joint count, tender joint count, patient asseessment of pain (VAS), patient's global assessment of disease activity (VAS), evaluator's global assessment of disease activity (VAS), patients's assessment of physical function as measured by the HAQ and CRP.

Secondary ID(s)

C-2006-009