E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Rheumatoid Arthritis (RA) is an inflammatory disease that chiefly affects patients’ joints |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10039073 |
E.1.2 | Term | Rheumatoid arthritis |
E.1.2 | System Organ Class | 10028395 - Musculoskeletal and connective tissue disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objectives are to assess the safety, tolerability, and efficacy (change from baseline in Disease Activity Score 28 [DAS28] using C-reactive protein [CRP]) of JNJ-40346527 200 mg/day (100 mg twice daily) for 12 weeks compared with placebo in subjects with active RA despite DMARD therapy. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are: •To assess the efficacy of JNJ-40346527 as measured by American College of Rheumatology (ACR) 20 and 50 response rates at Week 12.
•To characterize the population pharmacokinetics (PK) of JNJ-40346527 in adults with active RA despite DMARD therapy.
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
An optional intensive PK substudy will be conducted in subjects who sign a separate consent form. Blood samples will be collected at the Week 8 visit for measurement of plasma concentrations of JNJ-40346527 and its metabolites at predose and at 1, 2, 3, and 4, hours postdose.
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E.3 | Principal inclusion criteria |
Principal Inclusion Criteria in Lay Language (for a complete list of inclusion criteria refer to the protocol):
- Have had rheumatoid arthritis (RA) for at least 6 months prior to screening.
- Have been positive for, or are positive at screening for, either anti-cyclic citrullinated peptide (anti-CCP) antibody or rheumatoid factor (RF) in serum.
- Have active RA with at least 6 swollen and 6 tender joints, using a 66/68 joint count at the time of screening and at baseline, and serum CRP ≥ 0.80 mg/dL at screening.
- Have been treated with and tolerated at least one of the following medications for a minimum of 6 months prior to screening and must be on a stable dose for a minimum of 8 weeks prior to screening: methotrexate (MTX) treatment at dosages of 7.5 to 25 mg/week, inclusive; sulfasalazine not exceeding 3 g/d; hydroxychloroquine not exceeding 400 mg/d.
- If using nonsteroidal antiinflammatory drugs (NSAIDs), or other analgesics regularly for RA, patients must have been on a stable dose for at least 2 weeks prior to the first administration of study agent. If not using NSAIDs or other analgesics for RA, the patient must have not received NSAIDs or other analgesics for at least 2 weeks prior to the first administration of study agent.
- If using oral corticosteroids, must be on a stable dose of ≤ 10 mg/day of prednisone or an equipotent dose of another oral corticosteroid for at least 2 weeks prior to the first administration of study agent. If not using corticosteroids, the patient must have not received oral corticosteroids for at least 2 weeks prior to the first administration of study agent.
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E.4 | Principal exclusion criteria |
Principal Exclusion Criteria in Lay Language (for a complete list of exclusion criteria refer to the protocol):
- Has inflammatory diseases other than RA, including but not limited to adult onset Still’s disease, psoriatic arthritis, ankylosing spondylitis, systemic lupus erythematosus, and Lyme disease that might confound the evaluation of the benefit of study agent therapy.
- Has a history of juvenile idiopathic arthritis (JIA).
- Has current signs or symptoms of liver or renal insufficiency or cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, psychiatric, or metabolic disturbances that are severe, progressive, or uncontrolled.
- Has been treated in the time frames specified with any nonbiologic disease-modifying antirheumatic drugs (DMARDs), except for MTX, sulfasazine, and hydroxychloroquine, including, but not limited to: D-penicillamine, oral or parenteral gold salts, azathioprine, cyclosporine, tacrolimus, and mycophenolate mofetil within 4 weeks prior to the first administration of study agent; leflunomide within 12 weeks prior to the first administration of study agent unless the patient has undergone a drug elimination procedure at least 4 weeks prior to the first administration of study agent; any investigational nonbiologic DMARD within 4 weeks prior to the first administration of study agent or 5 half-lives of the DMARD, whichever is longer.
- Has ever received any approved or investigational biologic antirheumatic agent. These agents include, but are not limited to, infliximab, golimumab, certolizumab pegol, etanercept, adalimumab, abatacept, rituximab, tocilizumab, or anakinra.
- Has received drugs that potently inhibit or induce cytochrome P450 (CYP450) 3A4, CYP2C8, or CYP2C19 isoforms within 2 weeks or within 5 half-lives of the drug, whichever is longer, prior to the first dose of study medication.
- Has received intra-articular, epidural, intravertebral, intramuscular, or intravenous corticosteroids, including adrenocorticotropic hormone, within 4 weeks prior to the first dose of study medication.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is change from baseline in DAS28 (using CRP) at Week 12 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Major Secondary Endpoints: •ACR 20 response rates at Week 12
• DAS28 (using CRP) response rates at Week 12
Other Secondary Endpoints: •ACR 50/70 response rates at Week 12
•Change from baseline in DAS28 (using ESR) at Week 12
•DAS28 (using ESR) response rates at Week 12
• HAQ-DI response at Week 12
•Change from baseline in HAQ-DI score at Week 12
• Percent change from baseline in ESR levels at Week 12
• Percent change from baseline in ACR components at Week 12
•Change from baseline in Simplified Disease Activity Index at Week 12
• Change from baseline in Clinical Disease Activity Index at Week 12 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
biomarker analysis and assessment of tolerability |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |