E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10039073 |
E.1.2 | Term | Rheumatoid arthritis |
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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 objective of this study is to demonstrate, in patients with RA who have at least 5/68 tender and at least 5/66 swollen joints at baseline, the superiority of 120 mg LY2127399 every four weeks (Q4W) (LY A) or 90 mg LY2127399 every two weeks (Q2W) (LY B), each after a loading dose, compared to placebo as measured by the American College of Rheumatology 20% response rates (ACR20) over 24 weeks. |
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E.2.2 | Secondary objectives of the trial |
• To demonstrate, in patients with RA who have at least 5/68 tender and at least 5/66 swollen joints at baseline, the superiority of LY A or LY B compared to placebo over 24 weeks, as assessed by the: ACR 50% response rate (ACR50), ACR 70% response rates (ACR70), and ACR percent improvement (ACR-N) indices Individual components of the ACR Core Set Disease Activity Score based on a 28 joint count (DAS28) and C-reactive protein level (CRP) (DAS28-CRP) European League Against Rheumatism Responder Index based on the 28 joint count (EULAR-28) Health outcome measures: Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) Time to ACR20 response • To demonstrate, in patients with RA who have at least 5/68 tender and at least 5/66 swollen joints at baseline, the superiority of LY A or LY B compared to placebo over 24 weeks for subpopulations defined by concomitant DMARD as assessed by the: ACR20 and ACR50 indices DAS28-CRP |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Patients will be male and female aged ≥18 years of age with a diagnosis of moderately to severely active adult onset RA • Diagnosis of Rheumatoid Arthritis (RA) of more than 6 months and less than 15 years • Global Assessment of Disease Activity visual analog scale (VAS)greater than or equal to 20/100 mm • If on one or more conventional DMARDs at randomization, must have been on a stable dose for at least 8 weeks prior to study start. • Woman must not be pregnant, breastfeeding, or become pregnant during the study
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E.4 | Principal exclusion criteria |
• Use of unstable doses of non-steroidal inflammatory drugs (NSAIDS) in the past 6 weeks • Steroid injection or intravenous (iv) infusion in the last 6 weeks • Use of more than 10 mg/day of oral steroids in the last 6 weeks • Use of biologic DMARD concurrently or recently • History of a serious reaction to other biological DMARDs • Use of an oral calcineurin inhibitor (e.g., cyclosporin or tacrolimus) in the last 8 weeks • Surgery on a joint or other major surgery less than 2 months ago, or plans to have joint surgery or major surgery during the study • Active fibromyalgia, juvenile chronic arthritis, spondyloarthropathy, Crohn's disease, ulcerative colitis, psoriatic arthritis, or other systemic inflammatory condition except RA • Cervical cancer or squamous skin cancer within the past 3 years, or other cancer within the past 5 years • Received a live vaccine received within the past 12 weeks (for example, vaccines for measles, mumps, rubella, and chicken pox, and nasal-spray flu vaccines) • Hepatitis or human immunodeficiency virus (HIV) • A serious bacterial infection (for example, pneumonia or cellulitis) within 3 months or a serious bone or joint infection within 6 months • Symptoms of herpes zoster or herpes simplex within the last month • Active or latent tuberculosis (TB) • Current symptoms of a serious disorder or illness • Use of an investigational drug within the last month
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E.5 End points |
E.5.1 | Primary end point(s) |
• Percentage of patients with American College of Rheumatology 20% response (ACR20) • Percentage of patients with American College of Rheumatology 50% (ACR50) and 70% (ACR70) response • Mean percent improvement in ACR-N • Change from baseline to 24 weeks in Tender Joint Count (68 joint count) • Change from baseline to 24 weeks in Swollen Joint Count (66 joint count) • Change from baseline to 24 weeks in Patient's Assessment of Pain (VAS) • Change from baseline to 24 weeks in Patient's Global Assessment of Disease Activity (VAS) • Change from baseline to 24 weeks in Physician's Global Assessment of Disease Activity (VAS) • Change from baseline to 24 weeks in Health Assessment Questionnaire-Disability Index (HAQ-DI) • Change from baseline to 24 weeks in Disease Activity Score-C-Reactive Protein (DAS28-CRP) • Percentage of patients with DAS28-Based European League Against Rheumatism (EULAR) response • Change from baseline to 24 weeks in Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) domain and summary scores • Time to ACR20 response • Change from baseline to 24 weeks in absolute B cell counts • Change from baseline to 24 weeks in serum immunoglobulin (Ig) levels • Population Pharmacokinetics (PK) • Percentage of patients developing anti-LY2127399 antibodies |
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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 | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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.8.3 |
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.8.4.1 | Number of sites anticipated in Member State concerned | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 43 |
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 | Information not present in EudraCT |
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 | 3 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |