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 objectives of this study are to demonstrate, in patients on background MTX therapy, the superiority of 120 mg LY2127399 every 4 weeks (Q4W) (LY A) or 90 mg LY2127399 every 2 weeks (Q2W) (LY B), each after a loading dose, compared to placebo as follows:
American College of Rheumatology 20% response rates (ACR20) at Week 24 Structural progression as measured by van der Heijde modified Total Sharp Score (mTSS) at Week 52 Health Assessment Questionnaire-Disability Index (HAQ-DI) scores at Week 24.
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of the study are as follows: • To demonstrate, in patients on background MTX therapy, the superiority of LY A or LY B compared to placebo over 52 weeks • To evaluate structure (X-rays) • To evaluate the safety and tolerability of LY A or LY B compared to placebo. • To characterize the time course of change in absolute B cell counts, B cell subsets, and changes in serum Ig levels to treatment with LY2127399 versus placebo over 52 weeks. • To characterize the population PK of LY2127399 and explore PK/ PD relationships with efficacy, safety and biomarker endpoints. • To assess the potential development of anti LY2127399 antibodies and the impact on patient safety, efficacy, and PK of LY2127399. Additional exploratory measures will be studied, including: • To explore biomarkers that may be contained in serum, plasma, messenger ribonucleic acid (mRNA), and deoxyribonucleic acid (DNA) samples. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Male and female patients 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 • Regular use of methotrexate (MTX) in the past 12 weeks, with the dose being stable during the past 8 weeks • At least 8 tender and swollen joints • At least one erosion of a hand or foot joint observed on an X-ray • An abnormally high C-reactive protein (CRP) level or erythrocyte sedimentation rate (ESR) • Positive for Rheumatoid Factor (RF) or Anti-cyclic citrullinated peptide (CCP) antibody • 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 • History of an inadequate response to a biologic disease-modifying anti-rheumatic drug (DMARD) • History of a serious reaction to other biological DMARDs • History of the use of rituximab or other B cell therapy • Use of DMARDS other than MTX, hydroxychloroquine, or sulfasalazine within the last 8 weeks • Use of leflunomide within the last 12 weeks (unless cholestyramine was used to speed up the elimination of leflunomide) • 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 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) at Week 24 • Change from baseline to Week 52 in van der Heijde modified Total Sharp Score (mTSS) • Change from baseline to Week 24 in Health Assessment Questionnaire-Disability Index (HAQ-DI) • Percentage of patients with American College of Rheumatology 50% (ACR50) and 70% (ACR70) response • Change from baseline in Disease Activity Score C-Reactive Protein (DAS28-CRP) • Percentage of patients with DAS28-Based European League Against Rheumatism (EULAR) response • Change from baseline in Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) domain scores and summary scores • Change from baseline in Brief Fatigue Inventory (BFI) individual items and impact score • Change from baseline in duration of morning stiffness (minutes) • Percentage of patients with Major Clinical Response (MCR) during 52 weeks • Percentage of patients with change from baseline in mTSS less than or equal to 0 • Change from baseline in B cell subset counts • Population Pharmacokinetics (PK) • Percentage of patients developing anti-LY2127399 antibodies • Change from baseline in Brief Pain Inventory Short Form (BPI-sf) individual items and interference scores • Percentage of patients with structural inhibition at Week 52 • Change from baseline in mTSS • Change from baseline in serum immunoglobulin (Ig) levels • Change from baseline in joint space narrowing score and bone erosions score (components of mTSS) • Mean percent improvement in ACR N • Change from baseline in Tender Joint Count (68 joint count) • Change from baseline in Swollen Joint Count (66 joint count) • Change from baseline in Patient's Assessment of Pain (VAS) • Change from baseline in Patient's Global Assessment of Disease Activity (VAS) • Change from baseline in Physician's Global Assessment of Disease Activity (VAS) • Change from baseline to Week 52 in HAQ-DI • Change from baseline in absolute B cell counts • Percentage of patients with ACR20 at Week 52 • Time to ACR20 response |
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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 | 13 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 52 |
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 | 4 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |