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 |
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E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
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 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.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
•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
•Change from baseline to 24 weeks in CRP |
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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 | 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.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 5 |
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 | 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 |
Argentina |
Australia |
Bulgaria |
Colombia |
Croatia |
Hungary |
India |
Japan |
Lithuania |
Malaysia |
Mexico |
New Zealand |
Peru |
Poland |
Romania |
Russian Federation |
Slovakia |
South Africa |
Sri Lanka |
Taiwan |
Ukraine |
United States |
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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 |