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 | 9.1 |
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 |
To evaluate LY2127399 efficacy assessed by the proportion of patients who achieve an ACR50 response compared to placebo at 24 weeks in patients with RA, who have had an inadequate response or intolerance to treatment with at least 1 biologic TNFα inhibitor therapy. |
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E.2.2 | Secondary objectives of the trial |
• To evaluate LY2127399 efficacy compared to placebo over the 24-week study period as assessed by the: - Individual components of the ACR Core Set - Disease Activity Score based on the 28 joint count - EULAR28 • To evaluate LY2127399 safety and tolerability compared to placebo • To evaluate PD of disease-related biomarkers as compared to placebo. • To explore the potential associations between selected biomarkers and selected disease activity measures • To characterize LY2127399 PK in RA patients with inadequate response or intolerance to TNFα inhibitor therapy. • To evaluate the impact of LY2127399 compared to placebo over the 24-week study period on patient-reported outcomes as measured by the: - FACIT Fatigue Scale - Medical Outcomes Study 36-Item Short Form Health Survey
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Ambulatory males or females between the ages of 18 and 75 years, inclusive. •Women must not be pregnant, breastfeeding, or at risk to become pregnant during study participation and must have a negative pregnancy test. Women of childbearing potential must use a medically permitted form of contraception during the whole study and until B cell counts have returned to baseline levels or to within normal range (as specified by the performing laboratory). Methods of contraception considered acceptable are oral contraceptives, contraceptive patch, intrauterine device (IUD), vaginal ring, diaphragm, or condom with contraceptive gel. •Diagnosis of RA according to the ARA 1987 Revised Criteria for the Classification of RA (Arnett et al. 1988). •Have been treated for at least 3 months at approved doses with at least biologic TNFα inhibitor therapy and have had an inadequate response to such treatment in the opinion of the investigator OR have been intolerant to these agents regardless of treatment duration. Patients must have stopped etanercept >28 days, and infliximab or adalimumab >56 days prior to baseline. •Regular use of methotrexate for 16 weeks, and at a stable dose between 10 and 25 mg/wk, inclusive, for at least 8 weeks prior to baseline. •History of, or current, seropositive rheumatoid factor (RF). •ACR functional class I, II, or III. •Have active RA defined as at least 5/28 swollen and at least 5/28 tender joints based on the joint count specified. •Have a screening CRP of at least 1.2X ULN or a screening ESR of at least 28 mm/hr. •Clinical laboratory test results within normal reference range for the population or investigator site, or results with acceptable deviations as judged by the investigator. •Venous access sufficient to allow study drug administration and blood sampling as per the protocol. •Are reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures. •Have given written informed consent approved by Lilly or its designee and the ethical review board (ERB) governing the site.
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E.4 | Principal exclusion criteria |
• Had symptomatic herpes zoster within 3 months of enrollment. • Evidence of human immunodeficiency virus (HIV) and/or positive human HIV antibodies. • Evidence of hepatitis C and/or positive hepatitis C antibody. • Evidence of hepatitis B and/or positive hepatitis B surface antigen. • Evidence or suspicion of active tuberculosis (TB) by medical history, physical examination, and/or screening chest radiograph. • At the time of screening, a positive PPD test for TB. For the purpose of this study, a positive test is defined as induration ≥10 mm, between approximately 2 and 3 days after test application. Exceptions to this criterion include patients with a history of a positive PPD who have been treated with isoniazid (INH) (documented) for at least 6 months, or patients with a previous diagnosis of TB who have received appropriate treatment (documented) and have not been re-exposed to TB since their treatment was completed. • Have had other recent or ongoing infection that in the opinion of the investigator poses an unacceptable risk to participate in the study. • Exposed to a live vaccine within 3 months of enrollment or expected to need/receive a live vaccine during the course of the study. • Have significant hematological abnormalities, including haemoglobin less than 8.0 g/dL, total platelet count less than 100,000/μL, total white blood cell (WBC) count less than 3000/μL, neutrophil count less than 1000/μL, or lymphocyte count less than 200 cells/μL. • Have a screening serum creatinine >2.0 mg/dL. • Have known hypogammaglobulinemia or a serum IgG, IgM, or IgA concentration less than the lower limit of normal. • Have any history of chronic liver disease or with serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) concentration >1.2x the upper limit of normal. The AST and ALT may be repeated once within a week if the initial result exceeds this limit, and the lesser value accepted if it meets this criterion. • Blood donation of more than 500 mL within the last month. • Women with a positive pregnancy test or women who are lactating.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy variable is ACR50 responder index at 24 weeks after baseline.
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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 | Yes |
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 | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
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) | 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.8.3 |
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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 23 |
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 | No |
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 | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |