E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
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 examine the safety and tolerability of LY2189102 administered as multiple intravenous (IV) doses to Rheumatoid Arthritis (RA) patients who are receiving stable doses of Methotrexate (MTX). |
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E.2.2 | Secondary objectives of the trial |
To characterize LY2189102 pharmacokinetics during repeated IV dosing in RA patients who are taking concomitant MTX.
To characterize relationships between LY2189102 dose, exposure, and responses of selected pharmacodynamic endpoints, including: - clinical measures of disease activity: Simple Disease Activity Index (SDAI) and/or Disease Activity Score (based on 28-joint count) (DAS28), AND - biomarkers (for example, C-reactive protein [CRP] and other potential biomarkers of inflammation and/or structural damage), AND - clinical measures of disability (Health Assessment Questionnaire [HAQ]). |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
[1] Women and men who are 18 to 75 years of age. [2] Women must not be at risk to become pregnant during study participation. [3] Diagnosis of RA according to the American Rheumatism Association (ARA) 1988 Revised Criteria for the Classification of RA. [4] Regular use of MTX (7.5 mg to 25 mg weekly) for at least 3 months (with stable doses for at least 2 months) at the time of study entry. Additional oral DMARDs are allowed, but not required. [5] Active RA disease as defined by the following: Part A: - Presence of ≥3 swollen joints based on 28 diarthrodial joint assessment AND - Presence of ≥3 tender joints based on 28 diarthrodial joint assessment Part B: - Presence of ≥6 swollen joints based on 66 diarthrodial joint assessment (≥5 of which must be among those included in the 28 joint count), AND - CRP measurement >2x upper limit of normal (ULN) (0.574 mg/dL), AND - At least one of the following two criteria: ---- ≥6 tender joints based on 68 diarthrodial joint assessment (≥5 of which must be among those included in the 28 joint count) ---- ≥45 minutes of early morning stiffness
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E.4 | Principal exclusion criteria |
[12] History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, or metabolism or elimination of drugs or of constituting a risk when taking the study medication or interfering with the interpretation of data. [16] Evidence of systemic conditions associated with inflammation other than RA. [17] History of insulin-requiring diabetes mellitus. [18] Frequent exacerbations of asthma or chronic obstructive pulmonary disease. [19] History of respiratory infection within two weeks of study entry or a history of serious bacterial infections within two months of study entry. [20] Prior exposure to these agents within the following timeframe: - Anakinra (Kineret ® ) within 4 weeks of enrollment - Etanercept (Enbrel ® ) within 4 weeks of enrollment - Adalimumab (Humira ® ) within 8 weeks of enrollment - Infliximab (Remicade ® ) within 8 weeks of enrollment - Regeneron IL-1 Trap within 8 weeks of enrollment - AMG108 (Anti-IL-1 receptor type 1 [IL-1R1] antibody) within 16 weeks of enrollment. [21] In the judgment of the investigator, history of an inadequate therapeutic response to an adequate trial (at least one month) of a biologic agent targeting either IL-1 or TNF (Part B only). [22] Prior use of therapies targeting B cells within the past one year (such as Lymphostat B, LY2127399, rituximab [Rituxan ™] or cyclophosphamide [Cytoxan ® ]) unless the investigator determines that the patient’s B cell counts have recovered. [23] Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication, or within 60 days of the time of study entry for any RA experimental agent. [24] Use of any other biologic therapy for RA not specified by the protocol (for example, abatacept, anti-IL-6 receptor antibody, or anti-IL-15 antibody) within 5 half-lives of the last dose of the biologic agent (minimum 60 days). [25] Prior serious systemic allergic reactions to biologic therapy. [26] Use of other DMARDs other than MTX, hydroxychloroquine and sulfasalazine, in the 8 weeks prior to entry into this study (12 weeks for leflunomide). [27] Received a live vaccination (for example, FluMist ®) within 3 months of study entry, or who are anticipated to receive live vaccines during the time period of participation in this study. [28] Hemoglobin <10.0 g/dL. [30] Liver function tests (aspartate aminotransferase [AST], alanine aminotransferase [ALT]) >1.2X ULN. The AST and ALT may be repeated once if the initial result exceeds this limit, and the lesser value accepted if it meets this criterion. [31] Evidence of hepatitis C and/or positive hepatitis C antibody. [32] Evidence of hepatitis B and/or positive hepatitis B surface antigen. [33] Evidence of human immunodeficiency virus (HIV) and/or positive test for antibodies to HIV. [34] Evidence of tuberculosis (TB) as documented by positive tuberculin skin test (either history of past positive or screening tuberculin skin test >5 mm), medical history or chest radiograph. Study participants must have a screening purified protein derivative (PPD) test performed at screening and will be excluded if positive. [35] Women who are pregnant or become pregnant during the study, or are breast-feeding. |
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E.5 End points |
E.5.1 | Primary end point(s) |
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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 | Yes |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
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) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
Phase Ib/2 multiple dose safety and PK/PD study |
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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 | Yes |
E.8.1.7.1 | Other trial design description |
two-part modified dose escalation study |
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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.8.5 | 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 | 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 | Information not present in EudraCT |
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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Last visit of the last patient enrolled |
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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 | |
E.8.9.1 | In the Member State concerned months | |
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 | 2 |