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 | PT |
E.1.2 | Classification code | 10039073 |
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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 the study is to demonstrate, in patients with an inadequate response to one or more TNF-alpha (TNF-α) inhibitors, 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 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 an inadequate response to one or more TNF-α inhibitors, 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), Brief Fatigue Inventory (BFI), Brief Pain Inventory Modified Short Form(BPI-sf modified), and duration of morning stiffness. - Time to ACR20 response • To evaluate the safety and tolerability of LY A or LY B compared with placebo. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
FARMACOGENETICA: Versione:n/a Data:2010/09/09 Titolo:Opzionale, incluso nel protocollo principale. Obiettivi:Indagare il ruolo dei geni nella reazione dell’organismo al farmaco LY2127399.
FARMACOCINETICA/FARMACODINAMICA: Versione:n/a Data:2010/09/09 Titolo:Incluso nel protocollo principale. Obiettivi:Caratterizzare la farmacocinetica di LY2127399 nella popolazione e valutare le relazioni farmacocinetiche/farmacodinamiche con l`efficacia, la sicurezza e gli endpoint basati sui biomarcatori.
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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(of at least 6 months duration, but not longer than 15 years prior to screening) • Patients must have at least 8/68 tender and at least 8/66 swollen joints, as determined by the tender joint count and swollen joint count assessment forms. • Patients must have been treated at approved doses with at least one biologic TNF-α inhibitor therapy, and in the opinion of the Investigator EITHER: - stopped due to insufficient efficacy, or loss of efficacy, after at least 90 days of treatment, OR - stopped due to intolerance of such treatment, regardless of treatment duration. • Regular use of at least one conventional DMARD; must have been on a stable dose for at least 8 weeks prior to baseline • ACR functional class I, II, or III • Documented history of, or current, positive RF and/or anti-CCP Ab test. |
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E.4 | Principal exclusion criteria |
Patients will be excluded from the study if they meet any of the following criteria: 1. Use of an unstable dose (i.e., requiring dose adjustment) of NSAIDs (including cyclooxygenase-2 [COX-2] inhibitors) within 6 weeks prior to baseline (Visit 2). 2. Use of oral corticosteroids at average daily doses of >10 mg/day of prednisone or its equivalent within 6 weeks prior to baseline (Visit 2). 3. Have received any parenteral (including intraarticular) corticosteroid injection within 6 weeks of baseline (Visit 2). |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is the comparison between each LY2127399 dose and placebo in ACR20 response at Week 24 in patients with active RA who have an inadequate response to one or more TNF-α inhibitors. |
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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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 40 |
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 | 5 |
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 | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |