E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderately to Severely Active Rheumatoid Arthritis |
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E.1.1.1 | Medical condition in easily understood language |
Moderately to Severely Active Rheumatoid Arthritis |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 23.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10003268 |
E.1.2 | Term | Arthritis rheumatoid |
E.1.2 | System Organ Class | 100000004859 |
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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 the efficacy of LY3462817 in adult participants with moderately to severely active Rheumatoid Arthritis (RA) |
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E.2.2 | Secondary objectives of the trial |
To describe the safety and tolerability of LY3462817 compared to placebo To evaluate the effect of LY3462817 on measures of disease activity (ACR, SDAI, CDAI) To describe the effect of LY3462817 on patient-reported outcomes (PROs) To characterize the pharmacokinetics of LY3462817 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Have a diagnosis of adult onset RA as defined by the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for at least 3 months prior to screening • Have moderately to severely active RA defined by the presence of ≥6 swollen joints (based on 66 joint count) and ≥6 tender joints (based on 68 joint count) at screening and baseline. The distal interphalangeal joint should be evaluated but not included in the total count to determine eligibility • Have at least 1 of the following: - positive test results for rheumatoid factor or anti-citrullinated peptide antibodies at screening, OR - previous radiographs documenting bony erosions in hands or feet consistent with RA • Have C-reactive protein (CRP) >1.2 times upper limit of normal (ULN) per the central laboratory at screening • Demonstrated an inadequate response to, or loss of response or intolerance to: - at least 1 conventional synthetic disease-modifying antirheumatic drug (csDMARD) treatment OR - at least 1 biologic DMARD/tsDMARD treatment
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E.4 | Principal exclusion criteria |
• Class IV RA according to ACR revised response criteria • Have a diagnosis or history of malignant disease within 5 years prior to baseline, with the exceptions of: - basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years, or - cervical carcinoma in situ, with no evidence of recurrence within the 5 years prior to baseline • Have presence of confirmed cervical dysplasia • Have any of the following: - Human immunodeficiency virus (HIV) infection - Current infection with hepatitis B virus (HBV) (i.e., positive for hepatitis B surface antigen and/or polymerase chain reaction [PCR] positive for HBV DNA) - Current infection with hepatitis C virus (HCV) (i.e., positive for HCV RNA) - Active tuberculosis (TB) • Have failed more than 2 biologic DMARDs or tsDMARDs (e.g. excluded if have failed 2 bDMARDs and 1 tsDMARD) |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from Baseline on the Disease Activity Score Modified to Include the 28 Diarthrodial Joint Count-High-Sensitivity C-Reactive Protein (DAS28-hsCRP) |
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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 Participants Achieving 20% Improvement in American College of Rheumatology Criteria (ACR20), ACR50 and ACR70 • Change from Baseline for Mean Simplified Disease Activity Index (SDAI) • Change from Baseline for Mean Clinical Disease Activity Index (CDAI) • Change from Baseline on the 36 Item Short Form Health Survey (SF-36) • Pharmacokinetics (PK): Observed Concentration of LY3462817 |
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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 | 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 | No |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 16 |
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 |
Mexico |
United States |
Hungary |
Poland |
United Kingdom |
Czechia |
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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 | 5 |
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 | 9 |
E.8.9.2 | In all countries concerned by the trial days | 6 |