A Study in Rheumatoid Arthritis

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and tolerability of multiple doses of LY2439821 in Japanese patients with rheumatoid arthritis.

Official Title
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Multiple-Dose, Dose Escalation Study to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of LY2439821 in Japanese Patients With Rheumatoid Arthritis on Concomitant Methotrexate Treatment

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: LY2439821
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ambulatory male or female patients between the ages of 20 and 75 years Male patients: Agree to use a reliable method of birth control during the study including barrier contraceptives or a monogamous relationship with a partner who is not child bearing. Female patients: Are women who test negative for pregnancy at the time of entry based on a pregnancy test and are not breast feeding. Women of child bearing potential must agree to use a reliable method of birth control during the study. Patients who are between the body weight of 40 and 105 kilogram (kg) Patients who have an established diagnosis of Rheumatoid Arthritis (RA) Patients who have C reactive protein (CRP) measurement greater than the upper limit of normal or erythrocyte sedimentation rate of at least 28 millimeters per hour (mm/hr) Patients who have been treated with regular use of Methotrexate (MTX) for at least 12 weeks, and stable treatment (at least 7.5 milligrams per week (mg/week)) for at least 8 weeks Patients who have given written informed consent approved by the Sponsor and the Institutional Review Board (IRB) governing the investigational site Patients who have reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures Exclusion Criteria: Patients who use oral corticosteroids at average daily doses of >10 mg/day of prednisone or its equivalent or use of variable doses of oral corticosteroids within the last 4 weeks Patients who have had a live vaccination within the last 12 weeks, or intend to have a live vaccination during the course of the study, or have participated in a vaccine clinical study within the last 12 weeks Patients who have a diagnosis of any systemic inflammatory condition other than RA Patients who have evidence of active vasculitis or uveitis Patients who have a diagnosis of Felty's syndrome Patients who have had surgical treatment of a joint within the last 8 weeks, or will require it during the study Patients who have had lymphoma, leukemia, or any malignancy within the last 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease Patients who have suffered a serious bacterial infection within the last 12 weeks, or a recent or ongoing infection Patients who have an evidence or suspicion of active tuberculosis (TB) by medical history, physical examination, and/or chest radiograph or documentation of TB by a positive purified protein derivative (PPD) test Patients who have uncontrolled arterial hypertension characterized by a systolic blood pressure >160 mmHg or diastolic blood pressure >100 mmHg Patients who have an evidence of positive hepatitis B (HBV) surface antigen, positive hepatitis B surface antibody, positive hepatitis B core antibody, or hepatitis B DNA (HBV DNA); an evidence of human immunodeficiency virus (HIV), evidence of hepatitis B; or an evidence of hepatitis C Patients who have clinical laboratory test results at entry that are outside the normal reference range, or results with unacceptable deviations that are considered clinically significant by the investigator Patients who have a serum creatinine >2.0 milligrams per deciliter (mg/dL) Patients who have known hypogammaglobulinemia or a serum immunoglobulin (Ig) G (IgG), IgM, or IgA concentration less than the lower limit of normal Patients who have an abnormality in the 12 lead electrocardiogram (ECG). Patients who have donated of blood more than 200 mL within the past 30 days, or more than 400 milliliters (mL) within the past 90 days Patients who are currently enrolled in, or discontinued within the last 30 days from, a clinical trial involving an off label use of an investigational drug or device, or are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study. For unapproved Disease-Modifying Anti-Rheumatic Drug (DMARDs), have received 30 days or 5 fold of the half life prior to inclusion whichever is longer Patients who previously completed or withdrawn from this study or any other study investigating LY2439821 Patients who have been treated with any biologic DMARD currently or previously for 5 half lives Patients who have had serious reaction to other biologic Disease-Modifying Anti-Rheumatic Drug (DMARDs) Patients who have received non biologics DMARDs (other than MTX, sulfasalazine, bucillamine or hydroxychloroquine)

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 30 mg LY2439821<br>Administered subcutaneously at Week 0, 1, 2, 4, 6, 8 and 10 | Drug: LY2439821<br>* Administered subcutaneously<br>|
| Experimental: 80 mg LY2439821<br>Administered subcutaneously at Week 0, 1, 2, 4, 6, 8 and 10 | Drug: LY2439821<br>* Administered subcutaneously<br>|
| Experimental: 180 mg LY2439821<br>Administered subcutaneously at Week 0, 1, 2, 4, 6, 8 and 10 | Drug: LY2439821<br>* Administered subcutaneously<br>|
| Placebo Comparator: Placebo<br>Placebo is administered subcutaneously in the same manner as active drug in each dose group | Drug: Placebo<br>* Administered subcutaneously<br>|
| Experimental: 120 mg LY2439821<br>Administered subcutaneously at 240 mg as a single loading dose followed by 120 mg every week | Drug: LY2439821<br>* Administered subcutaneously<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Clinically Significant Effects | Clinically significant events were defined as serious and other non-serious adverse events. A summary of serious and all other non-serious adverse events is located in the Reported Adverse Event module. | Baseline up to 26 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage Change From Baseline to 16 Week Endpoint in C-Reactive Protein | C-reactive protein (CRP) is a disease related biomarker and measured in milligrams per liter. | Baseline, 16 weeks | 
| Percentage Change From Baseline to 16 Week Endpoint in Erythrocyte Sedimentation Rate (ESR) | Erythrocyte Sedimentation Rate (ESR) is a disease related biomarker and measured in millimeters per hour (mm/h). | Baseline, 16 weeks | 
| Change From Baseline to 26 Week Endpoint in Neutrophil Counts |  | Baseline, 26 weeks | 
| Change From Baseline to 26 Week Endpoint in Lymphocyte Counts |  | Baseline, 26 weeks | 
| Pharmacokinetics - Area Under the Concentration-time Curve (AUC) at Steady State (ss) | AUCτ,ss= area under the concentration versus time curve (τ) at steady state (ss) | Week 10 pre-dose up to 2 weeks post-dose (Week 12) | 
| Pharmacokinetics - Maximum Plasma Drug Concentration (Cmax) at Steady State (ss) | Cmax,ss = maximum observed drug concentration (Cmax) at steady state (ss) | Week 10 pre-dose up to 2 weeks post-dose (Week 12) | 
| Pharmacokinetics - Time of Maximum Observed Drug Concentration (Tmax) at Steady State (ss) | tmax,ss = time of maximum observed drug concentration (tmax) at steady state (ss) | Week 10 pre-dose up to 2 weeks post-dose (Week 12) |