A Safety and Pharmacokinetics Study in Participants With Rheumatoid Arthritis

Study Overview
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Brief Summary
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The purpose of this study is to examine the safety and efficacy of this antibody in participants with rheumatoid arthritis. Part A of the study is an initial dose escalation phase Part B of the study is a randomized allocation of the entire dosing group to parallel treatment assignments

Official Title
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A Phase 1b/2 Multiple-Dose Safety Study and Pharmacokinetic/ Pharmacodynamic Study of LY2189102 in Patients With Rheumatoid Arthritis

Conditions
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Arthritis, Rheumatoid

Intervention / Treatment
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* Drug: LY2189102
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: diagnosis of rheumatoid arthritis regular use of methotrexate active rheumatoid arthritis Exclusion Criteria: Juvenile Rheumatoid Arthritis evidence of tuberculosis women who are pregnant or become pregnant during study, or are breast-feeding

Ages Eligible for Study
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Minimum Age: 18 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: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A LY2189102 0.1 mg/kg/wk<br>Part A: 2 times (x) 0.1 milligrams/kilogram/week (mg/kg/wk) Loading dose, then 0.1 mg/kg/wk) X 4 weeks (wks), intravenous (IV) Part B: 2 x 0.02 mg/kg/wk Loading dose, then 0.02 mg/kg/wk X 4 wks, IV | Drug: LY2189102<br> <br> |
| Experimental: Part A LY2189102 0.3 mg/kg/wk<br>Part A: 2 x 0.3 mg/kg/wk Loading dose, then 0.3 mg/kg/wk X 4 wks, IV Part B: 2 x 0.15 mg/kg/wk Loading dose, then 0.15 mg/kg/wk X 4 wks, IV | Drug: LY2189102<br> <br> |
| Experimental: Part A LY2189102 1.0 mg/kg/wk<br>Part A: 2 x 1.0 mg/kg/wk Loading dose, then 1.0 mg/kg/wk X 4 wks, IV Part B: 2 x 1.0 mg/kg/wk Loading dose, then 1.0 mg/kg/wk X 4 wks, IV | Drug: LY2189102<br> <br> |
| Experimental: Part A LY2189102 2.5 mg/kg/wk<br>Part A: 2 x 2.5 mg/kg/wk Loading dose, then 2.5 mg/kg/wk X 4 wks, IV Part B: 2 x 2.5 mg/kg/wk Loading dose, then 2.5 mg/kg/wk X 4 wks, IV | Drug: LY2189102<br> <br> |
| Placebo Comparator: Placebo<br>IV, once weekly x 4 wks | Drug: placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events (AEs) | Clinically significant events were defined as serious AEs (SAEs) and other non-serious AEs regardless of causality. A summary of s SAEs and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module. | Baseline up to Day 98 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK): Area Under the Concentration Time Curve at Steady State for One Dosing Interval Time 0 to 168 Hours (AUC0-168 hr,ss) of LY2189102 | AUC0-168 hr,ss of individual participants was calculated by equation AUC=Dose/Clearance (CL), where the CL was estimated using a population PK model. Time frame for Part B: Day 1 predose, immediately after infusion (IAI), Day 14 and 28: predose and IAI, and Day 63 (Convenient time); | Part A: Day 1 predose and IAI, 2days post infusion, Day 14 and Day 28 predose and IAI, Day 35, 63 (convenient time) | 
| Change From Baseline in Simple Disease Activity Index Score (SDAI) | SDAI is calculated as the sum of 5 components: tender joint count (TJC) and swollen joint count (SJC), Patient Global Assessment (PtGA) of disease activity visual analog scale (VAS) and Physician's Global Assessment of Disease Activity (PGA) VAS, and C-reactive protein (CRP). Total Score scale range is 0 (remission) to 86 (high disease activity). A negative change from baseline indicated an improvement. Least Squares (LS) mean calculated using a repeated measures model and adjusted for baseline + treatment + time + treatment * time. | Baseline, Days 7, 21, 35, 63, and 98 | 
| Change From Baseline in Disease Activity Score 28-Joint Count (DAS28) | DAS28-4 (crp) is a modification of the original DAS based on TJC and SJC based on 28 joint counts, PGA VAS. DAS28-4 (crp) calculated as: 0.56*square root (sqrt) (TJC)+0.28*sqrt(SJC)+0.36*ln(CRP+1)+0.014*PGA+0.96. Scores ranged from 1.0-9.4, where lower scores indicated less disease activity. A decrease in DAS28-CRP indicated an improvement in participant's condition. LS mean calculated using a repeated measures model and adjusted for baseline + treatment + time + treatment * time. | Baseline, Days 7, 21, 35, 63, and 98 | 
| Change From Baseline in C-Reactive Protein (CRP) | CRP is a biomarker associated with inflammation and structural damage. A negative change from baseline indicates improvement. LS mean calculated using a repeated measures model and adjusted for baseline + treatment + time + treatment * time. | Baseline, Days 7, 14, 21, 28, 35, 63, and 98 | 
| Change From Baseline in Health Assessment Questionnaire (HAQ) Score | HAQ was a participant-reported questionnaire that consisted of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and daily activities. Participants assessed their ability to do each task over the past week using the following response categories: 0 (without any difficulty), 1 (with some difficulty), 2 (with much difficulty), and 3 (unable to do). The highest score for any question in a category was the score of that category unless special aids or devices or help from another person was required. Answers for at least 6 of the 8 disability domains were required to compute the participant's HAQ score. If the participant had scores for fewer than 6 categories, the HAQ score was considered missing. The HAQ score was calculated as the sum of the category scores divided by the number of categories scored, with a possible scores range from 0 to 3. Negative mean changes from baseline indicated improvement. | Baseline, Days 35, 63, and 98 |