A Safety and Pharmacokinetics Study in Participants With Rheumatoid Arthritis

Phase 1

Completed

Conditions: Arthritis, Rheumatoid

Interventions: Drug: LY2189102
Drug: placebo

Registration Number: NCT00380744

Lead Sponsor: Eli Lilly and Company

Brief Summary: 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

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 121

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Part A LY2189102 0.1 mg/kg/wk	LY2189102	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
Placebo	placebo	IV, once weekly x 4 wks
Part A LY2189102 2.5 mg/kg/wk	LY2189102	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
Part A LY2189102 0.3 mg/kg/wk	LY2189102	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
Part A LY2189102 1.0 mg/kg/wk	LY2189102	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

Primary Outcome Measures

Name	Time	Method
Number of Participants With Adverse Events (AEs)	Baseline up to Day 98	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.

Secondary Outcome Measures

Name	Time	Method
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	Part A: Day 1 predose and IAI, 2days post infusion, Day 14 and Day 28 predose and IAI, Day 35, 63 (convenient time)	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);
Change From Baseline in Simple Disease Activity Index Score (SDAI)	Baseline, Days 7, 21, 35, 63, and 98	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.
Change From Baseline in Disease Activity Score 28-Joint Count (DAS28)	Baseline, Days 7, 21, 35, 63, and 98	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.
Change From Baseline in C-Reactive Protein (CRP)	Baseline, Days 7, 14, 21, 28, 35, 63, and 98	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.
Change From Baseline in Health Assessment Questionnaire (HAQ) Score	Baseline, Days 35, 63, and 98	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.

Trial Locations

Locations (1): For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
🇵🇱
Wroclaw, Poland
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
🇵🇱Wroclaw, Poland