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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
Read More
Exclusion Criteria
  • Juvenile Rheumatoid Arthritis
  • evidence of tuberculosis
  • women who are pregnant or become pregnant during study, or are breast-feeding
Read More

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Part A LY2189102 0.1 mg/kg/wkLY2189102Part 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
Part A LY2189102 0.3 mg/kg/wkLY2189102Part 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/wkLY2189102Part 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
Part A LY2189102 2.5 mg/kg/wkLY2189102Part 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
PlaceboplaceboIV, once weekly x 4 wks
Primary Outcome Measures
NameTimeMethod
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
NameTimeMethod
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 LY2189102Part 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) ScoreBaseline, 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.

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Wroclaw, Poland

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