A Multi-Site Study to Evaluate the Safety and Effect of Study Drug on Participants With Rheumatoid Arthritis

Phase 2

Completed

Conditions: Arthritis, Rheumatoid

Interventions: Drug: LY2127399
Drug: Placebo

Registration Number: NCT00308282

Lead Sponsor: Eli Lilly and Company

Brief Summary: This study is a multicenter, double-blind, study to evaluate the safety and effectiveness of treatment with LY2127399 (in addition to the standard of care treatment, methotrexate) for participants with Rheumatoid Arthritis. Participants will receive three intravenous doses of LY2127399 or placebo. Participants will participate in 10 or more visits to the study site, over 6 months. Evaluation of safety and efficacy will be conducted throughout the study.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 136

Inclusion Criteria

Male or female between the ages of 18 and 75 years
Have given written informed consent approval
Women must not be at risk to become pregnant during study participation
Diagnosis of Rheumatoid Arthritis according to the 1987 revised American Rheumatism Association (ARA) criteria for the classification of RA
Serum C-reactive protein (CRP) measurement greater than the upper limit of normal (ULN, 0.574 mg/dL), or erythrocyte sedimentation rate (ESR) ≥28 mm/hr
Current, regular use of Methotrexate, at a stable dose
Biologic DMARD naïve, and have had an insufficient response (in the opinion of the investigator) to an adequate therapeutic dose of at least 1 oral DMARD

Exclusion Criteria

Use of excluded medications (reviewed by study doctor)
Surgical treatment of a joint with 2 months of study enrollment that is to be assessed in the study
Are unable to ambulate; that is, confined to bed or wheelchair bound
Have medical findings which, in the opinion of the study doctor, put participant at an unacceptable risk for participation in the study
Have had recent or ongoing infection which, in the opinion of the study doctor put participant at an unacceptable risk for participation.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
A	LY2127399	-
B	Placebo	-

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Achieving American College of Rheumatology 20% Response (ACR20) (Effectiveness of LY2127399 in Treating Rheumatoid Arthritis Using the ACR20 Scale)	Week 16	ACR Responder Index is a Composite of clinical, laboratory, and functional measures of rheumatoid arthritis (RA). ACR20 Responders: had ≥20% improvement from baseline in both tender and swollen joint counts and ≥20% improvement in at least 3 of 5 criteria: participant's and physician's global assessment of disease activity, Health Assessment Questionnaire-Disability Index (HAQ-DI) (which measured participants' perceived degree of difficulty performing daily activities), visual analog pain scale, and erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP).

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in the Disease Activity Score 28 Joint Count (DAS28-CRP)	Baseline, Week 24	Disease Activity Score (DAS) modified to include 28 joint count (DAS28) consisted of composite score of following variables: tender joint count (TJC28), swollen joint count (SJC28), CRP \[milligrams per liter (mg/L)\], and participant's global assessment of disease activity using visual analog scale (VAS) (participant global VAS). DAS28-CRP=0.56\square root (sqrt)(TJC28)+0.28\sqrt(SJC28)+0.36\natural log(CRP+1)+0.014\participant global VAS+0.96. Scores ranged from 1.0-9.4, where lower scores indicated less disease activity and remission is DAS28-CRP \<2.6. A negative change indicated an improvement.
European League Against Rheumatism (EULAR28) Response: Percentage of Participants With Combined Good and Moderate Responses	Baseline, Week 24	EULAR Responder index based on 28 joint counts categorizes clinical response based on improvement since baseline in DAS28-CRP. DAS28-CRP scores range from 1.0-9.4, where lower scores indicated less disease activity. High disease activity: DAS28-CRP \>5.1, low disease activity: DAS28-CRP \<3.2, and remission: DAS28-CRP \<2.6. Participants are categorized as EULAR responders or non-responders (NR) based on improvement of DAS28-CRP scores from baseline. EULAR DAS28-CRP responder index defines a good (absolute: \<3.2 or \>1.2 improvement from baseline), moderate (absolute: 3.2-5.1 or 0.6-1.2 improvement from baseline), or no response (absolute: \>5.1 or \<0.6 improvement from baseline). Percentage of participants with DAS28-CRP based EULAR response =(number of participants with specific response) / (number of participants analyzed in the group) \* 100.
Change From Baseline in CD20+ B Cell Number Count	Baseline, Week 24	CD20+ B-cells are a disease-related peripheral blood biomarker used to assess disease progression of Rheumatoid Arthritis (RA). A reduction in CD20+ B-cell values may indicate an improvement in RA symptoms.
Percentage of Participants Achieving ACR 50 and ACR70	Baseline through Week 24	ACR Responder Index: composite of clinical, laboratory, and functional measures of Rheumatoid Arthritis (RA). ACR50 and ACR70 Responder: had either a ≥50% or ≥70% improvement from baseline in both tender and swollen joint counts and either a ≥50% or ≥70% improvement in at least 3 of 5 criteria: participant's (Pt's) and physician's global assessment of disease activity, HAQ-DI (measured Pts' perceived degree of difficulty performing daily activities), joint pain, and CRP (respectively).
Change From Baseline (CFB) in Serum Immunoglobulins IgG, IgA and IgM	Baseline, Week 24	Immunoglobulins (Ig), or antibodies, are large proteins used by the immune system to identify and neutralize foreign particles such as bacteria and viruses. Their normal blood levels indicate proper immune status. A negative change indicates a decrease in Ig levels.
Number of Participants With Treatment Emergent Adverse Events (TEAE) (Safety of Repeat Doses (3) of LY2127399 Through Evaluation of Laboratory Tests, Vital Signs and Electrocardiograms)	Baseline through Study Completion (Up to 19 Months)	Treatment-emergent adverse events (TEAEs) were defined as those AEs with start date and time equal to or after the start of study medication infusion. In the case of a missing onset time for an AE, an AE with a start date equal to or greater than the dosing date was considered treatment-emergent. A summary of other nonserious AEs, and all SAE's, regardless of causality, is located in the Reported Adverse Events section. All participants who received at least one dose of study drug. Due to dosing errors (a participant received 60 mg LY2127399 in the placebo group), the safety population was adjusted to account for actual treatment received.
Evaluation of the Pharmacokinetics of LY2127399: Clearance	2 hours pre-dose, pre-dose, 1 hour and 4 hour(s) post dose	Population estimate of constant clearance as determined by population PK analysis. A 2-compartment model was used in PK modeling. Constant clearance is the PK parameter which describes the linear elimination of LY2127399 from serum.

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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Timisoara, Romania