A Study for Japanese Participants With Rheumatoid Arthritis (RA)

Phase 1

Completed

• Conditions: Rheumatoid Arthritis
• Interventions: Drug: Placebo; Drug: LY2127399 (Tabalumab)

• Registration Number: NCT01253226
• Lead Sponsor: Eli Lilly and Company

Brief Summary

This study will evaluate the safety and tolerability of multiple doses of LY2127399 (tabalumab) in Japanese participants with RA. The study consists of a 20-week treatment period. All participants will be followed for up to 12 weeks after the last study drug administration.

Detailed Description

Not available

Study Timeline

• Study Start: 2009-09
• Study First Submitted: 2010-12-01
• Study First Submitted QC: 2010-12-01
• Study First Posted: 2010-12-03
• Primary Completion: 2011-08
• Study Completion: 2011-08
• Results First Submitted: 2018-03-24
• Status Verified: 2018-10
• Results First Submitted QC: 2018-10-19
• Last Update Submitted: 2018-10-19
• Results First Posted: 2018-10-23
• Last Update Posted: 2018-10-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 32

Inclusion Criteria

• Have given written informed consent
• Women must not be pregnant, breastfeeding or be at risk to become pregnant during study participation
• Diagnosis of RA
• Active RA
• Current, regular use of Methotrexate, at a stable dose
• Body weight between 40 and 105 kilograms (kg), inclusive

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Exclusion Criteria

• Use of excluded medications (reviewed by study doctor)
• 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
• Evidence of tuberculosis
• Have systemic inflammatory condition other than RA

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo Q4W	Placebo	Q4W for 20 weeks
30 milligrams (mg) Tabalumab	LY2127399 (Tabalumab)	30 mg tabalumab every 4 weeks (Q4W) for 20 weeks (6 doses of study drug)
120 mg once every 2 weeks (Q2W) Tabalumab	LY2127399 (Tabalumab)	Initial loading dose of 240 mg tabalumab followed by 120 mg Q2W for 20 weeks (10 doses of study drug)
60 mg Tabalumab	LY2127399 (Tabalumab)	60 mg tabalumab Q4W for 20 weeks (6 doses of study drug)
120 mg Tabalumab	LY2127399 (Tabalumab)	120 mg tabalumab Q4W for 20 weeks (6 doses of study drug)
Placebo Q2W	Placebo	Q2W for 20 weeks

Primary Outcome Measures

Name	Time	Method
Number of Participants With Adverse Events (AEs) [Clinically Significant Effects]	Baseline through study completion (up to Week 32 plus up to 12 weeks for B cell monitoring)	Clinically significant effects are defined as serious AEs (SAEs) and other non-serious AEs regardless of causality. A summary of SAEs and other non-serious AEs regardless of causality is located in the Reported Adverse Events module.

Secondary Outcome Measures

Name	Time	Method
Percent Change From Baseline in Erythrocyte Sedimentation Rate (ESR)	Baseline, Weeks 4, 8, 16, and 24	ESR is a laboratory test that provides a non-specific measure of inflammation. The test assesses the rate at which red blood cells fall in a test tube. Reference ranges are gender-specific and can vary slightly among laboratories. The normal range is approximately ≤10 millimeters per hour (mm/h) for males and ≤20 mm/h for females. Higher scores indicate greater inflammation. The percent change from baseline in ESR=\[(post-baseline ESR- baseline ESR)/(baseline ESR)\]\*100. A decrease in ESR indicates an improvement in the participant's condition.
Pharmacokinetics (PK) of Tabalumab: Area Under the Concentration Time Curve (AUC)	Week 0: Day 1 [predose and 1 hour (h), 3 h, and 6 h postdose], Days 2, 3, and 5, and Weeks 1, 2, 3, and 4 postdose	The following parameters are reported for the first SC injection of tabalumab: AUC(0-tlast) defined as AUC from time 0 to time t, where t is the time at the end of the dosing interval; AUC(0-2W) defined as AUC from time 0 to Week 2; and AUC(0-tau) defined as AUC during 1 dosing interval at steady state.
Change From Baseline in Rheumatoid Factor (RF)	Baseline, Week 24	RF is an autoantibody (antibody directed against an organism's own tissues) most relevant in rheumatoid arthritis (RA). Higher RF levels indicate an aggressive RA and a higher risk of joint damage. A decrease in RF levels indicate an improvement in the participant's condition.
Change From Baseline in Serum Immunoglobulins (IgG, IgM, IgA)	Baseline, Weeks 4, 16, 24, and 32	Immunoglobulins, 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. Change from baseline serum immunoglobulin G (IgG), immunoglobulin M (IgM), and immunoglobulin A (IgA) levels are reported. A negative change indicates a decrease in immunoglobulin levels.
PK of Tabalumab: Maximum Observed Drug Concentration (Cmax)	Week 0: Day 1 Predose, 1 h, 3 h, and 6 h postdose	Cmax for the first SC injection of tabalumab is reported.
Percent Change From Baseline in B Cell [Cluster Designation 20+ (CD20+)] Counts	Baseline, Week 0 (Day 2), Weeks 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, and 32	B-lymphocyte antigen, CD20+, is an activated-glycosylated phosphoprotein expressed on the surface of all mature B cells. Percent change from baseline in B cell counts=\[(post-baseline CD20+ B cell count-baseline CD20+ B cell count)/(baseline CD20+ B cell count)\]\*100. A negative change indicates a decrease in cell count.
Change From Baseline in Anti-Cyclic Citrullinated Peptide (Anti-CCP) Antibody [Inova Enzyme-Linked Immunosorbent Assay (ELISA) Method]	Baseline, Week 24	During the analysis of anti-CCP, the analytical method was changed from the Inova ELISA method to the Roche Cobas 6000 method due to the discontinuation of a reagent used in the Inova ELISA method. The anti-CCP data are summarized separately for samples collected before and after the method change. No post-baseline samples from the 120 mg tabalumab Q4W and Q2W cohorts were analyzed using the Inova ELISA method. For both methods, a decrease in anti-CCP antibodies indicated an improvement in the participant's condition.
Change From Baseline in Anti-CCP Antibody (Roche Cobas 6000 Method)	Baseline, Week 24	During the analysis of anti-CCP, the analytical method was changed from the Inova ELISA method to the Roche Cobas 6000 method due to the discontinuation of a reagent used in the Inova ELISA method. The anti-CCP data are summarized separately for samples collected before and after the method change. No baseline samples from the 30 mg, 60 mg, and 120 mg tabalumab Q4W cohorts were analyzed using the Roche Cobas 6000 method. For both methods, a decrease in anti-CCP antibodies indicated an improvement in the participant's condition.
Percent Change From Baseline in CRP	Baseline, Weeks 4, 8, 16, and 24	CRP is an indicator of inflammation. The percent change from baseline in CRP=\[(post-baseline CRP- baseline CRP)/(baseline CRP)\]\*100. A negative change indicates an improvement in the participant's condition.

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.; 🇯🇵 Tokyo, Japan