A Study for Japanese Participants With Rheumatoid Arthritis (RA)

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Primary Purpose

Status

Completed

Phase

Phase 1

Locations

Japan

Study Type

Interventional

Intervention

LY2127399 (Tabalumab)

Placebo

About this trial

This is an interventional treatment trial for Rheumatoid Arthritis

Eligibility Criteria

20 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

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

Sites / Locations

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.
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.
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.
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.
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.
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.
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.
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.
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.
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.

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Arm Label

30 milligrams (mg) Tabalumab

60 mg Tabalumab

120 mg Tabalumab

Placebo Q4W

120 mg once every 2 weeks (Q2W) Tabalumab

Placebo Q2W

Arm Description

30 mg tabalumab every 4 weeks (Q4W) for 20 weeks (6 doses of study drug)

60 mg tabalumab Q4W for 20 weeks (6 doses of study drug)

120 mg tabalumab Q4W for 20 weeks (6 doses of study drug)

Q4W for 20 weeks

Initial loading dose of 240 mg tabalumab followed by 120 mg Q2W for 20 weeks (10 doses of study drug)

Q2W for 20 weeks

Outcomes

Primary Outcome Measures

Number of Participants With Adverse Events (AEs) [Clinically Significant Effects]

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

Pharmacokinetics (PK) of Tabalumab: Area Under the Concentration Time Curve (AUC)

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.

PK of Tabalumab: Maximum Observed Drug Concentration (Cmax)

Cmax for the first SC injection of tabalumab is reported.

Percent Change From Baseline in B Cell [Cluster Designation 20+ (CD20+)] Counts

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]

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)

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.

Change From Baseline in Rheumatoid Factor (RF)

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)

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.

Percent Change From Baseline in CRP

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.

Percent Change From Baseline in Erythrocyte Sedimentation Rate (ESR)

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.

Full Information

NCT ID

NCT01253226

First Posted

December 1, 2010

Last Updated

October 19, 2018

Sponsor

Eli Lilly and Company

1. Study Identification

Unique Protocol Identification Number

NCT01253226

Brief Title

A Study for Japanese Participants With Rheumatoid Arthritis (RA)

Official Title

Multiple-Dose, Dose-Escalation Study to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of LY2127399 in Japanese Patients With Rheumatoid Arthritis Treated With Methotrexate

Study Type

Interventional

2. Study Status

Record Verification Date

October 2018

Overall Recruitment Status

Completed

Study Start Date

September 2009 (undefined)

Primary Completion Date

August 2011 (Actual)

Study Completion Date

August 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Eli Lilly and Company

4. Oversight

Data Monitoring Committee

No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Rheumatoid Arthritis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

32 (Actual)

8. Arms, Groups, and Interventions

Arm Title

30 milligrams (mg) Tabalumab

Arm Type

Experimental

Arm Description

30 mg tabalumab every 4 weeks (Q4W) for 20 weeks (6 doses of study drug)

Arm Title

60 mg Tabalumab

Arm Type

Experimental

Arm Description

60 mg tabalumab Q4W for 20 weeks (6 doses of study drug)

Arm Title

120 mg Tabalumab

Arm Type

Experimental

Arm Description

120 mg tabalumab Q4W for 20 weeks (6 doses of study drug)

Arm Title

Placebo Q4W

Arm Type

Placebo Comparator

Arm Description

Q4W for 20 weeks

Arm Title

120 mg once every 2 weeks (Q2W) Tabalumab

Arm Type

Experimental

Arm Description

Initial loading dose of 240 mg tabalumab followed by 120 mg Q2W for 20 weeks (10 doses of study drug)

Arm Title

Placebo Q2W

Arm Type

Placebo Comparator

Arm Description

Q2W for 20 weeks

Intervention Type

Drug

Intervention Name(s)

LY2127399 (Tabalumab)

Other Intervention Name(s)

LY2127399, Tabalumab

Intervention Description

Administered subcutaneously

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Administered subcutaneously

Primary Outcome Measure Information:

Title

Number of Participants With Adverse Events (AEs) [Clinically Significant Effects]

Description

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.

Time Frame

Baseline through study completion (up to Week 32 plus up to 12 weeks for B cell monitoring)

Secondary Outcome Measure Information:

Title

Pharmacokinetics (PK) of Tabalumab: Area Under the Concentration Time Curve (AUC)

Description

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.

Time Frame

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

Title

PK of Tabalumab: Maximum Observed Drug Concentration (Cmax)

Description

Cmax for the first SC injection of tabalumab is reported.

Time Frame

Week 0: Day 1 Predose, 1 h, 3 h, and 6 h postdose

Title

Percent Change From Baseline in B Cell [Cluster Designation 20+ (CD20+)] Counts

Description

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.

Time Frame

Baseline, Week 0 (Day 2), Weeks 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, and 32

Title

Change From Baseline in Anti-Cyclic Citrullinated Peptide (Anti-CCP) Antibody [Inova Enzyme-Linked Immunosorbent Assay (ELISA) Method]

Description

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.

Time Frame

Baseline, Week 24

Title

Change From Baseline in Anti-CCP Antibody (Roche Cobas 6000 Method)

Description

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.

Time Frame

Baseline, Week 24

Title

Change From Baseline in Rheumatoid Factor (RF)

Description

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.

Time Frame

Baseline, Week 24

Title

Change From Baseline in Serum Immunoglobulins (IgG, IgM, IgA)

Description

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.

Time Frame

Baseline, Weeks 4, 16, 24, and 32

Title

Percent Change From Baseline in CRP

Description

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.

Time Frame

Baseline, Weeks 4, 8, 16, and 24

Title

Percent Change From Baseline in Erythrocyte Sedimentation Rate (ESR)

Description

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.

Time Frame

Baseline, Weeks 4, 8, 16, and 24

10. Eligibility

Sex

All

Minimum Age & Unit of Time

20 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

No

Eligibility Criteria

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 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Call 1-877-CTLILLY(1-877-285-4559) or 1-317-615-4559 Mon-Fri 9 AM-5 PM Eastern time (UTC/GMT - 5 hours, EST )

Organizational Affiliation

Eli Lilly and Company

Official's Role

Study Director

Facility Information:

Facility Name