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

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00308282
• Collaborator: (none)
• Enrollment: 136
• Locations: 14
• Arms: 2
• Actual Duration (Months): 18.7
• Patients Per Site: 9.7
• Patients Per Site Per Month: 0.5

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Arthritis, Rheumatoid	Drug: LY2127399; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 136 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Phase II Study of Safety and Efficacy of Intravenous LY2127399 in Patients With Rheumatoid Arthritis Treated With Methotrexate
• Actual Study Start Date: Mar 28, 2006
• Actual Primary Completion Date: Jun 18, 2007
• Actual Study Completion Date: Oct 18, 2007

Arms and Interventions

Arm	Intervention/Treatment
Experimental: A	Drug: LY2127399; 30 mg, 60 mg or 160 mg, IV (in the vein) in weeks 0, 3 and 6. Treatment duration: 6 weeks.
Placebo Comparator: B	Drug: Placebo; IV (in vein) in weeks 0, 3 and 6. Treatment duration: 6 weeks.

Outcome Measures

Primary Outcome Measures

1. 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

1. 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.

2. 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.

3. 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).

4. 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.

5. 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.

6. 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.

7. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
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.	Bacau		Romania	600114
2	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.	Baia Mare		Romania	430031
3	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.	Braila		Romania	810217
4	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.	Brasov		Romania	500365
5	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.	Bucharest		Romania	024092
6	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.	Cluj-Napoca		Romania	400006
7	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.	Constanta		Romania	900607
8	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.	Craiova		Romania	200322
9	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.	Iasi		Romania	707061
10	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.	Sf. Gheorghe		Romania	520064
11	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.	Sibiu		Romania	550245
12	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.	Targoviste		Romania	130083
13	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.	Targu-Mures		Romania	540136
14	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.	Timisoara		Romania	300002

Sponsors and Collaborators

• Eli Lilly and Company

Investigators

• Study Director: 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), Eli Lilly and Company

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Lilly Clinical Trial Registry

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT00308282
• Other Study ID Numbers: 11055; H9B-MC-BCDF
• First Posted: Mar 29, 2006
• Last Update Posted: Sep 10, 2019
• Last Verified: Aug 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Additional relevant MeSH terms: Arthritis; Arthritis, Rheumatoid

Study Results

Participant Flow

Recruitment Details	Study populations are based on randomized treatment groups. Safety and Pharmacokinetic (PK) populations were adjusted due to dosing errors and account for actual treatment received.
Pre-assignment Detail	Completers were defined as having completed 3 infusions and required follow-up visits.

Arm/Group Title	Placebo	30 mg LY2127399	60 mg LY2127399	160 mg LY2127399
Arm/Group Description	Placebo administered IV in weeks 0, 3 and 6. Treatment duration: 6 weeks.	30 milligram (mg) LY2127399 administered Intravenously (IV) in weeks 0, 3 and 6. Treatment duration: 6 weeks.	60 mg LY2127399 administered Intravenously (IV) in weeks 0, 3 and 6. Treatment duration: 6 weeks.	160 mg LY2127399 administered Intravenously (IV) in weeks 0, 3 and 6. Treatment duration: 6 weeks.
Period Title: Overall Study
STARTED	34	34	34	34
Received at Least One Dose of Study Drug	34	34	34	34
COMPLETED	31	30	33	32
NOT COMPLETED	3	4	1	2

Baseline Characteristics

Arm/Group Title	Placebo	30 mg LY2127399	60 mg LY2127399	160 mg LY2127399	Total
Arm/Group Description	Placebo administered IV in weeks 0, 3 and 6. Treatment duration: 6 weeks.	30 milligram (mg) LY2127399 administered Intravenously (IV) in weeks 0, 3 and 6. Treatment duration: 6 weeks.	60 mg LY2127399 administered Intravenously (IV) in weeks 0, 3 and 6. Treatment duration: 6 weeks.	160 mg LY2127399 administered Intravenously (IV) in weeks 0, 3 and 6. Treatment duration: 6 weeks.	Total of all reporting groups
Overall Participants	34	34	34	34	136
Age, Customized (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 73 years	34 100%	34 100%	34 100%	34 100%	136 100%
>=73 years	0 0%	0 0%	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	29 85.3%	31 91.2%	26 76.5%	29 85.3%	115 84.6%
Male	5 14.7%	3 8.8%	8 23.5%	5 14.7%	21 15.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%	0 0%	0 0%
Not Hispanic or Latino	34 100%	34 100%	34 100%	34 100%	136 100%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%	0 0%
White	34 100%	34 100%	34 100%	34 100%	136 100%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
ACR functional class (Count of Participants)
Class I	4 11.8%	4 11.8%	3 8.8%	7 20.6%	18 13.2%
Class II	15 44.1%	19 55.9%	19 55.9%	16 47.1%	69 50.7%
Class III	15 44.1%	11 32.4%	12 35.3%	11 32.4%	49 36%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Achieving American College of Rheumatology 20% Response (ACR20) (Effectiveness of LY2127399 in Treating Rheumatoid Arthritis Using the ACR20 Scale)
Description	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).
Time Frame	Week 16

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study drug who had a baseline and at least 1 post-baseline ACR value.

Arm/Group Title	Placebo	30 mg LY2127399	60 mg LY2127399	160 mg LY2127399
Arm/Group Description	Placebo administered IV in weeks 0, 3 and 6. Treatment duration: 6 weeks.	30 milligram (mg) LY2127399 administered Intravenously (IV) in weeks 0, 3 and 6. Treatment duration: 6 weeks.	60 mg LY2127399 administered Intravenously (IV) in weeks 0, 3 and 6. Treatment duration: 6 weeks.	160 mg LY2127399 administered Intravenously (IV) in weeks 0, 3 and 6. Treatment duration: 6 weeks.
Measure Participants	34	33	34	33
Number [percentage of participants]	29.4 86.5%	57.6 169.4%	67.6 198.8%	51.5 151.5%

2. Secondary Outcome

Title	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)
Description	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.
Time Frame	Baseline through Study Completion (Up to 19 Months)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo	30 mg LY2127399	60 mg LY2127399	160 mg LY2127399
Arm/Group Description	Placebo administered IV in weeks 0, 3 and 6. Treatment duration: 6 weeks.	30 milligram (mg) LY2127399 administered Intravenously (IV) in weeks 0, 3 and 6. Treatment duration: 6 weeks.	60 mg LY2127399 administered Intravenously (IV) in weeks 0, 3 and 6. Treatment duration: 6 weeks.	160 mg LY2127399 administered Intravenously (IV) in weeks 0, 3 and 6. Treatment duration: 6 weeks.
Measure Participants	33	34	35	34
Count of Participants [Participants]	15 44.1%	14 41.2%	15 44.1%	15 44.1%

3. Secondary Outcome

Title	Evaluation of the Pharmacokinetics of LY2127399: Clearance
Description	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.
Time Frame	2 hours pre-dose, pre-dose, 1 hour and 4 hour(s) post dose

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of LY2127399 and had evaluable PK data.

Arm/Group Title	30 mg LY2127399	60 mg LY2127399	160 mg LY2127399
Arm/Group Description	30 milligram (mg) LY2127399 administered Intravenously (IV) in weeks 0, 3 and 6. Treatment duration: 6 weeks.	60 mg LY2127399 administered Intravenously (IV) in weeks 0, 3 and 6. Treatment duration: 6 weeks.	160 mg LY2127399 administered Intravenously (IV) in weeks 0, 3 and 6. Treatment duration: 6 weeks.
Measure Participants	32	31	34
Mean (Standard Deviation) [Liters per Hour (L/Hr)]	0.0079 (0.0031)	0.0062 (0.0023)	0.0054 (0.0021)

4. Secondary Outcome

Title	Percentage of Participants Achieving ACR 50 and ACR70
Description	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).
Time Frame	Baseline through Week 24

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study drug who had a baseline and at least 1 post-baseline ACR value.

Arm/Group Title	Placebo	30 mg LY2127399	60 mg LY2127399	160 mg LY2127399
Arm/Group Description	Placebo administered IV in weeks 0, 3 and 6. Treatment duration: 6 weeks.	30 milligram (mg) LY2127399 administered Intravenously (IV) in weeks 0, 3 and 6. Treatment duration: 6 weeks.	60 mg LY2127399 administered Intravenously (IV) in weeks 0, 3 and 6. Treatment duration: 6 weeks.	160 mg LY2127399 administered Intravenously (IV) in weeks 0, 3 and 6. Treatment duration: 6 weeks.
Measure Participants	34	33	34	33
ACR50	20.6 60.6%	57.6 169.4%	55.9 164.4%	42.4 124.7%
ACR70	2.9 8.5%	24.2 71.2%	17.6 51.8%	9.1 26.8%

5. Secondary Outcome

Title	Change From Baseline in the Disease Activity Score 28 Joint Count (DAS28-CRP)
Description	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.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study drug who had a baseline and at least 1 post-baseline ACR value.

Arm/Group Title	Placebo	30 mg LY2127399	60 mg LY2127399	160 mg LY2127399
Arm/Group Description	Placebo administered IV in weeks 0, 3 and 6. Treatment duration: 6 weeks.	30 milligram (mg) LY2127399 administered Intravenously (IV) in weeks 0, 3 and 6. Treatment duration: 6 weeks.	60 mg LY2127399 administered Intravenously (IV) in weeks 0, 3 and 6. Treatment duration: 6 weeks.	160 mg LY2127399 administered Intravenously (IV) in weeks 0, 3 and 6. Treatment duration: 6 weeks.
Measure Participants	34	33	34	33
Mean (Standard Deviation) [units on a scale]	-0.78 (0.835)	-1.68 (0.862)	-1.62 (1.007)	-1.46 (0.899)

6. Secondary Outcome

Title	European League Against Rheumatism (EULAR28) Response: Percentage of Participants With Combined Good and Moderate Responses
Description	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.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study drug who had a baseline and at least 1 post-baseline ACR value.

Arm/Group Title	Placebo	30 mg LY2127399	60 mg LY2127399	160 mg LY2127399
Arm/Group Description	Placebo administered IV in weeks 0, 3 and 6. Treatment duration: 6 weeks.	30 milligram (mg) LY2127399 administered Intravenously (IV) in weeks 0, 3 and 6. Treatment duration: 6 weeks.	60 mg LY2127399 administered Intravenously (IV) in weeks 0, 3 and 6. Treatment duration: 6 weeks.	160 mg LY2127399 administered Intravenously (IV) in weeks 0, 3 and 6. Treatment duration: 6 weeks.
Measure Participants	34	33	34	33
Number [percentage of participants]	52.9 155.6%	90.9 267.4%	88.2 259.4%	81.8 240.6%

7. Secondary Outcome

Title	Change From Baseline (CFB) in Serum Immunoglobulins IgG, IgA and IgM
Description	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.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

All participants who received one dose of study drug and had post baseline serum immunoglobulin data.

Arm/Group Title	Placebo	30 mg LY2127399	60 mg LY2127399	160 mg LY2127399
Arm/Group Description	Placebo administered IV in weeks 0, 3 and 6. Treatment duration: 6 weeks.	30 milligram (mg) LY2127399 administered Intravenously (IV) in weeks 0, 3 and 6. Treatment duration: 6 weeks.	60 mg LY2127399 administered Intravenously (IV) in weeks 0, 3 and 6. Treatment duration: 6 weeks.	160 mg LY2127399 administered Intravenously (IV) in weeks 0, 3 and 6. Treatment duration: 6 weeks.
Measure Participants	32	31	31	33
IgG	6.2 (141.29)	-26.7 (185.55)	-97.2 (313.71)	-72.0 (163.20)
IgA	-18.9 (44.00)	-11.1 (42.28)	-27.5 (58.00)	-32.6 (39.71)
IgM	1.6 (15.99)	-7.1 (41.76)	-18.6 (55.50)	-29.0 (33.72)

8. Secondary Outcome

Title	Change From Baseline in CD20+ B Cell Number Count
Description	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.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

All participants who received one dose of study drug and had post baseline CD20+ cell data.

Arm/Group Title	Placebo	30 mg LY2127399	60 mg LY2127399	160 mg LY2127399
Arm/Group Description	Placebo administered IV in weeks 0, 3 and 6. Treatment duration: 6 weeks.	30 milligram (mg) LY2127399 administered Intravenously (IV) in weeks 0, 3 and 6. Treatment duration: 6 weeks.	60 mg LY2127399 administered Intravenously (IV) in weeks 0, 3 and 6. Treatment duration: 6 weeks.	160 mg LY2127399 administered Intravenously (IV) in weeks 0, 3 and 6. Treatment duration: 6 weeks.
Measure Participants	32	31	32	33
Mean (Standard Deviation) [Cells per microLiter]	-46.9 (74.51)	-56.3 (84.75)	-135.9 (179.6)	-59.2 (81.31)

Adverse Events

Adverse Event Reporting Description	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.
Arm/Group Title	Placebo		30 mg LY2127399		60 mg LY2127399		160 mg LY2127399
Arm/Group Description	Placebo administered IV in weeks 0, 3 and 6. Treatment duration: 6 weeks.		30 milligram (mg) LY2127399 administered Intravenously (IV) in weeks 0, 3 and 6. Treatment duration: 6 weeks.		60 mg LY2127399 administered Intravenously (IV) in weeks 0, 3 and 6. Treatment duration: 6 weeks.		160 mg LY2127399 administered Intravenously (IV) in weeks 0, 3 and 6. Treatment duration: 6 weeks.
All Cause Mortality
	Placebo		30 mg LY2127399		60 mg LY2127399		160 mg LY2127399
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		30 mg LY2127399		60 mg LY2127399		160 mg LY2127399
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/33 (9.1%)		2/34 (5.9%)		0/35 (0%)		3/34 (8.8%)
Blood and lymphatic system disorders
Anemia	1/33 (3%)		0/34 (0%)		0/35 (0%)		0/34 (0%)
Gastrointestinal disorders
Gastritis Haemorrhagic	1/33 (3%)		0/34 (0%)		0/35 (0%)		0/34 (0%)
Hepatobiliary disorders
Bile Duct Stone	1/33 (3%)		0/34 (0%)		0/35 (0%)		0/34 (0%)
Immune system disorders
Drug Hypersensitivity	0/33 (0%)		1/34 (2.9%)		0/35 (0%)		1/34 (2.9%)
Infections and infestations
Necrotising Fasciitis	1/33 (3%)		0/34 (0%)		0/35 (0%)		0/34 (0%)
Urinary Tract Infection	0/33 (0%)		0/34 (0%)		0/35 (0%)		1/34 (2.9%)
Musculoskeletal and connective tissue disorders
Rheumatoid Arthritis	0/33 (0%)		1/34 (2.9%)		0/35 (0%)		0/34 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Endometrial Cancer	0/33 (0%)		0/34 (0%)		0/35 (0%)		1/34 (2.9%)
Renal and urinary disorders
Hydronephrosis	0/33 (0%)		0/34 (0%)		0/35 (0%)		1/34 (2.9%)
Respiratory, thoracic and mediastinal disorders
Pleural Effusion	0/33 (0%)		0/34 (0%)		0/35 (0%)		1/34 (2.9%)
Other (Not Including Serious) Adverse Events
	Placebo		30 mg LY2127399		60 mg LY2127399		160 mg LY2127399
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	15/33 (45.5%)		14/34 (41.2%)		15/35 (42.9%)		15/34 (44.1%)
Blood and lymphatic system disorders
Leukopenia	2/33 (6.1%)		1/34 (2.9%)		0/35 (0%)		2/34 (5.9%)
Cardiac disorders
Ventricular Extrasystoles	0/33 (0%)		1/34 (2.9%)		3/35 (8.6%)		2/34 (5.9%)
Myocardial Ischemia	0/33 (0%)		1/34 (2.9%)		2/35 (5.7%)		0/34 (0%)
Gastrointestinal disorders
Abdominal pain upper	0/33 (0%)		3/34 (8.8%)		2/35 (5.7%)		2/34 (5.9%)
Nausea	1/33 (3%)		2/34 (5.9%)		3/35 (8.6%)		2/34 (5.9%)
General disorders
Chills	0/33 (0%)		1/34 (2.9%)		0/35 (0%)		0/34 (0%)
Injection Site Irritation	0/33 (0%)		0/34 (0%)		0/35 (0%)		1/34 (2.9%)
Malaise	1/33 (3%)		0/34 (0%)		0/35 (0%)		0/34 (0%)
Pyrexia	0/33 (0%)		0/34 (0%)		0/35 (0%)		1/34 (2.9%)
Thirst	0/33 (0%)		0/34 (0%)		0/35 (0%)		1/34 (2.9%)
Infections and infestations
Upper respiratory tract infections	0/33 (0%)		2/34 (5.9%)		0/35 (0%)		2/34 (5.9%)
Investigations
Alanine Aminotransferase Increased	4/33 (12.1%)		2/34 (5.9%)		3/35 (8.6%)		3/34 (8.8%)
Aspartate Aminotransferase Increased	4/33 (12.1%)		2/34 (5.9%)		3/35 (8.6%)		3/34 (8.8%)
Blood Pressure Increased	2/33 (6.1%)		2/34 (5.9%)		1/35 (2.9%)		1/34 (2.9%)
Gamma Glutamyl Transferase Increased	0/33 (0%)		2/34 (5.9%)		1/35 (2.9%)		1/34 (2.9%)
Blood Alkaline Phosphatase Increased	0/33 (0%)		2/34 (5.9%)		1/35 (2.9%)		0/34 (0%)
Musculoskeletal and connective tissue disorders
Back Pain	1/33 (3%)		1/34 (2.9%)		1/35 (2.9%)		1/34 (2.9%)
Nervous system disorders
Headache	1/33 (3%)		3/34 (8.8%)		2/35 (5.7%)		1/34 (2.9%)
Dizziness	2/33 (6.1%)		1/34 (2.9%)		0/35 (0%)		3/34 (8.8%)
Respiratory, thoracic and mediastinal disorders
Cough	0/33 (0%)		0/34 (0%)		1/35 (2.9%)		0/34 (0%)
Dyspnoea	0/33 (0%)		0/34 (0%)		1/35 (2.9%)		0/34 (0%)
Interstitial Lung Disease	1/33 (3%)		0/34 (0%)		0/35 (0%)		0/34 (0%)
Pharyngolaryngeal Pain	0/33 (0%)		0/34 (0%)		0/35 (0%)		1/34 (2.9%)
Pleural Effusion	1/33 (3%)		0/34 (0%)		0/35 (0%)		1/34 (2.9%)
Pleurisy	0/33 (0%)		0/34 (0%)		0/35 (0%)		1/34 (2.9%)
Rhinorrhoea	0/33 (0%)		0/34 (0%)		1/35 (2.9%)		0/34 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.