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A Safety and Efficacy Study of LymphoStat-B™ (Monoclonal Anti-BLyS Antibody) in Subjects With Rheumatoid Arthritis (RA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00071812
Recruitment Status : Completed
First Posted : November 5, 2003
Results First Posted : June 25, 2012
Last Update Posted : August 14, 2013
Sponsor:
Information provided by (Responsible Party):
Human Genome Sciences Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Arthritis, Rheumatoid
Interventions Drug: Placebo
Drug: Belimumab 1 mg/kg
Drug: Belimumab 4 mg/kg
Drug: Belimumab 10 mg/kg
Enrollment 283
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Placebo Plus SOC Belimumab 1 mg/kg Plus SOC Belimumab 4 mg/kg Plus SOC Belimumab 10 mg/kg Plus SOC
Hide Arm/Group Description Placebo IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study. Belimumab 1 mg/kg IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study. The 24-week open-label extension period of the study included patients who completed the 24-week double-blind period and opted to continue to receive the same dose in the 24-week open-label extension period of the study. Belimumab 4 mg/kg IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study. The 24-week open-label extension period of the study included patients who completed the 24-week double-blind period and opted to continue to receive the same dose in the 24-week open-label extension period of the study. Belimumab 10 mg/kg IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study. The 24 week-open label extension period of the study included patients who completed the 24-week double-blind period and opted to continue in the 24-week open-label period of the study and included patients who were originally randomized to the belimumab 10 mg/kg group in the double-blind period, patients who switched to belimumab 10 mg/kg at the investigator's discretion, and former placebo patients.
Period Title: 24-Week Double-Blind Period
Started 69 72 71 71
Completed 59 66 63 60
Not Completed 10 6 8 11
Reason Not Completed
Adverse Event             2             3             4             4
Lack of Efficacy             3             1             2             1
Lost to Follow-up             0             1             1             0
Withdrawal by Subject             5             1             1             5
Protocol Violation             0             0             0             1
Period Title: 24-Week Open-Label Extension Period
Started 0 [1] 11 [2] 8 [3] 218 [4]
Completed 0 11 7 178
Not Completed 0 0 1 40
Reason Not Completed
Adverse Event             0             0             0             7
Lack of Efficacy             0             0             0             17
Lost to Follow-up             0             0             0             2
Withdrawal by Subject             0             0             0             12
Lack of Compliance             0             0             1             2
[1]
Of 59: 56 switched to 10 mg/kg; 3 elected not to continue in the open-label extension.
[2]
Of 66: 53 switched to 10 mg/kg; 2 elected not continue in the open-label extension.
[3]
Of 63: 53 switched to 10 mg/kg; 2 elected not continue in the open-label extension.
[4]
Of 60: 56 continued with 10 mg/kg; 4 elected not to continue in the open-label extension.
Arm/Group Title Placebo Plus SOC Belimumab 1 mg/kg Plus SOC Belimumab 4 mg/kg Plus SOC Belimumab 10 mg/kg Plus SOC Total
Hide Arm/Group Description Placebo IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study Belimumab 1 mg/kg IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study Belimumab 4 mg/kg IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study Belimumab 10 mg/kg IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study Total of all reporting groups
Overall Number of Baseline Participants 69 72 71 71 283
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 69 participants 72 participants 71 participants 71 participants 283 participants
50.7  (8.8) 50.6  (8.3) 50.7  (10.2) 49.5  (9.3) 50.4  (9.1)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 69 participants 72 participants 71 participants 71 participants 283 participants
Female
56
  81.2%
56
  77.8%
60
  84.5%
54
  76.1%
226
  79.9%
Male
13
  18.8%
16
  22.2%
11
  15.5%
17
  23.9%
57
  20.1%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 69 participants 72 participants 71 participants 71 participants 283 participants
United States 55 61 59 59 234
Poland 14 11 12 12 49
1.Primary Outcome
Title Percentage of Patients With ACR20 (American College of Rheumatology) Response at Week 24, Based on Erythrocyte Sedimentation Rate (ESR)
Hide Description An ACR20 response is defined as having at least a 20% improvement in tender and swollen joints as well as a 20% improvement in 3 of 5 other criteria (patient assessment, physician assessment, pain scale, disability/functional questionnaire, and acute phase reactant value based on erythrocyte sedimentation rate [ESR]).
Time Frame Baseline, 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on a modified intention-to-treat (MITT) population, defined as all patients who were randomized and received at least 1 dose of study agent.
Arm/Group Title Placebo Plus SOC Belimumab 1 mg/kg Plus SOC Belimumab 4 mg/kg Plus SOC Belimumab 10 mg/kg Plus SOC
Hide Arm/Group Description:
Placebo IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study
Belimumab 1 mg/kg IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study
Belimumab 4 mg/kg IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study
Belimumab 10 mg/kg IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study
Overall Number of Participants Analyzed 69 72 71 71
Measure Type: Number
Unit of Measure: percentage of participants
15.9 34.7 25.4 28.2
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Plus SOC, Belimumab 1 mg/kg Plus SOC
Comments Patients who required rescue RA medications were declared nonresponders, as were patients who dropped out or were missing Week 24 data.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0097
Comments P-value was not adjusted for multiple testing.
Method Likelihood ratio chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter percent difference from placebo
Estimated Value 18.8
Confidence Interval (2-Sided) 95%
4.8 to 32.8
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo Plus SOC, Belimumab 4 mg/kg Plus SOC
Comments Patients who required rescue RA medications were declared nonresponders, as were patients who dropped out or were missing Week 24 data.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1677
Comments P-value was not adjusted for multiple testing.
Method Likelihood ratio chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter percent difference from placebo
Estimated Value 9.4
Confidence Interval (2-Sided) 95%
-3.9 to 22.7
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo Plus SOC, Belimumab 10 mg/kg Plus SOC
Comments Patients who required rescue RA medications were declared nonresponders, as were patients who dropped out or were missing Week 24 data.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0796
Comments P-value was not adjusted for multiple testing.
Method Likelihood ratio chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter percent difference from placebo
Estimated Value 12.2
Confidence Interval (2-Sided) 95%
-1.3 to 25.8
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Percentage of Patients With an ACR50 Response at Week 24, Based on ESR
Hide Description An ACR50 response is defined as having at least a 50% improvement in tender and swollen joints as well as a 50% improvement in 3 of 5 other criteria (patient assessment, physician assessment, pain scale, disability/functional questionnaire, and acute phase reactant value based on erythrocyte sedimentation rate [ESR]).
Time Frame Baseline, 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on a MITT population, defined as all patients who were randomized and received at least 1 dose of study agent.
Arm/Group Title Placebo Plus SOC Belimumab 1 mg/kg Plus SOC Belimumab 4 mg/kg Plus SOC Belimumab 10 mg/kg Plus SOC
Hide Arm/Group Description:
Placebo IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study
Belimumab 1 mg/kg IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study
Belimumab 4 mg/kg IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study
Belimumab 10 mg/kg IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study
Overall Number of Participants Analyzed 69 72 71 71
Measure Type: Number
Unit of Measure: percentage of participants
4.3 9.7 8.5 14.1
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Plus SOC, Belimumab 1 mg/kg Plus SOC
Comments Patients who required rescue RA medications were declared nonresponders, as were patients who dropped out or were missing Week 24 data.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2074
Comments P-value was not adjusted for multiple testing.
Method Likelihood ratio chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter percent difference from placebo
Estimated Value 5.4
Confidence Interval (2-Sided) 95%
-3.0 to 13.7
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo Plus SOC, Belimumab 4 mg/kg Plus SOC
Comments Patients who required rescue RA medications were declared nonresponders, as were patients who dropped out or were missing Week 24 data.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3177
Comments P-value was not adjusted for multiple testing.
Method Likelihood ratio chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter percent difference from placebo
Estimated Value 4.1
Confidence Interval (2-Sided) 95%
-4.0 to 12.2
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo Plus SOC, Belimumab 10 mg/kg Plus SOC
Comments Patients who required rescue RA medications were declared nonresponders, as were patients who dropped out or were missing Week 24 data.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0418
Comments P-value was not adjusted for multiple testing.
Method Likelihood ratio chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter percent difference from placebo
Estimated Value 9.7
Confidence Interval (2-Sided) 95%
0.3 to 19.2
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Percentage of Patients With an ACR70 Response at Week 24, Based on ESR
Hide Description An ACR70 response is defined as having at least a 70% improvement in tender and swollen joints as well as a 70% improvement in 3 of 5 other criteria (patient assessment, physician assessment, pain scale, disability/functional questionnaire, and acute phase reactant value based on erythrocyte sedimentation rate [ESR]).
Time Frame Baseline, 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on a MITT population, defined as all patients who were randomized and received at least 1 dose of study agent.
Arm/Group Title Placebo Plus SOC Belimumab 1 mg/kg Plus SOC Belimumab 4 mg/kg Plus SOC Belimumab 10 mg/kg Plus SOC
Hide Arm/Group Description:
Placebo IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study
Belimumab 1 mg/kg IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study
Belimumab 4 mg/kg IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study
Belimumab 10 mg/kg IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study
Overall Number of Participants Analyzed 69 72 71 71
Measure Type: Number
Unit of Measure: percentage of participants
2.9 5.6 1.4 2.8
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Plus SOC, Belimumab 1 mg/kg Plus SOC
Comments Patients who required rescue RA medications were declared nonresponders, as were patients who dropped out or were missing Week 24 data.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4299
Comments P-value was not adjusted for multiple testing.
Method Likelihood ratio chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter percent difference from placebo
Estimated Value 2.7
Confidence Interval (2-Sided) 95%
-4.0 to 9.3
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo Plus SOC, Belimumab 4 mg/kg Plus SOC
Comments Patients who required rescue RA medications were declared nonresponders, as were patients who dropped out or were missing Week 24 data.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5393
Comments P-value was not adjusted for multiple testing.
Method Likelihood ratio chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter percent difference from placebo
Estimated Value -1.5
Confidence Interval (2-Sided) 95%
-6.3 to 3.3
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo Plus SOC, Belimumab 10 mg/kg Plus SOC
Comments Patients who required rescue RA medications were declared nonresponders, as were patients who dropped out or were missing Week 24 data.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9769
Comments P-value was not adjusted for multiple testing.
Method Likelihood ratio chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter percent difference from placebo
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
-5.6 to 5.4
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Time to First ACR20 Response, Based on ESR
Hide Description The time to first ACR20 response (based on ESR) is defined as the time from the first dose to the first visit at which a patient first exhibited an ACR20 response, which may or may not have been sustained through Week 24.
Time Frame 0 to 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on a MITT population, defined as all patients who were randomized and received at least 1 dose of study agent.
Arm/Group Title Placebo Plus SOC Belimumab 1 mg/kg Plus SOC Belimumab 4 mg/kg Plus SOC Belimumab 10 mg/kg Plus SOC
Hide Arm/Group Description:
Placebo IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study
Belimumab 1 mg/kg IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study
Belimumab 4 mg/kg IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study
Belimumab 10 mg/kg IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study
Overall Number of Participants Analyzed 69 72 71 71
Median (Inter-Quartile Range)
Unit of Measure: days
112 [1] 
(84 to NA)
109
(60 to 168)
112 [1] 
(49 to NA)
111 [1] 
(57 to NA)
[1]
75th percentile could not be estimated because ≥40% of patients had no response
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Plus SOC, Belimumab 1 mg/kg Plus SOC
Comments Patients who required rescue RA medications were declared nonresponders, as were patients who dropped out or were missing Week 24 data. Patients who did not have any ACR response were censored at the last visit or exit visit, whichever occurred first. Patients who did not have an ACR response and discontinued from the study prior to study completion were censored at the last date on study.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1752
Comments P-value was not adjusted for multiple testing.
Method Log Rank
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo Plus SOC, Belimumab 4 mg/kg Plus SOC
Comments Patients who required rescue RA medications were declared nonresponders, as were patients who dropped out or were missing Week 24 data. Patients who did not have any ACR response were censored at the last visit or exit visit, whichever occurred first. Patients who did not have an ACR response and discontinued from the study prior to study completion were censored at the last date on study.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3440
Comments P-value was not adjusted for multiple testing.
Method Log Rank
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo Plus SOC, Belimumab 10 mg/kg Plus SOC
Comments Patients who required rescue RA medications were declared nonresponders, as were patients who dropped out or were missing Week 24 data. Patients who did not have any ACR response were censored at the last visit or exit visit, whichever occurred first. Patients who did not have an ACR response and discontinued from the study prior to study completion were censored at the last date on study.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4308
Comments P-value was not adjusted for multiple testing.
Method Log Rank
Comments [Not Specified]
5.Secondary Outcome
Title Time to First ACR50 Response, Based on ESR
Hide Description Measure not posted because time to ACR50 response was unable to be determined due to the small number of patients achieving an ACR50 response in the study.
Time Frame 0 to 24 weeks
Outcome Measure Data Not Reported
6.Secondary Outcome
Title Time to First ACR70 Response, Based on ESR
Hide Description Measure not posted because time to ACR70 response was unable to be determined due to the small number of patients achieving an ACR70 response in the study.
Time Frame 0 to 24 weeks
Outcome Measure Data Not Reported
7.Secondary Outcome
Title Mean Change in Disease Activity Score 28 (DAS28) at Week 24
Hide Description DAS is a composite index of a patient's level of RA disease activity. DAS28 is an abbreviated version of DAS, using a subset of 28 joints in the assessment, calculated based on 4 variables: 1) number of tender joints out of a total of 28 joints, 2) number of swollen joints out of a total of 28 joints, 3) ESR, 4) patient's global assessment of disease activity based on a 100-mm visual analog scale. The calculation provides a number on a scale from 0 to 10 (>5.1=active disease; <3.2=well controlled disease; <2.6=remission). Change from baseline >1.2 = good response and ≤0.6 = non-response.
Time Frame Baseline, 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on a MITT population, defined as all patients who were randomized and received at least 1 dose of study agent and who had both a baseline and a Week 24 DAS28 score.
Arm/Group Title Placebo Plus SOC Belimumab 1 mg/kg Plus SOC Belimumab 4 mg/kg Plus SOC Belimumab 10 mg/kg Plus SOC
Hide Arm/Group Description:
Placebo IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study
Belimumab 1 mg/kg IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study
Belimumab 4 mg/kg IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study
Belimumab 10 mg/kg IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study
Overall Number of Participants Analyzed 69 72 71 70
Mean (Standard Error)
Unit of Measure: scores on a scale
-0.9  (0.15) -1.3  (0.18) -0.9  (0.14) -1.5  (0.15)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Plus SOC, Belimumab 1 mg/kg Plus SOC
Comments Missing data was handled by using last observation carried forward (LOCF) imputation.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0958
Comments P-value was not adjusted for multiple testing.
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo Plus SOC, Belimumab 4 mg/kg Plus SOC
Comments Missing data was handled by using LOCF imputation.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7864
Comments P-value was not adjusted for multiple testing.
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo Plus SOC, Belimumab 10 mg/kg Plus SOC
Comments Missing data was handled by using LOCF imputation.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0051
Comments P-value was not adjusted for multiple testing.
Method t-test, 2 sided
Comments [Not Specified]
8.Secondary Outcome
Title Time to First DAS28 Response
Hide Description DAS28 response is defined as the time from the first dose to the first time at which a patient exhibited a “good” or a “moderate” improvement in RA disease activity, based on DAS28 improvements compared to baseline. Good response was defined as >1.2 change from baseline and DAS28 score ≤ 3.2. No response was defined as ≤ 0.6 change from baseline in DAS28 score or change between ≤ 1.2 and > 0.6 with a DAS28 score of > 5.1.
Time Frame 0 to 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on a MITT population, defined as all patients who were randomized and received at least 1 dose of study agent.
Arm/Group Title Placebo Plus SOC Belimumab 1 mg/kg Plus SOC Belimumab 4 mg/kg Plus SOC Belimumab 10 mg/kg Plus SOC
Hide Arm/Group Description:
Placebo IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study
Belimumab 1 mg/kg IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study
Belimumab 4 mg/kg IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study
Belimumab 10 mg/kg IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study
Overall Number of Participants Analyzed 69 72 71 71
Median (Full Range)
Unit of Measure: days
111
(56 to 168)
82
(51 to 114)
84
(33 to 168)
57
(30 to 111)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Plus SOC, Belimumab 1 mg/kg Plus SOC
Comments Patients who required rescue RA medications were declared nonresponders, as were patients who dropped out or were missing Week 24 data. Patients who did not have good or moderate improvement in DAS28 were censored at the last visit or exit visit, whichever occurred first. Patients who did not have good or moderate improvement in DAS28 and discontinued from the study prior to study completion were censored at the last date on study.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0960
Comments P-value was not adjusted for multiple testing.
Method Log Rank
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo Plus SOC, Belimumab 4 mg/kg Plus SOC
Comments Patients who required rescue RA medications were declared nonresponders, as were patients who dropped out or were missing Week 24 data. Patients who did not have good or moderate improvement in DAS28 were censored at the last visit or exit visit, whichever occurred first. Patients who did not have good or moderate improvement in DAS28 and discontinued from the study prior to study completion were censored at the last date on study.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2859
Comments P-value was not adjusted for multiple testing.
Method Log Rank
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo Plus SOC, Belimumab 10 mg/kg Plus SOC
Comments Patients who required rescue RA medications were declared nonresponders, as were patients who dropped out or were missing Week 24 data. Patients who did not have good or moderate improvement in DAS28 were censored at the last visit or exit visit, whichever occurred first. Patients who did not have good or moderate improvement in DAS28 and discontinued from the study prior to study completion were censored at the last date on study.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0109
Comments P-value was not adjusted for multiple testing.
Method Log Rank
Comments [Not Specified]
9.Secondary Outcome
Title Mean Change in Modified Total Sharp Score at Week 24
Hide Description The modified total Sharp score method was used to evaluate radiographs of hands/wrists for erosions (ERO) and joint space narrowing (JSN). The total modified Sharp score ranges from 0 (no radiographic damage) to 200 (worst possible radiographic damage) and is the sum of the normalized ERO score (range 0-100) and the normalized JSN score (range 0-100). Higher scores indicated more damage.
Time Frame Baseline, 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on a MITT population, defined as all patients who were randomized and received at least 1 dose of study agent and who had both a modified total Sharp score at baseline and at Week 24.
Arm/Group Title Placebo Plus SOC Belimumab 1 mg/kg Plus SOC Belimumab 4 mg/kg Plus SOC Belimumab 10 mg/kg Plus SOC
Hide Arm/Group Description:
Placebo IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study
Belimumab 1 mg/kg IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study
Belimumab 4 mg/kg IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study
Belimumab 10 mg/kg IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study
Overall Number of Participants Analyzed 67 70 66 68
Mean (Standard Error)
Unit of Measure: scores on a scale
0.7  (0.2) 0.3  (0.2) 0.3  (0.2) 0.6  (0.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Plus SOC, Belimumab 1 mg/kg Plus SOC
Comments Missing data was handled by using LOCF imputation.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1940
Comments P-value was not adjusted for multiple testing.
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo Plus SOC, Belimumab 4 mg/kg Plus SOC
Comments Missing data was handled by using LOCF imputation.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2561
Comments P-value was not adjusted for multiple testing.
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo Plus SOC, Belimumab 10 mg/kg Plus SOC
Comments Missing data was handled by using LOCF imputation.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8707
Comments P-value was not adjusted for multiple testing.
Method t-test, 2 sided
Comments [Not Specified]
10.Other Pre-specified Outcome
Title Adverse Events (AE) Overview
Hide Description Includes AEs reported in patients from the first dose of study agent throughout the study up to the Week 48/exit visit or 8 weeks following the last dose of study agent for patients who withdrew from this study or decided not to participate in the optional continuation protocol (LBRA99/NCT00583557).
Time Frame Up to 56 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Placebo Plus SOC Belimumab 1 mg/kg Plus SOC Belimumab 4 mg/kg Plus SOC Belimumab 10 mg/kg Plus SOC Open-label Extension Period: All Active
Hide Arm/Group Description:
Placebo IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study
Belimumab 1 mg/kg IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study
Belimumab 4 mg/kg IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study
Belimumab 10 mg/kg IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study
Includes all patients who completed the 24-week double-blind period and opted to continue in a 24-week open-label extension period. Belimumab patients received the same dose or were switched to 10 mg/kg at the investigator's discretion and former placebo patients received belimumab 10 mg/kg. AE onset may be during the extension phase or continuing from the double-blind period.
Overall Number of Participants Analyzed 69 72 71 71 237
Measure Type: Number
Unit of Measure: percentage of participants
Percent of patients with at least 1 AE 89.9 84.7 90.1 93.0 91.6
Percent of patients with at least 1 SAE 7.2 6.9 7.0 8.5 11.0
Percent of patients with an AE resulting in death 1.5 0 0 1.4 0
Time Frame Up to 56 weeks
Adverse Event Reporting Description Includes AEs reported in patients from the first dose of study agent throughout the study up to the Week 48/exit visit or 8 weeks following the last dose of study agent for patients who withdrew from this study or decided not to participate in the optional continuation protocol (LBRA99/NCT00583557).
 
Arm/Group Title Placebo Plus SOC Belimumab 1 mg/kg Plus SOC Belimumab 4 mg/kg Plus SOC Belimumab 10 mg/kg Plus SOC Open-label Extension Period: All Active
Hide Arm/Group Description Placebo IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study Belimumab 1 mg/kg IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study Belimumab 4 mg/kg IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study Belimumab 10 mg/kg IV plus standard therapy (SOC) for RA for 24-week double-blind period of the study Includes all patients who completed the 24-week double blind period and opted to continue in the 24-week open-label extension period. Belimumab patients received the same dose or were switched to 10 mg/kg at investigator discretion and former placebo patients received belimumab 10 mg/kg. AE onset may be during the extension phase or continuing from the double-blind period.
All-Cause Mortality
Placebo Plus SOC Belimumab 1 mg/kg Plus SOC Belimumab 4 mg/kg Plus SOC Belimumab 10 mg/kg Plus SOC Open-label Extension Period: All Active
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Plus SOC Belimumab 1 mg/kg Plus SOC Belimumab 4 mg/kg Plus SOC Belimumab 10 mg/kg Plus SOC Open-label Extension Period: All Active
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   5/69 (7.25%)   5/72 (6.94%)   5/71 (7.04%)   6/71 (8.45%)   26/237 (10.97%) 
Blood and lymphatic system disorders           
Anaemia * 1  0/69 (0.00%)  0/72 (0.00%)  0/71 (0.00%)  1/71 (1.41%)  1/237 (0.42%) 
Cardiac disorders           
Acute coronary syndrome * 1  0/69 (0.00%)  0/72 (0.00%)  1/71 (1.41%)  0/71 (0.00%)  0/237 (0.00%) 
Angina pectoris * 1  0/69 (0.00%)  1/72 (1.39%)  0/71 (0.00%)  0/71 (0.00%)  0/237 (0.00%) 
Cardiac arrest * 1  1/69 (1.45%)  0/72 (0.00%)  0/71 (0.00%)  0/71 (0.00%)  0/237 (0.00%) 
Coronary artery disease * 1  0/69 (0.00%)  0/72 (0.00%)  0/71 (0.00%)  0/71 (0.00%)  1/237 (0.42%) 
Myocardial infarction * 1  1/69 (1.45%)  0/72 (0.00%)  1/71 (1.41%)  0/71 (0.00%)  0/237 (0.00%) 
Supraventricular tachycardia * 1  0/69 (0.00%)  1/72 (1.39%)  0/71 (0.00%)  0/71 (0.00%)  1/237 (0.42%) 
Congenital, familial and genetic disorders           
Spondylolisthesis * 1  0/69 (0.00%)  0/72 (0.00%)  0/71 (0.00%)  0/71 (0.00%)  2/237 (0.84%) 
Gastrointestinal disorders           
Gastric ulcer * 1  0/69 (0.00%)  0/72 (0.00%)  1/71 (1.41%)  1/71 (1.41%)  0/237 (0.00%) 
Pancreatitis acute * 1  0/69 (0.00%)  1/72 (1.39%)  0/71 (0.00%)  0/71 (0.00%)  0/237 (0.00%) 
Small intestinal obstruction * 1  0/69 (0.00%)  0/72 (0.00%)  0/71 (0.00%)  0/71 (0.00%)  1/237 (0.42%) 
General disorders           
Malaise * 1  0/69 (0.00%)  0/72 (0.00%)  0/71 (0.00%)  0/71 (0.00%)  1/237 (0.42%) 
Non-cardiac chest pain * 1  1/69 (1.45%)  0/72 (0.00%)  1/71 (1.41%)  0/71 (0.00%)  0/237 (0.00%) 
Pyrexia * 1  0/69 (0.00%)  0/72 (0.00%)  0/71 (0.00%)  0/71 (0.00%)  1/237 (0.42%) 
Hepatobiliary disorders           
Cholecystitis * 1  1/69 (1.45%)  0/72 (0.00%)  0/71 (0.00%)  0/71 (0.00%)  0/237 (0.00%) 
Cholelithiasis * 1  1/69 (1.45%)  0/72 (0.00%)  0/71 (0.00%)  1/71 (1.41%)  0/237 (0.00%) 
Infections and infestations           
Cellulitis * 1  0/69 (0.00%)  0/72 (0.00%)  0/71 (0.00%)  0/71 (0.00%)  2/237 (0.84%) 
Clostridium colitis * 1  0/69 (0.00%)  0/72 (0.00%)  0/71 (0.00%)  1/71 (1.41%)  0/237 (0.00%) 
Groin abscess * 1  0/69 (0.00%)  0/72 (0.00%)  1/71 (1.41%)  0/71 (0.00%)  0/237 (0.00%) 
Pneumonia * 1  0/69 (0.00%)  0/72 (0.00%)  1/71 (1.41%)  1/71 (1.41%)  1/237 (0.42%) 
Pneumonia primary atypical * 1  0/69 (0.00%)  1/72 (1.39%)  0/71 (0.00%)  0/71 (0.00%)  0/237 (0.00%) 
Pyelonephritis * 1  0/69 (0.00%)  0/72 (0.00%)  0/71 (0.00%)  0/71 (0.00%)  1/237 (0.42%) 
Viral infection * 1  1/69 (1.45%)  0/72 (0.00%)  0/71 (0.00%)  0/71 (0.00%)  0/237 (0.00%) 
Injury, poisoning and procedural complications           
Femur fracture * 1  0/69 (0.00%)  0/72 (0.00%)  0/71 (0.00%)  0/71 (0.00%)  1/237 (0.42%) 
Medical device complication * 1  0/69 (0.00%)  0/72 (0.00%)  0/71 (0.00%)  0/71 (0.00%)  1/237 (0.42%) 
Musculoskeletal and connective tissue disorders           
Arthralgia * 1  0/69 (0.00%)  0/72 (0.00%)  1/71 (1.41%)  0/71 (0.00%)  3/237 (1.27%) 
Arthropathy * 1  1/69 (1.45%)  0/72 (0.00%)  0/71 (0.00%)  0/71 (0.00%)  0/237 (0.00%) 
Intervertebral disc protrusion * 1  0/69 (0.00%)  0/72 (0.00%)  0/71 (0.00%)  0/71 (0.00%)  1/237 (0.42%) 
Intervertebral disc space narrowing * 1  0/69 (0.00%)  0/72 (0.00%)  0/71 (0.00%)  0/71 (0.00%)  1/237 (0.42%) 
Localised osteoarthritis * 1  0/69 (0.00%)  0/72 (0.00%)  0/71 (0.00%)  0/71 (0.00%)  2/237 (0.84%) 
Osteoarthritis * 1  0/69 (0.00%)  0/72 (0.00%)  0/71 (0.00%)  1/71 (1.41%)  1/237 (0.42%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)           
Basal cell carcinoma * 1  0/69 (0.00%)  0/72 (0.00%)  0/71 (0.00%)  0/71 (0.00%)  1/237 (0.42%) 
Breast cancer * 1  0/69 (0.00%)  0/72 (0.00%)  0/71 (0.00%)  1/71 (1.41%)  0/237 (0.00%) 
Lung squamous cell carcinoma stage unspecified * 1  0/69 (0.00%)  0/72 (0.00%)  0/71 (0.00%)  0/71 (0.00%)  1/237 (0.42%) 
Squamous cell carcinoma of skin * 1  0/69 (0.00%)  0/72 (0.00%)  0/71 (0.00%)  1/71 (1.41%)  1/237 (0.42%) 
Vulval cancer * 1  0/69 (0.00%)  1/72 (1.39%)  0/71 (0.00%)  0/71 (0.00%)  0/237 (0.00%) 
Nervous system disorders           
Headache * 1  0/69 (0.00%)  0/72 (0.00%)  0/71 (0.00%)  0/71 (0.00%)  1/237 (0.42%) 
Psychiatric disorders           
Major depression * 1  0/69 (0.00%)  1/72 (1.39%)  0/71 (0.00%)  0/71 (0.00%)  0/237 (0.00%) 
Obsessive-compulsive disorder * 1  0/69 (0.00%)  0/72 (0.00%)  0/71 (0.00%)  0/71 (0.00%)  1/237 (0.42%) 
Renal and urinary disorders           
Cystocele * 1  0/69 (0.00%)  0/72 (0.00%)  0/71 (0.00%)  1/71 (1.41%)  0/237 (0.00%) 
Nephrolithiasis * 1  0/69 (0.00%)  0/72 (0.00%)  0/71 (0.00%)  0/71 (0.00%)  1/237 (0.42%) 
Renal colic * 1  0/69 (0.00%)  0/72 (0.00%)  0/71 (0.00%)  0/71 (0.00%)  1/237 (0.42%) 
Reproductive system and breast disorders           
Endometrial hypertrophy * 1  0/69 (0.00%)  0/72 (0.00%)  0/71 (0.00%)  0/71 (0.00%)  1/237 (0.42%) 
Ovarian cyst * 1  1/69 (1.45%)  0/72 (0.00%)  0/71 (0.00%)  0/71 (0.00%)  0/237 (0.00%) 
Respiratory, thoracic and mediastinal disorders           
Pleurisy * 1  0/69 (0.00%)  0/72 (0.00%)  0/71 (0.00%)  0/71 (0.00%)  1/237 (0.42%) 
Pneumonia aspiration * 1  0/69 (0.00%)  1/72 (1.39%)  0/71 (0.00%)  0/71 (0.00%)  0/237 (0.00%) 
Vascular disorders           
Hypertension * 1  0/69 (0.00%)  0/72 (0.00%)  0/71 (0.00%)  0/71 (0.00%)  1/237 (0.42%) 
Peripheral ischaemia * 1  0/69 (0.00%)  0/72 (0.00%)  0/71 (0.00%)  0/71 (0.00%)  1/237 (0.42%) 
Peripheral vascular disorder * 1  0/69 (0.00%)  1/72 (1.39%)  0/71 (0.00%)  0/71 (0.00%)  0/237 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 7.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Plus SOC Belimumab 1 mg/kg Plus SOC Belimumab 4 mg/kg Plus SOC Belimumab 10 mg/kg Plus SOC Open-label Extension Period: All Active
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   50/69 (72.46%)   47/72 (65.28%)   48/71 (67.61%)   54/71 (76.06%)   165/237 (69.62%) 
Gastrointestinal disorders           
Diarrhoea * 1  6/69 (8.70%)  6/72 (8.33%)  2/71 (2.82%)  8/71 (11.27%)  15/237 (6.33%) 
Mouth ulceration * 1  2/69 (2.90%)  1/72 (1.39%)  4/71 (5.63%)  0/71 (0.00%)  3/237 (1.27%) 
Nausea * 1  5/69 (7.25%)  1/72 (1.39%)  6/71 (8.45%)  3/71 (4.23%)  10/237 (4.22%) 
General disorders           
Fatigue * 1  4/69 (5.80%)  5/72 (6.94%)  6/71 (8.45%)  7/71 (9.86%)  18/237 (7.59%) 
Infusion site reaction * 1  1/69 (1.45%)  4/72 (5.56%)  0/71 (0.00%)  2/71 (2.82%)  4/237 (1.69%) 
Oedema peripheral * 1  4/69 (5.80%)  3/72 (4.17%)  9/71 (12.68%)  3/71 (4.23%)  25/237 (10.55%) 
Infections and infestations           
Bronchitis * 1  1/69 (1.45%)  4/72 (5.56%)  2/71 (2.82%)  2/71 (2.82%)  7/237 (2.95%) 
Nasopharyngitis * 1  1/69 (1.45%)  1/72 (1.39%)  4/71 (5.63%)  0/71 (0.00%)  9/237 (3.80%) 
Sinusitis * 1  2/69 (2.90%)  3/72 (4.17%)  7/71 (9.86%)  3/71 (4.23%)  13/237 (5.49%) 
Upper respiratory tract infection * 1  9/69 (13.04%)  6/72 (8.33%)  9/71 (12.68%)  10/71 (14.08%)  38/237 (16.03%) 
Urinary tract infection * 1  6/69 (8.70%)  8/72 (11.11%)  8/71 (11.27%)  4/71 (5.63%)  17/237 (7.17%) 
Injury, poisoning and procedural complications           
Contusion * 1  0/69 (0.00%)  4/72 (5.56%)  3/71 (4.23%)  0/71 (0.00%)  2/237 (0.84%) 
Musculoskeletal and connective tissue disorders           
Arthralgia * 1  16/69 (23.19%)  21/72 (29.17%)  15/71 (21.13%)  24/71 (33.80%)  75/237 (31.65%) 
Back pain * 1  2/69 (2.90%)  3/72 (4.17%)  2/71 (2.82%)  2/71 (2.82%)  18/237 (7.59%) 
Joint swelling * 1  3/69 (4.35%)  4/72 (5.56%)  6/71 (8.45%)  11/71 (15.49%)  21/237 (8.86%) 
Pain in extremity * 1  2/69 (2.90%)  6/72 (8.33%)  4/71 (5.63%)  4/71 (5.63%)  14/237 (5.91%) 
Nervous system disorders           
Dizziness * 1  3/69 (4.35%)  2/72 (2.78%)  2/71 (2.82%)  4/71 (5.63%)  9/237 (3.80%) 
Headache * 1  4/69 (5.80%)  7/72 (9.72%)  5/71 (7.04%)  8/71 (11.27%)  12/237 (5.06%) 
Renal and urinary disorders           
Haematuria * 1  4/69 (5.80%)  0/72 (0.00%)  1/71 (1.41%)  1/71 (1.41%)  4/237 (1.69%) 
Respiratory, thoracic and mediastinal disorders           
Cough * 1  2/69 (2.90%)  1/72 (1.39%)  3/71 (4.23%)  8/71 (11.27%)  12/237 (5.06%) 
Skin and subcutaneous tissue disorders           
Pruritus * 1  1/69 (1.45%)  7/72 (9.72%)  1/71 (1.41%)  2/71 (2.82%)  7/237 (2.95%) 
Vascular disorders           
Hypertension * 1  2/69 (2.90%)  4/72 (5.56%)  2/71 (2.82%)  2/71 (2.82%)  10/237 (4.22%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 7.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
For multi-center trials, no investigator will be authorized to publish study results from an individual center until the multi-center trial results are published. All manuscripts and abstracts must be submitted to the sponsor for review at least 30 days prior to submission for publication or for presentation at a scientific meeting. Proposed abstracts and publications will be reviewed promptly.
Results Point of Contact
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
Phone: 866-435-7343
Responsible Party: Human Genome Sciences Inc.
ClinicalTrials.gov Identifier: NCT00071812     History of Changes
Other Study ID Numbers: LBRA01
First Submitted: October 31, 2003
First Posted: November 5, 2003
Results First Submitted: February 27, 2012
Results First Posted: June 25, 2012
Last Update Posted: August 14, 2013