Trial Outcomes & Findings for Safety and Efficacy Study of Subcutaneous Belimumab and Intravenous Rituximab Co-administration in Subjects With Primary Sjogren's Syndrome (NCT NCT02631538)

Last Updated: 2021-06-09

Results Overview

An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, other situations based on medical or scientific judgment and is associated with liver injury and impaired liver function. Data for number of participants with SAE and non-SAE has been summarized.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

86 participants

Primary outcome timeframe

Up to Week 68

Results posted on

2021-06-09

Participant Flow

This study was conducted in 10 countries across 31 centers. Participants were randomized to receive one of the four treatments; Placebo, Belimumab + Rituximab Co-administration therapy, Belimumab Monotherapy or Rituximab Monotherapy.

A total of 162 participants were screened of which 76 were screen failures. A total of 86 participants were enrolled in this study.

Participant milestones

Participant milestones
Measure	Placebo Participants received belimumab matching placebo weekly subcutaneous injections up to Week 52 and rituximab matching placebo infusions at Weeks 8 and 10 in the treatment period. Participants then entered in a 16-week no-treatment General Follow-Up (GFU) period.	Belimumab + Rituximab Co-administration Therapy Participants received belimumab 200 milligrams (mg) weekly subcutaneous injections for 24 weeks followed by belimumab matching placebo injections weekly up to Week 52; along with rituximab 1000 mg intravenous infusions at Weeks 8 and 10 in the treatment period. Participants then entered in a 16-week no-treatment GFU period.	Belimumab Monotherapy Participants received 200 mg weekly subcutaneous injections of belimumab up to Week 52 and rituximab matching placebo infusions at Weeks 8 and 10 in the treatment period. Participants then entered in a 16-week no-treatment GFU period.	Rituximab Monotherapy Participants received 1000 mg intravenous rituximab infusions at Weeks 8 and 10 and weekly subcutaneous injections of belimumab matching placebo up to Week 52 in the treatment period. Participants then entered in a 16-week no-treatment GFU period.
Treatment Period (Up to Week 52) STARTED	13	24	24	25
Treatment Period (Up to Week 52) COMPLETED	9	17	19	17
Treatment Period (Up to Week 52) NOT COMPLETED	4	7	5	8
General Follow-up (GFU) (Up to Week 68) STARTED	9	17	19	17
General Follow-up (GFU) (Up to Week 68) COMPLETED	8	17	19	16
General Follow-up (GFU) (Up to Week 68) NOT COMPLETED	1	0	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received belimumab matching placebo weekly subcutaneous injections up to Week 52 and rituximab matching placebo infusions at Weeks 8 and 10 in the treatment period. Participants then entered in a 16-week no-treatment General Follow-Up (GFU) period.	Belimumab + Rituximab Co-administration Therapy Participants received belimumab 200 milligrams (mg) weekly subcutaneous injections for 24 weeks followed by belimumab matching placebo injections weekly up to Week 52; along with rituximab 1000 mg intravenous infusions at Weeks 8 and 10 in the treatment period. Participants then entered in a 16-week no-treatment GFU period.	Belimumab Monotherapy Participants received 200 mg weekly subcutaneous injections of belimumab up to Week 52 and rituximab matching placebo infusions at Weeks 8 and 10 in the treatment period. Participants then entered in a 16-week no-treatment GFU period.	Rituximab Monotherapy Participants received 1000 mg intravenous rituximab infusions at Weeks 8 and 10 and weekly subcutaneous injections of belimumab matching placebo up to Week 52 in the treatment period. Participants then entered in a 16-week no-treatment GFU period.
Treatment Period (Up to Week 52) Adverse Event	1	5	2	2
Treatment Period (Up to Week 52) Withdrawal by Subject	1	1	2	5
Treatment Period (Up to Week 52) Lack of Efficacy	1	1	0	0
Treatment Period (Up to Week 52) Physician Decision	1	0	0	1
Treatment Period (Up to Week 52) Reached stopping criteria	0	0	1	0
General Follow-up (GFU) (Up to Week 68) Lost to Follow-up	1	0	0	1

Baseline Characteristics

Safety and Efficacy Study of Subcutaneous Belimumab and Intravenous Rituximab Co-administration in Subjects With Primary Sjogren's Syndrome

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=13 Participants Participants received belimumab matching placebo weekly subcutaneous injections up to Week 52 and rituximab matching placebo infusions at Weeks 8 and 10 in the treatment period. Participants then entered in a 16-week no-treatment General Follow-Up (GFU) period.	Belimumab + Rituximab Co-administration Therapy n=24 Participants Participants received belimumab 200 milligrams (mg) weekly subcutaneous injections for 24 weeks followed by belimumab matching placebo injections weekly up to Week 52; along with rituximab 1000 mg intravenous infusions at Weeks 8 and 10 in the treatment period. Participants then entered in a 16-week no-treatment GFU period.	Belimumab Monotherapy n=24 Participants Participants received 200 mg weekly subcutaneous injections of belimumab up to Week 52 and rituximab matching placebo infusions at Weeks 8 and 10 in the treatment period. Participants then entered in a 16-week no-treatment GFU period.	Rituximab Monotherapy n=25 Participants Participants received 1000 mg intravenous rituximab infusions at Weeks 8 and 10 and weekly subcutaneous injections of belimumab matching placebo up to Week 52 in the treatment period. Participants then entered in a 16-week no-treatment GFU period.	Total n=86 Participants Total of all reporting groups
Age, Continuous	52.7 Years STANDARD_DEVIATION 12.67 • n=93 Participants	45.1 Years STANDARD_DEVIATION 10.93 • n=4 Participants	52.0 Years STANDARD_DEVIATION 11.49 • n=27 Participants	55.2 Years STANDARD_DEVIATION 15.07 • n=483 Participants	51.1 Years STANDARD_DEVIATION 13.06 • n=36 Participants
Sex: Female, Male Female	13 Participants n=93 Participants	22 Participants n=4 Participants	22 Participants n=27 Participants	23 Participants n=483 Participants	80 Participants n=36 Participants
Sex: Female, Male Male	0 Participants n=93 Participants	2 Participants n=4 Participants	2 Participants n=27 Participants	2 Participants n=483 Participants	6 Participants n=36 Participants
Race/Ethnicity, Customized African American/African Heritage	1 Participants n=93 Participants	2 Participants n=4 Participants	2 Participants n=27 Participants	1 Participants n=483 Participants	6 Participants n=36 Participants
Race/Ethnicity, Customized American Indian or Alaskan Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	1 Participants n=483 Participants	1 Participants n=36 Participants
Race/Ethnicity, Customized Asian - East Asian Heritage	0 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants	2 Participants n=483 Participants	4 Participants n=36 Participants
Race/Ethnicity, Customized White - Arabic/North African Heritage	0 Participants n=93 Participants	2 Participants n=4 Participants	3 Participants n=27 Participants	0 Participants n=483 Participants	5 Participants n=36 Participants
Race/Ethnicity, Customized White-White/Caucasian/European Heritage	12 Participants n=93 Participants	18 Participants n=4 Participants	18 Participants n=27 Participants	21 Participants n=483 Participants	69 Participants n=36 Participants
Race/Ethnicity, Customized African American/African Heritage and Asian Heritage	0 Participants n=93 Participants	1 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	1 Participants n=36 Participants

PRIMARY outcome

Timeframe: Up to Week 68

Population: Safety Population comprised of all participants who received at least one dose of study treatment.

Outcome measures

Outcome measures
Measure	Placebo n=13 Participants Participants received belimumab matching placebo weekly subcutaneous injections up to Week 52 and rituximab matching placebo infusions at Weeks 8 and 10 in the treatment period. Participants then entered in a 16-week no-treatment General Follow-Up (GFU) period.	Belimumab + Rituximab Co-administration Therapy n=24 Participants Participants received belimumab 200 milligrams (mg) weekly subcutaneous injections for 24 weeks followed by belimumab matching placebo injections weekly up to Week 52; along with rituximab 1000 mg intravenous infusions at Weeks 8 and 10 in the treatment period. Participants then entered in a 16-week no-treatment GFU period.	Belimumab Monotherapy n=24 Participants Participants received 200 mg weekly subcutaneous injections of belimumab up to Week 52 and rituximab matching placebo infusions at Weeks 8 and 10 in the treatment period. Participants then entered in a 16-week no-treatment GFU period.	Rituximab Monotherapy n=25 Participants Participants received 1000 mg intravenous rituximab infusions at Weeks 8 and 10 and weekly subcutaneous injections of belimumab matching placebo up to Week 52 in the treatment period. Participants then entered in a 16-week no-treatment GFU period.
Number of Participants With Serious Adverse Events (SAE) and Non-serious AEs (Non-SAE) Any SAE	0 Participants	3 Participants	2 Participants	4 Participants
Number of Participants With Serious Adverse Events (SAE) and Non-serious AEs (Non-SAE) Any non-SAE	12 Participants	24 Participants	23 Participants	17 Participants

PRIMARY outcome

Timeframe: Up to Week 68

Population: Safety Population

An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. AESIs were Malignant Neoplasms, Post-Administration Systemic Reactions (PASR), All Infections of Special Interest (opportunistic infections, herpes zoster, tuberculosis and sepsis), Depression/suicide/self-injury, Deaths and study specific AESI which includes: severe skin reaction per GlaxoSmithKline (GSK) Adjudication, cardiac disorders, Posterior Reversible Encephalopathy Syndrome (PRES) and Progressive multifocal leukoencephalopathy (PML). Data for number of participants with AESI has been summarized.

Outcome measures

Outcome measures
Measure	Placebo n=13 Participants Participants received belimumab matching placebo weekly subcutaneous injections up to Week 52 and rituximab matching placebo infusions at Weeks 8 and 10 in the treatment period. Participants then entered in a 16-week no-treatment General Follow-Up (GFU) period.	Belimumab + Rituximab Co-administration Therapy n=24 Participants Participants received belimumab 200 milligrams (mg) weekly subcutaneous injections for 24 weeks followed by belimumab matching placebo injections weekly up to Week 52; along with rituximab 1000 mg intravenous infusions at Weeks 8 and 10 in the treatment period. Participants then entered in a 16-week no-treatment GFU period.	Belimumab Monotherapy n=24 Participants Participants received 200 mg weekly subcutaneous injections of belimumab up to Week 52 and rituximab matching placebo infusions at Weeks 8 and 10 in the treatment period. Participants then entered in a 16-week no-treatment GFU period.	Rituximab Monotherapy n=25 Participants Participants received 1000 mg intravenous rituximab infusions at Weeks 8 and 10 and weekly subcutaneous injections of belimumab matching placebo up to Week 52 in the treatment period. Participants then entered in a 16-week no-treatment GFU period.
Number of Participants With Adverse Event of Special Interests (AESIs) PRES	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Adverse Event of Special Interests (AESIs) Cardiac Disorders	0 Participants	1 Participants	0 Participants	1 Participants
Number of Participants With Adverse Event of Special Interests (AESIs) Malignant Neoplasms	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Adverse Event of Special Interests (AESIs) PASR	4 Participants	2 Participants	3 Participants	5 Participants
Number of Participants With Adverse Event of Special Interests (AESIs) All Infections of Special Interest	2 Participants	1 Participants	3 Participants	2 Participants
Number of Participants With Adverse Event of Special Interests (AESIs) Depression/Suicide/Self-injury	0 Participants	3 Participants	5 Participants	1 Participants
Number of Participants With Adverse Event of Special Interests (AESIs) Deaths	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Adverse Event of Special Interests (AESIs) Severe Skin Reactions	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Adverse Event of Special Interests (AESIs) PML	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline (Screening [within 35 days prior to Day 0]), Week 12, Week 24, Week 36, Week 52 and Week 68

Population: Completer Population comprised of participants who completed the 52 Week treatment visits and general follow up phase of the study including the visit at Week 68. Only those participants with data available at the specified data points were analyzed (represented by n=X in category titles).

The ESSDAI is a physician assessed disease activity index developed by EULAR consortium consisting of twelve different clinically relevant organ specific domains; cutaneous, respiratory, renal, articular, muscular, peripheral nervous system, central nervous system, hematological, glandular, constitutional, lymphadenopathy and biological. Each domain has 3 or 4 possible activity levels (i.e., no, low, moderate, high \[if available\]) using a 4-point scale, ranging from 0 (No activity) to 3 (High activity). Higher score indicates high disease activity. Each domain is assigned a weight between 1 and 6. The Total ESSDAI Scores are obtained by multiplying the level of activity (domain score) by the domain weights, ranges between 0 (no activity) and 123 (highest activity). Higher score indicates more disease activity. Baseline value is the screening visit value (within 35 days prior to Day 0). Change from Baseline was defined as the post-dose visit value minus Baseline value.

Outcome measures

Outcome measures
Measure	Placebo n=8 Participants Participants received belimumab matching placebo weekly subcutaneous injections up to Week 52 and rituximab matching placebo infusions at Weeks 8 and 10 in the treatment period. Participants then entered in a 16-week no-treatment General Follow-Up (GFU) period.	Belimumab + Rituximab Co-administration Therapy n=17 Participants Participants received belimumab 200 milligrams (mg) weekly subcutaneous injections for 24 weeks followed by belimumab matching placebo injections weekly up to Week 52; along with rituximab 1000 mg intravenous infusions at Weeks 8 and 10 in the treatment period. Participants then entered in a 16-week no-treatment GFU period.	Belimumab Monotherapy n=19 Participants Participants received 200 mg weekly subcutaneous injections of belimumab up to Week 52 and rituximab matching placebo infusions at Weeks 8 and 10 in the treatment period. Participants then entered in a 16-week no-treatment GFU period.	Rituximab Monotherapy n=16 Participants Participants received 1000 mg intravenous rituximab infusions at Weeks 8 and 10 and weekly subcutaneous injections of belimumab matching placebo up to Week 52 in the treatment period. Participants then entered in a 16-week no-treatment GFU period.
Change From Baseline in European League Against Rheumatism (EULAR) Sjogren's Syndrome Disease Activity Index (ESSDAI) Total Scores Over Time Week 52;n=8, 17, 19 ,16	-2.87 Scores on a scale Standard Error 1.294	-5.67 Scores on a scale Standard Error 0.890	-4.76 Scores on a scale Standard Error 0.850	-4.32 Scores on a scale Standard Error 0.919
Change From Baseline in European League Against Rheumatism (EULAR) Sjogren's Syndrome Disease Activity Index (ESSDAI) Total Scores Over Time Week 12; n=8, 17, 19 ,15	-2.00 Scores on a scale Standard Error 1.449	-4.85 Scores on a scale Standard Error 0.996	-3.87 Scores on a scale Standard Error 0.949	-4.22 Scores on a scale Standard Error 1.048
Change From Baseline in European League Against Rheumatism (EULAR) Sjogren's Syndrome Disease Activity Index (ESSDAI) Total Scores Over Time Week 24; n=8, 17, 19 ,16	-2.87 Scores on a scale Standard Error 1.324	-5.32 Scores on a scale Standard Error 0.911	-3.87 Scores on a scale Standard Error 0.869	-5.25 Scores on a scale Standard Error 0.940
Change From Baseline in European League Against Rheumatism (EULAR) Sjogren's Syndrome Disease Activity Index (ESSDAI) Total Scores Over Time Week 36; n=8, 17, 19 ,16	-3.12 Scores on a scale Standard Error 1.520	-4.09 Scores on a scale Standard Error 1.045	-4.23 Scores on a scale Standard Error 0.995	-4.94 Scores on a scale Standard Error 1.079
Change From Baseline in European League Against Rheumatism (EULAR) Sjogren's Syndrome Disease Activity Index (ESSDAI) Total Scores Over Time Week 68;n=8, 17, 19 ,16	-1.75 Scores on a scale Standard Error 1.400	-5.73 Scores on a scale Standard Error 0.962	-3.87 Scores on a scale Standard Error 0.918	-4.38 Scores on a scale Standard Error 0.994

SECONDARY outcome

Timeframe: Baseline (Screening [within 35 days prior to Day 0]), Week 12, Week 24, Week 36, Week 52 and Week 68

Population: Completer Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in category titles).

Participants were instructed to chew a piece of paraffin wax for a period of 5 minutes and saliva was collected. The volume of saliva (milliliter) was divided by the duration of the test (minutes) to calculate the stimulated salivary flow rate (milliliter per minute). Baseline value is the screening visit value (within 35 days prior to Day 0).

Outcome measures

Outcome measures
Measure	Placebo n=8 Participants Participants received belimumab matching placebo weekly subcutaneous injections up to Week 52 and rituximab matching placebo infusions at Weeks 8 and 10 in the treatment period. Participants then entered in a 16-week no-treatment General Follow-Up (GFU) period.	Belimumab + Rituximab Co-administration Therapy n=17 Participants Participants received belimumab 200 milligrams (mg) weekly subcutaneous injections for 24 weeks followed by belimumab matching placebo injections weekly up to Week 52; along with rituximab 1000 mg intravenous infusions at Weeks 8 and 10 in the treatment period. Participants then entered in a 16-week no-treatment GFU period.	Belimumab Monotherapy n=19 Participants Participants received 200 mg weekly subcutaneous injections of belimumab up to Week 52 and rituximab matching placebo infusions at Weeks 8 and 10 in the treatment period. Participants then entered in a 16-week no-treatment GFU period.	Rituximab Monotherapy n=16 Participants Participants received 1000 mg intravenous rituximab infusions at Weeks 8 and 10 and weekly subcutaneous injections of belimumab matching placebo up to Week 52 in the treatment period. Participants then entered in a 16-week no-treatment GFU period.
Stimulated Salivary Flow Rate Over Time Week 36; n=8, 17, 19 ,15	0.404 Milliliter per minute Standard Deviation 0.2497	1.039 Milliliter per minute Standard Deviation 1.1027	0.506 Milliliter per minute Standard Deviation 0.4261	0.689 Milliliter per minute Standard Deviation 0.5907
Stimulated Salivary Flow Rate Over Time Baseline (Screening); n=8, 17, 19 ,16	0.470 Milliliter per minute Standard Deviation 0.2470	0.714 Milliliter per minute Standard Deviation 0.6294	0.425 Milliliter per minute Standard Deviation 0.3292	0.618 Milliliter per minute Standard Deviation 0.6211
Stimulated Salivary Flow Rate Over Time Week 12; n=8, 17, 19 ,16	0.486 Milliliter per minute Standard Deviation 0.2045	0.754 Milliliter per minute Standard Deviation 0.8342	0.493 Milliliter per minute Standard Deviation 0.3733	0.581 Milliliter per minute Standard Deviation 0.5265
Stimulated Salivary Flow Rate Over Time Week 24; n=8, 17, 19 ,16	0.554 Milliliter per minute Standard Deviation 0.3054	0.784 Milliliter per minute Standard Deviation 0.7900	0.454 Milliliter per minute Standard Deviation 0.4105	0.724 Milliliter per minute Standard Deviation 0.8901
Stimulated Salivary Flow Rate Over Time Week 52; n=8, 17, 19 ,16	0.531 Milliliter per minute Standard Deviation 0.3782	0.999 Milliliter per minute Standard Deviation 1.1457	0.582 Milliliter per minute Standard Deviation 0.6084	0.693 Milliliter per minute Standard Deviation 0.7813
Stimulated Salivary Flow Rate Over Time Week 68; n=8, 17, 19 ,15	0.361 Milliliter per minute Standard Deviation 0.1628	0.879 Milliliter per minute Standard Deviation 0.8167	0.517 Milliliter per minute Standard Deviation 0.4499	0.733 Milliliter per minute Standard Deviation 0.7850

SECONDARY outcome

Timeframe: Baseline (Screening [within 35 days prior to Day 0]), Week 12, Week 24, Week 36, Week 52 and Week 68

Population: Completer Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in category titles).

Oral dryness was reported by participants on a numeric response scale, ranging from 0 (no dryness) to 10 (maximal dryness), higher score indicates worst imaginable dryness. Baseline value is the screening visit value (within 35 days prior to Day 0).

Outcome measures

Outcome measures
Measure	Placebo n=8 Participants Participants received belimumab matching placebo weekly subcutaneous injections up to Week 52 and rituximab matching placebo infusions at Weeks 8 and 10 in the treatment period. Participants then entered in a 16-week no-treatment General Follow-Up (GFU) period.	Belimumab + Rituximab Co-administration Therapy n=17 Participants Participants received belimumab 200 milligrams (mg) weekly subcutaneous injections for 24 weeks followed by belimumab matching placebo injections weekly up to Week 52; along with rituximab 1000 mg intravenous infusions at Weeks 8 and 10 in the treatment period. Participants then entered in a 16-week no-treatment GFU period.	Belimumab Monotherapy n=19 Participants Participants received 200 mg weekly subcutaneous injections of belimumab up to Week 52 and rituximab matching placebo infusions at Weeks 8 and 10 in the treatment period. Participants then entered in a 16-week no-treatment GFU period.	Rituximab Monotherapy n=16 Participants Participants received 1000 mg intravenous rituximab infusions at Weeks 8 and 10 and weekly subcutaneous injections of belimumab matching placebo up to Week 52 in the treatment period. Participants then entered in a 16-week no-treatment GFU period.
Oral Dryness Numeric Response Scale (NRS) Over Time Week 12; n=8, 17, 19, 16	6.1 Scores on a scale Standard Deviation 2.59	5.7 Scores on a scale Standard Deviation 1.96	6.9 Scores on a scale Standard Deviation 2.32	5.1 Scores on a scale Standard Deviation 2.77
Oral Dryness Numeric Response Scale (NRS) Over Time Week 36; n=8, 17, 19, 16	5.8 Scores on a scale Standard Deviation 2.76	5.9 Scores on a scale Standard Deviation 2.26	6.6 Scores on a scale Standard Deviation 2.19	6.2 Scores on a scale Standard Deviation 2.51
Oral Dryness Numeric Response Scale (NRS) Over Time Week 52; n=8, 17, 19, 16	5.6 Scores on a scale Standard Deviation 2.13	5.7 Scores on a scale Standard Deviation 1.92	7.0 Scores on a scale Standard Deviation 2.40	6.3 Scores on a scale Standard Deviation 2.32
Oral Dryness Numeric Response Scale (NRS) Over Time Baseline (Screening); n= 8, 17, 19, 16	7.6 Scores on a scale Standard Deviation 1.51	7.4 Scores on a scale Standard Deviation 1.46	7.2 Scores on a scale Standard Deviation 2.14	7.3 Scores on a scale Standard Deviation 1.91
Oral Dryness Numeric Response Scale (NRS) Over Time Week 24; n=8, 17, 19, 15	5.8 Scores on a scale Standard Deviation 2.38	5.3 Scores on a scale Standard Deviation 1.83	6.8 Scores on a scale Standard Deviation 2.51	5.6 Scores on a scale Standard Deviation 2.72
Oral Dryness Numeric Response Scale (NRS) Over Time Week 68; n=8, 17, 19, 16	6.6 Scores on a scale Standard Deviation 2.26	6.1 Scores on a scale Standard Deviation 2.63	6.9 Scores on a scale Standard Deviation 2.34	6.1 Scores on a scale Standard Deviation 2.62

SECONDARY outcome

Timeframe: At Week 24

Population: Completer Population. Only those participants with data available at the specified data points were analyzed.

Minor salivary gland biopsies were taken for histological analysis to quantify CD20 B Cells.

Outcome measures

Outcome measures
Measure	Placebo n=8 Participants Participants received belimumab matching placebo weekly subcutaneous injections up to Week 52 and rituximab matching placebo infusions at Weeks 8 and 10 in the treatment period. Participants then entered in a 16-week no-treatment General Follow-Up (GFU) period.	Belimumab + Rituximab Co-administration Therapy n=10 Participants Participants received belimumab 200 milligrams (mg) weekly subcutaneous injections for 24 weeks followed by belimumab matching placebo injections weekly up to Week 52; along with rituximab 1000 mg intravenous infusions at Weeks 8 and 10 in the treatment period. Participants then entered in a 16-week no-treatment GFU period.	Belimumab Monotherapy n=15 Participants Participants received 200 mg weekly subcutaneous injections of belimumab up to Week 52 and rituximab matching placebo infusions at Weeks 8 and 10 in the treatment period. Participants then entered in a 16-week no-treatment GFU period.	Rituximab Monotherapy n=12 Participants Participants received 1000 mg intravenous rituximab infusions at Weeks 8 and 10 and weekly subcutaneous injections of belimumab matching placebo up to Week 52 in the treatment period. Participants then entered in a 16-week no-treatment GFU period.
Absolute Values for B-cells (Cluster of Differentiation 20 [CD20]) Within Salivary Gland Biopsy at Week 24	380.21719 Cells per millimeter square Standard Deviation 569.908102	8.65550 Cells per millimeter square Standard Deviation 20.199794	396.86058 Cells per millimeter square Standard Deviation 781.245844	650.76069 Cells per millimeter square Standard Deviation 1311.360352

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Belimumab + Rituximab Co-administration Therapy

Serious events: 3 serious events

Other events: 24 other events

Deaths: 1 deaths

Belimumab Monotherapy

Serious events: 2 serious events

Other events: 23 other events

Deaths: 0 deaths

Rituximab Monotherapy

Serious events: 4 serious events

Other events: 17 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=13 participants at risk Participants received belimumab matching placebo weekly subcutaneous injections up to Week 52 and rituximab matching placebo infusions at Weeks 8 and 10 in the treatment period. Participants then entered in a 16-week no-treatment General Follow-Up (GFU) period.	Belimumab + Rituximab Co-administration Therapy n=24 participants at risk Participants received belimumab 200 milligrams (mg) weekly subcutaneous injections for 24 weeks followed by belimumab matching placebo injections weekly up to Week 52; along with rituximab 1000 mg intravenous infusions at Weeks 8 and 10 in the treatment period. Participants then entered in a 16-week no-treatment GFU period.	Belimumab Monotherapy n=24 participants at risk Participants received 200 mg weekly subcutaneous injections of belimumab up to Week 52 and rituximab matching placebo infusions at Weeks 8 and 10 in the treatment period. Participants then entered in a 16-week no-treatment GFU period.	Rituximab Monotherapy n=25 participants at risk Participants received 1000 mg intravenous rituximab infusions at Weeks 8 and 10 and weekly subcutaneous injections of belimumab matching placebo up to Week 52 in the treatment period. Participants then entered in a 16-week no-treatment GFU period.
Infections and infestations Bronchitis	0.00% 0/13 • Serious adverse events (SAEs) and non-SAEs were collected up to Week 68. Safety Population was used to assess SAEs and non-SAEs which comprised of all participants who received at least one dose of study treatment.	0.00% 0/24 • Serious adverse events (SAEs) and non-SAEs were collected up to Week 68. Safety Population was used to assess SAEs and non-SAEs which comprised of all participants who received at least one dose of study treatment.	0.00% 0/24 • Serious adverse events (SAEs) and non-SAEs were collected up to Week 68. Safety Population was used to assess SAEs and non-SAEs which comprised of all participants who received at least one dose of study treatment.	4.0% 1/25 • Number of events 1 • Serious adverse events (SAEs) and non-SAEs were collected up to Week 68. Safety Population was used to assess SAEs and non-SAEs which comprised of all participants who received at least one dose of study treatment.
Infections and infestations Enterocolitis infectious	0.00% 0/13 • Serious adverse events (SAEs) and non-SAEs were collected up to Week 68. Safety Population was used to assess SAEs and non-SAEs which comprised of all participants who received at least one dose of study treatment.	4.2% 1/24 • Number of events 1 • Serious adverse events (SAEs) and non-SAEs were collected up to Week 68. Safety Population was used to assess SAEs and non-SAEs which comprised of all participants who received at least one dose of study treatment.	0.00% 0/24 • Serious adverse events (SAEs) and non-SAEs were collected up to Week 68. Safety Population was used to assess SAEs and non-SAEs which comprised of all participants who received at least one dose of study treatment.	0.00% 0/25 • Serious adverse events (SAEs) and non-SAEs were collected up to Week 68. Safety Population was used to assess SAEs and non-SAEs which comprised of all participants who received at least one dose of study treatment.
Infections and infestations Ophthalmic herpes zoster	0.00% 0/13 • Serious adverse events (SAEs) and non-SAEs were collected up to Week 68. Safety Population was used to assess SAEs and non-SAEs which comprised of all participants who received at least one dose of study treatment.	0.00% 0/24 • Serious adverse events (SAEs) and non-SAEs were collected up to Week 68. Safety Population was used to assess SAEs and non-SAEs which comprised of all participants who received at least one dose of study treatment.	0.00% 0/24 • Serious adverse events (SAEs) and non-SAEs were collected up to Week 68. Safety Population was used to assess SAEs and non-SAEs which comprised of all participants who received at least one dose of study treatment.	4.0% 1/25 • Number of events 1 • Serious adverse events (SAEs) and non-SAEs were collected up to Week 68. Safety Population was used to assess SAEs and non-SAEs which comprised of all participants who received at least one dose of study treatment.
Infections and infestations Pneumonia	0.00% 0/13 • Serious adverse events (SAEs) and non-SAEs were collected up to Week 68. Safety Population was used to assess SAEs and non-SAEs which comprised of all participants who received at least one dose of study treatment.	0.00% 0/24 • Serious adverse events (SAEs) and non-SAEs were collected up to Week 68. Safety Population was used to assess SAEs and non-SAEs which comprised of all participants who received at least one dose of study treatment.	4.2% 1/24 • Number of events 1 • Serious adverse events (SAEs) and non-SAEs were collected up to Week 68. Safety Population was used to assess SAEs and non-SAEs which comprised of all participants who received at least one dose of study treatment.	0.00% 0/25 • Serious adverse events (SAEs) and non-SAEs were collected up to Week 68. Safety Population was used to assess SAEs and non-SAEs which comprised of all participants who received at least one dose of study treatment.
Infections and infestations Pyelonephritis	0.00% 0/13 • Serious adverse events (SAEs) and non-SAEs were collected up to Week 68. Safety Population was used to assess SAEs and non-SAEs which comprised of all participants who received at least one dose of study treatment.	4.2% 1/24 • Number of events 1 • Serious adverse events (SAEs) and non-SAEs were collected up to Week 68. Safety Population was used to assess SAEs and non-SAEs which comprised of all participants who received at least one dose of study treatment.	0.00% 0/24 • Serious adverse events (SAEs) and non-SAEs were collected up to Week 68. Safety Population was used to assess SAEs and non-SAEs which comprised of all participants who received at least one dose of study treatment.	0.00% 0/25 • Serious adverse events (SAEs) and non-SAEs were collected up to Week 68. Safety Population was used to assess SAEs and non-SAEs which comprised of all participants who received at least one dose of study treatment.
Cardiac disorders Atrial flutter	0.00% 0/13 • Serious adverse events (SAEs) and non-SAEs were collected up to Week 68. Safety Population was used to assess SAEs and non-SAEs which comprised of all participants who received at least one dose of study treatment.	4.2% 1/24 • Number of events 1 • Serious adverse events (SAEs) and non-SAEs were collected up to Week 68. Safety Population was used to assess SAEs and non-SAEs which comprised of all participants who received at least one dose of study treatment.	0.00% 0/24 • Serious adverse events (SAEs) and non-SAEs were collected up to Week 68. Safety Population was used to assess SAEs and non-SAEs which comprised of all participants who received at least one dose of study treatment.	0.00% 0/25 • Serious adverse events (SAEs) and non-SAEs were collected up to Week 68. Safety Population was used to assess SAEs and non-SAEs which comprised of all participants who received at least one dose of study treatment.
Cardiac disorders Cardiac failure acute	0.00% 0/13 • Serious adverse events (SAEs) and non-SAEs were collected up to Week 68. Safety Population was used to assess SAEs and non-SAEs which comprised of all participants who received at least one dose of study treatment.	0.00% 0/24 • Serious adverse events (SAEs) and non-SAEs were collected up to Week 68. Safety Population was used to assess SAEs and non-SAEs which comprised of all participants who received at least one dose of study treatment.	0.00% 0/24 • Serious adverse events (SAEs) and non-SAEs were collected up to Week 68. Safety Population was used to assess SAEs and non-SAEs which comprised of all participants who received at least one dose of study treatment.	4.0% 1/25 • Number of events 1 • Serious adverse events (SAEs) and non-SAEs were collected up to Week 68. Safety Population was used to assess SAEs and non-SAEs which comprised of all participants who received at least one dose of study treatment.
Blood and lymphatic system disorders Neutropenia	0.00% 0/13 • Serious adverse events (SAEs) and non-SAEs were collected up to Week 68. Safety Population was used to assess SAEs and non-SAEs which comprised of all participants who received at least one dose of study treatment.	0.00% 0/24 • Serious adverse events (SAEs) and non-SAEs were collected up to Week 68. Safety Population was used to assess SAEs and non-SAEs which comprised of all participants who received at least one dose of study treatment.	0.00% 0/24 • Serious adverse events (SAEs) and non-SAEs were collected up to Week 68. Safety Population was used to assess SAEs and non-SAEs which comprised of all participants who received at least one dose of study treatment.	4.0% 1/25 • Number of events 1 • Serious adverse events (SAEs) and non-SAEs were collected up to Week 68. Safety Population was used to assess SAEs and non-SAEs which comprised of all participants who received at least one dose of study treatment.
Injury, poisoning and procedural complications Tendon rupture	0.00% 0/13 • Serious adverse events (SAEs) and non-SAEs were collected up to Week 68. Safety Population was used to assess SAEs and non-SAEs which comprised of all participants who received at least one dose of study treatment.	0.00% 0/24 • Serious adverse events (SAEs) and non-SAEs were collected up to Week 68. Safety Population was used to assess SAEs and non-SAEs which comprised of all participants who received at least one dose of study treatment.	0.00% 0/24 • Serious adverse events (SAEs) and non-SAEs were collected up to Week 68. Safety Population was used to assess SAEs and non-SAEs which comprised of all participants who received at least one dose of study treatment.	4.0% 1/25 • Number of events 1 • Serious adverse events (SAEs) and non-SAEs were collected up to Week 68. Safety Population was used to assess SAEs and non-SAEs which comprised of all participants who received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Sjogren's syndrome	0.00% 0/13 • Serious adverse events (SAEs) and non-SAEs were collected up to Week 68. Safety Population was used to assess SAEs and non-SAEs which comprised of all participants who received at least one dose of study treatment.	0.00% 0/24 • Serious adverse events (SAEs) and non-SAEs were collected up to Week 68. Safety Population was used to assess SAEs and non-SAEs which comprised of all participants who received at least one dose of study treatment.	4.2% 1/24 • Number of events 1 • Serious adverse events (SAEs) and non-SAEs were collected up to Week 68. Safety Population was used to assess SAEs and non-SAEs which comprised of all participants who received at least one dose of study treatment.	0.00% 0/25 • Serious adverse events (SAEs) and non-SAEs were collected up to Week 68. Safety Population was used to assess SAEs and non-SAEs which comprised of all participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Aspiration	0.00% 0/13 • Serious adverse events (SAEs) and non-SAEs were collected up to Week 68. Safety Population was used to assess SAEs and non-SAEs which comprised of all participants who received at least one dose of study treatment.	4.2% 1/24 • Number of events 1 • Serious adverse events (SAEs) and non-SAEs were collected up to Week 68. Safety Population was used to assess SAEs and non-SAEs which comprised of all participants who received at least one dose of study treatment.	0.00% 0/24 • Serious adverse events (SAEs) and non-SAEs were collected up to Week 68. Safety Population was used to assess SAEs and non-SAEs which comprised of all participants who received at least one dose of study treatment.	0.00% 0/25 • Serious adverse events (SAEs) and non-SAEs were collected up to Week 68. Safety Population was used to assess SAEs and non-SAEs which comprised of all participants who received at least one dose of study treatment.
Skin and subcutaneous tissue disorders Rash	0.00% 0/13 • Serious adverse events (SAEs) and non-SAEs were collected up to Week 68. Safety Population was used to assess SAEs and non-SAEs which comprised of all participants who received at least one dose of study treatment.	0.00% 0/24 • Serious adverse events (SAEs) and non-SAEs were collected up to Week 68. Safety Population was used to assess SAEs and non-SAEs which comprised of all participants who received at least one dose of study treatment.	0.00% 0/24 • Serious adverse events (SAEs) and non-SAEs were collected up to Week 68. Safety Population was used to assess SAEs and non-SAEs which comprised of all participants who received at least one dose of study treatment.	4.0% 1/25 • Number of events 1 • Serious adverse events (SAEs) and non-SAEs were collected up to Week 68. Safety Population was used to assess SAEs and non-SAEs which comprised of all participants who received at least one dose of study treatment.
Vascular disorders Hypotension	0.00% 0/13 • Serious adverse events (SAEs) and non-SAEs were collected up to Week 68. Safety Population was used to assess SAEs and non-SAEs which comprised of all participants who received at least one dose of study treatment.	0.00% 0/24 • Serious adverse events (SAEs) and non-SAEs were collected up to Week 68. Safety Population was used to assess SAEs and non-SAEs which comprised of all participants who received at least one dose of study treatment.	0.00% 0/24 • Serious adverse events (SAEs) and non-SAEs were collected up to Week 68. Safety Population was used to assess SAEs and non-SAEs which comprised of all participants who received at least one dose of study treatment.	4.0% 1/25 • Number of events 1 • Serious adverse events (SAEs) and non-SAEs were collected up to Week 68. Safety Population was used to assess SAEs and non-SAEs which comprised of all participants who received at least one dose of study treatment.

Other adverse events

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Publication restrictions are in place

Restriction type: OTHER