Trial Outcomes & Findings for A Study to Evaluate the Effect of Belimumab on Vaccine Responses in Subjects With Systemic Lupus Erythematosus (SLE) (NCT NCT01597492)

Last Updated: 2018-08-16

Results Overview

A positive immune response to at least one pneumococcal serotype is defined as a 2-fold or greater increase from pre-vaccination levels. For unquantifiable pre-vaccination antibody levels, a positive antibody response was considered as a post-vaccination level \>=0.6 micrograms (µg)/milliliter (mL). Post-vaccination pneumococcal titers were assessed on Day 28 (Week 4) prior to the first dose of belimumab in the early cohort and on Day 196 (Week 28) prior to the last belimumab dose in the late cohort. Evaluable participants for the early cohort included those who received the vaccination at Day 0 and had titers drawn at Week 4. For the late cohort, evaluable participants received at least 5 of the 7 doses of belimumab up through Week 24, received the vaccination at Week 24, and had titers drawn at Week 28.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

79 participants

Primary outcome timeframe

Four weeks after vaccination

Results posted on

2018-08-16

Participant Flow

Eligible participants with systemic lupus erythematosus (SLE) were randomized in 7:9 ratio to receive pneumonococcal vaccination either 4 weeks prior (early cohort) or 24 weeks after (late cohort) their first belimumab dose of 10 milligram (mg)/kilogram (kg) intravenously (IV).

A total of 79 participants were enrolled, of which 34 were randomised to the early cohort and 45 were randomized to the late cohort. All randomized participants received at least 1 dose of vaccine and/or belimumab and were included in the Intent-to-Treat (ITT) Population.

Participant milestones

Participant milestones
Measure	Belimumab Plus Early Vaccination Participants received pneumococcal vaccination on Day 0, 4 weeks prior to the first dose of belimumab. Open-label belimumab 10 mg/kg IV was dosed on Days 28, 42, 56, and every 28 days thereafter until Week 32 (a total of 9 doses) plus standard therapy for SLE.	Belimumab Plus Late Vaccination Participants received pneumococcal vaccination on Day 168 (Week 24). Open-label belimumab 10 mg/kg IV was dosed on Days 0, 14, 28, and every 28 days thereafter until Week 28 (a total of 9 doses) plus standard therapy for SLE.
Overall Study STARTED	34	45
Overall Study COMPLETED	28	41
Overall Study NOT COMPLETED	6	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Belimumab Plus Early Vaccination Participants received pneumococcal vaccination on Day 0, 4 weeks prior to the first dose of belimumab. Open-label belimumab 10 mg/kg IV was dosed on Days 28, 42, 56, and every 28 days thereafter until Week 32 (a total of 9 doses) plus standard therapy for SLE.	Belimumab Plus Late Vaccination Participants received pneumococcal vaccination on Day 168 (Week 24). Open-label belimumab 10 mg/kg IV was dosed on Days 0, 14, 28, and every 28 days thereafter until Week 28 (a total of 9 doses) plus standard therapy for SLE.
Overall Study Withdrawal by Subject	1	2
Overall Study Adverse Event	3	0
Overall Study Lost to Follow-up	0	2
Overall Study Other Reason	2	0

Baseline Characteristics

A Study to Evaluate the Effect of Belimumab on Vaccine Responses in Subjects With Systemic Lupus Erythematosus (SLE)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Belimumab Plus Early Vaccination n=34 Participants Participants received pneumococcal vaccination on Day 0, 4 weeks prior to the first dose of belimumab. Open-label belimumab 10 mg/kg IV was dosed on Days 28, 42, 56, and every 28 days thereafter until Week 32 (a total of 9 doses) plus standard therapy for SLE.	Belimumab Plus Late Vaccination n=45 Participants Participants received pneumococcal vaccination on Day 168 (Week 24). Open-label belimumab 10 mg/kg IV was dosed on Days 0, 14, 28, and every 28 days thereafter until Week 28 (a total of 9 doses) plus standard therapy for SLE.	Total n=79 Participants Total of all reporting groups
Age, Continuous	41.0 Years STANDARD_DEVIATION 12.57 • n=99 Participants	38.6 Years STANDARD_DEVIATION 12.31 • n=107 Participants	39.6 Years STANDARD_DEVIATION 12.40 • n=206 Participants
Sex: Female, Male Female	29 Participants n=99 Participants	43 Participants n=107 Participants	72 Participants n=206 Participants
Sex: Female, Male Male	5 Participants n=99 Participants	2 Participants n=107 Participants	7 Participants n=206 Participants
Race/Ethnicity, Customized White	25 Participants n=99 Participants	27 Participants n=107 Participants	52 Participants n=206 Participants
Race/Ethnicity, Customized Black or African American	8 Participants n=99 Participants	12 Participants n=107 Participants	20 Participants n=206 Participants
Race/Ethnicity, Customized Asian	1 Participants n=99 Participants	4 Participants n=107 Participants	5 Participants n=206 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	1 Participants n=107 Participants	1 Participants n=206 Participants
Race/Ethnicity, Customized Mixed Race	0 Participants n=99 Participants	1 Participants n=107 Participants	1 Participants n=206 Participants

PRIMARY outcome

Timeframe: Four weeks after vaccination

Population: As-treated Population: all participants who received at least one dose of belimumab. All analyses of vaccine titers were performed on the As-treated Population.

Outcome measures

Outcome measures
Measure	Belimumab Plus Early Vaccination n=33 Participants Participants received pneumococcal vaccination on Day 0, 4 weeks prior to the first dose of belimumab. Open-label belimumab 10 mg/kg IV was dosed on Days 28, 42, 56, and every 28 days thereafter until Week 32 (a total of 9 doses) plus standard therapy for SLE.	Belimumab Plus Late Vaccination n=41 Participants Participants received pneumococcal vaccination on Day 168 (Week 24). Open-label belimumab 10 mg/kg IV was dosed on Days 0, 14, 28, and every 28 days thereafter until Week 28 (a total of 9 doses) plus standard therapy for SLE.
Number of Participants With Positive Antibody Responses to at Least One of the 23 Pneumococcal Vaccine Serotypes 4 Weeks Post-vaccination	32 Participants	40 Participants

Adverse Events

Belimumab Plus Early Vaccination

Serious events: 4 serious events

Other events: 21 other events

Deaths: 0 deaths

Belimumab Plus Late Vaccination

Serious events: 3 serious events

Other events: 32 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

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

Measure	Belimumab Plus Early Vaccination n=34 participants at risk Belimumab plus Early Vaccination	Belimumab Plus Late Vaccination n=45 participants at risk Belimumab plus Late Vaccination
Cardiac disorders Any event	5.9% 2/34 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until follow-up (up to 8 weeks following administration of the last dose of belimumab). SAEs and non-serious AEs were reported for the ITT population, comprised of participants who were randomized to treatment, and received at least one dose of study medication. Treatment-emergent AEs were those that occurred on or after the first belimumab infusion, which was Week 4 for the early cohort and Week 0 for the late cohort.	2.2% 1/45 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until follow-up (up to 8 weeks following administration of the last dose of belimumab). SAEs and non-serious AEs were reported for the ITT population, comprised of participants who were randomized to treatment, and received at least one dose of study medication. Treatment-emergent AEs were those that occurred on or after the first belimumab infusion, which was Week 4 for the early cohort and Week 0 for the late cohort.
Cardiac disorders Angina pectoris	0.00% 0/34 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until follow-up (up to 8 weeks following administration of the last dose of belimumab). SAEs and non-serious AEs were reported for the ITT population, comprised of participants who were randomized to treatment, and received at least one dose of study medication. Treatment-emergent AEs were those that occurred on or after the first belimumab infusion, which was Week 4 for the early cohort and Week 0 for the late cohort.	2.2% 1/45 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until follow-up (up to 8 weeks following administration of the last dose of belimumab). SAEs and non-serious AEs were reported for the ITT population, comprised of participants who were randomized to treatment, and received at least one dose of study medication. Treatment-emergent AEs were those that occurred on or after the first belimumab infusion, which was Week 4 for the early cohort and Week 0 for the late cohort.
Cardiac disorders Cardiac failure congestive	2.9% 1/34 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until follow-up (up to 8 weeks following administration of the last dose of belimumab). SAEs and non-serious AEs were reported for the ITT population, comprised of participants who were randomized to treatment, and received at least one dose of study medication. Treatment-emergent AEs were those that occurred on or after the first belimumab infusion, which was Week 4 for the early cohort and Week 0 for the late cohort.	0.00% 0/45 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until follow-up (up to 8 weeks following administration of the last dose of belimumab). SAEs and non-serious AEs were reported for the ITT population, comprised of participants who were randomized to treatment, and received at least one dose of study medication. Treatment-emergent AEs were those that occurred on or after the first belimumab infusion, which was Week 4 for the early cohort and Week 0 for the late cohort.
Cardiac disorders Pericarditis lupus	2.9% 1/34 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until follow-up (up to 8 weeks following administration of the last dose of belimumab). SAEs and non-serious AEs were reported for the ITT population, comprised of participants who were randomized to treatment, and received at least one dose of study medication. Treatment-emergent AEs were those that occurred on or after the first belimumab infusion, which was Week 4 for the early cohort and Week 0 for the late cohort.	0.00% 0/45 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until follow-up (up to 8 weeks following administration of the last dose of belimumab). SAEs and non-serious AEs were reported for the ITT population, comprised of participants who were randomized to treatment, and received at least one dose of study medication. Treatment-emergent AEs were those that occurred on or after the first belimumab infusion, which was Week 4 for the early cohort and Week 0 for the late cohort.
Psychiatric disorders Any event	0.00% 0/34 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until follow-up (up to 8 weeks following administration of the last dose of belimumab). SAEs and non-serious AEs were reported for the ITT population, comprised of participants who were randomized to treatment, and received at least one dose of study medication. Treatment-emergent AEs were those that occurred on or after the first belimumab infusion, which was Week 4 for the early cohort and Week 0 for the late cohort.	4.4% 2/45 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until follow-up (up to 8 weeks following administration of the last dose of belimumab). SAEs and non-serious AEs were reported for the ITT population, comprised of participants who were randomized to treatment, and received at least one dose of study medication. Treatment-emergent AEs were those that occurred on or after the first belimumab infusion, which was Week 4 for the early cohort and Week 0 for the late cohort.
Psychiatric disorders Depression	0.00% 0/34 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until follow-up (up to 8 weeks following administration of the last dose of belimumab). SAEs and non-serious AEs were reported for the ITT population, comprised of participants who were randomized to treatment, and received at least one dose of study medication. Treatment-emergent AEs were those that occurred on or after the first belimumab infusion, which was Week 4 for the early cohort and Week 0 for the late cohort.	2.2% 1/45 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until follow-up (up to 8 weeks following administration of the last dose of belimumab). SAEs and non-serious AEs were reported for the ITT population, comprised of participants who were randomized to treatment, and received at least one dose of study medication. Treatment-emergent AEs were those that occurred on or after the first belimumab infusion, which was Week 4 for the early cohort and Week 0 for the late cohort.
Psychiatric disorders Suicidal ideation	0.00% 0/34 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until follow-up (up to 8 weeks following administration of the last dose of belimumab). SAEs and non-serious AEs were reported for the ITT population, comprised of participants who were randomized to treatment, and received at least one dose of study medication. Treatment-emergent AEs were those that occurred on or after the first belimumab infusion, which was Week 4 for the early cohort and Week 0 for the late cohort.	2.2% 1/45 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until follow-up (up to 8 weeks following administration of the last dose of belimumab). SAEs and non-serious AEs were reported for the ITT population, comprised of participants who were randomized to treatment, and received at least one dose of study medication. Treatment-emergent AEs were those that occurred on or after the first belimumab infusion, which was Week 4 for the early cohort and Week 0 for the late cohort.
Psychiatric disorders Suicide attempt	0.00% 0/34 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until follow-up (up to 8 weeks following administration of the last dose of belimumab). SAEs and non-serious AEs were reported for the ITT population, comprised of participants who were randomized to treatment, and received at least one dose of study medication. Treatment-emergent AEs were those that occurred on or after the first belimumab infusion, which was Week 4 for the early cohort and Week 0 for the late cohort.	2.2% 1/45 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until follow-up (up to 8 weeks following administration of the last dose of belimumab). SAEs and non-serious AEs were reported for the ITT population, comprised of participants who were randomized to treatment, and received at least one dose of study medication. Treatment-emergent AEs were those that occurred on or after the first belimumab infusion, which was Week 4 for the early cohort and Week 0 for the late cohort.
Renal and urinary disorders Any event	5.9% 2/34 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until follow-up (up to 8 weeks following administration of the last dose of belimumab). SAEs and non-serious AEs were reported for the ITT population, comprised of participants who were randomized to treatment, and received at least one dose of study medication. Treatment-emergent AEs were those that occurred on or after the first belimumab infusion, which was Week 4 for the early cohort and Week 0 for the late cohort.	0.00% 0/45 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until follow-up (up to 8 weeks following administration of the last dose of belimumab). SAEs and non-serious AEs were reported for the ITT population, comprised of participants who were randomized to treatment, and received at least one dose of study medication. Treatment-emergent AEs were those that occurred on or after the first belimumab infusion, which was Week 4 for the early cohort and Week 0 for the late cohort.
Renal and urinary disorders Chronic kidney disease	2.9% 1/34 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until follow-up (up to 8 weeks following administration of the last dose of belimumab). SAEs and non-serious AEs were reported for the ITT population, comprised of participants who were randomized to treatment, and received at least one dose of study medication. Treatment-emergent AEs were those that occurred on or after the first belimumab infusion, which was Week 4 for the early cohort and Week 0 for the late cohort.	0.00% 0/45 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until follow-up (up to 8 weeks following administration of the last dose of belimumab). SAEs and non-serious AEs were reported for the ITT population, comprised of participants who were randomized to treatment, and received at least one dose of study medication. Treatment-emergent AEs were those that occurred on or after the first belimumab infusion, which was Week 4 for the early cohort and Week 0 for the late cohort.
Renal and urinary disorders Glomerulonephritis proliferative	2.9% 1/34 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until follow-up (up to 8 weeks following administration of the last dose of belimumab). SAEs and non-serious AEs were reported for the ITT population, comprised of participants who were randomized to treatment, and received at least one dose of study medication. Treatment-emergent AEs were those that occurred on or after the first belimumab infusion, which was Week 4 for the early cohort and Week 0 for the late cohort.	0.00% 0/45 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until follow-up (up to 8 weeks following administration of the last dose of belimumab). SAEs and non-serious AEs were reported for the ITT population, comprised of participants who were randomized to treatment, and received at least one dose of study medication. Treatment-emergent AEs were those that occurred on or after the first belimumab infusion, which was Week 4 for the early cohort and Week 0 for the late cohort.
Investigations Any event	2.9% 1/34 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until follow-up (up to 8 weeks following administration of the last dose of belimumab). SAEs and non-serious AEs were reported for the ITT population, comprised of participants who were randomized to treatment, and received at least one dose of study medication. Treatment-emergent AEs were those that occurred on or after the first belimumab infusion, which was Week 4 for the early cohort and Week 0 for the late cohort.	0.00% 0/45 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until follow-up (up to 8 weeks following administration of the last dose of belimumab). SAEs and non-serious AEs were reported for the ITT population, comprised of participants who were randomized to treatment, and received at least one dose of study medication. Treatment-emergent AEs were those that occurred on or after the first belimumab infusion, which was Week 4 for the early cohort and Week 0 for the late cohort.
Investigations Transaminases increased	2.9% 1/34 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until follow-up (up to 8 weeks following administration of the last dose of belimumab). SAEs and non-serious AEs were reported for the ITT population, comprised of participants who were randomized to treatment, and received at least one dose of study medication. Treatment-emergent AEs were those that occurred on or after the first belimumab infusion, which was Week 4 for the early cohort and Week 0 for the late cohort.	0.00% 0/45 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until follow-up (up to 8 weeks following administration of the last dose of belimumab). SAEs and non-serious AEs were reported for the ITT population, comprised of participants who were randomized to treatment, and received at least one dose of study medication. Treatment-emergent AEs were those that occurred on or after the first belimumab infusion, which was Week 4 for the early cohort and Week 0 for the late cohort.
Metabolism and nutrition disorders Any event	2.9% 1/34 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until follow-up (up to 8 weeks following administration of the last dose of belimumab). SAEs and non-serious AEs were reported for the ITT population, comprised of participants who were randomized to treatment, and received at least one dose of study medication. Treatment-emergent AEs were those that occurred on or after the first belimumab infusion, which was Week 4 for the early cohort and Week 0 for the late cohort.	0.00% 0/45 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until follow-up (up to 8 weeks following administration of the last dose of belimumab). SAEs and non-serious AEs were reported for the ITT population, comprised of participants who were randomized to treatment, and received at least one dose of study medication. Treatment-emergent AEs were those that occurred on or after the first belimumab infusion, which was Week 4 for the early cohort and Week 0 for the late cohort.
Metabolism and nutrition disorders Hyperkalaemia	2.9% 1/34 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until follow-up (up to 8 weeks following administration of the last dose of belimumab). SAEs and non-serious AEs were reported for the ITT population, comprised of participants who were randomized to treatment, and received at least one dose of study medication. Treatment-emergent AEs were those that occurred on or after the first belimumab infusion, which was Week 4 for the early cohort and Week 0 for the late cohort.	0.00% 0/45 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until follow-up (up to 8 weeks following administration of the last dose of belimumab). SAEs and non-serious AEs were reported for the ITT population, comprised of participants who were randomized to treatment, and received at least one dose of study medication. Treatment-emergent AEs were those that occurred on or after the first belimumab infusion, which was Week 4 for the early cohort and Week 0 for the late cohort.
Nervous system disorders Any event	2.9% 1/34 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until follow-up (up to 8 weeks following administration of the last dose of belimumab). SAEs and non-serious AEs were reported for the ITT population, comprised of participants who were randomized to treatment, and received at least one dose of study medication. Treatment-emergent AEs were those that occurred on or after the first belimumab infusion, which was Week 4 for the early cohort and Week 0 for the late cohort.	0.00% 0/45 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until follow-up (up to 8 weeks following administration of the last dose of belimumab). SAEs and non-serious AEs were reported for the ITT population, comprised of participants who were randomized to treatment, and received at least one dose of study medication. Treatment-emergent AEs were those that occurred on or after the first belimumab infusion, which was Week 4 for the early cohort and Week 0 for the late cohort.
Nervous system disorders Subarachnoid haemorrhage	2.9% 1/34 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until follow-up (up to 8 weeks following administration of the last dose of belimumab). SAEs and non-serious AEs were reported for the ITT population, comprised of participants who were randomized to treatment, and received at least one dose of study medication. Treatment-emergent AEs were those that occurred on or after the first belimumab infusion, which was Week 4 for the early cohort and Week 0 for the late cohort.	0.00% 0/45 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until follow-up (up to 8 weeks following administration of the last dose of belimumab). SAEs and non-serious AEs were reported for the ITT population, comprised of participants who were randomized to treatment, and received at least one dose of study medication. Treatment-emergent AEs were those that occurred on or after the first belimumab infusion, which was Week 4 for the early cohort and Week 0 for the late cohort.