Trial Outcomes & Findings for Belimumab Assessment of Safety in SLE (NCT NCT01705977)

Last Updated: 2024-07-15

Results Overview

Number of participants who died during on-treatment period (Week 52) is reported. The on-treatment period was defined as first dose to last dose + 28 days (or death). The As-Treated Population was defined as all participants who were randomized and received at least one dose of study agent,grouped according to the actual treatment administered for the majority (greater than \[\>\]50 percent \[%\]) of the time. The on-treatment period was the primary analysis period for safety analyses.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

4019 participants

Primary outcome timeframe

Up to Week 52 (On-treatment period)

Results posted on

2024-07-15

Participant Flow

This was a global, multi-center, randomized, placebo-controlled double blind study that evaluated adverse events of special interest in adult participants with active, autoantibody-positive systemic lupus erythematosus (SLE) when treated with belimumab plus standard therapy versus participants who received placebo plus standard therapy for 1 year, followed by a Year 2-5 post-treatment follow-up period.

A total of 4019 participants were randomized in this study. 4003 participants who received at least one dose of study treatment contributed to the Intent-to-Treat (ITT) Population.

Participant milestones

Participant milestones
Measure	Placebo Participants received placebo via the intravenous route on Days 0, 14, 28 and every 28 days through Week 48 with a final visit conducted at Week 52. Participants continued to receive standard SLE treatment and were followed up until end of study (up to 5 years).	Belimumab 10 mg/kg Participants received belimumab 10 milligrams per kilogram (mg/kg) on Days 0, 14, 28 and every 28 days through Week 48 with a final visit conducted at Week 52. Participants continued to receive standard SLE treatment and were followed up until end of study (up to 5 years).
Treatment Period (Year 1) STARTED	2009	2010
Treatment Period (Year 1) Intent-to-Treat Population	2002	2001
Treatment Period (Year 1) COMPLETED	1729	1741
Treatment Period (Year 1) NOT COMPLETED	280	269
Follow-up Period (Years 2 to 5) STARTED	1670	1695
Follow-up Period (Years 2 to 5) COMPLETED	1474	1514
Follow-up Period (Years 2 to 5) NOT COMPLETED	196	181

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received placebo via the intravenous route on Days 0, 14, 28 and every 28 days through Week 48 with a final visit conducted at Week 52. Participants continued to receive standard SLE treatment and were followed up until end of study (up to 5 years).	Belimumab 10 mg/kg Participants received belimumab 10 milligrams per kilogram (mg/kg) on Days 0, 14, 28 and every 28 days through Week 48 with a final visit conducted at Week 52. Participants continued to receive standard SLE treatment and were followed up until end of study (up to 5 years).
Treatment Period (Year 1) Withdrawal by Subject	128	128
Treatment Period (Year 1) Adverse Event	57	49
Treatment Period (Year 1) Protocol Violation	2	4
Treatment Period (Year 1) Site closure	3	2
Treatment Period (Year 1) Lost to Follow-up	33	37
Treatment Period (Year 1) Physician Decision	48	38
Treatment Period (Year 1) Missing study conclusion form	2	2
Treatment Period (Year 1) Randomized but not treated	7	9
Follow-up Period (Years 2 to 5) Death	58	38
Follow-up Period (Years 2 to 5) Lost to Follow-up	75	89
Follow-up Period (Years 2 to 5) Withdrawal by Subject	44	36
Follow-up Period (Years 2 to 5) Missing	19	18

Baseline Characteristics

Belimumab Assessment of Safety in SLE

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=2002 Participants Participants received placebo via the intravenous route on Days 0, 14, 28 and every 28 days through Week 48 with a final visit conducted at Week 52. Participants continued to receive standard SLE treatment and were followed up until end of study (up to 5 years).	Belimumab 10 mg/kg n=2001 Participants Participants received belimumab 10 milligrams per kilogram (mg/kg) on Days 0, 14, 28 and every 28 days through Week 48 with a final visit conducted at Week 52. Participants continued to receive standard SLE treatment and were followed up until end of study (up to 5 years).	Total n=4003 Participants Total of all reporting groups
Age, Continuous	40.8 Years STANDARD_DEVIATION 12.74 • n=5 Participants	40.4 Years STANDARD_DEVIATION 12.75 • n=7 Participants	40.6 Years STANDARD_DEVIATION 12.74 • n=5 Participants
Sex: Female, Male Female	1853 Participants n=5 Participants	1848 Participants n=7 Participants	3701 Participants n=5 Participants
Sex: Female, Male Male	149 Participants n=5 Participants	153 Participants n=7 Participants	302 Participants n=5 Participants
Race/Ethnicity, Customized White/Caucasian-European Heritage	1070 Participants n=5 Participants	1080 Participants n=7 Participants	2150 Participants n=5 Participants
Race/Ethnicity, Customized White/Caucasian-Arabic/North African Heritage	19 Participants n=5 Participants	16 Participants n=7 Participants	35 Participants n=5 Participants
Race/Ethnicity, Customized Mixed White Race	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Asian-East Asian Heritage	310 Participants n=5 Participants	307 Participants n=7 Participants	617 Participants n=5 Participants
Race/Ethnicity, Customized Asian-South East Asian Heritage	172 Participants n=5 Participants	168 Participants n=7 Participants	340 Participants n=5 Participants
Race/Ethnicity, Customized Asian-Central/South Asian Heritage	8 Participants n=5 Participants	6 Participants n=7 Participants	14 Participants n=5 Participants
Race/Ethnicity, Customized Asian-Japanese Heritage	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized Mixed Asian Race	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized African American/African Heritage	155 Participants n=5 Participants	175 Participants n=7 Participants	330 Participants n=5 Participants
Race/Ethnicity, Customized Alaskan Native or American Indian	257 Participants n=5 Participants	228 Participants n=7 Participants	485 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	2 Participants n=5 Participants	5 Participants n=7 Participants	7 Participants n=5 Participants
Race/Ethnicity, Customized Missing	6 Participants n=5 Participants	14 Participants n=7 Participants	20 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to Week 52 (On-treatment period)

Population: As-Treated Population. One participant in placebo group who received belimumab \>50% of the time was reported in the belimumab group.

Outcome measures

Outcome measures
Measure	Placebo n=2001 Participants Participants received placebo via the intravenous route on Days 0, 14, 28 and every 28 days through Week 48 with a final visit conducted at Week 52. Participants continued to receive standard SLE treatment and were followed up until end of study (up to 5 years).	Belimumab 10 mg/kg n=2002 Participants Participants received belimumab 10 milligrams per kilogram (mg/kg) on Days 0, 14, 28 and every 28 days through Week 48 with a final visit conducted at Week 52. Participants continued to receive standard SLE treatment and were followed up until end of study (up to 5 years).
Number of Deaths - On Treatment Period (Week 52)	8 Participants	10 Participants

PRIMARY outcome

Timeframe: Up to Week 52 (On-treatment period)

Population: As-Treated Population. One participant in placebo group who received belimumab \>50% of the time was reported in the belimumab group. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

A summary of protocol defined AESIs including serious infections, opportunistic infections and other infections of interest (serious and non-serious), non-melanoma skin cancer (NMSC), malignancies (excluding NMSC), psychiatric events suggesting serious mood disorders and anxiety (serious depression), suicidality (using Columbia-Suicide Severity Rating Scale \[C-SSRS\]) and serious infusion and hypersensitivity reactions (SIHR) is reported. The on-treatment period (Week 52) was defined as first dose to last dose + 28 days (or death). The on-treatment period was the primary analysis period for safety analyses.

Outcome measures

Outcome measures
Measure	Placebo n=2001 Participants Participants received placebo via the intravenous route on Days 0, 14, 28 and every 28 days through Week 48 with a final visit conducted at Week 52. Participants continued to receive standard SLE treatment and were followed up until end of study (up to 5 years).	Belimumab 10 mg/kg n=2002 Participants Participants received belimumab 10 milligrams per kilogram (mg/kg) on Days 0, 14, 28 and every 28 days through Week 48 with a final visit conducted at Week 52. Participants continued to receive standard SLE treatment and were followed up until end of study (up to 5 years).
Number of Participants Who Reported Protocol Defined Adverse Events of Special Interest (AESI): On-treatment Period (Week 52) Malignancies (Excluding NMSC), n=2001, 2002	5 Participants	5 Participants
Number of Participants Who Reported Protocol Defined Adverse Events of Special Interest (AESI): On-treatment Period (Week 52) Serious Infections, n=2001, 2002	82 Participants	75 Participants
Number of Participants Who Reported Protocol Defined Adverse Events of Special Interest (AESI): On-treatment Period (Week 52) Opportunistic Infections and Other Infections of Interest, n=2001, 2002	50 Participants	36 Participants
Number of Participants Who Reported Protocol Defined Adverse Events of Special Interest (AESI): On-treatment Period (Week 52) NMSC, n=2001, 2002	3 Participants	4 Participants
Number of Participants Who Reported Protocol Defined Adverse Events of Special Interest (AESI): On-treatment Period (Week 52) Psychiatric Events Suggesting Serious Mood Disorders and Anxiety (Serious depression), n=2001, 2002	1 Participants	7 Participants
Number of Participants Who Reported Protocol Defined Adverse Events of Special Interest (AESI): On-treatment Period (Week 52) Suicidality (C-SSRS), n=1986, 1972	23 Participants	28 Participants
Number of Participants Who Reported Protocol Defined Adverse Events of Special Interest (AESI): On-treatment Period (Week 52) SIHR, n=2001, 2002	2 Participants	8 Participants

PRIMARY outcome

Timeframe: Up to Week 52 (On-treatment period)

Population: As-Treated Population. One participant in placebo group who received belimumab \>50% of the time was reported in the belimumab group.

An SAE is defined as any untoward medical occurrence that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect, associated with liver injury and impaired liver function or any other situations as per medical or scientific judgement. The on-treatment period (Week 52) was defined as first dose to last dose + 28 days (or death) and was the primary analysis period for safety analyses.

Outcome measures

Outcome measures
Measure	Placebo n=2001 Participants Participants received placebo via the intravenous route on Days 0, 14, 28 and every 28 days through Week 48 with a final visit conducted at Week 52. Participants continued to receive standard SLE treatment and were followed up until end of study (up to 5 years).	Belimumab 10 mg/kg n=2002 Participants Participants received belimumab 10 milligrams per kilogram (mg/kg) on Days 0, 14, 28 and every 28 days through Week 48 with a final visit conducted at Week 52. Participants continued to receive standard SLE treatment and were followed up until end of study (up to 5 years).
Number of Participants With Serious Adverse Events (SAEs) Reported During On-treatment Period (Week 52)	222 Participants	220 Participants

SECONDARY outcome

Timeframe: Up to Week 52 (On-study period)

Population: As-Treated Population. One participant in placebo group who received belimumab \>50% of the time was reported in the belimumab group.

Number of participants who died during on-study period (Week 52) is reported. The on-study period (which includes on and off treatment data) was defined as first dose to the end of the Week 52 study follow-up (or death). The on-study period was a supportive analysis period for safety analysis.

Outcome measures

Outcome measures
Measure	Placebo n=2001 Participants Participants received placebo via the intravenous route on Days 0, 14, 28 and every 28 days through Week 48 with a final visit conducted at Week 52. Participants continued to receive standard SLE treatment and were followed up until end of study (up to 5 years).	Belimumab 10 mg/kg n=2002 Participants Participants received belimumab 10 milligrams per kilogram (mg/kg) on Days 0, 14, 28 and every 28 days through Week 48 with a final visit conducted at Week 52. Participants continued to receive standard SLE treatment and were followed up until end of study (up to 5 years).
Number of Deaths Reported - On-study Period (Week 52)	22 Participants	13 Participants

SECONDARY outcome

Timeframe: Up to Week 52 (On-study period)

A summary of protocol defined AESIs including serious infections, opportunistic infections and other infections of interest (serious and non-serious), NMSC, malignancies (excluding NMSC), psychiatric events suggesting serious mood disorders and anxiety (serious depression), suicidality (using C-SSRS) and SIHR is reported. The on-study period (Week 52) (which includes on and off treatment data) was defined as first dose to the end of the Week 52 study follow-up (or death). The on-study period was a supportive analysis period for safety analysis.

Outcome measures

Outcome measures
Measure	Placebo n=2001 Participants Participants received placebo via the intravenous route on Days 0, 14, 28 and every 28 days through Week 48 with a final visit conducted at Week 52. Participants continued to receive standard SLE treatment and were followed up until end of study (up to 5 years).	Belimumab 10 mg/kg n=2002 Participants Participants received belimumab 10 milligrams per kilogram (mg/kg) on Days 0, 14, 28 and every 28 days through Week 48 with a final visit conducted at Week 52. Participants continued to receive standard SLE treatment and were followed up until end of study (up to 5 years).
Number of Participants Who Reported Protocol Defined AESI: On-study Period (Week 52) Serious Infections, n=2001, 2002	95 Participants	80 Participants
Number of Participants Who Reported Protocol Defined AESI: On-study Period (Week 52) Opportunistic Infections and Other Infections of Interest, n=2001, 2002	59 Participants	39 Participants
Number of Participants Who Reported Protocol Defined AESI: On-study Period (Week 52) Malignancies (Excluding NMC), n=2001, 2002	7 Participants	5 Participants
Number of Participants Who Reported Protocol Defined AESI: On-study Period (Week 52) NMSC, n=2001, 2002	3 Participants	4 Participants
Number of Participants Who Reported Protocol Defined AESI: On-study Period (Week 52) Psychiatric Events Suggesting Serious Mood Disorders and Anxiety (Serious depression), n=2001, 2002	1 Participants	7 Participants
Number of Participants Who Reported Protocol Defined AESI: On-study Period (Week 52) Suicidality (C-SSRS), n=1988, 1974	25 Participants	31 Participants
Number of Participants Who Reported Protocol Defined AESI: On-study Period (Week 52) SIHR, n=2001, 2002	2 Participants	8 Participants

SECONDARY outcome

Timeframe: Up to Week 52 (On-study period)

Population: As-Treated Population. One participant in placebo group who received belimumab \>50% of the time was reported in the belimumab group.

A SAE is defined as any untoward medical occurrence that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect, associated with liver injury and impaired liver function or any other situations as per medical or scientific judgement. The on-study period (Week 52) (which includes on and off treatment data) was defined as first dose to the end of the Week 52 study follow-up (or death) and was a supportive analysis period for safety analyses.

Outcome measures

Outcome measures
Measure	Placebo n=2001 Participants Participants received placebo via the intravenous route on Days 0, 14, 28 and every 28 days through Week 48 with a final visit conducted at Week 52. Participants continued to receive standard SLE treatment and were followed up until end of study (up to 5 years).	Belimumab 10 mg/kg n=2002 Participants Participants received belimumab 10 milligrams per kilogram (mg/kg) on Days 0, 14, 28 and every 28 days through Week 48 with a final visit conducted at Week 52. Participants continued to receive standard SLE treatment and were followed up until end of study (up to 5 years).
Number of Participants With SAEs Reported During On-study Period (Week 52)	241 Participants	233 Participants

SECONDARY outcome

Timeframe: Week 40 to Week 52

Population: ITT Population. Only those participants with Baseline prednisone\>7.5 mg/day were analyzed. The ITT population is defined as all participants who were randomized and received at least one dose of study agent and the analysis was performed per the treatment that a participant was randomized to receive, regardless of the actual treatment received.

The average daily prednisone dose during Weeks 40 to 52 is the sum of all prednisone doses to treat SLE from the day following the Week 40 visit date up to but not including the Week 52 study completion date divided by the number of days between Week 40 visit date and study completion date (study completion date - Week 40 visit date). Percentage of participants whose average prednisone dose has been reduced by \>=25% from Baseline to \<=7.5 mg/day during Weeks 40 through 52 in participants with average prednisone use greater than 7.5 mg/day at Baseline was compared between belimumab and placebo using a logistic regression model including treatment group, Baseline prednisone dose, screening safety of estrogen in lupus national assessment (SELENA) systemic lupus erythematosus disease activity index (SLEDAI) score (\<=9 versus \>=10) and region. Baseline is defined as the last available value measured prior to dosing on or before the date of first dose (Day 1).

Outcome measures

Outcome measures
Measure	Placebo n=990 Participants Participants received placebo via the intravenous route on Days 0, 14, 28 and every 28 days through Week 48 with a final visit conducted at Week 52. Participants continued to receive standard SLE treatment and were followed up until end of study (up to 5 years).	Belimumab 10 mg/kg n=986 Participants Participants received belimumab 10 milligrams per kilogram (mg/kg) on Days 0, 14, 28 and every 28 days through Week 48 with a final visit conducted at Week 52. Participants continued to receive standard SLE treatment and were followed up until end of study (up to 5 years).
Percentage of Participants Whose Average Prednisone (or Equivalent) Dose to Treat SLE Has Been Reduced by >=25% From Baseline to <=7.5 mg/Day During Weeks 40 Through 52	16.2 Percentage of Participants	19.9 Percentage of Participants

SECONDARY outcome

Timeframe: From 2 years to 5 years

Population: As-Treated Any Year 2-5 Follow-up Population consisted of all participants in the As-Treated population who completed at least one post-treatment follow-up visit for Year 2 to 5.

Number of participants with all-cause mortality during years 2 to 5 has been presented.

Outcome measures

Outcome measures
Measure	Placebo n=1670 Participants Participants received placebo via the intravenous route on Days 0, 14, 28 and every 28 days through Week 48 with a final visit conducted at Week 52. Participants continued to receive standard SLE treatment and were followed up until end of study (up to 5 years).	Belimumab 10 mg/kg n=1695 Participants Participants received belimumab 10 milligrams per kilogram (mg/kg) on Days 0, 14, 28 and every 28 days through Week 48 with a final visit conducted at Week 52. Participants continued to receive standard SLE treatment and were followed up until end of study (up to 5 years).
Number of Participants With All-cause Mortality During Years 2 to 5	58 Participants	38 Participants

SECONDARY outcome

Timeframe: From 2 years to 5 years

Population: As-Treated Any Year 2-5 Follow-up Population

Number of participants with new primary malignancies during years 2 to 5 has been presented.

Outcome measures

Outcome measures
Measure	Placebo n=1670 Participants Participants received placebo via the intravenous route on Days 0, 14, 28 and every 28 days through Week 48 with a final visit conducted at Week 52. Participants continued to receive standard SLE treatment and were followed up until end of study (up to 5 years).	Belimumab 10 mg/kg n=1695 Participants Participants received belimumab 10 milligrams per kilogram (mg/kg) on Days 0, 14, 28 and every 28 days through Week 48 with a final visit conducted at Week 52. Participants continued to receive standard SLE treatment and were followed up until end of study (up to 5 years).
Number of Participants With New Primary Malignancies During Years 2 to 5	22 Participants	24 Participants

Adverse Events

Placebo

Serious events: 241 serious events

Other events: 31 other events

Deaths: 80 deaths

Belimumab 10 mg/kg

Serious events: 233 serious events

Other events: 17 other events

Deaths: 51 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo n=2001 participants at risk Participants received placebo via the intravenous route on Days 0, 14, 28 and every 28 days through Week 48 with a final visit conducted at Week 52. Participants continued to receive standard SLE treatment and were followed up until end of study (up to 5 years).	Belimumab 10 mg/kg n=2002 participants at risk Participants received belimumab 10 milligrams per kilogram (mg/kg) on Days 0, 14, 28 and every 28 days through Week 48 with a final visit conducted at Week 52. Participants continued to receive standard SLE treatment and were followed up until end of study (up to 5 years).
Infections and infestations Herpes zoster	1.5% 31/2001 • Number of events 33 • AESIs and all SAEs were collected up to Week 52 (On-study period), all-cause mortality was collected up to end of study (up to 5 years) All-cause mortality, AESIs and SAEs are summarized for the As-Treated Population. Only AESIs and SAEs were collected up to Week 52, but not all AEs. All-cause mortality was collected up to end of study (up to 5 years). One participant in placebo group who received belimumab \>50% of the time was reported in the belimumab group	0.85% 17/2002 • Number of events 17 • AESIs and all SAEs were collected up to Week 52 (On-study period), all-cause mortality was collected up to end of study (up to 5 years) All-cause mortality, AESIs and SAEs are summarized for the As-Treated Population. Only AESIs and SAEs were collected up to Week 52, but not all AEs. All-cause mortality was collected up to end of study (up to 5 years). One participant in placebo group who received belimumab \>50% of the time was reported in the belimumab group

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.
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