NCT01345253

GSK1550188 A 52 Week Study of Belimumab Versus Placebo in the Treatment of Subjects With Systemic Lupus Erythematosus (SLE) Located in Northeast Asia

Completed Phase 3 Results posted Last updated 4 October 2019

What this trial tests

Phase 3 trial testing Belimumab in Systemic Lupus Erythematosus in 709 participants. Completed in 21 September 2018.

Timeline

23 May 2011

Primary endpoint
15 September 2015

21 September 2018

Quick facts

Lead sponsor	GlaxoSmithKline
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	709
Start date	23 May 2011
Primary completion	15 September 2015
Estimated completion	21 September 2018
Sites	47 locations across China, Japan, South Korea

Drugs / interventions tested

• Belimumab (BELIMUMAB) — full drug profile →
• Placebo

Conditions studied

• Systemic Lupus Erythematosus — all drugs for Systemic Lupus Erythematosus →

Sponsor

GlaxoSmithKline — full company profile →

Who can join

18 and older, any sex, with Systemic Lupus Erythematosus. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percent of Participants Achieving Systemic Lupus Erythematosus (SLE) Responder Index (SRI) Response Rate at Week 52 for Double-blind Phase. Primary · Week 52

SRI response is a composite index, defined as the percent of participants with \>=4 point reduction from Baseline in safety of estrogen in lupus national assessment (SELENA) systemic lupus erythematosus disease activity index (SLEDAI) score and no worsening (increase of \< 0.30 points from Baseline) in physicians global assessment (PGA) and no new British isles lupus assessment group (BILAG) A organ domain score or 2 new BILAG B organ domain scores compared with Baseline at the time of assessment (at Week 52 of the blinded period). A SELENA SLEDAI score of 0 would suggest no lupus activity; wh

Group	Value	95% CI
Placebo	40.1
Belimumab 10 mg/kg	53.8

Percent of Participants With >=4 Point Reduction From Baseline in SELENA SLEDAI Score at Week 52 for Double-blind Phase. Secondary · Baseline (Day 0) and Week 52

The SELENA SLEDAI score is a weighted index for assessing SLE disease activity in which signs and symptoms, laboratory tests and physician's assessment for each of 9 organ system were given a weighted score and summed if present at the time of the visit or in the preceding 10 days. A SELENA SLEDAI score of 0 would suggest no lupus activity; while a score of 105 is the maximum calculable if all items were scored as being present from active lupus. A decrease of 4 points or more equates to a clinically meaningful improvement. The Baseline value of a variable is defined as the value of the variab

Group	Value	95% CI
Placebo	42.2
Belimumab 10 mg/kg	55.7

Percent of Participants With SRI7 Response at Week 52 for Double-blind Phase. Secondary · Baseline (Day 0) and Week 52

SRI7 response is defined as the percent of participants with \>=7 point reduction from Baseline in SELENA SLEDAI score and no worsening (increase of \< 0.30 points from Baseline) in PGA and no new BILAG A organ domain score or 2 new BILAG B organ domain scores compared with Baseline at the time of assessment (at Week 52 of the blinded period). A SELENA SLEDAI score of 0 would suggest no lupus activity; while a score of 105 is the maximum calculable if all items were scored as being present from active lupus. PGA ranges from 0 (no activity) to 3 (severe activity). BILAG has no range. The higher

Group	Value	95% CI
Placebo	23.5
Belimumab 10 mg/kg	32.4

Number of Days of Daily Prednisone Dose <=7.5 mg/Day and/or Reduced by 50 Percent From Baseline Over 52 Weeks for Double-blind Phase. Secondary · Week 52

Number of days of daily prednisone dose \<=7.5 mg/day and/or reduced by 50 percent over time through each scheduled visit during the blinded period were compared between belimumab and placebo using Rank ANCOVA model which was used for comparing belimumab and placebo. The independent variables in the model included treatment group, Baseline prednisone dose level, country, Baseline SELENA SLEDAI score (\<=9 vs. \>=10) and complement levels (low C3 and/or C4 vs. no low C3 or C4). This analysis was perfomed on the participants who used prednisone \>7.5 mg/day at Baseline.

Group	Value	95% CI
Placebo	0.0	0.0 – 172.0
Belimumab 10 mg/kg	0.0	0.0 – 213.5

Time to First Severe SLE Flare Index (SFI) Flare Over 52 Weeks for Double-blind Phase. Secondary · 52 weeks

Time to first severe SLE flare is defined as the number of days from first treatment until the participant had an event (event date-treatement start date +1). If a participant had a severe SFI flare and received protocol restricted medication then the event date was the earliest of the first severe SFI flare date, and the treatment failure date. Analysis of severe SFI flare was performed on the modified SELENA SLEDAI SLE flare index in which the modification excluded severe flares that were triggered only by an increase in SELENA SLEDAI score to \>12. Analysis was from Cox proportional hazards

Group	Value	95% CI
Placebo	NA	NA – NA
Belimumab 10 mg/kg	NA	NA – NA

Percent of Participants Achieving SLE SRI Response Rate for Open-label (OL) Phase Secondary · Weeks 24 and 48 for Years 2, 3, 4, 5 and 6

SRI response is a composite index, defined as the percent of participants with \>=4 point reduction from Baseline in SELENA SLEDAI score and no worsening (increase of \< 0.30 points from Baseline) in PGA and no new BILAG A organ domain score or 2 new BILAG B organ domain scores compared with Baseline at time of assessment. Excludes participants with a SELENA SLEDAI score \<4 at baseline. Participants randomized to belimumab in double-blinded (DB) phase, Baseline is last available value before first belimumab dose received in DB phase. Participants randomized to placebo in DB phase, Baseline is

Week 24, Year 2, n=326

Group	Value	95% CI
Belimumab 10mg/kg (Open-label Phase)	66.0

Week 48, Year 2, n=299

Group	Value	95% CI
Belimumab 10mg/kg (Open-label Phase)	69.6

Week 24, Year 3, n=271

Group	Value	95% CI
Belimumab 10mg/kg (Open-label Phase)	72.3

Week 48, Year 3, n=247

Group	Value	95% CI
Belimumab 10mg/kg (Open-label Phase)	70.9

Week 24, Year 4, n=233

Group	Value	95% CI
Belimumab 10mg/kg (Open-label Phase)	71.7

Week 48, Year 4, n=194

Group	Value	95% CI
Belimumab 10mg/kg (Open-label Phase)	76.8

Week 24, Year 5, n= 156

Group	Value	95% CI
Belimumab 10mg/kg (Open-label Phase)	81.4

Week 48, Year 5, n= 82

Group	Value	95% CI
Belimumab 10mg/kg (Open-label Phase)	80.5

Adverse events — posted to ClinicalTrials.gov

Time frame: Serious adverse events (SAEs) and non-SAEs were collected from study treatment start and until 16 weeks after the last infusion. The data presented for belimumab open-label group represents safety events period starting from the first belimumab date and up to Year 6 Week 44.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo (Double-blind Phase)

Serious: 43/235 (18%)

Deaths: 1/235

Belimumab 10 mg/kg (Double-blind Phase)

Serious: 58/470 (12%)

Deaths: 0/470

Belimumab 10 mg/kg (Open-label Phase)

Serious: 96/424 (23%)

Deaths: 1/424

Serious adverse events (175 terms)

Reaction	System	Placebo (Double-blind Phase)	Belimumab 10 mg/kg (Double…	Belimumab 10 mg/kg (Open-l…
Lupus nephritis	Renal and urinary disorders	—	—	—
Herpes zoster	Infections and infestations	—	—	—
Osteonecrosis	Musculoskeletal and connective tissue disorders	—	—	—
Pneumonia	Infections and infestations	—	—	—
Pyrexia	General disorders	—	—	—
Appendicitis	Infections and infestations	—	—	—
Lung infection	Infections and infestations	—	—	—
Pyelonephritis acute	Infections and infestations	—	—	—
Salmonella sepsis	Infections and infestations	—	—	—
Proteinuria	Renal and urinary disorders	—	—	—
Renal failure	Renal and urinary disorders	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—
Uterine leiomyoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—
Necrosis ischaemic	Vascular disorders	—	—	—
SLE arthritis	Musculoskeletal and connective tissue disorders	—	—	—
Hepatic function abnormal	Hepatobiliary disorders	—	—	—
Nephrolithiasis	Renal and urinary disorders	—	—	—
Ureterolithiasis	Renal and urinary disorders	—	—	—
Fall	Injury, poisoning and procedural complications	—	—	—
Spinal compression fracture	Injury, poisoning and procedural complications	—	—	—
Loose body in joint	Musculoskeletal and connective tissue disorders	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—
Fibroadenoma of breast	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—
Granulocytopenia	Blood and lymphatic system disorders	—	—	—
Abortion spontaneous	Pregnancy, puerperium and perinatal conditions	—	—	—

Other adverse events (12 terms — click to expand)

Reaction	System	Placebo (Double-blind Phase)	Belimumab 10 mg/kg (Double…	Belimumab 10 mg/kg (Open-l…
Upper respiratory tract infection	Infections and infestations	—	—	—
Viral upper respiratory tract infection	Infections and infestations	—	—	—
Nasopharyngitis	Infections and infestations	—	—	—
Urinary tract infection	Infections and infestations	—	—	—
Upper respiratory tract infection bacterial	Infections and infestations	—	—	—
Pyrexia	General disorders	—	—	—
Herpes zoster	Infections and infestations	—	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—
Hypokalaemia	Metabolism and nutrition disorders	—	—	—
Headache	Nervous system disorders	—	—	—
Urinary tract infection bacterial	Infections and infestations	—	—	—

Most-reported serious reactions: Lupus nephritis, Herpes zoster, Osteonecrosis, Pneumonia, Pyrexia, Appendicitis, Lung infection, Pyelonephritis acute.

Data from ClinicalTrials.gov NCT01345253 adverse events section.

Sponsor's own description

The purpose of this study is to evaluate the efficacy and safety of belimumab in addition to standard therapy compared to placebo in subjects in Northeast Asia with systemic lupus erythematosus (SLE) over a 52 week period.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. The BAFF/APRIL system: emerging functions beyond B cell biology and autoimmunity.
   Vincent FB, Saulep-Easton D, Figgett WA, Fairfax KA, et al · · 2013 · cited 333× · PMID 23684423 · DOI 10.1016/j.cytogfr.2013.04.003
2. A pivotal phase III, randomised, placebo-controlled study of belimumab in patients with systemic lupus erythematosus located in China, Japan and South Korea.
   Zhang F, Bae SC, Bass D, Chu M, et al · · 2018 · cited 215× · PMID 29295825 · DOI 10.1136/annrheumdis-2017-211631
3. 10 Years of belimumab experience: What have we learnt?
   Levy RA, Gonzalez-Rivera T, Khamashta M, Fox NL, et al · · 2021 · cited 87× · PMID 34238087 · DOI 10.1177/09612033211028653
4. B-cell targeted therapeutics in clinical development.
   Blüml S, McKeever K, Ettinger R, Smolen J, et al · · 2013 · cited 74× · PMID 23566679 · DOI 10.1186/ar3906
5. Systemic lupus erythematosus biomarkers: the challenging quest.
   Arriens C, Wren JD, Munroe ME, Mohan C. · · 2017 · cited 52× · PMID 28013203 · DOI 10.1093/rheumatology/kew407
6. BAFF- and APRIL-targeted therapy in systemic autoimmune diseases.
   Nakayamada S, Tanaka Y. · · 2016 · cited 49× · PMID 29259679 · DOI 10.1186/s41232-016-0015-4
7. B cells in systemic lupus erythematosus: Targets of new therapies and surveillance tools.
   Parodis I, Gatto M, Sjöwall C. · · 2022 · cited 31× · PMID 36111105 · DOI 10.3389/fmed.2022.952304
8. Belimumab and antimalarials combined against renal flares in patients treated for extra-renal systemic lupus erythematosus: results from 4 phase III clinical trials.
   Gomez A, Jägerback S, Sjöwall C, Parodis I. · · 2024 · cited 28× · PMID 37228028 · DOI 10.1093/rheumatology/kead253