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

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ClinicalTrials.gov Identifier: NCT01345253

Recruitment Status : Completed

First Posted : May 2, 2011

Results First Posted : December 2, 2016

Last Update Posted : October 4, 2019

View this study on Beta.ClinicalTrials.gov

Sponsor:

Collaborator:

Human Genome Sciences Inc.

Information provided by (Responsible Party):

GlaxoSmithKline

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Systemic Lupus Erythematosus	Drug: Belimumab Drug: Placebo	Phase 3

Detailed Description:

The purpose of this study is to demonstrate the efficacy and safety of belimumab 10mg/kg administered intravenously (IV) every 4 weeks compared to placebo, in patients with SLE when added to standard of care therapy, as measured by the SLE Responder Index (SRI) at 52 weeks, defined by a composite endpoint using SELENA SLEDAI score, Physician's Global Assessment (PGA) and BILAG A and B organ domain scores.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	709 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	GSK1550188 A 52 Week Study of Belimumab Versus Placebo in the Treatment of Subjects With Systemic Lupus Erythematosus (SLE) Located in Northeast Asia
Actual Study Start Date :	May 23, 2011
Actual Primary Completion Date :	September 15, 2015
Actual Study Completion Date :	September 21, 2018

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Systemic lupus erythematosus

MedlinePlus related topics: Lupus

Drug Information available for: Belimumab

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: Belimumab 10mg/kg	Drug: Belimumab 10mg/kg administered intravenously. Dosing at Weeks 0, 2, and 4, then every 4 weeks through Week 48, with a final evaluation at Week 52. All study subjects will receive standard SLE therapies during the study.
Placebo Comparator: Placebo placebo	Drug: Placebo Administered intravenously. Dosing at Weeks 0, 2, and 4, and then every 4 weeks through Week 48, with a final evaluation at Week 52. All study subjects will receive standard SLE therapies during the study.

Outcome Measures

Primary Outcome Measures :

Percent of Participants Achieving Systemic Lupus Erythematosus (SLE) Responder Index (SRI) Response Rate at Week 52 for Double-blind Phase. [ Time Frame: 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; 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 thresholds of SELENA SLEDAI improvement (i.e., SRI5, SRI6, and SRI7) indicates a higher response (SRI5 is a 5 point SELENA SLEDAI reduction, SRI6 is a 6 point reduction, and SRI7 is a 7 point reduction).

Secondary Outcome Measures :

Percent of Participants With >=4 Point Reduction From Baseline in SELENA SLEDAI Score at Week 52 for Double-blind Phase. [ Time Frame: 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 variable measured at Day 0 prior to dosing. In case of multiple results on Day 0 prior to dosing, the latest result was used. If a Day 0 value was not available, the last available value prior to Day 0 was used.
Percent of Participants With SRI7 Response at Week 52 for Double-blind Phase. [ Time Frame: 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 thresholds of SELENA SLEDAI improvement (i.e., SRI5, SRI6, and SRI7) indicates a higher response (SRI5 is a 5 point SELENA SLEDAI reduction, SRI6 is a 6 point reduction, and SRI7 is a 7 point reduction).
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. [ Time Frame: 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.
Time to First Severe SLE Flare Index (SFI) Flare Over 52 Weeks for Double-blind Phase. [ Time Frame: 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 model for the comparison between belimumab and placebo adjusting for country, Baseline SELENA SLEDAI score (<=9 vs. >=10) and complement levels (low C3 and/or C4 vs. no low C3 or C4).
Percent of Participants Achieving SLE SRI Response Rate for Open-label (OL) Phase [ Time Frame: 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 last available value before receiving first belimumab dose in OL phase. Observed case data are presented.Year 6 Week 48 is the Exit Visit obtained by slotting the Exit Visit to Week 48. A SELENA SLEDAI score of 0 (no lupus activity) and a score of 105 (maximum). PGA ranges from 0 (no activity) to 3 (severe activity). BILAG has no range.

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Age 18 years and older.
Have a clinical diagnosis of SLE according to the American College of Rheumatology (ACR) classification criteria.
Have active SLE disease.
Have positive anti-nuclear antibody (ANA) test results.
Are on a stable SLE treatment regimen.
Females of childbearing age are willing to use appropriate contraception

Exclusion Criteria:

Have received treatment with any B cell targeted therapy at any time.
Have received a biologic investigational agent in the past year.
Have received 3 or more courses of systemic corticosteroids in the past year.
Have received intravenous (IV) cyclophosphamide within 180 days prior to Day 0.
Have severe lupus kidney disease.
Have active central nervous system (CNS) lupus.
Have had a major organ transplant.
Have significant unstable or uncontrolled acute or chronic diseases or conditions not due to SLE.
Have a planned surgical procedure.
Cancer within the last 5 years, except for adequately treated skin cancer, or carcinoma in situ of the uterine cervix.
Have required management of acute or chronic infections in the past 60 days.
Have current drug or alcohol abuse or dependence.
Have a historically positive test, or test positive at screening for HIV, Hepatitis B, or Hepatitis C.
Have an IgA deficiency.
Have severe laboratory Abnormalities.
Have had anaphylactic reaction to X-ray contrast agents or biologic agents.
Suicidal behavior or ideation.

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01345253

Locations

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China, Anhui
GSK Investigational Site
Hefei, Anhui, China, 230001
China, Guangdong
GSK Investigational Site
Guangzhou, Guangdong, China, 510080
GSK Investigational Site
Guangzhou, Guangdong, China, 510260
GSK Investigational Site
Guangzhou, Guangdong, China, 510630
China, Heilongjiang
GSK Investigational Site
Harbin, Heilongjiang, China, 150001
China, Hunan
GSK Investigational Site
Changsha, Hunan, China, 410008
GSK Investigational Site
Changsha, Hunan, China, 410011
China, Jiangsu
GSK Investigational Site
Nanjing, Jiangsu, China, 210029
GSK Investigational Site
Suzhou, Jiangsu, China, 215006
China, Shaanxi
GSK Investigational Site
Xian, Shaanxi, China, 710032
China, Shandong
GSK Investigational Site
Jinan, Shandong, China, 250012
China, Sichuan
GSK Investigational Site
Chengdu, Sichuan, China, 610041
China, Yunnan
GSK Investigational Site
Kunming, Yunnan, China, 650101
China, Zhejiang
GSK Investigational Site
Hangzhou, Zhejiang, China, 310009
China
GSK Investigational Site
Beijing, China, 100029
GSK Investigational Site
Beijing, China, 100032
GSK Investigational Site
Beijing, China, 100044
GSK Investigational Site
Chongqing, China, 400038
GSK Investigational Site
Shanghai, China, 200001
GSK Investigational Site
Shanghai, China, 200003
GSK Investigational Site
Shanghai, China, 200025
GSK Investigational Site
Shanghai, China, 200433
GSK Investigational Site
Tianjin, China, 300052
Japan
GSK Investigational Site
Chiba, Japan, 275-8580
GSK Investigational Site
Ehime, Japan, 791-0295
GSK Investigational Site
Fukuoka, Japan, 807-8555
GSK Investigational Site
Fukuoka, Japan, 810-8563
GSK Investigational Site
Hiroshima, Japan, 730-8619
GSK Investigational Site
Hiroshima, Japan, 739-0002
GSK Investigational Site
Hokkaido, Japan, 060-8604
GSK Investigational Site
Hokkaido, Japan, 060-8648
GSK Investigational Site
Hyogo, Japan, 675-8545
GSK Investigational Site
Miyagi, Japan, 980-8574
GSK Investigational Site
Nagasaki, Japan, 852-8501
GSK Investigational Site
Nagasaki, Japan, 857-1195
GSK Investigational Site
Okayama, Japan, 710-0824
GSK Investigational Site
Okinawa, Japan, 901-0243
GSK Investigational Site
Tochigi, Japan, 321-0293
GSK Investigational Site
Tokyo, Japan, 113-8431
Korea, Republic of
GSK Investigational Site
Busan, Korea, Republic of
GSK Investigational Site
Daegu, Korea, Republic of, 700-721
GSK Investigational Site
Incheon, Korea, Republic of, 400-711
GSK Investigational Site
Seoul, Korea, Republic of, 110-744
GSK Investigational Site
Seoul, Korea, Republic of, 133-792
GSK Investigational Site
Seoul, Korea, Republic of, 137-701
GSK Investigational Site
Seoul, Korea, Republic of
GSK Investigational Site
Suwon, Kyonggi-do, Korea, Republic of, 443-721

Sponsors and Collaborators

GlaxoSmithKline

Human Genome Sciences Inc.

Investigators

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Study Director:	GSK Clinical Trials	GlaxoSmithKline

More Information

Publications:

Zhang F, Bae SC, Bass D, Chu M, Egginton S, Gordon D, Roth DA, Zheng J, Tanaka Y. A pivotal phase III, randomised, placebo-controlled study of belimumab in patients with systemic lupus erythematosus located in China, Japan and South Korea. Ann Rheum Dis. 2018 Mar;77(3):355-363. doi: 10.1136/annrheumdis-2017-211631. Epub 2018 Jan 2.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Zhang F, Zheng J, Li Y, Wang G, Wang M, Su Y, Gu J, Li X, Bass D, Chu M, Curtis P, DeRose K, Kurrasch R, Lowe J, Meizlik P, Roth DA. Phase 3, long-term, open-label extension period of safety and efficacy of belimumab in patients with systemic lupus erythematosus in China, for up to 6 years. RMD Open. 2022 Apr;8(1):e001669. doi: 10.1136/rmdopen-2021-001669.

Gupta SV, Fanget MC, MacLauchlin C, Clausen VA, Li J, Cloutier D, Shen L, Robbie GJ, Mogalian E. Clinical and Preclinical Single-Dose Pharmacokinetics of VIR-2218, an RNAi Therapeutic Targeting HBV Infection. Drugs R D. 2021 Dec;21(4):455-465. doi: 10.1007/s40268-021-00369-w. Epub 2021 Nov 6.

Zhou X, Lee TI, Zhu M, Ma P. Prediction of Belimumab Pharmacokinetics in Chinese Pediatric Patients with Systemic Lupus Erythematosus. Drugs R D. 2021 Dec;21(4):407-417. doi: 10.1007/s40268-021-00363-2. Epub 2021 Oct 9.

Brunner HI, Abud-Mendoza C, Mori M, Pilkington CA, Syed R, Takei S, Viola DO, Furie RA, Navarra S, Zhang F, Bass DL, Eriksson G, Hammer AE, Ji BN, Okily M, Roth DA, Quasny H, Ruperto N. Efficacy and safety of belimumab in paediatric and adult patients with systemic lupus erythematosus: an across-study comparison. RMD Open. 2021 Sep;7(3):e001747. doi: 10.1136/rmdopen-2021-001747.

Hannon CW, McCourt C, Lima HC, Chen S, Bennett C. Interventions for cutaneous disease in systemic lupus erythematosus. Cochrane Database Syst Rev. 2021 Mar 9;3(3):CD007478. doi: 10.1002/14651858.CD007478.pub2.

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Responsible Party:	GlaxoSmithKline
ClinicalTrials.gov Identifier:	NCT01345253
Other Study ID Numbers:	113750
First Posted:	May 2, 2011 Key Record Dates
Results First Posted:	December 2, 2016
Last Update Posted:	October 4, 2019
Last Verified:	September 2019

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Studies a U.S. FDA-regulated Drug Product:	No
Studies a U.S. FDA-regulated Device Product:	No

Keywords provided by GlaxoSmithKline:


SLEDAI Asia placebo BLys PGA BILAG systemic lupus erythematosus SELENA Lupus	SRI efficacy B cell SLE Flare Index belimumab safety phase III B lymphocyte

Additional relevant MeSH terms:

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Lupus Erythematosus, Systemic Connective Tissue Diseases Autoimmune Diseases Immune System Diseases	Belimumab Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs

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