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

Systemic Lupus Erythematosus Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01345253
• Other study ID #: 113750
• Status: Completed
• Phase: Phase 3
• Start date: May 23, 2011
• Est. completion date: September 21, 2018

Study information

• Verified date: September 2019
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 709
• Est. completion date: September 21, 2018
• Est. primary completion date: September 15, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Lupus Erythematosus, Systemic
• Systemic Lupus Erythematosus

Intervention

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
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.

Locations

Country	Name	City	State
China	GSK Investigational Site	Beijing
China	GSK Investigational Site	Beijing
China	GSK Investigational Site	Beijing
China	GSK Investigational Site	Changsha	Hunan
China	GSK Investigational Site	Changsha	Hunan
China	GSK Investigational Site	Chengdu	Sichuan
China	GSK Investigational Site	Chongqing
China	GSK Investigational Site	Guangzhou	Guangdong
China	GSK Investigational Site	Guangzhou	Guangdong
China	GSK Investigational Site	Guangzhou	Guangdong
China	GSK Investigational Site	Hangzhou	Zhejiang
China	GSK Investigational Site	Harbin	Heilongjiang
China	GSK Investigational Site	Hefei	Anhui
China	GSK Investigational Site	Jinan	Shandong
China	GSK Investigational Site	Kunming	Yunnan
China	GSK Investigational Site	Nanjing	Jiangsu
China	GSK Investigational Site	Shanghai
China	GSK Investigational Site	Shanghai
China	GSK Investigational Site	Shanghai
China	GSK Investigational Site	Shanghai
China	GSK Investigational Site	Suzhou	Jiangsu
China	GSK Investigational Site	Tianjin
China	GSK Investigational Site	Xian	Shaanxi
Japan	GSK Investigational Site	Chiba
Japan	GSK Investigational Site	Ehime
Japan	GSK Investigational Site	Fukuoka
Japan	GSK Investigational Site	Fukuoka
Japan	GSK Investigational Site	Hiroshima
Japan	GSK Investigational Site	Hiroshima
Japan	GSK Investigational Site	Hokkaido
Japan	GSK Investigational Site	Hokkaido
Japan	GSK Investigational Site	Hyogo
Japan	GSK Investigational Site	Miyagi
Japan	GSK Investigational Site	Nagasaki
Japan	GSK Investigational Site	Nagasaki
Japan	GSK Investigational Site	Okayama
Japan	GSK Investigational Site	Okinawa
Japan	GSK Investigational Site	Tochigi
Japan	GSK Investigational Site	Tokyo
Korea, Republic of	GSK Investigational Site	Busan
Korea, Republic of	GSK Investigational Site	Daegu
Korea, Republic of	GSK Investigational Site	Incheon
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Suwon, Kyonggi-do

Sponsors (2)

Lead Sponsor	Collaborator
GlaxoSmithKline	Human Genome Sciences Inc.

Countries where clinical trial is conducted

China,  Japan,  Korea, Republic of, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent of Participants Achieving Systemic Lupus Erythematosus (SLE) Responder Index (SRI) Response Rate at Week 52 for Double-blind Phase.	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).	Week 52
Secondary	Percent of Participants With >=4 Point Reduction From Baseline in SELENA SLEDAI Score at Week 52 for Double-blind Phase.	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.	Baseline (Day 0) and Week 52
Secondary	Percent of Participants With SRI7 Response at Week 52 for Double-blind Phase.	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).	Baseline (Day 0) and Week 52
Secondary	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.	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.	Week 52
Secondary	Time to First Severe SLE Flare Index (SFI) Flare Over 52 Weeks for Double-blind Phase.	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).	52 weeks
Secondary	Percent of Participants Achieving SLE SRI Response Rate for Open-label (OL) Phase	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.	Weeks 24 and 48 for Years 2, 3, 4, 5 and 6