Efficacy and Safety of Belimumab in Patients With Active Lupus Nephritis (BLISS-LN)

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Belimumab Plus Standard of Care Versus Placebo Plus Standard of Care in Adult Subjects With Active Lupus Nephritis

The purpose of this study is to evaluate the efficacy, safety, and tolerability of belimumab in adult patients with active lupus nephritis.

Study Overview

• Status: Completed
• Conditions: Lupus Nephritis
• Intervention / Treatment: Biological: Placebo plus standard therapy; Drug: Standard therapy; Biological: Belimumab 10 mg/kg plus standard therapy

Detailed Description

Study participants receive standard therapy (induction and maintenance) for lupus nephritis in addition to receiving either placebo (no active medicine) or belimumab. Induction therapy starts before the first dose of study drug (belimumab or placebo). Maintenance therapy begins after completion of induction therapy and continues for the remainder of the study. Participants receive study drug throughout the entire study, during both induction and maintenance periods. The controlled period of the study is 104 weeks. The random assignment in this study is "1 to 1" which means you have an equal chance of receiving treatment with belimumab or placebo. Participants who successfully complete the 104-week study may enter into a 6-month open-label extension. All participants in the open-label extension receive belimumab.

• Study Type: Interventional
• Enrollment (Actual): 448
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1119ACN
    • GSK Investigational Site
  • Ciudad Autonoma Buenos Aires, Argentina, C1015ABO
    • GSK Investigational Site
  • Cordoba, Argentina, 5000
    • GSK Investigational Site
  • Mendoza, Argentina, 5500
    • GSK Investigational Site
  • Buenos Aires
    • Ciudad Autonoma Buenos Aires, Buenos Aires, Argentina, 1425
      • GSK Investigational Site
  • Tucumán
    • San Miguel de Tucuman, Tucumán, Argentina, CP 4000
      • GSK Investigational Site
• Belgium
  • Brussels, Belgium, 1090
    • GSK Investigational Site
  • Bruxelles, Belgium, 1200
    • GSK Investigational Site
  • Leuven, Belgium, 3000
    • GSK Investigational Site
• Brazil
  • Belo Horizonte, Minas Gerais, Brazil, 30150-221
    • GSK Investigational Site
  • Goiania, Brazil, 74110-120
    • GSK Investigational Site
  • Lajeado, Brazil, 95900-000
    • GSK Investigational Site
  • Salvador, Brazil, 40050-410
    • GSK Investigational Site
  • Minas Gerais
    • Belo Horizonte, Minas Gerais, Brazil, 30150-320
      • GSK Investigational Site
    • Juiz de Fora, Minas Gerais, Brazil, 36010-570
      • GSK Investigational Site
  • Rio Grande Do Sul
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90035-903
      • GSK Investigational Site
  • São Paulo
    • Sao Jose do Rio Preto, São Paulo, Brazil, 15090-000
      • GSK Investigational Site
    • Sao Paulo, São Paulo, Brazil, 04039-901
      • GSK Investigational Site
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2B7
      • GSK Investigational Site
  • Quebec
    • Montreal, Quebec, Canada, H3G 1A4
      • GSK Investigational Site
• China
  • Beijing, China, 100029
    • GSK Investigational Site
  • Chongqing, China, 400038
    • GSK Investigational Site
  • Fuzhou, China, 350005
    • GSK Investigational Site
  • Guangzhou, China, 510080
    • GSK Investigational Site
  • Nanning, China, 530021
    • GSK Investigational Site
  • Shanghai, China, 200025
    • GSK Investigational Site
  • Shanghai, China, 200040
    • GSK Investigational Site
  • Shanghai, China, 200127
    • GSK Investigational Site
  • Shenzhen, China, 518035
    • GSK Investigational Site
  • Xian, China
    • GSK Investigational Site
  • Hubei
    • Wuhan, Hubei, China, 430030
      • GSK Investigational Site
  • Hunan
    • Changsha, Hunan, China, 410008
      • GSK Investigational Site
  • Jiangxi
    • Nanchang, Jiangxi, China, 330006
      • GSK Investigational Site
  • Liaoning
    • Shenyang, Liaoning, China, 110004
      • GSK Investigational Site
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • GSK Investigational Site
• Colombia
  • Bogota, Colombia
    • GSK Investigational Site
• Czechia
  • Olomouc, Czechia, 775 20
    • GSK Investigational Site
  • Praha 2, Czechia, 128 08
    • GSK Investigational Site
  • Praha 2, Czechia, 128 50
    • GSK Investigational Site
• France
  • Cean Cedex 09, France, 14033
    • GSK Investigational Site
  • Créteil cedex, France, 94010
    • GSK Investigational Site
  • Lille Cedex, France, 59037
    • GSK Investigational Site
  • Paris, France, 75013
    • GSK Investigational Site
  • Strasbourg Cedex, France, 67091
    • GSK Investigational Site
  • Toulouse Cedex 9, France, 31059
    • GSK Investigational Site
  • Vandoeuvre-Les-Nancy, France, 54511
    • GSK Investigational Site
• Germany
  • Berlin, Germany, 10117
    • GSK Investigational Site
  • Goettingen, Germany, 37075
    • GSK Investigational Site
  • Baden-Wuerttemberg
    • Freiburg, Baden-Wuerttemberg, Germany, 79106
      • GSK Investigational Site
  • Niedersachsen
    • Hannover, Niedersachsen, Germany, 30625
      • GSK Investigational Site
  • Nordrhein-Westfalen
    • Essen, Nordrhein-Westfalen, Germany, 45122
      • GSK Investigational Site
    • Muenster, Nordrhein-Westfalen, Germany, 48149
      • GSK Investigational Site
  • Rheinland-Pfalz
    • Mainz, Rheinland-Pfalz, Germany, 55131
      • GSK Investigational Site
  • Sachsen
    • Dresden, Sachsen, Germany, 01307
      • GSK Investigational Site
  • Schleswig-Holstein
    • Luebeck, Schleswig-Holstein, Germany, 23538
      • GSK Investigational Site
  • Thueringen
    • Jena, Thueringen, Germany, 07740
      • GSK Investigational Site
• Hong Kong
  • Hong Kong, Hong Kong
    • GSK Investigational Site
• Hungary
  • Miskolc, Hungary, 3526
    • GSK Investigational Site
  • Szeged, Hungary, 6725
    • GSK Investigational Site
• Korea, Republic of
  • Busan, Korea, Republic of, 49201
    • GSK Investigational Site
  • Daejeon, Korea, Republic of, 301-721
    • GSK Investigational Site
  • Daejeon, Korea, Republic of, 35233
    • GSK Investigational Site
  • Jeju Special Self-Governing Prov., Korea, Republic of, 690-767
    • GSK Investigational Site
  • Jeonju-si, Korea, Republic of, 561-712
    • GSK Investigational Site
  • Seoul, Korea, Republic of, 120-752
    • GSK Investigational Site
  • Seoul, Korea, Republic of, 04763
    • GSK Investigational Site
  • Seoul, Korea, Republic of, 06273
    • GSK Investigational Site
  • Seoul, Korea, Republic of, 06591
    • GSK Investigational Site
  • Suwon, Korea, Republic of, 16247
    • GSK Investigational Site
  • Suwon-si, Gyeonggi-do, Korea, Republic of, 16499
    • GSK Investigational Site
• Mexico
  • Mexico, Mexico, 7760
    • GSK Investigational Site
  • México, D.F., Mexico, 14080
    • GSK Investigational Site
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 45040
      • GSK Investigational Site
  • Michoacán
    • Morelia, Michoacán, Mexico, 58260
      • GSK Investigational Site
  • Morelos
    • Cuernavaca, Morelos, Mexico, 62170
      • GSK Investigational Site
• Netherlands
  • Groningen, Netherlands, 9728 NT
    • GSK Investigational Site
  • Leiden, Netherlands, 2333 ZA
    • GSK Investigational Site
  • Maastricht, Netherlands, 6229 HX
    • GSK Investigational Site
• Philippines
  • Cebu City, Philippines, 6000
    • GSK Investigational Site
  • Davao City, Philippines, 8000
    • GSK Investigational Site
  • Iloilo City, Philippines, 5000
    • GSK Investigational Site
  • Lipa City, Batangas, Philippines, 4217
    • GSK Investigational Site
  • Manila, Philippines, 1000
    • GSK Investigational Site
• Russian Federation
  • Moscow, Russian Federation, 125284
    • GSK Investigational Site
  • Orenburg, Russian Federation, 460000
    • GSK Investigational Site
  • St. Petersburg, Russian Federation, 197022
    • GSK Investigational Site
  • Ufa, Russian Federation, 450005
    • GSK Investigational Site
• Spain
  • Barcelona, Spain, 08025
    • GSK Investigational Site
  • Barcelona, Spain, 8035
    • GSK Investigational Site
  • Palma de Mallorca, Spain, 07010
    • GSK Investigational Site
  • Valencia, Spain, 46017
    • GSK Investigational Site
  • Vigo/ Pontevedra, Spain, 36200
    • GSK Investigational Site
• Taiwan
  • Gueishan Township,Taoyuan County, Taiwan, 333
    • GSK Investigational Site
  • Kaohsiung, Taiwan, 83301
    • GSK Investigational Site
  • Taichung, Taiwan, 40705
    • GSK Investigational Site
• Thailand
  • Khon Kaen, Thailand, 40002
    • GSK Investigational Site
  • Muang, Thailand, 50200
    • GSK Investigational Site
  • Rajathevee, Thailand, 10400
    • GSK Investigational Site
  • Saimai, Thailand, 10220
    • GSK Investigational Site
• United Kingdom
  • London, United Kingdom, E1 1BB
    • GSK Investigational Site
  • London, United Kingdom, SE1 7EH
    • GSK Investigational Site
• United States
  • California
    • La Palma, California, United States, 90623
      • GSK Investigational Site
    • San Leandro, California, United States, 94578
      • GSK Investigational Site
    • Torrance, California, United States, 90502
      • GSK Investigational Site
  • Florida
    • Gainesville, Florida, United States, 32610
      • GSK Investigational Site
    • Miami, Florida, United States, 33136
      • GSK Investigational Site
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • GSK Investigational Site
  • New York
    • Brooklyn, New York, United States, 11203
      • GSK Investigational Site
    • Great Neck, New York, United States, 11021
      • GSK Investigational Site
    • Manhasset, New York, United States, 11030
      • GSK Investigational Site
    • New York, New York, United States, 10032
      • GSK Investigational Site
    • New York, New York, United States, 10016
      • GSK Investigational Site
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • GSK Investigational Site
  • Ohio
    • Columbus, Ohio, United States, 43203
      • GSK Investigational Site
  • Pennsylvania
    • Bethlehem, Pennsylvania, United States, 18017
      • GSK Investigational Site
    • Philadelphia, Pennsylvania, United States, 19140
      • GSK Investigational Site
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • GSK Investigational Site
  • Wisconsin
    • Onalaska, Wisconsin, United States, 54650
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• Clinical diagnosis of SLE by American College of Rheumatology (ACR) criteria.
• Biopsy confirmed active lupus nephritis.
• Clinically active lupus renal disease at screening requiring /receiving induction therapy with Standard of Care medications.
• Autoantibody-positive.

Key Exclusion Criteria:

• Pregnant or nursing.
• On dialysis within the past year.
• Treatment with belimumab within the past year .
• Receipt of induction therapy with cyclophosphamide within 3 months prior to induction therapy for the study.
• Receipt of any B cell targeted therapy (for example, rituximab), investigational biological agent within the past year.
• Severe active central nervous system (CNS) lupus.
• Required management of acute or chronic infections within the past 60 days.
• Current drug or alcohol abuse or dependence.
• Tested positive for human immunodeficiency virus (HIV), hepatitis B, or hepatitis C.
• History of severe allergic reaction to contrast agents or biological medicines.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo plus standard therapy; Placebo IV plus standard therapy; placebo administered on Days 0, 14, 28, and then every 28 days thereafter through Week 100, with a final evaluation at Week 104 in the double-blind period. In the open-label extension period, placebo patients who opt to participate will receive belimumab 10 mg/kg IV every 28 days for an additional 6 months.	Biological: Placebo plus standard therapy; Placebo plus standard therapy; Drug: Standard therapy; The standard therapies allowed in this study are: - High-dose steroids (for example, methylprednisolone) plus cyclophosphamide for induction therapy followed by azathioprine for maintenance therapy OR - High-dose steroids plus mycophenolate for induction therapy followed by mycophenolate for maintenance therapy
Experimental: Belimumab 10 mg/kg plus standard therapy; Belimumab 10 mg/kg IV plus standard therapy; belimumab administered on Days 0, 14, 28, and then every 28 days thereafter through Week 100, with a final evaluation at Week 104 in the double-blind period. In the open-label extension period, patients who opt to participate will continue to receive belimumab 10 mg/kg IV every 28 days for an additional 6 months.	Drug: Standard therapy; The standard therapies allowed in this study are: - High-dose steroids (for example, methylprednisolone) plus cyclophosphamide for induction therapy followed by azathioprine for maintenance therapy OR - High-dose steroids plus mycophenolate for induction therapy followed by mycophenolate for maintenance therapy; Biological: Belimumab 10 mg/kg plus standard therapy; Belimumab 10 mg/kg plus standard therapy; Other Names: BENLYSTA™

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Double-blind Period: Percentage of Participants With Primary Efficacy Renal Response (PERR) at Week 104	PERR is defined as urinary protein creatinine ratio <=0.7, estimated glomerular filtration rate (eGRF) was not more than 20 percent (%) below the pre-flare value or >=60 milliliters per minute per 1.73 square meter (mL/min/1.73m^2) and was not a treatment failure. Analysis was performed using a logistic regression model for the comparison between Belimumab and Placebo with covariates treatment group, induction regimen (CYC vs. MMF), race (Black vs. Non-Black), Baseline urine protein-creatinine ratio (uPCR), and Baseline eGFR. Modified Intent-to-treat (mITT) Population consisted of all randomized participants who received at least one dose of study treatment and were not excluded due to Good Clinical Practice (GCP) non-compliance. Percentage of participants with PERR at Week 104 has been presented.	Week 104
Open-label Period: Number of Participants Reporting Adverse Events (AEs) and Serious AEs (SAEs)	An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporarily associated with the use of a medicinal product, whether or not considered related to the medicinal product. A SAE is any untoward medical occurrence that, at any dose: resulting in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, any other situation according to medical or scientific judgment or all events of possible drug-induced liver injury with hyperbilirubinemia were categorized as SAE. Number of participants with AEs and SAEs have been reported.	From first open-label dose (Day 1) up to open-label Week 32 (8 weeks after last dose)
Open-label Period: Number of Participants Reporting Adverse Events of Special Interest (AESI)	An AESI is one of scientific and medical concern specific to the product, for which ongoing monitoring and rapid communication by investigator to sponsor can be appropriate. A summary of protocol defined AESIs include malignant neoplasms including and excluding non-melanoma skin cancer (NMSC), post-infusion systemic reactions (PISR), all infections of special interest (opportunistic infections [OI], Herpes Zoster [HZ], tuberculosis [TB], and sepsis), depression (including mood disorders and anxiety)/suicide/self-injury and deaths.	From first open-label dose (Day 1) up to open-label Week 32 (8 weeks after last dose)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Double-blind Period: Percentage of Participants With Complete Renal Response (CRR) at Week 104	CRR is defined as urinary protein creatinine ratio <0.5, eGRF was not more than 10% below the pre-flare value or >=90 mL/min/1.73m^2 and was not a treatment failure. Analysis was performed using a logistic regression model for the comparison between Belimumab and Placebo with covariates of induction regimen (CYC vs. MMF), race (Black vs. Non-Black), Baseline uPCR and Baseline eGFR. Percentage of participants with CRR at Week 104 has been presented.	Week 104
Double-blind Period: Percentage of Participants With PERR at Week 52	PERR is defined as urinary protein creatinine ratio <=0.7, eGRF was not more than 20% below the pre-flare value or >=60 mL/min/1.73m^2 and was not a treatment failure. Analysis was performed using a logistic regression model for the comparison between Belimumab and Placebo with covariates of induction regimen (CYC vs. MMF), race (Black vs. Non-Black), uPCR, and Baseline eGFR. Percentage of participants with PERR at Week 52 has been presented.	Week 52
Double-blind Period: Number of Participants With Time to Death or Renal Related Event	Events are defined as the first event experienced among the following: death, progression to end stage renal disease, doubling of serum creatinine from Baseline, renal worsening or renal-related treatment failure. Participants who discontinued randomized treatment, withdrew from the study, were lost to follow-up, or had a non renal-related treatment failure were censored. Participants who completed the 104-week treatment period were censored at the Week 104 visit. Time to event is defined as event date minus treatment start date plus one. Analysis was performed using Cox proportional hazards model for the comparison between Belimumab and Placebo adjusting for induction regimen, race, Baseline uPCR and Baseline eGFR. Number of participants with time to death or renal related event up to Week 104 has been presented.	Up to Week 104
Double-blind Period: Percentage of Participants With Ordinal Renal Response (ORR) at Week 104	ORR is defined with respect to reproducible responses that included CRR, partial RR (PRR) and non responder. CRR is reported when uPCR was <0.5, eGFR was not more than 10% below pre-flare GFR or within normal range and not a treatment failure. PRR is >=50% decrease from Baseline in uPCR and one of the following: value <1 if Baseline <=3, or value <3 if the Baseline was >3, eGFR not more than 10% below Baseline GFR or within normal range and not a treatment failure and not a CRR. Non responder is reported when neither CRR nor PRR criteria was met. Percentage of participants reporting CRR, PRR and non responders at Week 104 has been presented.	Week 104
Double-blind Period: Number of Participants Reporting On-treatment AEs and SAEs	An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporarily associated with the use of a medicinal product, whether or not considered related to the medicinal product. A SAE is any untoward medical occurrence that, at any dose: resulting in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, any other situation according to medical or scientific judgment or all events of possible drug-induced liver injury with hyperbilirubinemia were categorized as SAE. Number of participants with on-treatment AEs and SAEs has been reported.	Up to Week 104
Double-blind Period: Number of Participants Reporting AESI	An AESI is one of scientific and medical concern specific to the product, for which ongoing monitoring and rapid communication by investigator to sponsor can be appropriate. A summary of protocol defined AESIs include malignant neoplasms including and excluding non-melanoma skin cancer (NMSC), post-infusion systemic reactions (PISR), all infections of special interest (opportunistic infections [OI], Herpes Zoster [HZ], tuberculosis [TB], and sepsis), depression (including mood disorders and anxiety)/suicide/self-injury and deaths. On-treatment data is displayed.	Up to Week 104

Collaborators and Investigators

• Sponsor: Human Genome Sciences Inc., a GSK Company
• Collaborators: GlaxoSmithKline

Publications and helpful links

General Publications

• Furie R, Rovin BH, Houssiau F, Contreras G, Teng YKO, Curtis P, Green Y, Okily M, Madan A, Roth DA. Safety and Efficacy of Belimumab in Patients with Lupus Nephritis: Open-Label Extension of BLISS-LN Study. Clin J Am Soc Nephrol. 2022 Nov;17(11):1620-1630. doi: 10.2215/CJN.02520322. Epub 2022 Oct 27.
• Rovin BH, Furie R, Teng YKO, Contreras G, Malvar A, Yu X, Ji B, Green Y, Gonzalez-Rivera T, Bass D, Gilbride J, Tang CH, Roth DA. A secondary analysis of the Belimumab International Study in Lupus Nephritis trial examined effects of belimumab on kidney outcomes and preservation of kidney function in patients with lupus nephritis. Kidney Int. 2022 Feb;101(2):403-413. doi: 10.1016/j.kint.2021.08.027. Epub 2021 Sep 22.
• Furie R, Rovin BH, Houssiau F, Malvar A, Teng YKO, Contreras G, Amoura Z, Yu X, Mok CC, Santiago MB, Saxena A, Green Y, Ji B, Kleoudis C, Burriss SW, Barnett C, Roth DA. Two-Year, Randomized, Controlled Trial of Belimumab in Lupus Nephritis. N Engl J Med. 2020 Sep 17;383(12):1117-1128. doi: 10.1056/NEJMoa2001180.

Study record dates

Study Major Dates

• Study Start (Actual): July 12, 2012
• Primary Completion (Actual): July 25, 2019
• Study Completion (Actual): March 12, 2020

Study Registration Dates

• First Submitted: July 10, 2012
• First Submitted That Met QC Criteria: July 10, 2012
• First Posted (Estimate): July 12, 2012

Study Record Updates

• Last Update Posted (Actual): March 19, 2021
• Last Update Submitted That Met QC Criteria: February 23, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: Lupus; SLE; Systemic Lupus Erythematosus; Kidney Diseases; Nephritis; Antibodies; Autoimmune Disease; Glomerulonephritis; Belimumab
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Kidney Diseases; Urologic Diseases; Connective Tissue Diseases; Glomerulonephritis; Lupus Erythematosus, Systemic; Nephritis; Lupus Nephritis; Physiological Effects of Drugs; Immunosuppressive Agents; Immunologic Factors; Belimumab
• Other Study ID Numbers: 114054; 2011-004570-28 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
• IPD Sharing Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints of the study.
• IPD Sharing Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No