A Study of Belimumab in Subjects With Systemic Lupus Erythematosus (SLE) (BLISS-52)

A Phase 3, Multi-Center, Randomized, Double-Blind, Placebo-Controlled, 52-Wk Study to Evaluate the Efficacy and Safety of Belimumab (HGS1006, LymphoStat-B™), a Fully Human Monoclonal Anti-BLyS Antibody, in Subjects With Systemic Lupus Erythematosus (SLE)

The purpose of this study is to evaluate the efficacy, safety, tolerability, and impact on quality of life of two different doses of belimumab administered in addition to standard therapy in subjects with active, autoantibody-positive systemic lupus erythematosus (SLE) disease.

Study Overview

• Status: Completed
• Conditions: Systemic Lupus Erythematosus
• Intervention / Treatment: Drug: Placebo; Drug: Belimumab 1 mg/kg; Drug: Belimumab 10 mg/kg

• Study Type: Interventional
• Enrollment (Actual): 865
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1280AEB
    • Hospital Britanico de Buenos Aires
  • Buenos Aires, Argentina, C1417EYG
    • Centro Privado de Medicina Familiar
  • Buenos Aires, Argentina, C1419AHN
    • Hospital Sírio Libanês
  • Buenos Aires, Argentina, C1426AAL
    • Atencion Integral en Reumatologia
  • Buenos Aires, Argentina, C1427ARO
    • Instituto de Investigaciones Medicas
  • Ciudad Autonoma de Buenos Aires, Argentina, C1015ABO
    • OMI, Organización Médica de Investigación
  • Ciudad Autonoma de Buenos Aires, Argentina, C1055AAF
    • CIER, Centro de Investigaciones en Enfermedades Reumáticas
  • Ciudad Autonoma de Buenos Aires, Argentina, C1405DCS
    • Hospital General de Agudos Carlos G. Durand
  • La Plata, Argentina, B1904CFH
    • Hospital Interzonal General San Martín
  • Rosario, Argentina, S2000PBJ
    • CAICI, Instituto Centralizado de Asistencia e Investigación Clínica Integral
  • San Miguel de Tucuman, Argentina, T4000AXL
    • Centro Medico Privado de Reumatologia
• Australia
  • Daw Park, Australia, 5041
    • Repatriation Hospital
  • Melbourne, Australia, 3168
    • Monash Medical Centre
  • Melbourne, Australia, 3144
    • Emeritus Research, Cabrini Hospital
  • Shenton Park, Australia, 6008
    • Royal Perth Hospital
• Brazil
  • Campinas, Brazil, 13083-888
    • Hospital de Clínicas - UNICAMP
  • Curitiba, Brazil, 80060-240
    • Hospital das Clínicas - Universidade do Paraná
  • Fortaleza, Brazil, 50670-901
    • Hospital de Clínicas - Universidade Federal de Pernambuco
  • Goiânia, Brazil, 74110-120
    • Hospital Geral de Goiânia
  • Juiz de Fora, Brazil, 36010-570
    • Hospital Universitário - Universidade Federal de Juiz de Fora
  • Porto Alegre, Brazil, 90610-000
    • Hospital Sao Lucas da PUC-RS
  • Rio de Janeiro, Brazil, 20551-030
    • Hospital Universitario Pedro Ernesto - UERJ
  • Rio de Janeiro, Brazil, 21941-913
    • Hospital Unversitario Clementino Fraga Filho UFRJ
  • Salvador, Brazil, 40050-410
    • Hospital Santa Izabel
  • São Paulo, Brazil, 04027-000
    • Hospital Abreu Sodré
  • São Paulo, Brazil, 04039-901
    • Hospital do Servidor Público Estadual de São Paulo - Francisco Morato de Oliveira
  • São Paulo, Brazil, 04266-010
    • Hospital Heliópolis
• Chile
  • Santiago, Chile, 8207257
    • Hospital Dr. Sótero del Río
  • Santiago, Chile, 8431657
    • Clinica Dávila
  • Santiago, Chile, 8330033
    • Pontificia Universidad Catolica de Chile
  • Viña del Mar, Chile, 2570017
    • Hospital Dr. Gustavo Fricke
• Colombia
  • Barranquilla, Colombia
    • Centro de Reumatologia y Ortopedia
  • Bogota, Colombia
    • Fundacion Instituto de Reumatologia Fernando Chalem
  • Bogotá, Colombia
    • Centrode de Investigaciones en Reumatologia Especialidades Medicas (CIREEH)
  • Bogotá, Colombia
    • Riesgo de Fracturas
  • Bucaramanga, Colombia
    • SERVIMED
  • Medellín, Colombia
    • Corporación para Investigaciones Biológicas (CIB)
  • Medellín, Colombia
    • Office of Dr. Jose Molina
  • Cundinamarca
    • Bogota, Cundinamarca, Colombia
      • Office of Dr. Guzman
  • Santander
    • Bucaramanga, Santander, Colombia
      • Fundación Oftalmológica de Santander Clínica Carlos Ardila Lulle
• Hong Kong
  • Chai Wan, Hong Kong
    • Pamela Youde Nethersole Eastern Hospital
  • Shatin, Hong Kong
    • Rheumatology Assessment and Treatment Center, Pok Oi Hospital
  • Tuen Mun, Hong Kong
    • Tuen Mun Hospital
• India
  • Bangalore, India, 560 034
    • St. John's Medical College Hospital
  • Hyderabaad, India, 500 082
    • Nizam's Institute of Medical Sciences
  • Hyderabaad, India, 500 003
    • Krishna Institute of Medical Sciences
  • Hyderabad, India, 500 033
    • Apollo Hospitals
  • Lucknow, India, 226018
    • Chhatrapati Shahuji Maharaj Medical University
  • Mumbai, India, 400 012
    • King Edward Memorial (K.E.M.) Hospital
  • Trivandrum, India, 695029
    • Kerala Institute of Medical Sciences
• Korea, Republic of
  • Daegu, Korea, Republic of, 700-721
    • Kyungpook National Univesity Hospital
  • Daejeon, Korea, Republic of, 302-799
    • Eulji University Hospital
  • Inchon, Korea, Republic of, 400-711
    • Inha University Hospital
  • Pusan, Korea, Republic of, 602-739
    • Pusan National University Hospital
  • Pusan, Korea, Republic of, 602-715
    • Dong-A University Hospital 3-1 (Dept. Rhuematology)
  • Seoul, Korea, Republic of, 110-744
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 133-792
    • The Hospital for Rheumatic Diseases, Hanyang University Hospital
  • Seoul, Korea, Republic of, 137-701
    • Catholic Universtigy of Korea, Kangnam St. Mary's Hospital
  • Seoul, Korea, Republic of, 150-713
    • Catholic University, Yoido St. Mary's Hospital
  • Suwon, Korea, Republic of, 443-721
    • Ajou University Hospital
• Peru
  • Lima, Peru, Callao 2
    • Hospital Nacional Alberto Sabogal Sologuren ESSALUD
  • Lima, Peru, L 13
    • Hospital Nacional Guillermo Almenara Irigoyen ESSALUD
  • Lima, Peru, L 27
    • Clinica Ricardo Palma Anexo 9 - Javier Prado Este
  • Lima, Peru, L 33
    • Instituto de Ginecología y Reproducción
• Philippines
  • Cebu City, Philippines, 6000
    • Chong Hua Hospital
  • Davao City, Philippines, 8000
    • Davao Medical Center
  • Las Pinas City, Philippines, 1740
    • University of Perpetual Help -Rizal
  • Manila City, Philippines, 1000
    • Philippine General Hospital
  • Manila City, Philippines, 1008
    • University of Santo Tomas Hospital
  • Quezon City, Philippines, 1102
    • St. Luke's Medical Center
• Romania
  • Bucharest, Romania, 020125
    • Spitalul Clinic Colentina
  • Bucharest, Romania, 011170
    • Spitalul Clinic Sf Maria
  • Bucharest, Romania, 020125
    • Spitalul de Urgenta al Ministerului Administratiei si Internelor Prof. Dr. Dimitrie Gerota
  • Bucharest, Romania, 020475
    • Spitalul Clinic Dr. Ion Cantacuzino
  • Cluj Napoca, Romania, 40006
    • Spitalul Clinic Judetean de Urgenta Cluj-Napoca
• Russian Federation
  • Moscow, Russian Federation, 115522
    • State Institution Scientific Research Institute of Rheumatology
  • St. Petersburg, Russian Federation, 190068
    • St. Petersburg City Hospital (Rheumatology Center)
  • St.-Petersburg, Russian Federation, 191015
    • Academy of Post-Graduated Education
  • St.-Petersburg, Russian Federation, 194291
    • St.-Petersburg Region Clinical Hospital
  • Yaroslavl, Russian Federation, 150003
    • Soloviev's City Clinical Hospital,
  • Yaroslavl, Russian Federation, 190068
    • City Healthcare Institution Municipal Hospital NPZ,
• Taiwan
  • Chia-Yi, Taiwan, 622
    • Buddhist Tzu Chi General Hospital, Dalin
  • Haulien, Taiwan, 970
    • Buddhist Tzu Chi General Hospital - Hualien
  • Kaohsiung, Taiwan, 813
    • Kaohsiung Veterans General Hospital
  • Kaohsiung, Taiwan, 807
    • Chung-Ho Memorial Hospital, Kaohsiung Medical University
  • Kaosiung, Taiwan, 833
    • Chang Gung Memorial Hospital, Kaosiung
  • Keelung, Taiwan, 204
    • Chang Gung Memorial Hospital-Keelung
  • Taichung, Taiwan, 404
    • China Medical University Hospital
  • Taichung, Taiwan, 402
    • Chung Shan Medical University Hospital
  • Taichung, Taiwan, 407
    • Taichung Veterans General Hospital
  • Taipei, Taiwan, 100
    • National Taiwan University Hospital
  • Tau-Yuan County, Taiwan, 333
    • Chang Gung Memorial Hospital, Linko

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 ACR criteria.
• Active SLE disease.
• Autoantibody-positive.
• On stable SLE treatment regimen.

Key Exclusion Criteria:

• Pregnant or nursing
• Have received treatment with any B cell targeted therapy.
• Have received treatment with a biological investigational agent in the past year.
• Have received IV cyclophosphamide within 180 days of Day 0.
• Have severe lupus kidney disease.
• Have active central nervous system (CNS) lupus.
• Have required management of acute or chronic infections within 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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Placebo IV plus standard therapy; placebo administered on Days 0, 14, 28, and every 28 days thereafter through Week 48.
Experimental: Belimumab 1 mg/kg	Drug: Belimumab 1 mg/kg; Belimumab 1 mg/kg IV plus standard therapy on Days 0, 14, 28, and every 28 days thereafter through Week 48.; Other Names: BENLYSTA™ (formerly LymphoStat-B™)
Experimental: Belimumab 10 mg/kg	Drug: Belimumab 10 mg/kg; Belimumab 10 mg/kg IV plus standard therapy on Days 0, 14, 28, and every 28 days thereafter through Week 48.; Other Names: BENLYSTA™ (formerly LymphoStat-B™)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SLE Responder Index (SRI) Response Rate at Week 52	Percentage of subjects with a ≥ 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. SELENA SLEDAI is calculated from 24 individual descriptors; 0 indicates inactive disease and the maximum theoretical score is 105; scores > 20 are rare. PGA is a visual analog scale scored from 0 to 3 (1=mild, 2=moderate, 3=severe). BILAG uses a single score for each of the 8 organ domains; range is from severe to no disease (A to E).	Baseline, 52 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent of Subjects With a ≥ 4 Point Reduction From Baseline in SELENA SLEDAI Score at Wk 52.		Baseline, 52 weeks
Mean Change in Physician's Global Assessment (PGA) at Wk 24.	The PGA is a visual analog scale scored from 0 to 3. A score of 1 corresponds to mild lupus disease activity. A score of 2 correlates with moderate disease activity and a score of 3 with severe disease activity.	Baseline, 24 weeks
Mean Change From Baseline in Medical Outcomes 36-Item Short Form Health Survey (SF-36) Physical Component Summary Score (PCS) at Wk 24.	The SF-36 is a generic health related quality of life (HRQOL) measurement. The survey includes 36 questions grouped to 8 domains and 2 summary measures (physical and mental health component, PCS and MCS, respectively) assessing HRQOL. Responses are scored according to the SF-36v2™ manual. A score is calculated for each SF-36 domain based on the patient's response to each question within it. This is then transformed to a scale ranging from 0 (worst) to 100 (best) points. The PCS is norm-based where the mean=50 and standard deviation (SD)=10. Higher scores represent better physical health.	Baseline, 24 weeks
Percent of Subjects Whose Average Prednisone Dose Has Been Reduced by ≥ 25% From Baseline to ≤ 7.5 mg/Day During Weeks 40 Through 52		Baseline, Weeks 40 through 52

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events (AE) Overview	SEE ALSO ADVERSE EVENTS RESULTS SECTION	Up to 56 Weeks

Collaborators and Investigators

• Sponsor: Human Genome Sciences Inc.
• Collaborators: GlaxoSmithKline

Publications and helpful links

General Publications

• 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.
• Rendas-Baum R, Baranwal N, Joshi AV, Park J, Kosinski M. Psychometric properties of FACIT-Fatigue in systemic lupus erythematosus: a pooled analysis of three phase 3 randomised, double-blind, parallel-group controlled studies (BLISS-SC, BLISS-52, BLISS-76). J Patient Rep Outcomes. 2021 Apr 8;5(1):33. doi: 10.1186/s41687-021-00298-x.
• Maslen T, Bruce IN, D'Cruz D, Ianosev M, Bass DL, Wilkinson C, Roth DA. Efficacy of belimumab in two serologically distinct high disease activity subgroups of patients with systemic lupus erythematosus: post-hoc analysis of data from the phase III programme. Lupus Sci Med. 2021 Feb;8(1):e000459. doi: 10.1136/lupus-2020-000459.
• Gomez A, Hani Butrus F, Johansson P, Akerstrom E, Soukka S, Emamikia S, Enman Y, Pettersson S, Parodis I. Impact of overweight and obesity on patient-reported health-related quality of life in systemic lupus erythematosus. Rheumatology (Oxford). 2021 Mar 2;60(3):1260-1272. doi: 10.1093/rheumatology/keaa453.
• van Vollenhoven RF, Navarra SV, Levy RA, Thomas M, Heath A, Lustine T, Adamkovic A, Fettiplace J, Wang ML, Ji B, Roth D. Long-term safety and limited organ damage in patients with systemic lupus erythematosus treated with belimumab: a Phase III study extension. Rheumatology (Oxford). 2020 Feb 1;59(2):281-291. doi: 10.1093/rheumatology/kez279.
• Furie R, Petri MA, Strand V, Gladman DD, Zhong ZJ, Freimuth WW; BLISS-52 and BLISS-76 Study Groups. Clinical, laboratory and health-related quality of life correlates of Systemic Lupus Erythematosus Responder Index response: a post hoc analysis of the phase 3 belimumab trials. Lupus Sci Med. 2014 Jun 26;1(1):e000031. doi: 10.1136/lupus-2014-000031. eCollection 2014.
• Petri MA, van Vollenhoven RF, Buyon J, Levy RA, Navarra SV, Cervera R, Zhong ZJ, Freimuth WW; BLISS-52 and BLISS-76 Study Groups. Baseline predictors of systemic lupus erythematosus flares: data from the combined placebo groups in the phase III belimumab trials. Arthritis Rheum. 2013 Aug;65(8):2143-53. doi: 10.1002/art.37995.
• Strand V, Levy RA, Cervera R, Petri MA, Birch H, Freimuth WW, Zhong ZJ, Clarke AE; BLISS-52 and -76 Study Groups. Improvements in health-related quality of life with belimumab, a B-lymphocyte stimulator-specific inhibitor, in patients with autoantibody-positive systemic lupus erythematosus from the randomised controlled BLISS trials. Ann Rheum Dis. 2014 May;73(5):838-44. doi: 10.1136/annrheumdis-2012-202865. Epub 2013 Mar 22.
• Wallace DJ, Navarra S, Petri MA, Gallacher A, Thomas M, Furie R, Levy RA, van Vollenhoven RF, Cooper S, Zhong ZJ, Freimuth W, Cervera R; BLISS-52 and -76, and LBSL02 Study Groups. Safety profile of belimumab: pooled data from placebo-controlled phase 2 and 3 studies in patients with systemic lupus erythematosus. Lupus. 2013 Feb;22(2):144-54. doi: 10.1177/0961203312469259. Epub 2012 Dec 4.
• van Vollenhoven RF, Petri MA, Cervera R, Roth DA, Ji BN, Kleoudis CS, Zhong ZJ, Freimuth W. Belimumab in the treatment of systemic lupus erythematosus: high disease activity predictors of response. Ann Rheum Dis. 2012 Aug;71(8):1343-9. doi: 10.1136/annrheumdis-2011-200937. Epub 2012 Feb 15.
• Stohl W, Hiepe F, Latinis KM, Thomas M, Scheinberg MA, Clarke A, Aranow C, Wellborne FR, Abud-Mendoza C, Hough DR, Pineda L, Migone TS, Zhong ZJ, Freimuth WW, Chatham WW; BLISS-52 Study Group; BLISS-76 Study Group. Belimumab reduces autoantibodies, normalizes low complement levels, and reduces select B cell populations in patients with systemic lupus erythematosus. Arthritis Rheum. 2012 Jul;64(7):2328-37. doi: 10.1002/art.34400.
• Navarra SV, Guzman RM, Gallacher AE, Hall S, Levy RA, Jimenez RE, Li EK, Thomas M, Kim HY, Leon MG, Tanasescu C, Nasonov E, Lan JL, Pineda L, Zhong ZJ, Freimuth W, Petri MA; BLISS-52 Study Group. Efficacy and safety of belimumab in patients with active systemic lupus erythematosus: a randomised, placebo-controlled, phase 3 trial. Lancet. 2011 Feb 26;377(9767):721-31. doi: 10.1016/S0140-6736(10)61354-2. Epub 2011 Feb 4.

Helpful Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Study record dates

Study Major Dates

• Study Start: May 1, 2007
• Primary Completion (Actual): May 1, 2009
• Study Completion (Actual): March 1, 2010

Study Registration Dates

• First Submitted: January 17, 2007
• First Submitted That Met QC Criteria: January 17, 2007
• First Posted (Estimate): January 19, 2007

Study Record Updates

• Last Update Posted (Estimate): December 12, 2016
• Last Update Submitted That Met QC Criteria: October 28, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: Lupus; SLE; Systemic Lupus Erythematosus; Autoimmune Diseases; Antibodies; Belimumab
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Connective Tissue Diseases; Lupus Erythematosus, Systemic; Physiological Effects of Drugs; Immunosuppressive Agents; Immunologic Factors; Belimumab
• Other Study ID Numbers: HGS1006-C1057; BLISS-52 (Other Identifier: Human Genome Sciences Inc.); 110752 (Other Identifier: GSK)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Study Data/Documents

1. Informed Consent Form
   Information identifier: HGS1006-C1057
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Clinical Study Report
   Information identifier: HGS1006-C1057
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Study Protocol
   Information identifier: HGS1006-C1057
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Annotated Case Report Form
   Information identifier: HGS1006-C1057
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Dataset Specification
   Information identifier: HGS1006-C1057
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Statistical Analysis Plan
   Information identifier: HGS1006-C1057
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Individual Participant Data Set
   Information identifier: HGS1006-C1057
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register