Clinical trial NCT00424476: A Study of Belimumab in Subjects With Systemic Lupus Erythematosus (SLE)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Systemic Lupus Erythematosus
Keywords: Autoimmune Diseases
Lupus
SLE
Systemic Lupus Erythematosus
Belimumab
Antibodies
Lead sponsor: Human Genome Sciences Inc.
Sponsor class: INDUSTRY
Collaborators: name: GlaxoSmithKline
First posted: 2007-01-19
Enrollment: 865
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: SLE Responder Index (SRI) Response Rate at Week 52
timeFrame: Baseline, 52 weeks
Secondary outcomes:
measure: Percent of Subjects With a ≥ 4 Point Reduction From Baseline in SELENA SLEDAI Score at Wk 52.
timeFrame: Baseline, 52 weeks
measure: Mean Change in Physician's Global Assessment (PGA) at Wk 24.
timeFrame: Baseline, 24 weeks
measure: Mean Change From Baseline in Medical Outcomes 36-Item Short Form Health Survey (SF-36) Physical Component Summary Score (PCS) at Wk 24.
timeFrame: Baseline, 24 weeks
measure: Percent of Subjects Whose Average Prednisone Dose Has Been Reduced by ≥ 25% From Baseline to ≤ 7.5 mg/Day During Weeks 40 Through 52
timeFrame: Baseline, Weeks 40 through 52
Other outcomes:
measure: Adverse Events (AE) Overview
timeFrame: Up to 56 Weeks
Locations:
city: Buenos Aires
country: Argentina
facility: Hospital Britanico de Buenos Aires
city: Buenos Aires
country: Argentina
facility: Centro Privado de Medicina Familiar
city: Buenos Aires
country: Argentina
facility: Hospital Sirio Libanes
city: Buenos Aires
country: Argentina
facility: Atencion Integral en Reumatologia
city: Buenos Aires
country: Argentina
facility: Instituto de Investigaciones Medicas
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: OMI, Organización Médica de Investigación
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: CIER, Centro de Investigaciones en Enfermedades Reumáticas
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: Hospital General de Agudos Carlos G. Durand
city: La Plata
country: Argentina
facility: Hospital Interzonal General San Martín
city: Rosario
country: Argentina
facility: CAICI, Instituto Centralizado de Asistencia e Investigación Clínica Integral
city: San Miguel de Tucuman
country: Argentina
facility: Centro Medico Privado de Reumatologia
city: Daw Park
country: Australia
facility: Repatriation Hospital
city: Melbourne
country: Australia
facility: Emeritus Research, Cabrini Hospital
city: Melbourne
country: Australia
facility: Monash Medical Centre
city: Shenton Park
country: Australia
facility: Royal Perth Hospital
city: Campinas
country: Brazil
facility: Hospital de Clínicas - UNICAMP
city: Curitiba
country: Brazil
facility: Hospital das Clínicas - Universidade do Paraná
city: Fortaleza
country: Brazil
facility: Hospital de Clínicas - Universidade Federal de Pernambuco
city: Goiânia
country: Brazil
facility: Hospital Geral de Goiânia
city: Juiz de Fora
country: Brazil
facility: Hospital Universitário - Universidade Federal de Juiz de Fora
city: Porto Alegre
country: Brazil
facility: Hospital São Lucas da PUC-RS
city: Rio de Janeiro
country: Brazil
facility: Hospital Universitário Pedro Ernesto - UERJ
city: Rio de Janeiro
country: Brazil
facility: Hospital Unversitario Clementino Fraga Filho UFRJ
city: Salvador
country: Brazil
facility: Hospital Santa Izabel
city: São Paulo
country: Brazil
facility: Hospital Abreu Sodré
city: São Paulo
country: Brazil
facility: Hospital do Servidor Público Estadual de São Paulo - Francisco Morato de Oliveira
city: São Paulo
country: Brazil
facility: Hospital Heliópolis
city: Santiago
country: Chile
facility: Hospital Dr. Sotero del Rio
city: Santiago
country: Chile
facility: Pontificia Universidad Católica de Chile
city: Santiago
country: Chile
facility: Clínica Dávila
city: Viña del Mar
country: Chile
facility: Hospital Dr. Gustavo Fricke
city: Bogota
country: Colombia
facility: Office of Dr. Guzman
state: Cundinamarca
city: Bucaramanga
country: Colombia
facility: Fundación Oftalmologica de Santander Clinica Carlos Ardila Lulle
state: Santander
city: Barranquilla
country: Colombia
facility: Centro de Reumatologia y Ortopedia
city: Bogota
country: Colombia
facility: Fundación Instituto de Reumatología Fernando Chalem
city: Bogotá
country: Colombia
facility: Centrode de Investigaciones en Reumatologia Especialidades Medicas (CIREEH)
city: Bogotá
country: Colombia
facility: Riesgo de Fracturas
city: Bucaramanga
country: Colombia
facility: SERVIMED
city: Medellín
country: Colombia
facility: Corporación para Investigaciones Biológicas (CIB)
city: Medellín
country: Colombia
facility: Office of Dr. Jose Molina
city: Chai Wan
country: Hong Kong
facility: Pamela Youde Nethersole Eastern Hospital
city: Shatin
country: Hong Kong
facility: Rheumatology Assessment and Treatment Center, Pok Oi Hospital
city: Tuen Mun
country: Hong Kong
facility: Tuen Mun Hospital
city: Bangalore
country: India
facility: St. John's Medical College Hospital
city: Hyderabaad
country: India
facility: Krishna Institute of Medical Sciences
city: Hyderabaad
country: India
facility: Nizam's Institute of Medical Sciences
city: Hyderabad
country: India
facility: Apollo Hospitals
city: Lucknow
country: India
facility: Chhatrapati Shahuji Maharaj Medical University
city: Mumbai
country: India
facility: King Edward Memorial (K.E.M.) Hospital
city: Trivandrum
country: India
facility: Kerala Institute of Medical Sciences
city: Daegu
country: Korea, Republic of
facility: Kyungpook National Univesity Hospital
city: Daejeon
country: Korea, Republic of
facility: Eulji University Hospital
city: Inchon
country: Korea, Republic of
facility: Inha University Hospital
city: Pusan
country: Korea, Republic of
facility: Dong-A University Hospital 3-1 (Dept. Rhuematology)
city: Pusan
country: Korea, Republic of
facility: Pusan National University Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: The Hospital for Rheumatic Diseases, Hanyang University Hospital
city: Seoul
country: Korea, Republic of
facility: Catholic Universtigy of Korea, Kangnam St. Mary's Hospital
city: Seoul
country: Korea, Republic of
facility: Catholic University, Yoido St. Mary's Hospital
city: Suwon
country: Korea, Republic of
facility: Ajou University Hospital
city: Lima
country: Peru
facility: Hospital Nacional Alberto Sabogal Sologuren ESSALUD
city: Lima
country: Peru
facility: Hospital Nacional Guillermo Almenara Irigoyen ESSALUD
city: Lima
country: Peru
facility: Clinica Ricardo Palma Anexo 9 - Javier Prado Este
city: Lima
country: Peru
facility: Instituto de Ginecología y Reproducción
city: Cebu City
country: Philippines
facility: Chong Hua Hospital
city: Davao City
country: Philippines
facility: Davao Medical Center
city: Las Pinas City
country: Philippines
facility: University of Perpetual Help -Rizal
city: Manila City
country: Philippines
facility: Philippine General Hospital
city: Manila City
country: Philippines
facility: University of Santo Tomas Hospital
city: Quezon City
country: Philippines
facility: St. Luke's Medical Center
city: Bucharest
country: Romania
facility: Spitalul Clinic Sf Maria
city: Bucharest
country: Romania
facility: Spitalul Clinic Colentina
city: Bucharest
country: Romania
facility: Spitalul de Urgenta al Ministerului Administratiei si Internelor Prof. Dr. Dimitrie Gerota
city: Bucharest
country: Romania
facility: Spitalul Clinic Dr. Ion Cantacuzino
city: Cluj Napoca
country: Romania
facility: Spitalul Clinic Judetean de Urgenta Cluj-Napoca
city: Moscow
country: Russian Federation
facility: State Institution Scientific Research Institute of Rheumatology
city: St. Petersburg
country: Russian Federation
facility: St. Petersburg City Hospital (Rheumatology Center)
city: St.-Petersburg
country: Russian Federation
facility: Academy of Post-Graduated Education
city: St.-Petersburg
country: Russian Federation
facility: St.-Petersburg Region Clinical Hospital
city: Yaroslavl
country: Russian Federation
facility: Soloviev's City Clinical Hospital,
city: Yaroslavl
country: Russian Federation
facility: City Healthcare Institution Municipal Hospital NPZ,
city: Chia-Yi
country: Taiwan
facility: Buddhist Tzu Chi General Hospital, Dalin
city: Haulien
country: Taiwan
facility: Buddhist Tzu Chi General Hospital - Hualien
city: Kaohsiung
country: Taiwan
facility: Chung-Ho Memorial Hospital, Kaohsiung Medical University
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Veterans General Hospital
city: Kaosiung
country: Taiwan
facility: Chang Gung Memorial Hospital, Kaosiung
city: Keelung
country: Taiwan
facility: Chang Gung Memorial Hospital-Keelung
city: Taichung
country: Taiwan
facility: Chung Shan Medical University Hospital
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Tau-Yuan County
country: Taiwan
facility: Chang Gung Memorial Hospital, Linko
Study officials:
affiliation: Human Genome Sciences Inc.
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.