A Study of Belimumab in Subjects With Systemic Lupus Erythematosus

Systemic Lupus Erythematosus Clinical Trial

— BLISS-76  

Official title:

A Phase 3, Multi-Center, Randomized, Double-Blind, Placebo-Controlled, 76-Week 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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00410384
• Other study ID #: HGS1006-C1056
• Secondary ID: BLISS-76110751
• Status: Completed
• Phase: Phase 3
• First received: December 8, 2006
• Last updated: February 13, 2014
• Start date: December 2006
• Est. completion date: March 2010

Study information

• Verified date: February 2014
• Source: Human Genome Sciences Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Paul-Ehrlich-InstitutRomania: Ministry of Public HealthUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyUnited States: Food and Drug AdministrationAustria: Agency for Health and Food SafetyFrance: Ministry of HealthBelgium: Federal Agency for Medicinal Products and Health ProductsSpain: Agencia Española de Medicamentos y Productos SanitariosItaly: Ministry of HealthPoland: Ministry of HealthCanada: Health CanadaMexico: Ministry of HealthIsrael: Ministry of HealthSweden: Medical Products AgencyNetherlands: The Central Committee on Research Involving Human Subjects (CCMO)Czech Republic: State Institute for Drug Control
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 819
• Est. completion date: March 2010
• Est. primary completion date: September 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lupus Erythematosus, Systemic
• Systemic Lupus Erythematosus

Intervention

Drug:
• Placebo
Placebo IV plus standard therapy; placebo administered on Days 0, 14, 28, and every 28 days thereafter through 72 weeks.
• Belimumab 1 mg/kg
Belimumab 1 mg/kg IV plus standard therapy; belimumab 1 mg/kg administered on Days 0, 14, 28, and every 28 days thereafter through 72 weeks.
• Belimumab 10 mg/kg
Belimumab 10 mg/kg IV plus standard therapy; belimumab 10 mg/kg administered on Days 0, 14, 28, and every 28 days thereafter through 72 weeks.

Locations

Country	Name	City	State
Austria	Universitatsklinik fur innere Medizin	Graz
Austria	Rheumazentrum Favoriten	Vienna
Belgium	Cliniques Universitaires	Brussels
Belgium	University Hospital	Leuven
Belgium	CHU Sart Tilman	Liege
Canada	McGill University Health Centre, Montreal General Hospital	Montreal
Canada	Centre for Prognosis Studies in Rheaumatic Diseases	Toronto	Ontario
Canada	Toronto Western Hospital	Toronto	Ontario
Costa Rica	Hospital Clinica Biblica	San Jose
Czech Republic	University Hospital Brno	Brno
Czech Republic	University Hospital Hradec Kralove	Hradec Kralove
Czech Republic	University Hospital Olomouc	Olomouc
Czech Republic	Institute of Rheumatology	Prague
France	CHU Hospital de Bicetre	Le Kremlin Bicetre
France	Hospital Huriez	Lille Cedex
France	Nouvel Hospital Civil - Medecine Interne et Immunologie Clinique	Stasbourg
France	Hospital FOCH	Suresnes Cedex
France	Centre Hospitalier Universitarie (CHU) - PURPAA	Toulouse
Germany	Kerckhoff-Klink Bad Nauheim	Bad Nauheim
Germany	Charite	Berlin
Germany	Schlossparkklinik	Berlin
Germany	Uniklinik Dusseldorf-Klinik for Endokrinologie, Diabetologie and Rheumatologie Klinik	Dusseldorf
Germany	FA Universitat Erlangen Nurnberg	Erlangen
Germany	Universitatsklinikum Frankfurt	Frankfurt
Germany	Medizinische Universitatsklinik	Freiburg
Germany	Medizinische Hochschule Hannover	Hannover
Germany	Friedrich Schiller Universitat	Jena
Germany	Universitatsklinik Schleswig-Holstein, Campus Kiel	Kiel
Germany	Universitatsklinikum Leipzig	Leipzig
Germany	Universitatsklinik Mainz	Mainz
Germany	Universitatsklinikum Tubingen	Tubingen
Israel	Soroka University Medical Center	Beer-Sheva
Israel	B'nai-Zion Medical Center	Haifa
Israel	Carmel Medical Center	Haifa
Israel	Rambam Medical Center	Haifa
Israel	Beilinson Hospital, Rabin Medical Center	Petach Tikva
Israel	Sheba Medical Center	Ramat Gan
Israel	Kaplan Medical Center	Rehovot
Israel	Tel-Aviv Saurasky Medical Center	Tel-Aviv
Italy	A. O. Ospedaliera-Universitaria Arcispedale	Ferrara
Italy	A.O. Ospedale San Carlo Borromeo	Milano
Italy	Policlinico di Modena	Modena
Italy	Policlinico Universitario of Padova	Padova
Italy	A.O. San Camillo	Rome
Italy	Policlinico Umberto 1	Rome
Italy	U.O. di reumatologia Presidio Ospedaliero di Scafati	Scafati
Italy	Azienda Ospedaliero University-Santa Maria della Misericordia	Udine
Mexico	Hospital Civil de Guadalajara "Fray Antonio Alcalde"	Guadalajara
Mexico	Instituto Jalisciense de Investigacion Clinica	Jalisco
Mexico	Hospital General de México	Mexico City
Mexico	Hospital Regional 1o de Octubre - ISSSTE	Mexico City
Mexico	Insituto Nacional de Ciencias Medicas y Nutricion Salvador Zubirin	Mexico City
Mexico	Hospital Central de S.L.P. "Iganico Morones Prieto"	San Luis Potosi
Mexico	Instituto de Seguridad Social del Estado de Mexico y Municipios	Toluca
Netherlands	Leiden University Medical Center	Leiden
Netherlands	University Medical Center Maastricht	Maastricht
Netherlands	Erasmus Medical Center	Rotterdam
Netherlands	Ikazia Ziekenhuis	Rotterdam
Poland	Szpital Uniwerytecki nr Zim. dr. Jana Biziela	Bydgoszcz
Poland	Szpital Specjalistyczny Sw. Lukasza	Konskie
Poland	Malopolskie Centrum Medyczne	Krakow
Poland	Gabinety Profesorow Osrodek Baden Klinicznych	Lublin
Poland	Klinika Reumatologii im Prof. Eleonory Reicher	Warszawa
Poland	Akademicki Szpital Klinika Reumatologii Chorob Wewnetrznych	Wroclaw
Puerto Rico	Ponce School of Medicine	Ponce
Puerto Rico	University of Puerto Rico Medical Center	Rio Piedras
Romania	Spitalul Clinic "Sf Maria"	Bucuresti
Romania	Spitalul Clinic Colentina	Bucuresti
Slovakia	Narodny Ustav Reumatickych Chorob	Piestany
Spain	Hospital Clinic i Provincial Barcelona	Barcelona
Spain	Hospital La Vall d'Hebron	Barcelona
Spain	Hospital Universitario San Cecilio	Granada
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Regional Universitario de SAS - Carlos Haya	Malaga
Spain	Hospital Son Dureta	Mallorca
Sweden	Sahlgrensja University Hospital	Goteborg
Sweden	Karolinska Universitetssjukhuset	Stockholm
United Kingdom	St. Thomas Hospital	London
United Kingdom	Freeman Hospital	Newcastle upon Tyne
United States	University of Michigan Medical Center - Regents of University of Michigan	Ann Arbor	Michigan
United States	Arthritis Clinic of Northern Virginia, P.C.	Arlington	Virginia
United States	Emory University	Atlanta	Georgia
United States	Walter Chase	Austin	Texas
United States	Arthritis and Rheumatic Disease Specialties	Aventura	Florida
United States	Johns Hopkins University	Baltimore	Maryland
United States	Ochsner Clinic Foundation	Baton Rouge	Louisiana
United States	East Penn Rheumatology Associates	Bethlehem	Pennsylvania
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Selah Medical Clinical Research Unit	Boise	Idaho
United States	Tufts - New England Medical Center	Boston	Massachusetts
United States	Montefiore Medical Center	Bronx	New York
United States	SUNY-Downstate Medical Center	Brooklyn	New York
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	Low Country Rheumatology, PA/Low Country Research Center	Charleston	South Carolina
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Rheumatology Associates, SC	Chicago	Illinois
United States	University of Chicago Hospitals	Chicago	Illinois
United States	Arthritis Associates of Colorado Springs	Colorado Springs	Colorado
United States	Ohio State University	Columbus	Ohio
United States	Osteoporosis and Clinical Trials Center	Cumberland	Maryland
United States	University of Texas - Southwestern Medical Center	Dallas	Texas
United States	STAT Research, Inc.	Dayton	Ohio
United States	Stafford Medical Associates, PA	Dover	New Hampshire
United States	Altoona Center for Clinical Research	Duncanville	Pennsylvania
United States	Texas Tech University Health Sciences Center	El Paso	Texas
United States	Palmetto Clinical Trial at Piedmont Arthritis Clinic	Greenville	South Carolina
United States	Physicians East, PA	Greenville	North Carolina
United States	Osteoporosis & Clinical Trials Center	Hagerstown	Maryland
United States	Accurate Clinical Research	Houston	Texas
United States	Houston Institute for Clinical Research	Houston	Texas
United States	The Rheumatic Disease Clinical Research Center	Houston	Texas
United States	Talbert Medical Group	Huntington Beach	California
United States	Kansas University Medical Center	Kansas City	Kansas
United States	North Shore-LIJ Health System/Rheumatology and Allergy Clinic	Lake Success	New York
United States	Fiechtner Research, Inc.	Lansing	Michigan
United States	Valerius Medical Group & Research Ctr of Greater Long Beach, Inc.	Long Beach	California
United States	UCLA Rheumatology	Los Angeles	California
United States	University of Southern California	Los Angeles	California
United States	Wallace Rheumatic Study Center	Los Angeles	California
United States	Kentuckiana Center for Better Bone and Joint Health	Louisville	Kentucky
United States	Feinstein Institute	Manhasset	New York
United States	University of Miami-Division of Rheumatology and Immunology	Miami	Florida
United States	Medical Specialists Clinical Research	Munster	Indiana
United States	Hopital for Joint Diseases	New York	New York
United States	Hospital for Special Surgery	New York	New York
United States	Oklahoma Medical Research Center	Oklahoma City	Oklahoma
United States	Gundersen Clinic, Ltd.	Onalaska	Wisconsin
United States	Rheumatology Associates of Central Florida	Orlando	Florida
United States	Arizona Arthritis and Rheumatology Research, PPLC	Paradise Valley	Arizona
United States	University of Pittsburgh	Pittsburgh	Pennsylvania
United States	AAIR Research Center	Rochester	New York
United States	Rheumatology Clinic	Salt Lake City	Utah
United States	Arthritis Center of South Texas	San Antonio	Texas
United States	Arthritis Care Center, Inc.	San Jose	California
United States	The Seattle Arthritis Clinic	Seattle	Washington
United States	Rheumatology Associates	Smithtown	New York
United States	Arthritis Northwest, PLLC	Spokane	Washington
United States	Washington University School of Medicine	St. Louis	Missouri
United States	Texas Research Center	Sugar Land	Texas
United States	Southwest Florida Clinical Research Center	Tampa	Florida
United States	Tampa Medical Group, P.A.	Tampa	Florida
United States	The University of Arizona Arthritis Center	Tucson	Arizona
United States	Oklahoma Center For Arthritis Therapy & Research	Tulsa	Oklahoma
United States	Inland Rheumatic Disease Specialties	Upland	California
United States	Washington Hospital Center	Washington	District of Columbia
United States	Wake Forest University Health Services	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Human Genome Sciences Inc.	GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Austria,  Belgium,  Canada,  Costa Rica,  Czech Republic,  France,  Germany,  Israel,  Italy,  Mexico,  Netherlands,  Poland,  Puerto Rico,  Romania,  Slovakia,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Adverse Event (AE) Overview	SEE ALSO ADVERSE EVENT RESULTS SECTION	Up to 80 Weeks	Yes
Primary	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	No
Secondary	SRI Response Rate at Week 76	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, 76 Weeks	No
Secondary	Percent of Subjects With a = 4 Point Reduction From Baseline in SELENA SLEDAI Score at Week 52.		Baseline, 52 Weeks	No
Secondary	Mean Change in Physician's Global Assessment (PGA) at Week 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	No
Secondary	Mean Change From Baseline in Medical Outcomes 36-Item Short Form Health Survey (SF-36) Physical Component Summary Score (PCS) at Week 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	No
Secondary	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 40-52	No