Belimumab Assessment of Safety in SLE

Systemic Lupus Erythematosus Clinical Trial

— BASE  

Official title:

A Randomized, Double-Blind, Placebo-Controlled 52-Week Study to Assess Adverse Events of Special Interest in Adults With Active, Autoantibody-Positive Systemic Lupus Erythematosus Receiving Belimumab

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01705977
• Other study ID #: 115467
• Secondary ID: 2011-005667-25HG
• Status: Completed
• Phase: Phase 4
• Start date: November 27, 2012
• Est. completion date: August 10, 2022

Study information

• Verified date: August 2023
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to further enhance the existing knowledge regarding the side effects of belimumab when given with other lupus medicines to adults with active systemic lupus erythematosus (SLE). This study mainly focuses on collecting information on serious events that are not that common or may only be seen with long-term treatment. These events include death, serious infections and other infections of interest, cancers, serious mental health problems, including depression and suicide, and serious infusion and hypersensitivity reactions. This study is being done to help understand if treatment with belimumab increases the risk for these types of events. This study will also see if patients receiving belimumab with other lupus medicines can reduce their use of steroids, such as prednisone, over 1 year.

Description:

Study participants receive standard therapy for SLE in addition to receiving the study drug, either placebo (no active medicine) or belimumab. The controlled period of the study is 52 weeks. The random assignment in this study is "1 to 1" which means that participants have an equal chance of receiving belimumab or placebo. After completion of the 52-week study period, participants will be contacted by phone annually for 4 more years to assess health status. Following the 52-week controlled period, participants who wish to continue treatment with belimumab may be able to do so by being prescribed commercially available belimumab. If belimumab is not commercially available in the participant's country, the participant may be able to receive belimumab under a separate continuation protocol.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 4019
• Est. completion date: August 10, 2022
• Est. primary completion date: July 30, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

• Clinical diagnosis of SLE by American College of Rheumatology (ACR) criteria.
• Active SLE disease.
• Autoantibody-positive.
• On stable SLE treatment regimen which may include corticosteroids (for example, prednisone), antimalarial (for example, hydroxychloroquine) and/or immunosuppressants (for example, azathioprine, methotrexate, mycophenolate).

Key Exclusion Criteria:

• Pregnant or nursing.
• Have received treatment with any of the following: belimumab, either as a marketed product or as an investigational agent; any B cell targeted therapy (for example, rituximab) in the past year; or any biological agent (for example, adalimumab, etanercept, infliximab, or anakinra) in the past 90 days.
• Have received a live vaccine within the past 30 days.
• Have severe active lupus kidney disease.
• Have severe active central nervous system (CNS) lupus.
• Current or past positive for human immunodeficiency virus (HIV), hepatitis B, or hepatitis C.

Related Conditions & MeSH terms

• Lupus Erythematosus, Systemic
• Systemic Lupus Erythematosus

Intervention

Biological:
• Placebo plus standard therapy
Placebo plus standard therapy
• Belimumab 10 mg/kg plus standard therapy
Belimumab 10 mg/kg plus standard therapy

Other:
• Standard therapy
Standard therapy comprises any of the following (alone or in combination): corticosteroids, antimalarials, non-steroidal anti-inflammatory drugs (NSAIDs), and immunosuppressives; other biologics are not permitted.

Locations

Country	Name	City	State
Argentina	GSK Investigational Site	Buenos Aires
Argentina	GSK Investigational Site	Buenos Aires
Argentina	GSK Investigational Site	Capital Federal	Buenos Aires
Argentina	GSK Investigational Site	Ciudad Autonoma Buenos Aires	Buenos Aires
Argentina	GSK Investigational Site	Ciudad Autonoma Buenos Aires	Buenos Aires
Argentina	GSK Investigational Site	Cordoba
Argentina	GSK Investigational Site	La Plata	Buenos Aires
Argentina	GSK Investigational Site	Lanús	Buenos Aires
Argentina	GSK Investigational Site	Mar del Plata	Buenos Aires
Argentina	GSK Investigational Site	Mendoza
Argentina	GSK Investigational Site	Rosario	Santa Fe
Argentina	GSK Investigational Site	Rosario	Santa Fe
Argentina	GSK Investigational Site	San Miguel de Tucumán	Tucumán
Argentina	GSK Investigational Site	Tucuman
Argentina	GSK Investigational Site	Venado Tuerto	Santa Fe
Argentina	GSK Investigational Site	Zarate	Buenos Aires
Australia	GSK Investigational Site	Fitzroy	Victoria
Australia	GSK Investigational Site	Garran	Australian Capital Territory
Australia	GSK Investigational Site	Herston	Queensland
Australia	GSK Investigational Site	Sydney	New South Wales
Brazil	GSK Investigational Site	Belo Horizonte	Minas Gerais
Brazil	GSK Investigational Site	Belo Horizonte, Minas Gerais
Brazil	GSK Investigational Site	Campinas
Brazil	GSK Investigational Site	Campo Grande
Brazil	GSK Investigational Site	Cuiaba	Mato Grosso
Brazil	GSK Investigational Site	Curitiba	Paraná
Brazil	GSK Investigational Site	Goiania
Brazil	GSK Investigational Site	Itajaí	Santa Catarina
Brazil	GSK Investigational Site	Juiz de Fora	Minas Gerais
Brazil	GSK Investigational Site	Lajeado
Brazil	GSK Investigational Site	Porto Alegre	Rio Grande Do Sul
Brazil	GSK Investigational Site	Porto Alegre	Rio Grande Do Sul
Brazil	GSK Investigational Site	Rio de Janeiro
Brazil	GSK Investigational Site	Salvador
Brazil	GSK Investigational Site	Sao Jose do Rio Preto	São Paulo
Brazil	GSK Investigational Site	Sao Paulo	São Paulo
Brazil	GSK Investigational Site	São Paulo
Brazil	GSK Investigational Site	São Paulo
Bulgaria	GSK Investigational Site	Pleven
Bulgaria	GSK Investigational Site	Plovdiv
Bulgaria	GSK Investigational Site	Plovdiv
Bulgaria	GSK Investigational Site	Ruse
Bulgaria	GSK Investigational Site	Shumen
Bulgaria	GSK Investigational Site	Sofia
Bulgaria	GSK Investigational Site	Stara Zagora
Bulgaria	GSK Investigational Site	Targovisthe
Bulgaria	GSK Investigational Site	Veliko Tarnovo
Canada	GSK Investigational Site	Brampton	Ontario
Canada	GSK Investigational Site	Vaughan	Ontario
Chile	GSK Investigational Site	La Serena
Chile	GSK Investigational Site	Santigo
Colombia	GSK Investigational Site	Armenia
Colombia	GSK Investigational Site	Barranquilla
Colombia	GSK Investigational Site	Bogota
Colombia	GSK Investigational Site	Bucaramanga
Colombia	GSK Investigational Site	Chia
Colombia	GSK Investigational Site	Medellin
Croatia	GSK Investigational Site	Osijek
Croatia	GSK Investigational Site	Rijeka
Czechia	GSK Investigational Site	Brno
Czechia	GSK Investigational Site	Praha 2
Czechia	GSK Investigational Site	Praha 5
Czechia	GSK Investigational Site	Zlin
Estonia	GSK Investigational Site	Tallinn
Hong Kong	GSK Investigational Site	Hong Kong
Hong Kong	GSK Investigational Site	Shatin
Hungary	GSK Investigational Site	Budapest
Hungary	GSK Investigational Site	Budapest
Hungary	GSK Investigational Site	Debrecen
Hungary	GSK Investigational Site	Debrecen
Hungary	GSK Investigational Site	Gyula
Hungary	GSK Investigational Site	Zalaegerszeg
Indonesia	GSK Investigational Site	Bandung
Indonesia	GSK Investigational Site	Denpasar
Indonesia	GSK Investigational Site	Malang
Indonesia	GSK Investigational Site	Palembang
Indonesia	GSK Investigational Site	Yogyakarta
Italy	GSK Investigational Site	Firenze	Toscana
Italy	GSK Investigational Site	Milano	Lombardia
Italy	GSK Investigational Site	Padova	Veneto
Italy	GSK Investigational Site	Pisa
Italy	GSK Investigational Site	Roma	Lazio
Korea, Republic of	GSK Investigational Site	Daegu
Korea, Republic of	GSK Investigational Site	Daejeon
Korea, Republic of	GSK Investigational Site	Daejeon
Korea, Republic of	GSK Investigational Site	Gwangju
Korea, Republic of	GSK Investigational Site	Incheon
Korea, Republic of	GSK Investigational Site	Jeonju-si
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	Seoul
Korea, Republic of	GSK Investigational Site	Suwon
Korea, Republic of	GSK Investigational Site	Suwon-si
Lithuania	GSK Investigational Site	Klaipeda
Malaysia	GSK Investigational Site	Ipoh
Malaysia	GSK Investigational Site	Kota Bahru
Malaysia	GSK Investigational Site	Kota Kinabalu
Malaysia	GSK Investigational Site	Kuala Lumpur
Malaysia	GSK Investigational Site	Kuala Terengganu
Malaysia	GSK Investigational Site	Selangor
Malaysia	GSK Investigational Site	Seremban, Negeri Sembilan
Mexico	GSK Investigational Site	Cuautitlan Izcalli	Estado De México
Mexico	GSK Investigational Site	D.F
Mexico	GSK Investigational Site	Guadalajara
Mexico	GSK Investigational Site	Guadalajara	Jalisco
Mexico	GSK Investigational Site	Guadalajara	Jalisco
Mexico	GSK Investigational Site	Merida	Yucatán
Mexico	GSK Investigational Site	Mexico
Mexico	GSK Investigational Site	Mexico
Mexico	GSK Investigational Site	Monterrey	Nuevo León
Mexico	GSK Investigational Site	San Luis Potosí
Mexico	GSK Investigational Site	San Luis Potosí
Mexico	GSK Investigational Site	Torreon
Mexico	GSK Investigational Site	Torreon	Coahuila
New Zealand	GSK Investigational Site	Auckland
New Zealand	GSK Investigational Site	Wellington
Peru	GSK Investigational Site	Arequipa
Peru	GSK Investigational Site	Lima
Peru	GSK Investigational Site	Lima
Peru	GSK Investigational Site	Lima
Peru	GSK Investigational Site	Lima
Peru	GSK Investigational Site	Lima
Peru	GSK Investigational Site	Lima
Peru	GSK Investigational Site	Lima
Philippines	GSK Investigational Site	Angeles City, Pampanga
Philippines	GSK Investigational Site	Cebu City
Philippines	GSK Investigational Site	Davao City
Philippines	GSK Investigational Site	Iloilo City
Philippines	GSK Investigational Site	Las Pinas
Philippines	GSK Investigational Site	Manila
Philippines	GSK Investigational Site	Manila
Philippines	GSK Investigational Site	Quezon City
Poland	GSK Investigational Site	Bydgoszcz
Poland	GSK Investigational Site	Gdansk
Poland	GSK Investigational Site	Krakow
Portugal	GSK Investigational Site	Almada
Portugal	GSK Investigational Site	Coimbra
Portugal	GSK Investigational Site	Lisboa
Portugal	GSK Investigational Site	Lisboa
Portugal	GSK Investigational Site	Porto
Portugal	GSK Investigational Site	Porto
Portugal	GSK Investigational Site	Viseu
Romania	GSK Investigational Site	Bucharest
Romania	GSK Investigational Site	Galati
Romania	GSK Investigational Site	Targu Mures
Russian Federation	GSK Investigational Site	Barnaul
Russian Federation	GSK Investigational Site	Kemerovo
Russian Federation	GSK Investigational Site	Kursk
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Saint-Petersburg
Russian Federation	GSK Investigational Site	Saratov
Russian Federation	GSK Investigational Site	St. Petersburg
Serbia	GSK Investigational Site	Belgrade
Serbia	GSK Investigational Site	Belgrade
Serbia	GSK Investigational Site	Krusevac
Serbia	GSK Investigational Site	Niska Banja
Serbia	GSK Investigational Site	Sabac
Slovakia	GSK Investigational Site	Piestany
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Bilbao
Spain	GSK Investigational Site	Castellón
Spain	GSK Investigational Site	Cordoba
Spain	GSK Investigational Site	Getafe/Madrid
Spain	GSK Investigational Site	Granada
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Malaga
Spain	GSK Investigational Site	Sevilla
Spain	GSK Investigational Site	Seville
Spain	GSK Investigational Site	Valencia
Spain	GSK Investigational Site	Valencia
Spain	GSK Investigational Site	Vilajoyosa
Switzerland	GSK Investigational Site	St. Gallen
Switzerland	GSK Investigational Site	Zuerich
Taiwan	GSK Investigational Site	Chiayi County
Taiwan	GSK Investigational Site	Gueishan Township,Taoyuan County
Taiwan	GSK Investigational Site	Kaohsiung
Taiwan	GSK Investigational Site	Taichung
Taiwan	GSK Investigational Site	Taichung
Taiwan	GSK Investigational Site	Taipei
Taiwan	GSK Investigational Site	Taipei
Taiwan	GSK Investigational Site	Taipei
Thailand	GSK Investigational Site	Bangkok
Thailand	GSK Investigational Site	Bangkok
Thailand	GSK Investigational Site	Chiang Mai
Ukraine	GSK Investigational Site	Chernivtsi
Ukraine	GSK Investigational Site	Donetsk
Ukraine	GSK Investigational Site	Donetsk
Ukraine	GSK Investigational Site	Ivano-Frankivsk
Ukraine	GSK Investigational Site	Kharkiv
Ukraine	GSK Investigational Site	Kyiv
Ukraine	GSK Investigational Site	Kyiv
Ukraine	GSK Investigational Site	Lviv
Ukraine	GSK Investigational Site	Odesa
Ukraine	GSK Investigational Site	Poltava
Ukraine	GSK Investigational Site	Ternopil
Ukraine	GSK Investigational Site	Uzhgorod
Ukraine	GSK Investigational Site	Vinnytsia
Ukraine	GSK Investigational Site	Vinnytsia
Ukraine	GSK Investigational Site	Vinnytsya
Ukraine	GSK Investigational Site	Zaporizhzhia
United States	GSK Investigational Site	Anniston	Alabama
United States	GSK Investigational Site	Arlington	Virginia
United States	GSK Investigational Site	Beckley	West Virginia
United States	GSK Investigational Site	Birmingham	Alabama
United States	GSK Investigational Site	Cedar Rapids	Iowa
United States	GSK Investigational Site	Chapel Hill	North Carolina
United States	GSK Investigational Site	Charlotte	North Carolina
United States	GSK Investigational Site	Charlotte	North Carolina
United States	GSK Investigational Site	Cincinnati	Ohio
United States	GSK Investigational Site	Clarksburg	West Virginia
United States	GSK Investigational Site	Clearwater	Florida
United States	GSK Investigational Site	Columbus	Ohio
United States	GSK Investigational Site	Covina	California
United States	GSK Investigational Site	Cypress	Texas
United States	GSK Investigational Site	Dallas	Texas
United States	GSK Investigational Site	Duncansville	Pennsylvania
United States	GSK Investigational Site	Glendale	Arizona
United States	GSK Investigational Site	Hialeah	Florida
United States	GSK Investigational Site	Hixson	Tennessee
United States	GSK Investigational Site	Houston	Texas
United States	GSK Investigational Site	Houston	Texas
United States	GSK Investigational Site	Houston	Texas
United States	GSK Investigational Site	Huntington Beach	California
United States	GSK Investigational Site	Huntsville	Alabama
United States	GSK Investigational Site	Jackson	Mississippi
United States	GSK Investigational Site	Kalispell	Montana
United States	GSK Investigational Site	La Mesa	California
United States	GSK Investigational Site	Las Vegas	Nevada
United States	GSK Investigational Site	Long Beach	California
United States	GSK Investigational Site	Los Angeles	California
United States	GSK Investigational Site	McKinney	Texas
United States	GSK Investigational Site	Memphis	Tennessee
United States	GSK Investigational Site	Mesa	Arizona
United States	GSK Investigational Site	Murrieta	California
United States	GSK Investigational Site	New York	New York
United States	GSK Investigational Site	New York	New York
United States	GSK Investigational Site	Orangeburg	South Carolina
United States	GSK Investigational Site	Phoenix	Arizona
United States	GSK Investigational Site	Phoenix	Arizona
United States	GSK Investigational Site	Rock Hill	South Carolina
United States	GSK Investigational Site	Sacramento	California
United States	GSK Investigational Site	Saint Clair Shores	Michigan
United States	GSK Investigational Site	San Leandro	California
United States	GSK Investigational Site	Spokane	Washington
United States	GSK Investigational Site	Summerville	South Carolina
United States	GSK Investigational Site	Tampa	Florida
United States	GSK Investigational Site	Webster	Texas
United States	GSK Investigational Site	West Bloomfield	Michigan
United States	GSK Investigational Site	Wyomissing	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Brazil,  Bulgaria,  Canada,  Chile,  Colombia,  Croatia,  Czechia,  Estonia,  Hong Kong,  Hungary,  Indonesia,  Italy,  Korea, Republic of,  Lithuania,  Malaysia,  Mexico,  New Zealand,  Peru,  Philippines,  Poland,  Portugal,  Romania,  Russian Federation,  Serbia,  Slovakia,  Spain,  Switzerland,  Taiwan,  Thailand,  Ukraine, 

References & Publications (1)

Sheikh S, Scheinberg MA, Wei CC, Tegzova D, Stohl W, Acayaba de Toledo R, Mucenic T, Abello M, Maksimowicz-McKinnon K, Abud Mendoza C, Navarra S, Garcia M, Garcia de la Torre I, Ordi Ros J, Nami A, Levy R, Bass D, Ross J, Punwaney R, Harris J, Pierce A, Thorneloe K, Ji B, Roth D. Mortality and adverse events of special interest in adult patients with active, auto-antibody-positive systemic lupus erythematosus receiving intravenous belimumab (BASE): a global, randomised, double-blind, placebo-controlled, multicentre Phase 4 trial. Lancet Rheumatol. 2020; DOI: 10.1016/S2665-9913(20)30355-6

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Deaths - On Treatment Period (Week 52)	Number of participants who died during on-treatment period (Week 52) is reported. The on-treatment period was defined as first dose to last dose + 28 days (or death). The As-Treated Population was defined as all participants who were randomized and received at least one dose of study agent,grouped according to the actual treatment administered for the majority (greater than [>]50 percent [%]) of the time. The on-treatment period was the primary analysis period for safety analyses.	Up to Week 52 (On-treatment period)
Primary	Number of Participants Who Reported Protocol Defined Adverse Events of Special Interest (AESI): On-treatment Period (Week 52)	A summary of protocol defined AESIs including serious infections, opportunistic infections and other infections of interest (serious and non-serious), non-melanoma skin cancer (NMSC), malignancies (excluding NMSC), psychiatric events suggesting serious mood disorders and anxiety (serious depression), suicidality (using Columbia-Suicide Severity Rating Scale [C-SSRS]) and serious infusion and hypersensitivity reactions (SIHR) is reported. The on-treatment period (Week 52) was defined as first dose to last dose + 28 days (or death). The on-treatment period was the primary analysis period for safety analyses.	Up to Week 52 (On-treatment period)
Primary	Number of Participants With Serious Adverse Events (SAEs) Reported During On-treatment Period (Week 52)	An SAE is defined as any untoward medical occurrence that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect, associated with liver injury and impaired liver function or any other situations as per medical or scientific judgement. The on-treatment period (Week 52) was defined as first dose to last dose + 28 days (or death) and was the primary analysis period for safety analyses.	Up to Week 52 (On-treatment period)
Secondary	Number of Deaths Reported - On-study Period (Week 52)	Number of participants who died during on-study period (Week 52) is reported. The on-study period (which includes on and off treatment data) was defined as first dose to the end of the Week 52 study follow-up (or death). The on-study period was a supportive analysis period for safety analysis.	Up to Week 52 (On-study period)
Secondary	Number of Participants Who Reported Protocol Defined AESI: On-study Period (Week 52)	A summary of protocol defined AESIs including serious infections, opportunistic infections and other infections of interest (serious and non-serious), NMSC, malignancies (excluding NMSC), psychiatric events suggesting serious mood disorders and anxiety (serious depression), suicidality (using C-SSRS) and SIHR is reported. The on-study period (Week 52) (which includes on and off treatment data) was defined as first dose to the end of the Week 52 study follow-up (or death). The on-study period was a supportive analysis period for safety analysis.	Up to Week 52 (On-study period)
Secondary	Number of Participants With SAEs Reported During On-study Period (Week 52)	A SAE is defined as any untoward medical occurrence that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect, associated with liver injury and impaired liver function or any other situations as per medical or scientific judgement. The on-study period (Week 52) (which includes on and off treatment data) was defined as first dose to the end of the Week 52 study follow-up (or death) and was a supportive analysis period for safety analyses.	Up to Week 52 (On-study period)
Secondary	Percentage of Participants Whose Average Prednisone (or Equivalent) Dose to Treat SLE Has Been Reduced by >=25% From Baseline to <=7.5 mg/Day During Weeks 40 Through 52	The average daily prednisone dose during Weeks 40 to 52 is the sum of all prednisone doses to treat SLE from the day following the Week 40 visit date up to but not including the Week 52 study completion date divided by the number of days between Week 40 visit date and study completion date (study completion date - Week 40 visit date). Percentage of participants whose average prednisone dose has been reduced by >=25% from Baseline to <=7.5 mg/day during Weeks 40 through 52 in participants with average prednisone use greater than 7.5 mg/day at Baseline was compared between belimumab and placebo using a logistic regression model including treatment group, Baseline prednisone dose, screening safety of estrogen in lupus national assessment (SELENA) systemic lupus erythematosus disease activity index (SLEDAI) score (<=9 versus >=10) and region. Baseline is defined as the last available value measured prior to dosing on or before the date of first dose (Day 1).	Week 40 to Week 52
Secondary	Number of Participants With All-cause Mortality During Years 2 to 5	Number of participants with all-cause mortality during years 2 to 5 has been presented.	From 2 years to 5 years
Secondary	Number of Participants With New Primary Malignancies During Years 2 to 5	Number of participants with new primary malignancies during years 2 to 5 has been presented.	From 2 years to 5 years