Efficacy and Safety of Belimumab in Patients With Active Lupus Nephritis

Lupus Nephritis Clinical Trial

— BLISS-LN  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01639339
• Other study ID #: 114054
• Secondary ID: 2011-004570-28
• Status: Completed
• Phase: Phase 3
• Start date: July 12, 2012
• Est. completion date: March 12, 2020

Study information

• Verified date: February 2021
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 448
• Est. completion date: March 12, 2020
• Est. primary completion date: July 25, 2019
• 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.

• 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.

Related Conditions & MeSH terms

• Lupus Nephritis
• Nephritis

Intervention

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

Locations

Country	Name	City	State
Argentina	GSK Investigational Site	Buenos Aires
Argentina	GSK Investigational Site	Ciudad Autonoma Buenos Aires
Argentina	GSK Investigational Site	Ciudad Autonoma Buenos Aires	Buenos Aires
Argentina	GSK Investigational Site	Cordoba
Argentina	GSK Investigational Site	Mendoza
Argentina	GSK Investigational Site	San Miguel de Tucuman	Tucumán
Belgium	GSK Investigational Site	Brussels
Belgium	GSK Investigational Site	Bruxelles
Belgium	GSK Investigational Site	Leuven
Brazil	GSK Investigational Site	Belo Horizonte	Minas Gerais
Brazil	GSK Investigational Site	Belo Horizonte, Minas Gerais
Brazil	GSK Investigational Site	Goiania
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	Salvador
Brazil	GSK Investigational Site	Sao Jose do Rio Preto	São Paulo
Brazil	GSK Investigational Site	Sao Paulo	São Paulo
Canada	GSK Investigational Site	Edmonton	Alberta
Canada	GSK Investigational Site	Montreal	Quebec
China	GSK Investigational Site	Beijing
China	GSK Investigational Site	Changsha	Hunan
China	GSK Investigational Site	Chengdu	Sichuan
China	GSK Investigational Site	Chongqing
China	GSK Investigational Site	Fuzhou
China	GSK Investigational Site	Guangzhou
China	GSK Investigational Site	Nanchang	Jiangxi
China	GSK Investigational Site	Nanning
China	GSK Investigational Site	Shanghai
China	GSK Investigational Site	Shanghai
China	GSK Investigational Site	Shanghai
China	GSK Investigational Site	Shenyang	Liaoning
China	GSK Investigational Site	Shenzhen
China	GSK Investigational Site	Wuhan	Hubei
China	GSK Investigational Site	Xian
Colombia	GSK Investigational Site	Bogota
Czechia	GSK Investigational Site	Olomouc
Czechia	GSK Investigational Site	Praha 2
Czechia	GSK Investigational Site	Praha 2
France	GSK Investigational Site	Cean Cedex 09
France	GSK Investigational Site	Créteil cedex
France	GSK Investigational Site	Lille Cedex
France	GSK Investigational Site	Paris
France	GSK Investigational Site	Strasbourg Cedex
France	GSK Investigational Site	Toulouse Cedex 9
France	GSK Investigational Site	Vandoeuvre-Les-Nancy
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Dresden	Sachsen
Germany	GSK Investigational Site	Essen	Nordrhein-Westfalen
Germany	GSK Investigational Site	Freiburg	Baden-Wuerttemberg
Germany	GSK Investigational Site	Goettingen
Germany	GSK Investigational Site	Hannover	Niedersachsen
Germany	GSK Investigational Site	Jena	Thueringen
Germany	GSK Investigational Site	Luebeck	Schleswig-Holstein
Germany	GSK Investigational Site	Mainz	Rheinland-Pfalz
Germany	GSK Investigational Site	Muenster	Nordrhein-Westfalen
Hong Kong	GSK Investigational Site	Hong Kong
Hungary	GSK Investigational Site	Miskolc
Hungary	GSK Investigational Site	Szeged
Korea, Republic of	GSK Investigational Site	Busan
Korea, Republic of	GSK Investigational Site	Daejeon
Korea, Republic of	GSK Investigational Site	Daejeon
Korea, Republic of	GSK Investigational Site	Jeju Special Self-Governing Prov.
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	Suwon
Korea, Republic of	GSK Investigational Site	Suwon-si, Gyeonggi-do
Mexico	GSK Investigational Site	Cuernavaca	Morelos
Mexico	GSK Investigational Site	Guadalajara	Jalisco
Mexico	GSK Investigational Site	Mexico
Mexico	GSK Investigational Site	México, D.F.
Mexico	GSK Investigational Site	Morelia	Michoacán
Netherlands	GSK Investigational Site	Groningen
Netherlands	GSK Investigational Site	Leiden
Netherlands	GSK Investigational Site	Maastricht
Philippines	GSK Investigational Site	Cebu City
Philippines	GSK Investigational Site	Davao City
Philippines	GSK Investigational Site	Iloilo City
Philippines	GSK Investigational Site	Lipa City, Batangas
Philippines	GSK Investigational Site	Manila
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Orenburg
Russian Federation	GSK Investigational Site	St. Petersburg
Russian Federation	GSK Investigational Site	Ufa
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Palma de Mallorca
Spain	GSK Investigational Site	Valencia
Spain	GSK Investigational Site	Vigo/ Pontevedra
Taiwan	GSK Investigational Site	Gueishan Township,Taoyuan County
Taiwan	GSK Investigational Site	Kaohsiung
Taiwan	GSK Investigational Site	Taichung
Thailand	GSK Investigational Site	Khon Kaen
Thailand	GSK Investigational Site	Muang
Thailand	GSK Investigational Site	Rajathevee
Thailand	GSK Investigational Site	Saimai
United Kingdom	GSK Investigational Site	London
United Kingdom	GSK Investigational Site	London
United States	GSK Investigational Site	Bethlehem	Pennsylvania
United States	GSK Investigational Site	Brooklyn	New York
United States	GSK Investigational Site	Chapel Hill	North Carolina
United States	GSK Investigational Site	Charleston	South Carolina
United States	GSK Investigational Site	Columbus	Ohio
United States	GSK Investigational Site	Gainesville	Florida
United States	GSK Investigational Site	Great Neck	New York
United States	GSK Investigational Site	La Palma	California
United States	GSK Investigational Site	Manhasset	New York
United States	GSK Investigational Site	Miami	Florida
United States	GSK Investigational Site	New York	New York
United States	GSK Investigational Site	New York	New York
United States	GSK Investigational Site	Onalaska	Wisconsin
United States	GSK Investigational Site	Philadelphia	Pennsylvania
United States	GSK Investigational Site	Saint Louis	Missouri
United States	GSK Investigational Site	San Leandro	California
United States	GSK Investigational Site	Torrance	California

Sponsors (2)

Lead Sponsor	Collaborator
Human Genome Sciences Inc., a GSK Company	GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Argentina,  Belgium,  Brazil,  Canada,  China,  Colombia,  Czechia,  France,  Germany,  Hong Kong,  Hungary,  Korea, Republic of,  Mexico,  Netherlands,  Philippines,  Russian Federation,  Spain,  Taiwan,  Thailand,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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)
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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