The purpose of this study is to evaluate the efficacy, safety, and tolerability of belimumab in adult patients with active lupus nephritis.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
448
Placebo plus standard therapy
Belimumab 10 mg/kg plus 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
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.
Time frame: Week 104
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.
Time frame: From first open-label dose (Day 1) up to open-label Week 32 (8 weeks after last dose)
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.
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GSK Investigational Site
La Palma, California, United States
GSK Investigational Site
San Leandro, California, United States
GSK Investigational Site
Torrance, California, United States
GSK Investigational Site
Gainesville, Florida, United States
GSK Investigational Site
Miami, Florida, United States
GSK Investigational Site
St Louis, Missouri, United States
GSK Investigational Site
Brooklyn, New York, United States
GSK Investigational Site
Great Neck, New York, United States
GSK Investigational Site
Manhasset, New York, United States
GSK Investigational Site
New York, New York, United States
...and 108 more locations
Time frame: From first open-label dose (Day 1) up to open-label Week 32 (8 weeks after last dose)
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.
Time frame: Week 104
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.
Time frame: Week 52
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.
Time frame: Up to Week 104
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.
Time frame: Week 104
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.
Time frame: Up to Week 104
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.
Time frame: Up to Week 104