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Efficacy and Safety of Belimumab in Patients With Active Lupus Nephritis (BLISS-LN)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01639339
Recruitment Status : Completed
First Posted : July 12, 2012
Results First Posted : July 7, 2020
Last Update Posted : July 7, 2020
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
GlaxoSmithKline ( Human Genome Sciences Inc., a GSK Company )

Tracking Information
First Submitted Date  ICMJE July 10, 2012
First Posted Date  ICMJE July 12, 2012
Results First Submitted Date  ICMJE June 17, 2020
Results First Posted Date  ICMJE July 7, 2020
Last Update Posted Date July 7, 2020
Actual Study Start Date  ICMJE July 12, 2012
Actual Primary Completion Date July 25, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 17, 2020)
Percentage of Participants With Primary Efficacy Renal Response (PERR) at Week 104 [ Time Frame: Week 104 ]
PERR is defined as urinary protein creatinine ratio <=0.7, estimated glomerular filtration rate (eGFR) 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 of 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 in one of 2 sites excluded due to GCP compliance. Percentage of participants with PERR at Week 104 has been presented.
Original Primary Outcome Measures  ICMJE
 (submitted: July 10, 2012)
Number of participants with a renal response at Week 104 [ Time Frame: 104 weeks ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 17, 2020)
  • Percentage of Participants With Complete Renal Response (CRR) at Week 104 [ Time Frame: 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.
  • Percentage of Participants With PERR at Week 52 [ Time Frame: 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.
  • Number of Participants With Time to Death or Renal Related Event [ Time Frame: Up to Week 104 ]
    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, withdrawn from the study, or are lost to follow-up were censored on the date of the event. 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.
  • Percentage of Participants With Ordinal Renal Response (ORR) at Week 104 [ Time Frame: 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: July 10, 2012)
  • Number of participants with a complete renal response at Week 104 [ Time Frame: 104 weeks ]
  • Number of participants with a renal response at Week 52 [ Time Frame: 52 weeks ]
  • Number of participants who experienced adverse events [ Time Frame: Up to 136 weeks ]
Current Other Pre-specified Outcome Measures
 (submitted: June 17, 2020)
  • Number of Participants Reporting On-treatment Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Up to Week 104 ]
    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, 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 AE/ SAE has been reported.
  • Number of Participants Reporting On-treatment Adverse Events of Special Interest (AESI) [ Time Frame: Up to Week 104 ]
    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 AE with death occurring anytime). Number of participants reporting on-treatment AESI has been presented.
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy and Safety of Belimumab in Patients With Active Lupus Nephritis
Official Title  ICMJE 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
Brief Summary The purpose of this study is to evaluate the efficacy, safety, and tolerability of belimumab in adult patients with active lupus nephritis.
Detailed 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Lupus Nephritis
Intervention  ICMJE
  • Biological: Placebo plus standard therapy
    Placebo plus standard therapy
  • Biological: Belimumab 10 mg/kg plus standard therapy
    Belimumab 10 mg/kg plus standard therapy
    Other Name: BENLYSTA™
  • 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

Study Arms  ICMJE
  • Placebo Comparator: Placebo plus standard therapy
    Placebo IV plus standard therapy; placebo administered on Days 0, 14, 28, and then every 28 days thereafter through Week 100, with a final evaluation at Week 104 in the double-blind period. In the open-label extension period, placebo patients who opt to participate will receive belimumab 10 mg/kg IV every 28 days for an additional 6 months.
    Interventions:
    • Biological: Placebo plus standard therapy
    • Drug: Standard therapy
  • Experimental: Belimumab 10 mg/kg plus standard therapy
    Belimumab 10 mg/kg IV plus standard therapy; belimumab administered on Days 0, 14, 28, and then every 28 days thereafter through Week 100, with a final evaluation at Week 104 in the double-blind period. In the open-label extension period, patients who opt to participate will continue to receive belimumab 10 mg/kg IV every 28 days for an additional 6 months.
    Interventions:
    • Biological: Belimumab 10 mg/kg plus standard therapy
    • Drug: Standard therapy
Publications * Furie R, Rovin BH, Houssiau F, Malvar A, Teng YKO, Contreras G, Amoura Z, Yu X, Mok CC, Santiago MB, Saxena A, Green Y, Ji B, Kleoudis C, Burriss SW, Barnett C, Roth DA. Two-Year, Randomized, Controlled Trial of Belimumab in Lupus Nephritis. N Engl J Med. 2020 Sep 17;383(12):1117-1128. doi: 10.1056/NEJMoa2001180.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 18, 2019)
448
Original Estimated Enrollment  ICMJE
 (submitted: July 10, 2012)
464
Actual Study Completion Date  ICMJE March 12, 2020
Actual Primary Completion Date July 25, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE 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,   United States
Removed Location Countries Czech Republic
 
Administrative Information
NCT Number  ICMJE NCT01639339
Other Study ID Numbers  ICMJE 114054
2011-004570-28 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints of the study.
Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
URL: http://clinicalstudydatarequest.com
Responsible Party GlaxoSmithKline ( Human Genome Sciences Inc., a GSK Company )
Study Sponsor  ICMJE Human Genome Sciences Inc., a GSK Company
Collaborators  ICMJE GlaxoSmithKline
Investigators  ICMJE
Study Director: GSK Clinical Trials GlaxoSmithKline
PRS Account GlaxoSmithKline
Verification Date June 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP