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

• 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: Human Genome Sciences Inc., a GSK Company
• Collaborator: GlaxoSmithKline
• Information provided by (Responsible Party): GlaxoSmithKline ( Human Genome Sciences Inc., a GSK Company )

Tracking Information

• First Submitted Date: July 10, 2012
• First Posted Date: July 12, 2012
• Results First Submitted Date: June 17, 2020
• Results First Posted Date: July 7, 2020
• Last Update Posted Date: July 7, 2020
• Actual Study Start Date: July 12, 2012
• Actual Primary Completion Date: July 25, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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 (submitted: July 10, 2012): Number of participants with a renal response at Week 104 [ Time Frame: 104 weeks ]

Current Secondary Outcome Measures (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 (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: Efficacy and Safety of Belimumab in Patients With Active Lupus Nephritis
• 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
• 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: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Lupus Nephritis

Intervention

• 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

• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 18, 2019): 448
• Original Estimated Enrollment (submitted: July 10, 2012): 464
• Actual Study Completion Date: March 12, 2020
• Actual Primary Completion Date: July 25, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: 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: NCT01639339
• Other Study ID Numbers: 114054; 2011-004570-28 ( EudraCT Number )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• 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: Human Genome Sciences Inc., a GSK Company
• Collaborators: GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials; GlaxoSmithKline

• PRS Account: GlaxoSmithKline
• Verification Date: June 2020