A Study of Belimumab in Subjects With Systemic Lupus Erythematosus (SLE) (BLISS-52)

• Percent of Subjects With a ≥ 4 Point Reduction From Baseline in SELENA SLEDAI Score at Wk 52. [ Time Frame: Baseline, 52 weeks ] [ Designated as safety issue: No ]
• Mean Change in Physician's Global Assessment (PGA) at Wk 24. [ Time Frame: Baseline, 24 weeks ] [ Designated as safety issue: No ]
  The PGA is a visual analog scale scored from 0 to 3. A score of 1 corresponds to mild lupus disease activity. A score of 2 correlates with moderate disease activity and a score of 3 with severe disease activity.
• Mean Change From Baseline in Medical Outcomes 36-Item Short Form Health Survey (SF-36) Physical Component Summary Score (PCS) at Wk 24. [ Time Frame: Baseline, 24 weeks ] [ Designated as safety issue: No ]
  The SF-36 is a generic health related quality of life (HRQOL) measurement. The survey includes 36 questions grouped to 8 domains and 2 summary measures (physical and mental health component, PCS and MCS, respectively) assessing HRQOL. Responses are scored according to the SF-36v2™ manual. A score is calculated for each SF-36 domain based on the patient's response to each question within it. This is then transformed to a scale ranging from 0 (worst) to 100 (best) points. The PCS is norm-based where the mean=50 and standard deviation (SD)=10. Higher scores represent better physical health.
• Percent of Subjects Whose Average Prednisone Dose Has Been Reduced by ≥ 25% From Baseline to ≤ 7.5 mg/Day During Weeks 40 Through 52 [ Time Frame: Baseline, Weeks 40 through 52 ] [ Designated as safety issue: No ]

The purpose of this study is to evaluate the efficacy, safety, tolerability, and impact on quality of life of two different doses of belimumab administered in addition to standard therapy in subjects with active, autoantibody-positive systemic lupus erythematosus (SLE) disease.

• Drug: Placebo
  Placebo IV plus standard therapy; placebo administered on Days 0, 14, 28, and every 28 days thereafter through Week 48.
• Drug: Belimumab 1 mg/kg
  Belimumab 1 mg/kg IV plus standard therapy on Days 0, 14, 28, and every 28 days thereafter through Week 48.
  Other Name: BENLYSTA™ (formerly LymphoStat-B™)
• Drug: Belimumab 10 mg/kg
  Belimumab 10 mg/kg IV plus standard therapy on Days 0, 14, 28, and every 28 days thereafter through Week 48.
  Other Name: BENLYSTA™ (formerly LymphoStat-B™)

• Placebo Comparator: Placebo
  Intervention: Drug: Placebo
• Experimental: Belimumab 1 mg/kg
  Intervention: Drug: Belimumab 1 mg/kg
• Experimental: Belimumab 10 mg/kg
  Intervention: Drug: Belimumab 10 mg/kg

• Wallace DJ, Navarra S, Petri MA, Gallacher A, Thomas M, Furie R, Levy RA, van Vollenhoven RF, Cooper S, Zhong ZJ, Freimuth W, Cervera R; BLISS-52 and -76, and LBSL02 Study Groups. Safety profile of belimumab: pooled data from placebo-controlled phase 2 and 3 studies in patients with systemic lupus erythematosus. Lupus. 2013;22(2):144-54. doi: 10.1177/0961203312469259. Epub 2012 Dec 4.
• van Vollenhoven RF, Petri MA, Cervera R, Roth DA, Ji BN, Kleoudis CS, Zhong ZJ, Freimuth W. Belimumab in the treatment of systemic lupus erythematosus: high disease activity predictors of response. Ann Rheum Dis. 2012 Aug;71(8):1343-9. Epub 2012 Feb 15.
• Stohl W, Hiepe F, Latinis KM, Thomas M, Scheinberg MA, Clarke A, Aranow C, Wellborne FR, Abud-Mendoza C, Hough DR, Pineda L, Migone TS, Zhong ZJ, Freimuth WW, Chatham WW; BLISS-52 Study Group; BLISS-76 Study Group. Belimumab reduces autoantibodies, normalizes low complement levels, and reduces select B cell populations in patients with systemic lupus erythematosus. Arthritis Rheum. 2012 Jul;64(7):2328-37. doi: 10.1002/art.34400.
• Navarra SV, Guzmán RM, Gallacher AE, Hall S, Levy RA, Jimenez RE, Li EK, Thomas M, Kim HY, León MG, Tanasescu C, Nasonov E, Lan JL, Pineda L, Zhong ZJ, Freimuth W, Petri MA; BLISS-52 Study Group. Efficacy and safety of belimumab in patients with active systemic lupus erythematosus: a randomised, placebo-controlled, phase 3 trial. Lancet. 2011 Feb 26;377(9767):721-31. Epub 2011 Feb 4.

Key Inclusion Criteria:

• Clinical diagnosis of SLE by ACR criteria.
• Active SLE disease.
• Autoantibody-positive.
• On stable SLE treatment regimen.

Key Exclusion Criteria:

• Pregnant or nursing
• Have received treatment with any B cell targeted therapy.
• Have received treatment with a biological investigational agent in the past year.
• Have received IV cyclophosphamide within 180 days of Day 0.
• Have severe lupus kidney disease.
• Have active central nervous system (CNS) lupus.
• Have required management of acute or chronic infections within the past 60 days.
• Have current drug or alcohol abuse or dependence.
• Have a historically positive test or test positive at screening for HIV, hepatitis B, or hepatitis C.