A Study of Belimumab in Subjects With Systemic Lupus Erythematosus (SLE) - Full Text View

Purpose

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.

Condition	Intervention	Phase
Systemic Lupus Erythematosus	Drug: Placebo Drug: Belimumab 1 mg/kg Drug: Belimumab 10 mg/kg	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment
Official Title:	A Phase 3, Multi-Center, Randomized, Double-Blind, Placebo-Controlled, 76-Week Study to Evaluate the Efficacy and Safety of Belimumab (HGS1006, LymphoStat-B™), a Fully Human Monoclonal Anti-BLyS Antibody, in Subjects With Systemic Lupus Erythematosus (SLE)

Resource links provided by NLM:

MedlinePlus related topics: Autoimmune Diseases Lupus

Drug Information available for: Belimumab

U.S. FDA Resources

Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:

SLE Responder Index (SRI) Response Rate at Week 52 [ Time Frame: Baseline, 52 Weeks ] [ Designated as safety issue: No ]
Percentage of subjects with a ≥ 4 point reduction from baseline in SELENA SLEDAI score, and no worsening (increase of < 0.30 points from baseline) in PGA, and no new BILAG A organ domain score or 2 new BILAG B organ domain scores compared with baseline.

SELENA SLEDAI is calculated from 24 individual descriptors; 0 indicates inactive disease and the maximum theoretical score is 105; scores > 20 are rare. PGA is a visual analog scale scored from 0 to 3 (1=mild, 2=moderate, 3=severe). BILAG uses a single score for each of the 8 organ domains; range is from severe to no disease (A to E).

Secondary Outcome Measures:

SRI Response Rate at Week 76 [ Time Frame: Baseline, 76 Weeks ] [ Designated as safety issue: No ]
Percentage of subjects with a ≥ 4 point reduction from baseline in SELENA SLEDAI score, and no worsening (increase of < 0.30 points from baseline) in PGA, and no new BILAG A organ domain score or 2 new BILAG B organ domain scores compared with baseline.

SELENA SLEDAI is calculated from 24 individual descriptors; 0 indicates inactive disease and the maximum theoretical score is 105; scores > 20 are rare. PGA is a visual analog scale scored from 0 to 3 (1=mild, 2=moderate, 3=severe). BILAG uses a single score for each of the 8 organ domains; range is from severe to no disease (A to E).
Percent of Subjects With a ≥ 4 Point Reduction From Baseline in SELENA SLEDAI Score at Week 52. [ Time Frame: Baseline, 52 Weeks ] [ Designated as safety issue: No ]
Mean Change in Physician's Global Assessment (PGA) at Week 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 Week 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 40-52 ] [ Designated as safety issue: No ]

Other Outcome Measures:

Adverse Event (AE) Overview [ Time Frame: Up to 80 Weeks ] [ Designated as safety issue: Yes ]
SEE ALSO ADVERSE EVENT RESULTS SECTION

Enrollment:	819
Study Start Date:	February 2007
Study Completion Date:	March 2010
Primary Completion Date:	September 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Placebo Comparator: Placebo	Drug: Placebo Placebo IV plus standard therapy; placebo administered on Days 0, 14, 28, and every 28 days thereafter through 72 weeks. Other Name: Placebo
Experimental: Belimumab 1 mg/kg	Drug: Belimumab 1 mg/kg Belimumab 1 mg/kg IV plus standard therapy; belimumab 1 mg/kg administered on Days 0, 14, 28, and every 28 days thereafter through 72 weeks. Other Name: LymphoStat-B™, belimumab
Experimental: Belimumab 10 mg/kg	Drug: Belimumab 10 mg/kg Belimumab 10 mg/kg IV plus standard therapy; belimumab 10 mg/kg administered on Days 0, 14, 28, and every 28 days thereafter through 72 weeks. Other Name: LymphoStat-B™, belimumab

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00410384

Show 146 Study Locations

Sponsors and Collaborators

GlaxoSmithKline

Investigators

Study Director:

GSK Clinical Trials

GlaxoSmithKline

More Information

No publications provided by GlaxoSmithKline

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

Chatham WW, Wallace DJ, Stohl W, Latinis KM, Manzi S, McCune WJ, Tegzová D, McKay JD, Avila-Armengol HE, Utset TO, Zhong ZJ, Hough DR, Freimuth WW, Migone TS; BLISS-76 Study Group. Effect of belimumab on vaccine antigen antibodies to influenza, pneumococcal, and tetanus vaccines in patients with systemic lupus erythematosus in the BLISS-76 trial. J Rheumatol. 2012 Aug;39(8):1632-40. Epub 2012 Jun 15.

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.

Furie R, Petri M, Zamani O, Cervera R, Wallace DJ, Tegzová D, Sanchez-Guerrero J, Schwarting A, Merrill JT, Chatham WW, Stohl W, Ginzler EM, Hough DR, Zhong ZJ, Freimuth W, van Vollenhoven RF; BLISS-76 Study Group. A phase III, randomized, placebo-controlled study of belimumab, a monoclonal antibody that inhibits B lymphocyte stimulator, in patients with systemic lupus erythematosus. Arthritis Rheum. 2011 Dec;63(12):3918-30.

Responsible Party:	GlaxoSmithKline
ClinicalTrials.gov Identifier:	NCT00410384 History of Changes
Other Study ID Numbers:	110751, BLISS-76, HGS1006-C1056
Study First Received:	December 8, 2006
Results First Received:	April 7, 2011
Last Updated:	December 10, 2012
Health Authority:	Austria: Agency for Health and Food Safety Belgium: Federal Agency for Medicinal Products and Health Products Canada: Health Canada Czech Republic: State Institute for Drug Control France: Ministry of Health Germany: Paul-Ehrlich-Institut Israel: Ministry of Health Italy: Ministry of Health Mexico: Ministry of Health Netherlands: The Central Committee on Research Involving Human Subjects (CCMO) Poland: Ministry of Health Romania: Ministry of Public Health Spain: Agencia Española de Medicamentos y Productos Sanitarios Sweden: Medical Products Agency United Kingdom: Medicines and Healthcare Products Regulatory Agency United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:

SLE
Lupus
Systemic Lupus Erythematosus

Antibodies
Autoimmune Diseases
Belimumab

Additional relevant MeSH terms:

Lupus Erythematosus, Systemic
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases

ClinicalTrials.gov processed this record on June 18, 2013

A Study of Belimumab in Subjects With Systemic Lupus Erythematosus (SLE) (BLISS-76)