Phase 2 Study of Belimumab Administered Subcutaneously to Subjects With Systemic Lupus Erythematosus (SLE)

A Phase 2, Multi-Center, Randomized, Open Label, Trial to Evaluate the Safety, Tolerability, and Biological Activity of 2 Dosing Schedules of Belimumab (HGS1006, LymphoStat-B™), a Fully Human Monoclonal Anti-BLyS Antibody, Administered Subcutaneously to Subjects With Systemic Lupus Erythematosus (SLE)

The purpose of this study is to test the safety and tolerability of repeated subcutaneous (SC) doses of belimumab in subjects with SLE.

Study Overview

• Status: Terminated
• Conditions: Systemic Lupus Erythematosus
• Intervention / Treatment: Drug: Belimumab 100 mg SC; Drug: Belimumab 100 mg SC

Detailed Description

This clinical trial will evaluate the safety, pharmacokinetics (PK), and effect on biomarkers of repeated subcutaneous (SC) administration of belimumab in subjects with SLE. As data permit, an exploratory pharmacodynamic analysis will be performed to evaluate the correlation between belimumab serum exposure, PGA, SELENA SELDAI, and biomarker effects.

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Phase 2

Contacts and Locations

Study Locations

• Mexico
  • San Lusi Potosi, Mexico, 78240
    • Hospital Central "Igancio Morones Prieto"
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35249-7201
      • University of Alabama at Birmingham
  • California
    • Long Beach, California, United States, 90806
      • Valerious Medical Group Research Center
  • Florida
    • Tampa, Florida, United States, 33614
      • Tampa Medical Group, PA
  • Michigan
    • Lansing, Michigan, United States, 48910
      • Fiechtner Research, Inc.
  • New York
    • Brooklyn, New York, United States, 11203
      • SUNY Downstate Medical Center
    • Lake Success, New York, United States, 11042
      • North Shore-LIJ Health System/Rheumatology, Allergy, Immunology
    • Smithtown, New York, United States, 11787
      • Rheumatology Associates
  • Ohio
    • Dayton, Ohio, United States, 45408
      • STAT Research, Inc.
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74104
      • Oklahoma Center For Arthritis Therapy & Research
  • Texas
    • Houston, Texas, United States, 77074
      • Houston Institute for Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Clinical diagnosis of SLE by American College of Rheumatology (ACR) criteria
• Active SLE disease
• On stable SLE treatment regimen

Exclusion Criteria:

• Pregnant or nursing
• Have received treatment with an B cell targeted therapy
• Have received treatment with a biologic investigational agent in the past year
• Have received intravenous (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 with the past 60 days
• Have current drug or alcohol abuse or dependence or within the past year
• Have a historically positive test or test positive at screening for human immunodeficiency virus (HIV), hepatitis B, or hepatitis C
• Have a history of an allergic or anaphylactic reaction to drugs, food, or insects requiring medical intervention

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Belimumab Q2WKS; Every other week: 100 mg of belimumab (1 injection) subcutaneous (under the skin) on days 0, 7, and 14, then every other week until final evaluation at Week 24 with option to continue receiving belimumab at the same dose through 144 week continuation period.	Drug: Belimumab 100 mg SC; Belimumab 100 mg SC for 1 injection on Days 0, 7, 14, and then every two weeks.; Other Names: LymphoStat-B™; Drug: Belimumab 100 mg SC; Belimumab 100mg SC for 2 injections (of 100mg each) on Days 0, 2, and 4, then 100 mg (1 injection) three times per week.
Experimental: Belimumab 3X/WK; Three times weekly: 200 mg of belimumab (2 injections of 100 mg each) subcutaneous (under the skin) on days 0, 2, and 4 then 100 mg three times a week until final evaluation at Week 24 with option to continue receiving belimumab at the same dose through 144 week continuation period.	Drug: Belimumab 100 mg SC; Belimumab 100 mg SC for 1 injection on Days 0, 7, 14, and then every two weeks.; Other Names: LymphoStat-B™; Drug: Belimumab 100 mg SC; Belimumab 100mg SC for 2 injections (of 100mg each) on Days 0, 2, and 4, then 100 mg (1 injection) three times per week.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of the Number of Participants Who Experienced Adverse Events (AEs) During the 24 Week Period.	SEE ALSO ADVERSE EVENTS RESULTS SECTION	Up to 24 weeks
Absolute Change From Baseline in CD20+ (Total) B Cells at Week 24		Baseline, 24 weeks
Median Percent Change From Baseline in CD20+ (Total) B Cells at Week 24.		Baseline, 24 Weeks
Absolute Change From Baseline in CD20+/CD27- (Naive) B Cells at Week 24		Baseline, 24 weeks
Median Percent Change From Baseline in CD20+/CD27-(Naive) B Cells at Week 24		Baseline, 24 weeks
Absolute Change From Baseline in CD20+/CD69+ (Activated) B Cells at Week 24		Baseline, 24 Weeks
Median Percent Change From Baseline in CD20+/CD69+ (Activated) B Cells at Week 24		Baseline, 24 Weeks
Absolute Change From Baseline in CD20+/CD27+ (Memory) B Cells at Week 24		Baseline, 24 Weeks
Median Percent Change From Baseline in CD20+/CD27+ (Memory) B Cells at Week 24		Baseline, 24 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Serum Belimumab Concentration Levels (Pharmacokinetic [PK]) Over 24 Weeks.		Baseline, 24 weeks
Absolute Change From Baseline in IgA at Week 24		Baseline, 24 Weeks
Median Percent Change From Baseline in IgA at Week 24		Baseline, 24 weeks
Absolute Change From Baseline in IgG at Week 24		Baseline, 24 Weeks
Median Percent Change From Baseline in IgG at Week 24		Baseline, 24 Weeks
Absolute Change From Baseline in IgM at Week 24		Baseline, 24 Weeks
Median Percent Change From Baseline in IgM at Week 24		Baseline, 24 weeks
Absolute Change From Baseline in Physician's Global Assessment (PGA) Score at Week 24	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.	Baseline, 24 Weeks
Mean Percent Change From Baseline in PGA Score at Week 24.	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.	Baseline, 24 weeks
Absolute Change From Baseline in the Safety of Estrogen in Lupus Erythematosus National Assessment SLE Disease Activity Index (SELENA SLEDAI) Score at Week 24	SELENA SLEDAI is calculated from 24 individual descriptors; 0 indicates inactive disease and the maximum theoretical score is 105; scores > 20 are rare.	Baseline, 24 Weeks
Mean Percent Change From Baseline in the SELENA SLEDAI Score at Week 24		Baseline, 24 weeks
Absolute Change From Baseline in Complement C3 at Week 24		Baseline, 24 Weeks
Median Percent Change From Baseline in Compliment C3 at Week 24		Baseline, 24 Weeks
Absolute Change From Baseline in Complement C4 at Week 24		Baseline, 24 weeks
Median Percent Change From Baseline in Complement C4 at Week 24		Baseline, 24 Weeks
Absolute Change From Baseline in Anti-Double-Stranded DNA (Anti-dsDNA)at Week 24		Baseline, 24 Weeks
Median Percent Change From Baseline in Anti-dsDNA at Week 24		Baseline, 24 weeks
Absolute Change From Baseline in High Density Lipoproteins (HDL) at Week 24		Baseline, 24 Weeks
Median Percent Change From Baseline in HDL at Week 24		Baseline, 24 week
Absolute Change From Baseline in Total Cholesterol at Week 24		Baseline, 24 Weeks
Median Percent Change From Baseline in Total Cholesterol at Week 24		Baseline, 24 Weeks
Median Percent Change From Baseline in Triglycerides at Week 24		Baseline, 24 weeks
Absolute Change From Baseline in Triglycerides at Week 24		Baseline, 24 Weeks

Collaborators and Investigators

• Sponsor: Human Genome Sciences Inc.
• Collaborators: GlaxoSmithKline

Publications and helpful links

General Publications

• van Vollenhoven RF, Navarra SV, Levy RA, Thomas M, Heath A, Lustine T, Adamkovic A, Fettiplace J, Wang ML, Ji B, Roth D. Long-term safety and limited organ damage in patients with systemic lupus erythematosus treated with belimumab: a Phase III study extension. Rheumatology (Oxford). 2020 Feb 1;59(2):281-291. doi: 10.1093/rheumatology/kez279.

Study record dates

Study Major Dates

• Study Start: October 1, 2008
• Primary Completion (Actual): October 1, 2009
• Study Completion (Actual): March 1, 2012

Study Registration Dates

• First Submitted: August 8, 2008
• First Submitted That Met QC Criteria: August 11, 2008
• First Posted (Estimate): August 12, 2008

Study Record Updates

• Last Update Posted (Estimate): August 7, 2013
• Last Update Submitted That Met QC Criteria: August 1, 2013
• Last Verified: March 1, 2013

More Information

Terms related to this study

• Keywords: Lupus; SLE; Systemic Lupus Erythematosus; Autoimmune Diseases; Antibodies; Belimumab
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Connective Tissue Diseases; Lupus Erythematosus, Systemic; Physiological Effects of Drugs; Immunosuppressive Agents; Immunologic Factors; Belimumab
• Other Study ID Numbers: HGS1006-1070; 112232 (Other Identifier: GlaxoSmithKline)