A Study to Evaluate the Effect of Belimumab on Vaccine Responses in Subjects With Systemic Lupus Erythematosus (SLE)

Study Overview
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Brief Summary
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The purpose of this study is to assess the impact of belimumab on immune response to pneumococcal vaccine in subjects with Systemic Lupus Erythematosus (SLE).

Detailed Description
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All patients in this study will receive belimumab plus standard therapy for SLE and vaccination against pneumococcus. Patients will be randomized to receive pneumococcal vaccination either 4 weeks prior (early vaccination group) or 24 weeks after (late vaccination group) their first belimumab dose. Vaccine response will be assessed 4 weeks after vaccine administration.

Official Title
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A Phase 4, Multi-Center, Randomized, Open-Label Study to Evaluate the Effect of BENLYSTA™ (Belimumab; HGS1006) on Vaccine Responses in Subjects With Systemic Lupus Erythematosus (SLE)

Conditions
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Systemic Lupus Erythematosus

Intervention / Treatment
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* Biological: Belimumab plus Early Vaccination
* Biological: Belimumab plus Late Vaccination


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Clinical diagnosis of SLE by American College of Rheumatology (ACR) criteria. Active SLE disease. Autoantibody-positive. Have antibodies with titers >1.0 microgram (mcg)/mL to no more than 9 of the 23 serotypes present in the pneumococcal vaccine. Have the ability to understand the requirements of the study, provide written informed consent, and comply with the study protocol procedures. Key Exclusion Criteria: Pregnant or nursing. Have received any prior treatment with belimumab. Have received a live vaccine within the past 30 days. Have received a pneumococcal vaccination with the past 5 years. Have a history of severe allergic reaction to a vaccine, contrast agents (such as those used for x-rays and CT scans), or biological medicines. Have required management of an infection or have had infections that keep coming back within the past 60 days. Hepatitis B: Serologic evidence of Hepatitis B (HB) infection based on the results of testing for HB surface antigen (HBsAg) and anti-HB core antibody (anti-HBc): Subjects positive for HBsAg are excluded. Subjects negative for HBsAg but positive for anti-HBc, regardless of anti-HBs antibody status, are excluded. Hepatitis C: Positive test for Hepatitis C antibody. Known human immunodeficiency virus (HIV) infection. Have current drug or alcohol abuse or dependence. Have a Grade 3/4 immunoglobulin (Ig)G deficiency (IgG level <400 milligrams [mg]/ deciliter [dL]) or IgA deficiency (IgA level <10 mg/dL). Subjects who have evidence of serious suicide risk including any history of suicidal behavior in the last 6 months and/or suicidal ideation with some intent to act in the last 2 months or who in the investigator's judgment, pose a significant suicide risk.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Belimumab plus Early Vaccination<br>Belimumab plus Early Vaccination | Biological: Belimumab plus Early Vaccination<br>* Belimumab 10 mg/kg IV plus standard therapy for SLE is administered on Days 28, 42, 56, and every 28 days thereafter through Week 32 (9 doses). Pneumococcal vaccination is administered 4 weeks prior to the first dose of belimumab.<br>* Other names: BENLYSTA™;|
| Experimental: Belimumab plus Late Vaccination<br>Belimumab plus Late Vaccination | Biological: Belimumab plus Late Vaccination<br>* Belimumab 10 mg/kg IV plus standard therapy for SLE is administered on Days 0, 14, 28, and then every 28 days thereafter through Week 28 (9 doses). Pneumococcal vaccination is administered 24 weeks after the first dose of belimumab.<br>* Other names: BENLYSTA™;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Positive Antibody Responses to at Least One of the 23 Pneumococcal Vaccine Serotypes 4 Weeks Post-vaccination | A positive immune response to at least one pneumococcal serotype is defined as a 2-fold or greater increase from pre-vaccination levels. For unquantifiable pre-vaccination antibody levels, a positive antibody response was considered as a post-vaccination level >=0.6 micrograms (µg)/milliliter (mL). Post-vaccination pneumococcal titers were assessed on Day 28 (Week 4) prior to the first dose of belimumab in the early cohort and on Day 196 (Week 28) prior to the last belimumab dose in the late cohort. Evaluable participants for the early cohort included those who received the vaccination at Day 0 and had titers drawn at Week 4. For the late cohort, evaluable participants received at least 5 of the 7 doses of belimumab up through Week 24, received the vaccination at Week 24, and had titers drawn at Week 28. | Four weeks after vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Antibodies, Vaccines, SLE, Immune System Diseases, Biological Therapy, Autoimmune Diseases, Pneumococcal Vaccines, Lupus, Immunoglobulins, Vaccination, Belimumab, Biological Agents, Immunization