Systemic Lupus Erythematosus
Conditions
Keywords
Antibodies, Vaccines, SLE, Immune System Diseases, Biological Therapy, Autoimmune Diseases, Pneumococcal Vaccines, Lupus, Immunoglobulins, Vaccination, Belimumab, Biological Agents, Immunization
Brief summary
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
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.
Interventions
BIOLOGICALBelimumab plus Early Vaccination
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.
BIOLOGICALBelimumab plus Late Vaccination
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.
Sponsors
GlaxoSmithKline
Human Genome Sciences Inc., a GSK Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Positive Antibody Responses to at Least One of the 23 Pneumococcal Vaccine Serotypes 4 Weeks Post-vaccination | Four weeks after 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. |
Countries
United States
Participant flow
Recruitment details
Eligible participants with systemic lupus erythematosus (SLE) were randomized in 7:9 ratio to receive pneumonococcal vaccination either 4 weeks prior (early cohort) or 24 weeks after (late cohort) their first belimumab dose of 10 milligram (mg)/kilogram (kg) intravenously (IV).
Pre-assignment details
A total of 79 participants were enrolled, of which 34 were randomised to the early cohort and 45 were randomized to the late cohort. All randomized participants received at least 1 dose of vaccine and/or belimumab and were included in the Intent-to-Treat (ITT) Population.
Participants by arm
| Arm | Count |
|---|---|
| Belimumab Plus Early Vaccination Participants received pneumococcal vaccination on Day 0, 4 weeks prior to the first dose of belimumab. Open-label belimumab 10 mg/kg IV was dosed on Days 28, 42, 56, and every 28 days thereafter until Week 32 (a total of 9 doses) plus standard therapy for SLE. | 34 |
| Belimumab Plus Late Vaccination Participants received pneumococcal vaccination on Day 168 (Week 24). Open-label belimumab 10 mg/kg IV was dosed on Days 0, 14, 28, and every 28 days thereafter until Week 28 (a total of 9 doses) plus standard therapy for SLE. | 45 |
| Total | 79 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 0 |
| Overall Study | Lost to Follow-up | 0 | 2 |
| Overall Study | Other Reason | 2 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 2 |
Baseline characteristics
| Characteristic | Belimumab Plus Early Vaccination | Belimumab Plus Late Vaccination | Total |
|---|---|---|---|
| Age, Continuous | 41.0 Years STANDARD_DEVIATION 12.57 | 38.6 Years STANDARD_DEVIATION 12.31 | 39.6 Years STANDARD_DEVIATION 12.4 |
| Race/Ethnicity, Customized Asian | 1 Participants | 4 Participants | 5 Participants |
| Race/Ethnicity, Customized Black or African American | 8 Participants | 12 Participants | 20 Participants |
| Race/Ethnicity, Customized Mixed Race | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 25 Participants | 27 Participants | 52 Participants |
| Sex: Female, Male Female | 29 Participants | 43 Participants | 72 Participants |
| Sex: Female, Male Male | 5 Participants | 2 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 21 / 34 | 32 / 45 |
| serious Total, serious adverse events | 4 / 34 | 3 / 45 |
Outcome results
Primary
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.
Time frame: Four weeks after vaccination
Population: As-treated Population: all participants who received at least one dose of belimumab. All analyses of vaccine titers were performed on the As-treated Population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Belimumab Plus Early Vaccination | Number of Participants With Positive Antibody Responses to at Least One of the 23 Pneumococcal Vaccine Serotypes 4 Weeks Post-vaccination | 32 Participants |
| Belimumab Plus Late Vaccination | Number of Participants With Positive Antibody Responses to at Least One of the 23 Pneumococcal Vaccine Serotypes 4 Weeks Post-vaccination | 40 Participants |