Belimumab Treatment Holiday and Treatment Re-start Study in Lupus Patients
Sponsor
GlaxoSmithKline (Industry)
Overall Status
Completed
CT.gov ID
NCT02119156
Collaborator
(none)
80
20
3
55.1
4
0.1
Study Details
Study Description
Brief Summary
This study will assess the effect of a 24-week withdrawal followed by a 28-week reintroduction of belimumab 10 mg/kg plus standard of care medications in subjects with stable low systemic lupus erythematosus (SLE) disease activity. Rebound phenomenon will be assessed for subjects who have permanently withdrawn from further belimumab treatment.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 3 |
Detailed Description
This study will assess the effect of a 24-week withdrawal of belimumab followed by a 28-week reintroduction of belimumab 10 mg/kg plus standard of care medications on immunogenicity, markers of biological activity, efficacy, and safety in subjects with stable low systemic lupus erythematosus (SLE) disease activity. Additionally, this study will assess rebound phenomenon in subjects with any disease level of SLE who have permanently withdrawn from further belimumab treatment
Study Design
Study Type:
Interventional
Actual Enrollment
:
80 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
An Open-label, Non-randomized, 52-Week Study to Evaluate Treatment Holidays and Rebound Phenomenon After Treatment With Belimumab 10 mg/kg in Systemic Lupus Erythematosus Subjects
Actual Study Start Date
:
May 13, 2014
Actual Primary Completion Date
:
Dec 14, 2018
Actual Study Completion Date
:
Dec 14, 2018
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Treatment Holiday Group Subjects in the Treatment Holiday Group will undergo a 6 month belimumab treatment holiday while remaining on standard of care SLE therapy, then re-start belimumab therapy for 6 months while receiving standard of care SLE therapy. |
Drug: Belimumab
Monthly intravenous infusions dosed as 10 mg/kg body weight
|
| Active Comparator: Control Group Subjects in the Control Group will continue to receive monthly belimumab therapy, in addition to standard of care SLE therapy for 52 weeks. |
Drug: Belimumab
Monthly intravenous infusions dosed as 10 mg/kg body weight
|
| No Intervention: Long-Term Discontinuation Group Subjects in the Long-Term Discontinuation Group have elected to discontinue further belimumab therapy and will remain on standard of care SLE therapy as directed by the investigator, and agree to return for monthly visits for 52 weeks. |
Outcome Measures
Primary Outcome Measures
- Median Time to First SLE Flare Index (SFI) [Up to 52 weeks]
SFI Flare was defined as a mild/moderate or severe flare according to the modified Safety of Estrogen in Lupus National Assessment Systemic Lupus Erythematosus Disease Activity Index (SELENA SLEDAI) SLE Flare Index (modified excluded severe flares from the SELENA SLEDAI flare assessment that were triggered only by an increase in SELENA SLEDAI score to >12).Time to first SFI flare is defined as the number of days from Day 0 visit date to the date the participant has a flare (event date - Day 0 visit date + 1) in the 52 Week/Holiday phase; (event date - treatment re-start date + 1) in the Re-start Holiday phase. Day 0 visit date is defined as Day 0 from present study. Median time to first SFI flare is reported; estimated using the product-limit method.
Secondary Outcome Measures
- Rate of SLE Index Flare Per Subject Year [Up to 52 weeks]
Rate per subject year of SFI flare was calculated as total number of flares divided by total subject years in interval. The total subject years for each participant was calculated as (Week 52/ Exit visit date minus Day 0 visit date + 1) for Long-term discontinuation and treatment control groups. For treatment holiday phase group the subject-years for each participant was calculated as (Week 24/Treatment Re-start/Exit visit date minus Day 0 Visit date + 1)/365.25. For re-start treatment holiday phase group the subject-years for each participant was calculated as (Week 52/Exit visit date minus Week 24/Treatment Re-start date + 1)/365.25. Day 0 visit date is defined as Day 0 from present study.
- Median Time to First Severe SFI Flare [Up to 52 weeks]
The SLE Flare Index categorizes SLE flare as "mild or moderate" or "severe" based on a positive assessment for at least 1 of 5 variables as follows: Change in SELENA SLEDAI score from the most recent assessment to current; Change in signs or symptoms of disease activity; Change in prednisone dosage; Use of new medications for disease activity or hospitalization; Change in Physician's Global Assessment (PGA) score; Hospitalization for SLE activity is an additional category included only for a severe flare. Time to first severe flare is defined as (event date-Day 0 visit date) + 1 for Long-term discontinuation, treatment control groups and holiday phase group. For holiday phase group data censored at last flare assessment by treatment re-start date. Time to first severe flare is defined as (event date-treatment re-start date) + 1 for Re-start treatment holiday group. Median time to first severe SFI flare is reported; estimated using the product-limit method.
- Number of Participants With Evidence of Rebound [Up to 24 weeks]
Rebound is defined as SELENA SLEDAI score during the first 24 weeks that exceeds the Baseline SELENA SLEDAI score in the participant's respective original parent study. Baseline is defined as the Day 0 visit from the parent study. SELENA SLEDAI assessments consist of 24 individual weighted items in which signs and symptoms, laboratory tests, and physician's assessment for each of 9 organ systems are given a weighted score and summed if present (marked 'Yes') at the time of the visit or in the preceding 10 days. The maximum theoretical score is 105 (all 24 descriptors present simultaneously) with 0 indicating inactive disease (marked 'No'). Any time during the first 24 weeks of this study has been reported.
- Number of Participants With Confirmed True Positive Belimumab Anti-drug Antibodies (ADA) [Up to 52 weeks]
Immunogenicity assay results were categorized as negative or positive. A persistent positive result was defined as a positive post-Day 0 visit immunogenic response that occurred for at least 2 consecutive assessments or a single result at the final assessment. A transient positive result was defined as a single post-Day 0 visit positive immunogenic response that did not occur at the final assessment. Any time post-Day 0 visit data are reported (or post-Week 24 for Treatment Holiday - Restart phase). Day 0 visit date is defined as Day 0 from present study.
- Percentage Change From Baseline in Immunoglobulin [Baseline (Day 0 from parent studies); Day 0 and 8, 16, 24, 32, 40, 48 and 52 weeks]
Serum samples were collected at indicated time-points for analysis of immunoglobulins: Immunoglobulin G (IgG), Immunoglobulin A (IgA), and Immunoglobulin M (IgM). Baseline is defined as the Day 0 visit from parent studies. Percentage change from Baseline is equal to 100* (value at specified visit minus Baseline value) divided by Baseline value.
- Percentage Change From Baseline in Autoantibody:Anti-double Stranded Deoxyribonucleic Acid (dsDNA) [Baseline (Day 0 from parent studies); Day 0 and 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 weeks]
Blood samples were collected at indicated time-points for analysis of autoantibodies like dsDNA. Baseline is defined as the Day 0 visit from parent studies. Percentage change from Baseline is equal to 100* (Value at specified visit minus Baseline value) divided by Baseline value.
- Percentage Change From Baseline in Autoantibody: Antinuclear Antibody (ANA) [Baseline (Day 0 from parent studies); Day 0 and 24 and 52 weeks]
Blood samples were collected at indicated time-points for analysis of autoantibodies like ANA. Only participants who had an ANA value measured in INDEX at the parent studies Baseline were included in this analysis. Baseline is defined as the Day 0 visit from parent studies. Percentage change from Baseline is equal to 100* (Value at specified visit minus Baseline value) divided by Baseline value.
- Percentage Change From Baseline in Complement Levels [Baseline (Day 0 from parent studies); Day 0 and 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 weeks]
Blood samples were collected at indicated time-points for analysis of complement levels like complement 3 (C3) and complement 4 (C4). Baseline is defined as the Day 0 visit from parent studies. Percentage change from Baseline is equal to 100* (Value at specified visit minus Baseline value) divided by Baseline value.
- Percentage Change From Baseline in B Cell Subsets [Baseline (Day 0 from parent studies); Day 0 and 8, 16, 24, 32, 40 and 52 weeks]
Blood samples were collected at indicated time-points for analysis of Activated B cells subsets like Activated CD19+CD20+CD69+, cluster of differentiation 20+ (CD20+), Memory CD19+CD20+CD27+, Naive CD19+CD20+CD27-, Plasma CD19+CD20-CD138+, Plasmacytoid CD19+CD20+CD138+, and SLE Subset CD19+CD38b+CD27b+Lymph. Baseline is defined as the Day 0 visit from parent studies. Percentage change from Baseline is equal to 100* (Value at specified visit minus Baseline value) divided by Baseline value.
- Percentage Change From 24 Week in B Cell Subsets: Treatment Holiday Group (Re-start Phase) [Week 24, 32, 40 and 52 weeks]
Blood samples were collected at indicated time-points for analysis of Activated B cells subsets like Activated CD19+CD20+CD69+, CD20+, Memory CD19+CD20+CD27+, Naive CD19+CD20+CD27-, Plasma CD19+CD20-CD138+, Plasmacytoid CD19+CD20+CD138+, and SLE Subset CD19+CD38b+CD27b+Lymph. Percentage change from Week 24 of present study was calculated as 100*(value at specified visit - Week 24 value) divided by week 24 value. The data below is only reported for the Treatment Holiday Group (Re-start phase). Participants in this group restarted belimumab therapy one day after Week 24, hence the Baseline for this outcome measure was Week 24 visit. No other groups were measured for this outcome.
- SELENA SLEDAI Scores Change From Baseline [Baseline (Day 0 from parent studies); Day 0 and 4, 8, 12, 16, 20, 24, 28, 32,36, 40, 44, 48 and 52 weeks]
SELENA SLEDAI assessments consist of 24 individual weighted items in which signs and symptoms, laboratory tests, and physician's assessment for each of 9 organ systems are given a weighted score and summed if present (marked 'Yes') at the time of the visit or in the preceding 10 days. The maximum theoretical score is 105 (all 24 descriptors present simultaneously) with 0 indicating inactive disease (marked 'No'). Data are reported at the specified time-points from Day 0 (of present study) up to Week 52. Baseline is defined as the Day 0 from parent studies. Change from Baseline is equal to (Value at specified visit minus Baseline value).
- Number of Days of Daily Prednisone Dose >=7.5 mg/Day and/or Increased by 25 Percent From Day 0 of This Study [Day 0 to Week 24; Week 24 to Week 52; Day 0 to Week 52]
All corticosteroids are converted to a prednisone equivalent average daily dose (mg/day). The average daily dose at Day 0 was used to assess the relative change in daily dose on a given day. The average daily dose at Day 0 was calculated as sum of the daily dose across all days from the Screening visit date up to and including Day 0 visit date divided by the number of days in the time period. Data reported are the median number of days on which the specified criteria was met for Day 0 to Week 24, Week 24 to Week 52, Day 0 to Week 52. For treatment holiday group, Day 0 to Week 24 corresponds to holiday phase, Week 24 to Week 52 corresponds to treatment Re-start phase.
- Number of Days of Daily Prednisone Dose <=7.5 mg/Day and/or Decreased by 25 Percent From Day 0 of This Study [Day 0 to Week 24; Week 24 to Week 52; Day 0 to Week 52]
All corticosteroids are converted to a prednisone equivalent average daily dose (mg/day). The average daily dose at Day 0 was used to assess the relative change in daily dose on a given day. The average daily dose at Day 0 was calculated as sum of the daily dose across all days from the Screening visit date up to and including Day 0 visit date divided by the number of days in the time period. Data reported are the median number of days on which the specified criteria was met for Day 0 to Week 24, Week 24 to Week 52, Day 0 to Week 52. For treatment holiday group, Day 0 to Week 24 corresponds to holiday phase, Week 24 to Week 52 corresponds to treatment Re-start phase.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Received a minimun of 6 months therapy with with belimumab 10 mg/kg in their current SLE belimumab continuation study.
-
Be 18 years of age at the Day 0 visit.
-
Non-prenant, non-lactating females willing to comply with specific birth control requirements as set forth in the protocol.
-
Able to provide written informed consent to participate.
-
Subjects who wish to enroll in the control group and the group taking a 6 month belimumab treatment holiday will need a SELENA SLEDAI score of 3 or less after the minimum of 6 months belimumab therapy, as well as having C3 and C4 complement levels at or above the lower limit of the central laboratory reference range, and are on a stable SLE treatment regimen during the 30 day screening period prior to Day 0.
-
Subjects who wish to enroll in the long-term discontinuation group have voluntarily withdrawn from their continuation studies.
Exclusion Criteria:
-
Subjects who have developed clinical evidence of significant, unstable or uncontrolled, acute or chronic diseases not due to SLE, or experienced an adverse event (AE) in their belimumab continuation study that could, in the opinion of the principle investigator, put the subject at undue risk.
-
Subjects who have developed any other medical diseases, laboratory abnormalities, or conditions that, in the opinion of the principle investigator, makes the subject unsuitable for the study.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | GSK Investigational Site | Los Angeles | California | United States | 90048 |
| 2 | GSK Investigational Site | Manhasset | New York | United States | 11030 |
| 3 | GSK Investigational Site | Dallas | Texas | United States | 75246 |
| 4 | GSK Investigational Site | Hefei | Anhui | China | 230001 |
| 5 | GSK Investigational Site | Suzhou | Jiangsu | China | 215006 |
| 6 | GSK Investigational Site | Hangzhou | Zhejiang | China | 310009 |
| 7 | GSK Investigational Site | Beijing | China | 100032 | |
| 8 | GSK Investigational Site | Beijing | China | 100044 | |
| 9 | GSK Investigational Site | Chiba | Japan | 275-8580 | |
| 10 | GSK Investigational Site | Ehime | Japan | 791-0295 | |
| 11 | GSK Investigational Site | Hokkaido | Japan | 060-8604 | |
| 12 | GSK Investigational Site | Miyagi | Japan | 980-8574 | |
| 13 | GSK Investigational Site | Nagasaki | Japan | 857-1195 | |
| 14 | GSK Investigational Site | Tokyo | Japan | 104-8560 | |
| 15 | GSK Investigational Site | Tokyo | Japan | 162-8655 | |
| 16 | GSK Investigational Site | Daegu | Korea, Republic of | 700-721 | |
| 17 | GSK Investigational Site | Seoul | Korea, Republic of | 110-744 | |
| 18 | GSK Investigational Site | Seoul | Korea, Republic of | 133-792 | |
| 19 | GSK Investigational Site | Seoul | Korea, Republic of | ||
| 20 | GSK Investigational Site | Suwon, Kyonggi-do | Korea, Republic of | 443-721 |
Sponsors and Collaborators
- GlaxoSmithKline
Investigators
- Study Director: GSK Clinical Trials, GlaxoSmithKline
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT02119156
Other Study ID Numbers:
- 116027
First Posted:
Apr 21, 2014
Last Update Posted:
Jan 31, 2020
Last Verified:
Jan 1, 2020
Keywords provided by GlaxoSmithKline
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | This was multi-center study to evaluate temporary discontinuation of belimumab 10 milligram(mg)/kilogram(kg) for 24 weeks followed by reintroduction of belimumab 10 mg/kg Intravenous (IV) for 28 weeks, in participants with low Systemic Lupus Erythematosus (SLE) disease activity receiving belimumab plus standard of care. |
|---|---|
| Pre-assignment Detail | A total of 80 participants were enrolled for this study. Participants were enrolled across 20 sites in China, Japan, Korea and the United States. |
| Arm/Group Title | Long-term Discontinuation Group | Treatment Control Group | Treatment Holiday Group |
|---|---|---|---|
| Arm/Group Description | Participants in this group discontinued belimumab 10 mg/kg therapy for 52 weeks but remained on standard of care therapy. Participants from BEL114333 (NCT01597622), BEL112233 (NCT00724867) and BEL112626 (NCT00583362) were part of this group. Participants had been treated with belimumab for at least 6 months in one of these continuation studies but had withdrawn from belimumab therapy for no longer than 8 weeks prior to entry into this study. | Participants in this group continued to receive monthly belimumab 10 mg/kg therapy, in addition to standard of care SLE therapy for 52 weeks. Participants from BEL113750 (NCT01345253) and BEL114333 (NCT01597622) were part of this group. Participants had been treated with belimumab for at least 6 months in one of these continuation studies prior to entry into this study. Eligible participants on completion of 52-weeks entered Maintenance period and received belimumab 10 mg/kg every 4 weeks until Week 48 of subsequent years (Maintenance is Year 2, 3, 4). | Participants in the Treatment Holiday Group underwent a 24-week belimumab treatment holiday while remaining on standard of care SLE therapy, then re-started belimumab therapy for further 28 weeks while receiving standard of care SLE therapy. Participants from BEL113750 (NCT01345253) and BEL114333 (NCT01597622) were part of this group. Participants had been treated with belimumab for at least 6 months in one of these continuation studies prior to entry into this study. Eligible participants on completion of 52-weeks entered Maintenance period and received belimumab 10 mg/kg every 4 weeks until Week 48 of subsequent years (Maintenance is Year 2, 3, 4). |
| Period Title: Treatment Phase (Up to 52 Weeks) | |||
| STARTED | 39 | 29 | 12 |
| COMPLETED | 33 | 27 | 11 |
| NOT COMPLETED | 6 | 2 | 1 |
| Period Title: Treatment Phase (Up to 52 Weeks) | |||
| STARTED | 0 | 16 | 10 |
| COMPLETED | 0 | 6 | 3 |
| NOT COMPLETED | 0 | 10 | 7 |
Baseline Characteristics
| Arm/Group Title | Long-term Discontinuation Group | Treatment Control Group | Treatment Holiday Group | Total |
|---|---|---|---|---|
| Arm/Group Description | Participants in this group discontinued belimumab 10 mg/kg therapy for 52 weeks but remained on standard of care therapy. Participants from BEL114333 (NCT01597622), BEL112233 (NCT00724867) and BEL112626 (NCT00583362) were part of this group. Participants had been treated with belimumab for at least 6 months in one of these continuation studies but had withdrawn from belimumab therapy for no longer than 8 weeks prior to entry into this study. | Participants in this group continued to receive monthly belimumab 10 mg/kg therapy, in addition to standard of care SLE therapy for 52 weeks. Participants from BEL113750 (NCT01345253) and BEL114333 (NCT01597622) were part of this group. Participants had been treated with belimumab for at least 6 months in one of these continuation studies prior to entry into this study. Eligible participants on completion of 52-weeks entered Maintenance period and received belimumab 10 mg/kg every 4 weeks until Week 48 of subsequent years (Maintenance is Year 2, 3, 4). | Participants in the Treatment Holiday Group underwent a 24-week belimumab treatment holiday while remaining on standard of care SLE therapy, then re-started belimumab therapy for further 28 weeks while receiving standard of care SLE therapy. Participants from BEL113750 (NCT01345253) and BEL114333 (NCT01597622) were part of this group. Participants had been treated with belimumab for at least 6 months in one of these continuation studies prior to entry into this study. Eligible participants on completion of 52-weeks entered Maintenance period and received belimumab 10 mg/kg every 4 weeks until Week 48 of subsequent years (Maintenance is Year 2, 3, 4). | Total of all reporting groups |
| Overall Participants | 39 | 29 | 12 | 80 |
| Age (Years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [Years] |
38.9
(12.01)
|
40.6
(9.76)
|
38.1
(8.04)
|
39.4
(10.63)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
35
89.7%
|
27
93.1%
|
9
75%
|
71
88.8%
|
| Male |
4
10.3%
|
2
6.9%
|
3
25%
|
9
11.3%
|
| Race/Ethnicity, Customized (Count of Participants) | ||||
| White/Caucasian/European Heritage |
9
23.1%
|
0
0%
|
0
0%
|
9
11.3%
|
| Asian: Central/South Asian Heritage |
1
2.6%
|
0
0%
|
0
0%
|
1
1.3%
|
| Asian: East Asian Heritage |
23
59%
|
27
93.1%
|
4
33.3%
|
54
67.5%
|
| Asian: Japanese Heritage |
0
0%
|
2
6.9%
|
8
66.7%
|
10
12.5%
|
| African American/African Heritage |
5
12.8%
|
0
0%
|
0
0%
|
5
6.3%
|
| Native Hawaiian or Other Pacific Islander |
1
2.6%
|
0
0%
|
0
0%
|
1
1.3%
|
Outcome Measures
| Title | Median Time to First SLE Flare Index (SFI) |
|---|---|
| Description | SFI Flare was defined as a mild/moderate or severe flare according to the modified Safety of Estrogen in Lupus National Assessment Systemic Lupus Erythematosus Disease Activity Index (SELENA SLEDAI) SLE Flare Index (modified excluded severe flares from the SELENA SLEDAI flare assessment that were triggered only by an increase in SELENA SLEDAI score to >12).Time to first SFI flare is defined as the number of days from Day 0 visit date to the date the participant has a flare (event date - Day 0 visit date + 1) in the 52 Week/Holiday phase; (event date - treatment re-start date + 1) in the Re-start Holiday phase. Day 0 visit date is defined as Day 0 from present study. Median time to first SFI flare is reported; estimated using the product-limit method. |
| Time Frame | Up to 52 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat (ITT) Population comprised of all participants who enrolled in the study, excluding screen failures. |
| Arm/Group Title | Long-term Discontinuation Group | Treatment Control Group | Treatment Holiday Group - Holiday Phase | Treatment Holiday Group - Re-start Phase |
|---|---|---|---|---|
| Arm/Group Description | Participants in this group discontinued belimumab 10 mg/kg therapy for 52 weeks but remained on standard of care therapy. Participants from BEL114333 (NCT01597622), BEL112233 (NCT00724867) and BEL112626 (NCT00583362) were part of this group. Participants had been treated with belimumab for at least 6 months in one of these continuation studies but had withdrawn from belimumab therapy for no longer than 8 weeks prior to entry into this study. | Participants in this group continued to receive monthly belimumab 10 mg/kg therapy, in addition to standard of care SLE therapy for 52 weeks. Participants from BEL113750 (NCT01345253) and BEL114333 (NCT01597622) were part of this group. Participants had been treated with belimumab for at least 6 months in one of these continuation studies prior to entry into this study. Eligible participants on completion of 52-weeks entered Maintenance period and received belimumab 10 mg/kg every 4 weeks until Week 48 of subsequent years (Maintenance is Year 2, 3, 4). | Participants in the Treatment Holiday Group underwent a 24-week belimumab treatment holiday while remaining on standard of care SLE therapy, Holiday Phase was Day 0 visit to Week 24/Treatment Re-start phase. Participants from BEL113750 (NCT01345253) and BEL114333 (NCT01597622) were part of this group. Participants had been treated with belimumab for at least 6 months in one of these continuation studies prior to entry into this study. In the event of a severe flare, participants were allowed to enter Maintenance Phase and receive belimumab 10 mg/Kg every 4 weeks until Week 48 of subsequent years (Maintenance is Year 2, 3, 4). | Following Treatment holiday phase for 24 weeks, participants re-started belimumab therapy for 28 weeks while receiving standard of care SLE therapy for 52 weeks. Re-start Phase started one day after Week 24 up to Week 52. Participants from BEL113750 (NCT01345253) and BEL114333 (NCT01597622) were part of this group. Participants had been treated with belimumab for at least 6 months in one of these continuation studies prior to entry into this study. Eligible participants on completion of 52-weeks entered Maintenance period and received belimumab 10 mg/kg every 4 weeks until Week 48 of subsequent years (Maintenance is Year 2, 3, 4). |
| Measure Participants | 39 | 29 | 12 | 11 |
| Median (Inter-Quartile Range) [Days] |
183.0
|
NA
|
NA
|
NA
|
| Title | Rate of SLE Index Flare Per Subject Year |
|---|---|
| Description | Rate per subject year of SFI flare was calculated as total number of flares divided by total subject years in interval. The total subject years for each participant was calculated as (Week 52/ Exit visit date minus Day 0 visit date + 1) for Long-term discontinuation and treatment control groups. For treatment holiday phase group the subject-years for each participant was calculated as (Week 24/Treatment Re-start/Exit visit date minus Day 0 Visit date + 1)/365.25. For re-start treatment holiday phase group the subject-years for each participant was calculated as (Week 52/Exit visit date minus Week 24/Treatment Re-start date + 1)/365.25. Day 0 visit date is defined as Day 0 from present study. |
| Time Frame | Up to 52 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population |
| Arm/Group Title | Long-term Discontinuation Group | Treatment Control Group | Treatment Holiday Group - Holiday Phase | Treatment Holiday Group - Re-start Phase |
|---|---|---|---|---|
| Arm/Group Description | Participants in this group discontinued belimumab 10 mg/kg therapy for 52 weeks but remained on standard of care therapy. Participants from BEL114333 (NCT01597622), BEL112233 (NCT00724867) and BEL112626 (NCT00583362) were part of this group. Participants had been treated with belimumab for at least 6 months in one of these continuation studies but had withdrawn from belimumab therapy for no longer than 8 weeks prior to entry into this study. | Participants in this group continued to receive monthly belimumab 10 mg/kg therapy, in addition to standard of care SLE therapy for 52 weeks. Participants from BEL113750 (NCT01345253) and BEL114333 (NCT01597622) were part of this group. Participants had been treated with belimumab for at least 6 months in one of these continuation studies prior to entry into this study. Eligible participants on completion of 52-weeks entered Maintenance period and received belimumab 10 mg/kg every 4 weeks until Week 48 of subsequent years (Maintenance is Year 2, 3, 4). | Participants in the Treatment Holiday Group underwent a 24-week belimumab treatment holiday while remaining on standard of care SLE therapy, Holiday Phase was Day 0 visit to Week 24/Treatment Re-start phase. Participants from BEL113750 (NCT01345253) and BEL114333 (NCT01597622) were part of this group. Participants had been treated with belimumab for at least 6 months in one of these continuation studies prior to entry into this study. In the event of a severe flare, participants were allowed to enter Maintenance Phase and receive belimumab 10 mg/Kg every 4 weeks until Week 48 of subsequent years (Maintenance is Year 2, 3, 4). | Following Treatment holiday phase for 24 weeks, participants re-started belimumab therapy for 28 weeks while receiving standard of care SLE therapy for 52 weeks. Re-start Phase started one day after Week 24 up to Week 52. Participants from BEL113750 (NCT01345253) and BEL114333 (NCT01597622) were part of this group. Participants had been treated with belimumab for at least 6 months in one of these continuation studies prior to entry into this study. Eligible participants on completion of 52-weeks entered Maintenance period and received belimumab 10 mg/kg every 4 weeks until Week 48 of subsequent years (Maintenance is Year 2, 3, 4). |
| Measure Participants | 39 | 29 | 12 | 11 |
| Number [Flares per Subject-year] |
2.1
|
0.6
|
1.0
|
0.3
|
| Title | Median Time to First Severe SFI Flare |
|---|---|
| Description | The SLE Flare Index categorizes SLE flare as "mild or moderate" or "severe" based on a positive assessment for at least 1 of 5 variables as follows: Change in SELENA SLEDAI score from the most recent assessment to current; Change in signs or symptoms of disease activity; Change in prednisone dosage; Use of new medications for disease activity or hospitalization; Change in Physician's Global Assessment (PGA) score; Hospitalization for SLE activity is an additional category included only for a severe flare. Time to first severe flare is defined as (event date-Day 0 visit date) + 1 for Long-term discontinuation, treatment control groups and holiday phase group. For holiday phase group data censored at last flare assessment by treatment re-start date. Time to first severe flare is defined as (event date-treatment re-start date) + 1 for Re-start treatment holiday group. Median time to first severe SFI flare is reported; estimated using the product-limit method. |
| Time Frame | Up to 52 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population. |
| Arm/Group Title | Long-term Discontinuation Group | Treatment Control Group | Treatment Holiday Group - Holiday Phase | Treatment Holiday Group - Re-start Phase |
|---|---|---|---|---|
| Arm/Group Description | Participants in this group discontinued belimumab 10 mg/kg therapy for 52 weeks but remained on standard of care therapy. Participants from BEL114333 (NCT01597622), BEL112233 (NCT00724867) and BEL112626 (NCT00583362) were part of this group. Participants had been treated with belimumab for at least 6 months in one of these continuation studies but had withdrawn from belimumab therapy for no longer than 8 weeks prior to entry into this study. | Participants in this group continued to receive monthly belimumab 10 mg/kg therapy, in addition to standard of care SLE therapy for 52 weeks. Participants from BEL113750 (NCT01345253) and BEL114333 (NCT01597622) were part of this group. Participants had been treated with belimumab for at least 6 months in one of these continuation studies prior to entry into this study. Eligible participants on completion of 52-weeks entered Maintenance period and received belimumab 10 mg/kg every 4 weeks until Week 48 of subsequent years (Maintenance is Year 2, 3, 4). | Participants in the Treatment Holiday Group underwent a 24-week belimumab treatment holiday while remaining on standard of care SLE therapy, Holiday Phase was Day 0 visit to Week 24/Treatment Re-start phase. Participants from BEL113750 (NCT01345253) and BEL114333 (NCT01597622) were part of this group. Participants had been treated with belimumab for at least 6 months in one of these continuation studies prior to entry into this study. In the event of a severe flare, participants were allowed to enter Maintenance Phase and receive belimumab 10 mg/Kg every 4 weeks until Week 48 of subsequent years (Maintenance is Year 2, 3, 4). | Following Treatment holiday phase for 24 weeks, participants re-started belimumab therapy for 28 weeks while receiving standard of care SLE therapy for 52 weeks. Re-start Phase started one day after Week 24 up to Week 52. Participants from BEL113750 (NCT01345253) and BEL114333 (NCT01597622) were part of this group. Participants had been treated with belimumab for at least 6 months in one of these continuation studies prior to entry into this study. Eligible participants on completion of 52-weeks entered Maintenance period and received belimumab 10 mg/kg every 4 weeks until Week 48 of subsequent years (Maintenance is Year 2, 3, 4). |
| Measure Participants | 39 | 29 | 12 | 11 |
| Median (Inter-Quartile Range) [Days] |
NA
|
NA
|
NA
|
NA
|
| Title | Number of Participants With Evidence of Rebound |
|---|---|
| Description | Rebound is defined as SELENA SLEDAI score during the first 24 weeks that exceeds the Baseline SELENA SLEDAI score in the participant's respective original parent study. Baseline is defined as the Day 0 visit from the parent study. SELENA SLEDAI assessments consist of 24 individual weighted items in which signs and symptoms, laboratory tests, and physician's assessment for each of 9 organ systems are given a weighted score and summed if present (marked 'Yes') at the time of the visit or in the preceding 10 days. The maximum theoretical score is 105 (all 24 descriptors present simultaneously) with 0 indicating inactive disease (marked 'No'). Any time during the first 24 weeks of this study has been reported. |
| Time Frame | Up to 24 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population. |
| Arm/Group Title | Long-term Discontinuation Group | Treatment Control Group | Treatment Holiday Group |
|---|---|---|---|
| Arm/Group Description | Participants in this group discontinued belimumab 10 mg/kg therapy for 52 weeks but remained on standard of care therapy. Participants from BEL114333 (NCT01597622), BEL112233 (NCT00724867) and BEL112626 (NCT00583362) were part of this group. Participants had been treated with belimumab for at least 6 months in one of these continuation studies but had withdrawn from belimumab therapy for no longer than 8 weeks prior to entry into this study. | Participants in this group continued to receive monthly belimumab 10 mg/kg therapy, in addition to standard of care SLE therapy for 52 weeks. Participants from BEL113750 (NCT01345253) and BEL114333 (NCT01597622) were part of this group. Participants had been treated with belimumab for at least 6 months in one of these continuation studies prior to entry into this study. Eligible participants on completion of 52-weeks entered Maintenance period and received belimumab 10 mg/kg every 4 weeks until Week 48 of subsequent years (Maintenance is Year 2, 3, 4). | Participants in the Treatment Holiday Group underwent a 24-week belimumab treatment holiday while remaining on standard of care SLE therapy, then re-started belimumab therapy for further 28 weeks while receiving standard of care SLE therapy. Participants from BEL113750 (NCT01345253) and BEL114333 (NCT01597622) were part of this group. Participants had been treated with belimumab for at least 6 months in one of these continuation studies prior to entry into this study. Eligible participants on completion of 52-weeks entered Maintenance period and received belimumab 10 mg/kg every 4 weeks until Week 48 of subsequent years (Maintenance is Year 2, 3, 4). |
| Measure Participants | 39 | 29 | 12 |
| Count of Participants [Participants] |
2
5.1%
|
2
6.9%
|
0
0%
|
| Title | Number of Participants With Confirmed True Positive Belimumab Anti-drug Antibodies (ADA) |
|---|---|
| Description | Immunogenicity assay results were categorized as negative or positive. A persistent positive result was defined as a positive post-Day 0 visit immunogenic response that occurred for at least 2 consecutive assessments or a single result at the final assessment. A transient positive result was defined as a single post-Day 0 visit positive immunogenic response that did not occur at the final assessment. Any time post-Day 0 visit data are reported (or post-Week 24 for Treatment Holiday - Restart phase). Day 0 visit date is defined as Day 0 from present study. |
| Time Frame | Up to 52 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population. |
| Arm/Group Title | Long-term Discontinuation Group | Treatment Control Group | Treatment Holiday Group - Holiday Phase | Treatment Holiday Group - Re-start Phase |
|---|---|---|---|---|
| Arm/Group Description | Participants in this group discontinued belimumab 10 mg/kg therapy for 52 weeks but remained on standard of care therapy. Participants from BEL114333 (NCT01597622), BEL112233 (NCT00724867) and BEL112626 (NCT00583362) were part of this group. Participants had been treated with belimumab for at least 6 months in one of these continuation studies but had withdrawn from belimumab therapy for no longer than 8 weeks prior to entry into this study. | Participants in this group continued to receive monthly belimumab 10 mg/kg therapy, in addition to standard of care SLE therapy for 52 weeks. Participants from BEL113750 (NCT01345253) and BEL114333 (NCT01597622) were part of this group. Participants had been treated with belimumab for at least 6 months in one of these continuation studies prior to entry into this study. Eligible participants on completion of 52-weeks entered Maintenance period and received belimumab 10 mg/kg every 4 weeks until Week 48 of subsequent years (Maintenance is Year 2, 3, 4). | Participants in the Treatment Holiday Group underwent a 24-week belimumab treatment holiday while remaining on standard of care SLE therapy, Holiday Phase was Day 0 visit to Week 24/Treatment Re-start phase. Participants from BEL113750 (NCT01345253) and BEL114333 (NCT01597622) were part of this group. Participants had been treated with belimumab for at least 6 months in one of these continuation studies prior to entry into this study. In the event of a severe flare, participants were allowed to enter Maintenance Phase and receive belimumab 10 mg/Kg every 4 weeks until Week 48 of subsequent years (Maintenance is Year 2, 3, 4). | Following Treatment holiday phase for 24 weeks, participants re-started belimumab therapy for 28 weeks while receiving standard of care SLE therapy for 52 weeks. Re-start Phase started one day after Week 24 up to Week 52. Participants from BEL113750 (NCT01345253) and BEL114333 (NCT01597622) were part of this group. Participants had been treated with belimumab for at least 6 months in one of these continuation studies prior to entry into this study. Eligible participants on completion of 52-weeks entered Maintenance period and received belimumab 10 mg/kg every 4 weeks until Week 48 of subsequent years (Maintenance is Year 2, 3, 4). |
| Measure Participants | 39 | 29 | 12 | 11 |
| Negative |
39
100%
|
29
100%
|
12
100%
|
11
13.8%
|
| Persistent positive |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Transient positive |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Percentage Change From Baseline in Immunoglobulin |
|---|---|
| Description | Serum samples were collected at indicated time-points for analysis of immunoglobulins: Immunoglobulin G (IgG), Immunoglobulin A (IgA), and Immunoglobulin M (IgM). Baseline is defined as the Day 0 visit from parent studies. Percentage change from Baseline is equal to 100* (value at specified visit minus Baseline value) divided by Baseline value. |
| Time Frame | Baseline (Day 0 from parent studies); Day 0 and 8, 16, 24, 32, 40, 48 and 52 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). |
| Arm/Group Title | Long-term Discontinuation Group | Treatment Control Group | Treatment Holiday Group - Holiday Phase | Treatment Holiday Group - Re-start Phase |
|---|---|---|---|---|
| Arm/Group Description | Participants in this group discontinued belimumab 10 mg/kg therapy for 52 weeks but remained on standard of care therapy. Participants from BEL114333 (NCT01597622), BEL112233 (NCT00724867) and BEL112626 (NCT00583362) were part of this group. Participants had been treated with belimumab for at least 6 months in one of these continuation studies but had withdrawn from belimumab therapy for no longer than 8 weeks prior to entry into this study. | Participants in this group continued to receive monthly belimumab 10 mg/kg therapy, in addition to standard of care SLE therapy for 52 weeks. Participants from BEL113750 (NCT01345253) and BEL114333 (NCT01597622) were part of this group. Participants had been treated with belimumab for at least 6 months in one of these continuation studies prior to entry into this study. Eligible participants on completion of 52-weeks entered Maintenance period and received belimumab 10 mg/kg every 4 weeks until Week 48 of subsequent years (Maintenance is Year 2, 3, 4). | Participants in the Treatment Holiday Group underwent a 24-week belimumab treatment holiday while remaining on standard of care SLE therapy, Holiday Phase was Day 0 visit to Week 24/Treatment Re-start phase. Participants from BEL113750 (NCT01345253) and BEL114333 (NCT01597622) were part of this group. Participants had been treated with belimumab for at least 6 months in one of these continuation studies prior to entry into this study. In the event of a severe flare, participants were allowed to enter Maintenance Phase and receive belimumab 10 mg/Kg every 4 weeks until Week 48 of subsequent years (Maintenance is Year 2, 3, 4). | Following Treatment holiday phase for 24 weeks, participants re-started belimumab therapy for 28 weeks while receiving standard of care SLE therapy for 52 weeks. Re-start Phase started one day after Week 24 up to Week 52. Participants from BEL113750 (NCT01345253) and BEL114333 (NCT01597622) were part of this group. Participants had been treated with belimumab for at least 6 months in one of these continuation studies prior to entry into this study. Eligible participants on completion of 52-weeks entered Maintenance period and received belimumab 10 mg/kg every 4 weeks until Week 48 of subsequent years (Maintenance is Year 2, 3, 4). |
| Measure Participants | 39 | 29 | 12 | 11 |
| IgA,Day 0,n=31,29, 12,0 |
-19.205
|
-25.909
|
-22.193
|
|
| IgA,Week 8,n=37,29, 11,0 |
-21.028
|
-31.455
|
-24.242
|
|
| IgA, Week 16,n=36,27, 11,0 |
-22.052
|
-31.016
|
-20.202
|
|
| IgA, Week 24,n=31,27, 11,0 |
-20.570
|
-28.000
|
-21.711
|
|
| IgA, Week 32,n=34,27,0,10 |
-11.243
|
-29.703
|
-23.363
|
|
| IgA, Week 40,n=33,25,0,11 |
-10.769
|
-30.617
|
-24.579
|
|
| IgA, Week 48,n=33,27,0,10 |
-16.000
|
-34.091
|
-33.936
|
|
| IgA, Week 52,n=33,27,0,10 |
-14.859
|
-30.698
|
-31.663
|
|
| IgG,Day 0,n=39,29, 12,0 |
-13.939
|
-29.524
|
-19.481
|
|
| IgG,Week 8,n=37,29, 11,0 |
-19.169
|
-29.048
|
-25.571
|
|
| IgG, Week 16,n=36,27, 11,0 |
-16.169
|
-29.818
|
-21.642
|
|
| IgG, Week 24,n=31,27, 11,0 |
-17.982
|
-26.241
|
-17.886
|
|
| IgG, Week 32,n=34,27,0,10 |
-9.798
|
-23.288
|
-18.611
|
|
| IgG, Week 40,n=34,25,0,11 |
-6.955
|
-25.532
|
-26.484
|
|
| IgG, Week 48,n=33,27,0,10 |
-14.063
|
-25.133
|
-20.596
|
|
| IgG, Week 52,n=33,27,0,10 |
-11.258
|
-23.596
|
-23.754
|
|
| IgM,Day 0,n=31,29, 12,0 |
-47.059
|
-53.608
|
-44.326
|
|
| IgM,Week 8,n=37,29, 11,0 |
-49.174
|
-53.659
|
-50.943
|
|
| IgM, Week 16,n=36,27, 11,0 |
-50.077
|
-54.945
|
-45.926
|
|
| IgM, Week 24,n=31,27, 11,0 |
-39.496
|
-50.909
|
-45.161
|
|
| IgM, Week 32,n=34,27,0,10 |
-34.887
|
-52.577
|
-46.548
|
|
| IgM, Week 40,n=34,25,0,11 |
-37.870
|
-52.381
|
-48.889
|
|
| IgM, Week 48,n=33,27,0,10 |
-31.707
|
-53.636
|
-48.268
|
|
| IgM, Week 52,n=33,27,0,10 |
-30.921
|
-51.648
|
-57.966
|
| Title | Percentage Change From Baseline in Autoantibody:Anti-double Stranded Deoxyribonucleic Acid (dsDNA) |
|---|---|
| Description | Blood samples were collected at indicated time-points for analysis of autoantibodies like dsDNA. Baseline is defined as the Day 0 visit from parent studies. Percentage change from Baseline is equal to 100* (Value at specified visit minus Baseline value) divided by Baseline value. |
| Time Frame | Baseline (Day 0 from parent studies); Day 0 and 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). |
| Arm/Group Title | Long-term Discontinuation Group | Treatment Control Group | Treatment Holiday Group - Holiday Phase | Treatment Holiday Group - Re-start Phase |
|---|---|---|---|---|
| Arm/Group Description | Participants in this group discontinued belimumab 10 mg/kg therapy for 52 weeks but remained on standard of care therapy. Participants from BEL114333 (NCT01597622), BEL112233 (NCT00724867) and BEL112626 (NCT00583362) were part of this group. Participants had been treated with belimumab for at least 6 months in one of these continuation studies but had withdrawn from belimumab therapy for no longer than 8 weeks prior to entry into this study. | Participants in this group continued to receive monthly belimumab 10 mg/kg therapy, in addition to standard of care SLE therapy for 52 weeks. Participants from BEL113750 (NCT01345253) and BEL114333 (NCT01597622) were part of this group. Participants had been treated with belimumab for at least 6 months in one of these continuation studies prior to entry into this study. Eligible participants on completion of 52-weeks entered Maintenance period and received belimumab 10 mg/kg every 4 weeks until Week 48 of subsequent years (Maintenance is Year 2, 3, 4). | Participants in the Treatment Holiday Group underwent a 24-week belimumab treatment holiday while remaining on standard of care SLE therapy, Holiday Phase was Day 0 visit to Week 24/Treatment Re-start phase. Participants from BEL113750 (NCT01345253) and BEL114333 (NCT01597622) were part of this group. Participants had been treated with belimumab for at least 6 months in one of these continuation studies prior to entry into this study. In the event of a severe flare, participants were allowed to enter Maintenance Phase and receive belimumab 10 mg/Kg every 4 weeks until Week 48 of subsequent years (Maintenance is Year 2, 3, 4). | Following Treatment holiday phase for 24 weeks, participants re-started belimumab therapy for 28 weeks while receiving standard of care SLE therapy for 52 weeks. Re-start Phase started one day after Week 24 up to Week 52. Participants from BEL113750 (NCT01345253) and BEL114333 (NCT01597622) were part of this group. Participants had been treated with belimumab for at least 6 months in one of these continuation studies prior to entry into this study. Eligible participants on completion of 52-weeks entered Maintenance period and received belimumab 10 mg/kg every 4 weeks until Week 48 of subsequent years (Maintenance is Year 2, 3, 4). |
| Measure Participants | 39 | 29 | 12 | 11 |
| Day 0,n=39,29,12, 0 |
-82.8
|
-69.4
|
-81.3
|
|
| Week 4,n=39,29,12, 0 |
-82.8
|
-65.9
|
-83.2
|
|
| Week 8,n=37,29, 11,0 |
-74.3
|
-70.3
|
-81.6
|
|
| Week 12,n=38,29, 11,0 |
-77.3
|
-68.9
|
-85.0
|
|
| Week 16,n=36,27, 11,0 |
-78.4
|
-72.8
|
-79.7
|
|
| Week 20,n=34,27, 11,0 |
-82.8
|
-70.3
|
-79.9
|
|
| Week 24,n=31,27, 11,0 |
-82.8
|
-71.8
|
-75.0
|
|
| Week 28,n=35,27,0,10 |
-69.8
|
-72.3
|
-79.9
|
|
| Week 32,n=34,27,0,11 |
-77.9
|
-71.4
|
-79.6
|
|
| Week 36,n=34,27,0,11 |
-75.1
|
-71.0
|
-80.8
|
|
| Week 40,n=34,25,0,11 |
-73.6
|
-87.4
|
-79.9
|
|
| Week 44,n=34,27,0,10 |
-62.0
|
-77.7
|
-82.5
|
|
| Week 48,n=33,27,0,10 |
-71.8
|
-76.6
|
-80.6
|
|
| Week 52,n=33,27,0,10 |
-65.3
|
-78.3
|
-79.5
|
| Title | Percentage Change From Baseline in Autoantibody: Antinuclear Antibody (ANA) |
|---|---|
| Description | Blood samples were collected at indicated time-points for analysis of autoantibodies like ANA. Only participants who had an ANA value measured in INDEX at the parent studies Baseline were included in this analysis. Baseline is defined as the Day 0 visit from parent studies. Percentage change from Baseline is equal to 100* (Value at specified visit minus Baseline value) divided by Baseline value. |
| Time Frame | Baseline (Day 0 from parent studies); Day 0 and 24 and 52 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). |
| Arm/Group Title | Long-term Discontinuation Group | Treatment Control Group | Treatment Holiday Group - Holiday Phase | Treatment Holiday Group - Re-start Phase |
|---|---|---|---|---|
| Arm/Group Description | Participants in this group discontinued belimumab 10 mg/kg therapy for 52 weeks but remained on standard of care therapy. Participants from BEL114333 (NCT01597622), BEL112233 (NCT00724867) and BEL112626 (NCT00583362) were part of this group. Participants had been treated with belimumab for at least 6 months in one of these continuation studies but had withdrawn from belimumab therapy for no longer than 8 weeks prior to entry into this study. | Participants in this group continued to receive monthly belimumab 10 mg/kg therapy, in addition to standard of care SLE therapy for 52 weeks. Participants from BEL113750 (NCT01345253) and BEL114333 (NCT01597622) were part of this group. Participants had been treated with belimumab for at least 6 months in one of these continuation studies prior to entry into this study. Eligible participants on completion of 52-weeks entered Maintenance period and received belimumab 10 mg/kg every 4 weeks until Week 48 of subsequent years (Maintenance is Year 2, 3, 4). | Participants in the Treatment Holiday Group underwent a 24-week belimumab treatment holiday while remaining on standard of care SLE therapy, Holiday Phase was Day 0 visit to Week 24/Treatment Re-start phase. Participants from BEL113750 (NCT01345253) and BEL114333 (NCT01597622) were part of this group. Participants had been treated with belimumab for at least 6 months in one of these continuation studies prior to entry into this study. In the event of a severe flare, participants were allowed to enter Maintenance Phase and receive belimumab 10 mg/Kg every 4 weeks until Week 48 of subsequent years (Maintenance is Year 2, 3, 4). | Following Treatment holiday phase for 24 weeks, participants re-started belimumab therapy for 28 weeks while receiving standard of care SLE therapy for 52 weeks. Re-start Phase started one day after Week 24 up to Week 52. Participants from BEL113750 (NCT01345253) and BEL114333 (NCT01597622) were part of this group. Participants had been treated with belimumab for at least 6 months in one of these continuation studies prior to entry into this study. Eligible participants on completion of 52-weeks entered Maintenance period and received belimumab 10 mg/kg every 4 weeks until Week 48 of subsequent years (Maintenance is Year 2, 3, 4). |
| Measure Participants | 21 | 27 | 10 | 9 |
| Day 0,n=21,27, 10,0 |
-15.044
|
-24.938
|
-32.336
|
|
| Week 24,n=20,26, 10,0 |
5.723
|
-27.434
|
-29.771
|
|
| Week 52,n=19,26,0,9 |
-16.455
|
-45.961
|
-35.539
|
| Title | Percentage Change From Baseline in Complement Levels |
|---|---|
| Description | Blood samples were collected at indicated time-points for analysis of complement levels like complement 3 (C3) and complement 4 (C4). Baseline is defined as the Day 0 visit from parent studies. Percentage change from Baseline is equal to 100* (Value at specified visit minus Baseline value) divided by Baseline value. |
| Time Frame | Baseline (Day 0 from parent studies); Day 0 and 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). |
| Arm/Group Title | Long-term Discontinuation Group | Treatment Control Group | Treatment Holiday Group - Holiday Phase | Treatment Holiday Group - Re-start Phase |
|---|---|---|---|---|
| Arm/Group Description | Participants in this group discontinued belimumab 10 mg/kg therapy for 52 weeks but remained on standard of care therapy. Participants from BEL114333 (NCT01597622), BEL112233 (NCT00724867) and BEL112626 (NCT00583362) were part of this group. Participants had been treated with belimumab for at least 6 months in one of these continuation studies but had withdrawn from belimumab therapy for no longer than 8 weeks prior to entry into this study. | Participants in this group continued to receive monthly belimumab 10 mg/kg therapy, in addition to standard of care SLE therapy for 52 weeks. Participants from BEL113750 (NCT01345253) and BEL114333 (NCT01597622) were part of this group. Participants had been treated with belimumab for at least 6 months in one of these continuation studies prior to entry into this study. Eligible participants on completion of 52-weeks entered Maintenance period and received belimumab 10 mg/kg every 4 weeks until Week 48 of subsequent years (Maintenance is Year 2, 3, 4). | Participants in the Treatment Holiday Group underwent a 24-week belimumab treatment holiday while remaining on standard of care SLE therapy, Holiday Phase was Day 0 visit to Week 24/Treatment Re-start phase. Participants from BEL113750 (NCT01345253) and BEL114333 (NCT01597622) were part of this group. Participants had been treated with belimumab for at least 6 months in one of these continuation studies prior to entry into this study. In the event of a severe flare, participants were allowed to enter Maintenance Phase and receive belimumab 10 mg/Kg every 4 weeks until Week 48 of subsequent years (Maintenance is Year 2, 3, 4). | Following Treatment holiday phase for 24 weeks, participants re-started belimumab therapy for 28 weeks while receiving standard of care SLE therapy for 52 weeks. Re-start Phase started one day after Week 24 up to Week 52. Participants from BEL113750 (NCT01345253) and BEL114333 (NCT01597622) were part of this group. Participants had been treated with belimumab for at least 6 months in one of these continuation studies prior to entry into this study. Eligible participants on completion of 52-weeks entered Maintenance period and received belimumab 10 mg/kg every 4 weeks until Week 48 of subsequent years (Maintenance is Year 2, 3, 4). |
| Measure Participants | 39 | 29 | 12 | 11 |
| C3, Day 0,n=39,27,12, 0 |
10.3
|
7.2
|
32.1
|
|
| C3, Week 4,n=39,29,12, 0 |
15.4
|
16.0
|
14.8
|
|
| C3,Week 8,n=37,29, 11,0 |
13.6
|
19.8
|
31.4
|
|
| C3,Week 12,n=38,29, 11,0 |
10.9
|
14.1
|
30.4
|
|
| C3,Week 16,n=36,27, 11,0 |
15.2
|
20.5
|
32.2
|
|
| C3,Week 20,n=34,27, 11,0 |
15.4
|
13.6
|
30.0
|
|
| C3,Week 24,n=31,27, 11,0 |
17.3
|
19.8
|
44.2
|
|
| C3,Week 28,n=35,27,0,10 |
15.8
|
15.4
|
31.3
|
|
| C3,Week 32,n=34,27,0,11 |
13.8
|
21.6
|
31.6
|
|
| C3,Week 36,n=34,27,0,11 |
9.4
|
17.0
|
26.0
|
|
| C3,Week 40,n=34,25,0,11 |
12.8
|
17.3
|
41.8
|
|
| C3,Week 44,n=34,27,0,10 |
14.1
|
22.7
|
38.9
|
|
| C3,Week 48,n=33,27,0,10 |
15.4
|
15.9
|
30.4
|
|
| C3,Week 52,n=33,27,0,10 |
5.9
|
21.9
|
36.5
|
|
| C4, Day 0,n=39,27,12, 0 |
36.4
|
27.8
|
70.8
|
|
| C4, Week 4,n=39,29,12, 0 |
31.6
|
47.4
|
39.7
|
|
| C4,Week 8,n=37,29, 11,0 |
37.5
|
71.4
|
58.3
|
|
| C4,Week 12,n=38,29, 11,0 |
27.6
|
68.4
|
64.3
|
|
| C4,Week 16,n=36,27, 11,0 |
35.4
|
50.0
|
41.7
|
|
| C4,Week 20,n=34,27, 11,0 |
32.6
|
64.3
|
58.3
|
|
| C4,Week 24,n=31,27, 11,0 |
34.8
|
57.1
|
66.7
|
|
| C4,Week 28,n=35,27,0,10 |
31.3
|
66.7
|
50.6
|
|
| C4,Week 32,n=34,27,0,11 |
27.6
|
92.9
|
58.3
|
|
| C4,Week 36,n=34,27,0,11 |
29.2
|
50.0
|
58.3
|
|
| C4,Week 40,n=34,25,0,11 |
32.1
|
73.3
|
58.3
|
|
| C4,Week 44,n=34,27,0,10 |
20.5
|
57.1
|
60.7
|
|
| C4,Week 48,n=33,27,0,10 |
31.3
|
64.3
|
34.5
|
|
| C4,Week 52,n=33,27,0,10 |
17.6
|
63.2
|
58.3
|
| Title | Percentage Change From Baseline in B Cell Subsets |
|---|---|
| Description | Blood samples were collected at indicated time-points for analysis of Activated B cells subsets like Activated CD19+CD20+CD69+, cluster of differentiation 20+ (CD20+), Memory CD19+CD20+CD27+, Naive CD19+CD20+CD27-, Plasma CD19+CD20-CD138+, Plasmacytoid CD19+CD20+CD138+, and SLE Subset CD19+CD38b+CD27b+Lymph. Baseline is defined as the Day 0 visit from parent studies. Percentage change from Baseline is equal to 100* (Value at specified visit minus Baseline value) divided by Baseline value. |
| Time Frame | Baseline (Day 0 from parent studies); Day 0 and 8, 16, 24, 32, 40 and 52 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). |
| Arm/Group Title | Long-term Discontinuation Group | Treatment Control Group | Treatment Holiday Group - Holiday Phase | Treatment Holiday Group - Re-start Phase |
|---|---|---|---|---|
| Arm/Group Description | Participants in this group discontinued belimumab 10 mg/kg therapy for 52 weeks but remained on standard of care therapy. Participants from BEL114333 (NCT01597622), BEL112233 (NCT00724867) and BEL112626 (NCT00583362) were part of this group. Participants had been treated with belimumab for at least 6 months in one of these continuation studies but had withdrawn from belimumab therapy for no longer than 8 weeks prior to entry into this study. | Participants in this group continued to receive monthly belimumab 10 mg/kg therapy, in addition to standard of care SLE therapy for 52 weeks. Participants from BEL113750 (NCT01345253) and BEL114333 (NCT01597622) were part of this group. Participants had been treated with belimumab for at least 6 months in one of these continuation studies prior to entry into this study. Eligible participants on completion of 52-weeks entered Maintenance period and received belimumab 10 mg/kg every 4 weeks until Week 48 of subsequent years (Maintenance is Year 2, 3, 4). | Participants in the Treatment Holiday Group underwent a 24-week belimumab treatment holiday while remaining on standard of care SLE therapy, Holiday Phase was Day 0 visit to Week 24/Treatment Re-start phase. Participants from BEL113750 (NCT01345253) and BEL114333 (NCT01597622) were part of this group. Participants had been treated with belimumab for at least 6 months in one of these continuation studies prior to entry into this study. In the event of a severe flare, participants were allowed to enter Maintenance Phase and receive belimumab 10 mg/Kg every 4 weeks until Week 48 of subsequent years (Maintenance is Year 2, 3, 4). | Following Treatment holiday phase for 24 weeks, participants re-started belimumab therapy for 28 weeks while receiving standard of care SLE therapy for 52 weeks. Re-start Phase started one day after Week 24 up to Week 52. Participants from BEL113750 (NCT01345253) and BEL114333 (NCT01597622) were part of this group. Participants had been treated with belimumab for at least 6 months in one of these continuation studies prior to entry into this study. Eligible participants on completion of 52-weeks entered Maintenance period and received belimumab 10 mg/kg every 4 weeks until Week 48 of subsequent years (Maintenance is Year 2, 3, 4). |
| Measure Participants | 16 | 2 | 8 | 7 |
| Memory CD19+CD20+CD27+, Day 0,n=16,2,8,0 |
-69.0
|
-76.1
|
-43.2
|
|
| Memory CD19+CD20+CD27+, Week 8,n=15,2,5,0 |
-73.7
|
-78.9
|
-50.0
|
|
| Memory CD19+CD20+CD27+,Week16,n=14,2,6,0 |
-83.4
|
-69.2
|
-60.7
|
|
| Memory CD19+CD20+CD27+,Week24,n=13,2,6,0 |
-86.7
|
-59.7
|
-65.0
|
|
| Memory CD19+CD20+CD27+,Week32,n=12,2,0,7 |
-85.8
|
-73.3
|
-20.0
|
|
| Memory CD19+CD20+CD27+,Week40,n=13,2,0,7 |
-80.0
|
-65.6
|
0.0
|
|
| Memory CD19+CD20+CD27+,Week52,n=13,2,0,6 |
-81.8
|
-78.9
|
-10.0
|
|
| Naive CD19+CD20+CD27-,Day 0,n=16,2,8,0 |
-78.3
|
-91.6
|
-81.0
|
|
| Naive CD19+CD20+CD27-,Week 8,n=15,2,5,0 |
-80.5
|
-94.3
|
-83.0
|
|
| Naive CD19+CD20+CD27-,Week16,n=14,2,6,0 |
-76.4
|
-89.6
|
-81.0
|
|
| Naive CD19+CD20+CD27-,Week 24,n=13,2,6,0 |
-45.7
|
-92.9
|
-54.2
|
|
| Naive CD19+CD20+CD27-,Week 32,n=12,2,0,7 |
-39.8
|
-92.2
|
-73.5
|
|
| Naive CD19+CD20+CD27-,Week 40,n=13,2,0,7 |
-6.8
|
-92.6
|
-68.4
|
|
| Naive CD19+CD20+CD27-,Week 52,n=13,2,0,6 |
17.1
|
-92.7
|
-77.9
|
|
| Plasma CD19+CD20-CD138+,Day0,n=11,2,8,0 |
-96.2
|
45.8
|
-56.7
|
|
| Plasma CD19+CD20-CD138+,Week8,n=10,2,7,0 |
-100.0
|
752.7
|
-88.6
|
|
| Plasma CD19+CD20-CD138+, Week16,n=9,2,7,0 |
-97.8
|
535.2
|
-53.5
|
|
| Plasma CD19+CD20-CD138+,Week24,n=9,2,7,0 |
-88.8
|
68.9
|
-79.1
|
|
| Plasma CD19+CD20-CD138+,Week32,n=9,2,0,7 |
-76.0
|
182.5
|
-41.3
|
|
| Plasma CD19+CD20-CD138+,Week40,n=9,2,0,7 |
-53.4
|
-9.0
|
-86.5
|
|
| Plasma CD19+CD20-CD138+,Week52,n=9,2,0,6 |
-75.5
|
-43.8
|
-53.8
|
|
| Plasmacytoid CD19+CD20+CD138+,Day 0,n=11,2,8,0 |
-98.9
|
118.1
|
-75.5
|
|
| Plasmacytoid CD19+CD20+CD138+,Week8,n=10,2,7,0 |
-97.6
|
14.1
|
-75.0
|
|
| Plasmacytoid CD19+CD20+CD138+,Week16,n=9,2,7,0 |
-98.7
|
226.3
|
-75.9
|
|
| Plasmacytoid CD19+CD20+CD138+,Week24,n=9,2,7,0 |
-98.5
|
-16.3
|
-15.0
|
|
| Plasmacytoid CD19+CD20+CD138+,Week32,n=9,2,0,7 |
-95.4
|
-24.1
|
-52.5
|
|
| Plasmacytoid CD19+CD20+CD138+,Week40,n=9,2,0,7 |
-93.4
|
-31.3
|
2.5
|
|
| Plasmacytoid CD19+CD20+CD138+,Week 52,n=9,2,0,6 |
-96.1
|
202.5
|
32.2
|
|
| SLE Subset CD19+CD38b+CD27b+Lymph,Day0,n=11,2,8,0 |
-28.3
|
-67.9
|
-66.7
|
|
| SLE Subset CD19+CD38b+CD27b+Lymph,Week8,n=10,2,7,0 |
-30.5
|
-91.7
|
-71.9
|
|
| SLE Subset CD19+CD38b+CD27b+Lymph,Week16,n=9,2,7,0 |
21.3
|
-74.2
|
-48.6
|
|
| SLE Subset CD19+CD38b+CD27b+Lymph,Week24,n=9,2,7,0 |
25.2
|
-64.7
|
152.3
|
|
| SLE Subset CD19+CD38b+CD27b+Lymph,Week32,n=9,2,0,7 |
-8.4
|
-37.5
|
-4.6
|
|
| SLE Subset CD19+CD38b+CD27b+Lymph,Week40,n=9,2,0,7 |
-8.5
|
-66.3
|
-24.6
|
|
| SLE Subset CD19+CD38b+CD27b+Lymph,Week52,n=9,2,0,6 |
-23.5
|
-81.4
|
0.7
|
|
| CD20+ Day 0,n=16,2,8,0 |
-75.2
|
-88.1
|
-77.1
|
|
| CD20+ Week 8,n=15,2,5,0 |
-79.9
|
-91.0
|
-80.9
|
|
| CD20+,Week16,n=14,2,6,0 |
-75.4
|
-84.3
|
-80.4
|
|
| CD20+,Week24,n=13,2,6,0 |
-52.0
|
-87.7
|
-53.4
|
|
| CD20+,Week32,n=12,2,0,7 |
-49.0
|
-87.4
|
-66.2
|
|
| CD20+,Week40,n=13,2,0,7 |
-15.2
|
-86.6
|
-59.1
|
|
| CD20+,Week52,n=13,2,0,6 |
-12.0
|
-89.8
|
-71.8
|
|
| Activated CD19+CD20+CD69+,Day0, n=11,1,8,0 |
-99.8
|
-86.1
|
-65.1
|
|
| Activated CD19+CD20+CD69+, Week8, n=10,1,7,0 |
-99.6
|
-97.1
|
-76.3
|
|
| Activated CD19+CD20+CD69+, Week16, n=9,1,7,0 |
-98.9
|
-93.4
|
-72.3
|
|
| Activated CD19+CD20+CD69+,Week24, n=9,1,7,0 |
-99.7
|
-94.2
|
-50.9
|
|
| Activated CD19+CD20+CD69+,Week32, n=9,1,0,7 |
-98.0
|
-86.9
|
-54.5
|
|
| Activated CD19+CD20+CD69+, Week40, n=9,1,0,7 |
-98.1
|
-100.0
|
-47.5
|
|
| Activated CD19+CD20+CD69+, Week52, n=9,1,0,6 |
-96.9
|
-100.0
|
-27.4
|
| Title | Percentage Change From 24 Week in B Cell Subsets: Treatment Holiday Group (Re-start Phase) |
|---|---|
| Description | Blood samples were collected at indicated time-points for analysis of Activated B cells subsets like Activated CD19+CD20+CD69+, CD20+, Memory CD19+CD20+CD27+, Naive CD19+CD20+CD27-, Plasma CD19+CD20-CD138+, Plasmacytoid CD19+CD20+CD138+, and SLE Subset CD19+CD38b+CD27b+Lymph. Percentage change from Week 24 of present study was calculated as 100*(value at specified visit - Week 24 value) divided by week 24 value. The data below is only reported for the Treatment Holiday Group (Re-start phase). Participants in this group restarted belimumab therapy one day after Week 24, hence the Baseline for this outcome measure was Week 24 visit. No other groups were measured for this outcome. |
| Time Frame | Week 24, 32, 40 and 52 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population. Participants in this group restarted belimumab therapy one day after Week 24, hence the Baseline for this outcome measure was Week 24 visit. The data below is only reported for the Treatment Holiday Group and no other groups were measured. |
| Arm/Group Title | Treatment Holiday Group - Re-start Phase |
|---|---|
| Arm/Group Description | Following Treatment holiday phase for 24 weeks, participants re-started belimumab therapy for 28 weeks while receiving standard of care SLE therapy for 52 weeks. Re-start Phase started one day after Week 24 up to Week 52. Participants from BEL113750 (NCT01345253) and BEL114333 (NCT01597622) were part of this group. Participants had been treated with belimumab for at least 6 months in one of these continuation studies prior to entry into this study. Eligible participants on completion of 52-weeks entered Maintenance period and received belimumab 10 mg/kg every 4 weeks until Week 48 of subsequent years (Maintenance is Year 2, 3, 4). |
| Measure Participants | 11 |
| Memory CD19+CD20+CD27+, Week 32 |
100.0
|
| Memory CD19+CD20+CD27+, Week 40 |
83.3
|
| Memory CD19+CD20+CD27+,Week52 |
66.7
|
| Naive CD19+CD20+CD27-,Week 32 |
-19.0
|
| Naive CD19+CD20+CD27-,Week 40 |
-12.5
|
| Naive CD19+CD20+CD27-,Week52 |
-35.6
|
| Plasma CD19+CD20-CD138+,Week32 |
-16.3
|
| Plasma CD19+CD20-CD138+, Week40 |
-59.8
|
| Plasma CD19+CD20-CD138+,Week52 |
-48.0
|
| Plasmacytoid CD19+CD20+CD138+,Week32 |
-35.7
|
| Plasmacytoid CD19+CD20+CD138+,Week40 |
-64.3
|
| Plasmacytoid CD19+CD20+CD138+,Week52 |
-55.0
|
| SLE SubsetCD19+CD38b+CD27b+Lymph,Week32 |
-55.4
|
| SLE SubsetCD19+CD38b+CD27b+Lymph,Week40 |
-56.9
|
| SLE SubsetCD19+CD38b+CD27b+Lymph,Week52 |
-67.2
|
| CD20+, Week 32 |
-3.3
|
| CD20+, Week 40 |
2.2
|
| CD20+, Week 52 |
-20.0
|
| Activated CD19+CD20+CD69+,Week32 |
-28.8
|
| Activated CD19+CD20+CD69+,Week40 |
-23.8
|
| Activated CD19+CD20+CD69+,Week52 |
-66.7
|
| Title | SELENA SLEDAI Scores Change From Baseline |
|---|---|
| Description | SELENA SLEDAI assessments consist of 24 individual weighted items in which signs and symptoms, laboratory tests, and physician's assessment for each of 9 organ systems are given a weighted score and summed if present (marked 'Yes') at the time of the visit or in the preceding 10 days. The maximum theoretical score is 105 (all 24 descriptors present simultaneously) with 0 indicating inactive disease (marked 'No'). Data are reported at the specified time-points from Day 0 (of present study) up to Week 52. Baseline is defined as the Day 0 from parent studies. Change from Baseline is equal to (Value at specified visit minus Baseline value). |
| Time Frame | Baseline (Day 0 from parent studies); Day 0 and 4, 8, 12, 16, 20, 24, 28, 32,36, 40, 44, 48 and 52 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles). |
| Arm/Group Title | Long-term Discontinuation | Treatment Control Group | Treatment Holiday Group - Holiday Phase | Treatment Holiday Group - Re-start Phase |
|---|---|---|---|---|
| Arm/Group Description | Participants in this group discontinued belimumab 10 mg/kg therapy for 52 weeks but remained on standard of care therapy. Participants from BEL114333 (NCT01597622), BEL112233 (NCT00724867) and BEL112626 (NCT00583362) were part of this group. Participants had been treated with belimumab for at least 6 months in one of these continuation studies but had withdrawn from belimumab therapy for no longer than 8 weeks prior to entry into this study. | Participants in this group continued to receive monthly belimumab 10 mg/kg therapy, in addition to standard of care SLE therapy for 52 weeks. Participants from BEL113750 (NCT01345253) and BEL114333 (NCT01597622) were part of this group. Participants had been treated with belimumab for at least 6 months in one of these continuation studies prior to entry into this study. Eligible participants on completion of 52-weeks entered Maintenance period and received belimumab 10 mg/kg every 4 weeks until Week 48 of subsequent years (Maintenance is Year 2, 3, 4). | Participants in the Treatment Holiday Group underwent a 24-week belimumab treatment holiday while remaining on standard of care SLE therapy, Holiday Phase was Day 0 visit to Week 24/Treatment Re-start phase. Participants from BEL113750 (NCT01345253) and BEL114333 (NCT01597622) were part of this group. Participants had been treated with belimumab for at least 6 months in one of these continuation studies prior to entry into this study. In the event of a severe flare, participants were allowed to enter Maintenance Phase and receive belimumab 10 mg/Kg every 4 weeks until Week 48 of subsequent years (Maintenance is Year 2, 3, 4). | Following Treatment holiday phase for 24 weeks, participants re-started belimumab therapy for 28 weeks while receiving standard of care SLE therapy for 52 weeks. Re-start Phase started one day after Week 24 up to Week 52. Participants from BEL113750 (NCT01345253) and BEL114333 (NCT01597622) were part of this group. Participants had been treated with belimumab for at least 6 months in one of these continuation studies prior to entry into this study. Eligible participants on completion of 52-weeks entered Maintenance period and received belimumab 10 mg/kg every 4 weeks until Week 48 of subsequent years (Maintenance is Year 2, 3, 4). |
| Measure Participants | 39 | 29 | 12 | 11 |
| Day 0,n=39,29,12, 0 |
-6.2
(4.12)
|
-6.9
(3.62)
|
-6.3
(4.31)
|
|
| Week 4,n=39,29,12, 0 |
-5.9
(5.07)
|
-6.6
(3.44)
|
-6.1
(4.01)
|
|
| Week 8,n=38,29, 11,0 |
-6.4
(4.18)
|
-7.0
(3.73)
|
-5.9
(4.16)
|
|
| Week 12,n=38,29, 11,0 |
-6.1
(4.28)
|
-7.0
(3.75)
|
-6.3
(3.95)
|
|
| Week 16,n=36,27, 11,0 |
-6.4
(5.21)
|
-6.8
(4.05)
|
-6.1
(3.96)
|
|
| Week 20,n=36,27, 11,0 |
-6.9
(4.17)
|
-6.9
(3.23)
|
-6.1
(3.96)
|
|
| Week 24,n=36,27, 11,0 |
-6.4
(4.45)
|
-6.7
(3.45)
|
-5.4
(4.01)
|
|
| Week 28,n=35,27,0,10 |
-5.8
(4.22)
|
-7.0
(3.32)
|
-5.5
(5.36)
|
|
| Week 32,n=34,27,0,11 |
-5.7
(4.59)
|
-7.1
(3.38)
|
-6.1
(4.01)
|
|
| Week 36,n=34,27,0,11 |
-5.0
(4.42)
|
-6.7
(3.59)
|
-5.9
(4.01)
|
|
| Week 40,n=34,27,0,11 |
-5.2
(4.30)
|
-7.2
(3.37)
|
-6.6
(4.30)
|
|
| Week 44,n=34,27,0,11 |
-5.8
(4.15)
|
-7.3
(3.49)
|
-6.3
(4.65)
|
|
| Week 48,n=33,27,0,11 |
-5.7
(4.30)
|
-7.3
(3.28)
|
-6.1
(3.91)
|
|
| Week 52,n=33,27,0,11 |
-5.0
(4.39)
|
-6.9
(3.69)
|
-5.5
(4.08)
|
| Title | Number of Days of Daily Prednisone Dose >=7.5 mg/Day and/or Increased by 25 Percent From Day 0 of This Study |
|---|---|
| Description | All corticosteroids are converted to a prednisone equivalent average daily dose (mg/day). The average daily dose at Day 0 was used to assess the relative change in daily dose on a given day. The average daily dose at Day 0 was calculated as sum of the daily dose across all days from the Screening visit date up to and including Day 0 visit date divided by the number of days in the time period. Data reported are the median number of days on which the specified criteria was met for Day 0 to Week 24, Week 24 to Week 52, Day 0 to Week 52. For treatment holiday group, Day 0 to Week 24 corresponds to holiday phase, Week 24 to Week 52 corresponds to treatment Re-start phase. |
| Time Frame | Day 0 to Week 24; Week 24 to Week 52; Day 0 to Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population. Only those participants who met specified criteria (>=7.5 mg/day and/or increased by 25%) within specified time period were analyzed (represented by n= X in the category titles). |
| Arm/Group Title | Long-term Discontinuation Group | Treatment Control Group | Treatment Holiday Group |
|---|---|---|---|
| Arm/Group Description | Participants in this group discontinued belimumab 10 mg/kg therapy for 52 weeks but remained on standard of care therapy. Participants from BEL114333 (NCT01597622), BEL112233 (NCT00724867) and BEL112626 (NCT00583362) were part of this group. Participants had been treated with belimumab for at least 6 months in one of these continuation studies but had withdrawn from belimumab therapy for no longer than 8 weeks prior to entry into this study. | Participants in this group continued to receive monthly belimumab 10 mg/kg therapy, in addition to standard of care SLE therapy for 52 weeks. Participants from BEL113750 (NCT01345253) and BEL114333 (NCT01597622) were part of this group. Participants had been treated with belimumab for at least 6 months in one of these continuation studies prior to entry into this study. Eligible participants on completion of 52-weeks entered Maintenance period and received belimumab 10 mg/kg every 4 weeks until Week 48 of subsequent years (Maintenance is Year 2, 3, 4). | Participants in the Treatment Holiday Group underwent a 24-week belimumab treatment holiday while remaining on standard of care SLE therapy, then re-started belimumab therapy for further 28 weeks while receiving standard of care SLE therapy. Participants from BEL113750 (NCT01345253) and BEL114333 (NCT01597622) were part of this group. Participants had been treated with belimumab for at least 6 months in one of these continuation studies prior to entry into this study. Eligible participants on completion of 52-weeks entered Maintenance period and received belimumab 10 mg/kg every 4 weeks until Week 48 of subsequent years (Maintenance is Year 2, 3, 4). |
| Measure Participants | 13 | 12 | 6 |
| Day 0 to Week 24, n=11, 12, 6 |
143.0
|
170.0
|
168.0
|
| Day 0 to Week 52, n=13, 12, 6 |
278.0
|
364.0
|
364.0
|
| Week 24 to Week 52, n=10, 9, 5 |
167.5
|
196.0
|
196.0
|
| Title | Number of Days of Daily Prednisone Dose <=7.5 mg/Day and/or Decreased by 25 Percent From Day 0 of This Study |
|---|---|
| Description | All corticosteroids are converted to a prednisone equivalent average daily dose (mg/day). The average daily dose at Day 0 was used to assess the relative change in daily dose on a given day. The average daily dose at Day 0 was calculated as sum of the daily dose across all days from the Screening visit date up to and including Day 0 visit date divided by the number of days in the time period. Data reported are the median number of days on which the specified criteria was met for Day 0 to Week 24, Week 24 to Week 52, Day 0 to Week 52. For treatment holiday group, Day 0 to Week 24 corresponds to holiday phase, Week 24 to Week 52 corresponds to treatment Re-start phase. |
| Time Frame | Day 0 to Week 24; Week 24 to Week 52; Day 0 to Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population. Only those participants who met specified criteria (<=7.5 mg/day and/or decreased by 25%) within specified time period were analyzed (represented by n= X in the category titles). |
| Arm/Group Title | Long-term Discontinuation Group | Treatment Control Group | Treatment Holiday Group |
|---|---|---|---|
| Arm/Group Description | Participants in this group discontinued belimumab 10 mg/kg therapy for 52 weeks but remained on standard of care therapy. Participants from BEL114333 (NCT01597622), BEL112233 (NCT00724867) and BEL112626 (NCT00583362) were part of this group. Participants had been treated with belimumab for at least 6 months in one of these continuation studies but had withdrawn from belimumab therapy for no longer than 8 weeks prior to entry into this study. | Participants in this group continued to receive monthly belimumab 10 mg/kg therapy, in addition to standard of care SLE therapy for 52 weeks. Participants from BEL113750 (NCT01345253) and BEL114333 (NCT01597622) were part of this group. Participants had been treated with belimumab for at least 6 months in one of these continuation studies prior to entry into this study. Eligible participants on completion of 52-weeks entered Maintenance period and received belimumab 10 mg/kg every 4 weeks until Week 48 of subsequent years (Maintenance is Year 2, 3, 4). | Participants in the Treatment Holiday Group underwent a 24-week belimumab treatment holiday while remaining on standard of care SLE therapy, then re-started belimumab therapy for further 28 weeks while receiving standard of care SLE therapy. Participants from BEL113750 (NCT01345253) and BEL114333 (NCT01597622) were part of this group. Participants had been treated with belimumab for at least 6 months in one of these continuation studies prior to entry into this study. Eligible participants on completion of 52-weeks entered Maintenance period and received belimumab 10 mg/kg every 4 weeks until Week 48 of subsequent years (Maintenance is Year 2, 3, 4). |
| Measure Participants | 25 | 19 | 6 |
| Day 0 to Week 24, n=23,19, 6 |
168.0
|
168.0
|
166.0
|
| Day 0 to Week 52, n=25,19, 6 |
362.0
|
364.0
|
364.0
|
| Week 24 to Week 52, n=24,18, 5 |
195.0
|
196.0
|
200.0
|
Adverse Events
| Time Frame | Non-serious adverse events and serious adverse events (SAE) were collected up to 52 weeks for all treatment groups. For Treatment Control and Treatment Holiday Re-start, it also included 16 weeks follow up after the last dose of belimumab for participants who did not continue in Maintenance phase. For Maintenance phase, non-SAE and SAE were collected until Week 48 of subsequent years (Maintenance is Year 2, 3, 4) and includes 16 weeks follow up after last dose of belimumab. | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Treatment holiday group had two phases holiday phase was Day 0 visit to Week 24/Treatment Re-start phase and Re-start phase started one day after Week 24 up to Week 52. Non-serious adverse events and SAEs were collected for ITT Population. | |||||||||||
| Arm/Group Title | Treatment Phase: Long-term Discontinuation Group | Treatment Phase: Treatment Control Group | Treatment Phase: Treatment Holiday Group - Holiday Phase | Treatment Phase: Treatment Holiday Group - Re-start Phase | Maintenance Phase: Treatment Control | Maintenance Phase: Treatment Holiday | ||||||
| Arm/Group Description | Participants in this group discontinued belimumab 10 mg/kg therapy for 52 weeks but remained on standard of care therapy. Participants from BEL114333 (NCT01597622), BEL112233 (NCT00724867) and BEL112626 (NCT00583362) were part of this group. Participants had been treated with belimumab for at least 6 months in one of these continuation studies but had withdrawn from belimumab therapy for no longer than 8 weeks prior to entry into this study. | Participants in this group continued to receive monthly belimumab 10 mg/kg therapy, in addition to standard of care SLE therapy for 52 weeks. Participants from BEL113750 (NCT01345253) and BEL114333 (NCT01597622) were part of this group. Participants had been treated with belimumab for at least 6 months in one of these continuation studies prior to entry into this study. Eligible participants on completion of 52-weeks entered Maintenance period and received belimumab 10 mg/kg every 4 weeks until Week 48 of subsequent years (Maintenance is Year 2, 3, 4). | Participants in the Treatment Holiday Group underwent a 24-week belimumab treatment holiday while remaining on standard of care SLE therapy, Holiday Phase was Day 0 visit to Week 24/Treatment Re-start phase. Participants from BEL113750 (NCT01345253) and BEL114333 (NCT01597622) were part of this group. Participants had been treated with belimumab for at least 6 months in one of these continuation studies prior to entry into this study. In the event of a severe flare, participants were allowed to enter Maintenance Phase and receive belimumab 10 mg/Kg every 4 weeks until Week 48 of subsequent years (Maintenance is Year 2, 3, 4). | Following Treatment holiday phase for 24 weeks, participants re-started belimumab therapy for 28 weeks while receiving standard of care SLE therapy for 52 weeks. Re-start Phase started one day after Week 24 up to Week 52. Participants from BEL113750 (NCT01345253) and BEL114333 (NCT01597622) were part of this group. Participants had been treated with belimumab for at least 6 months in one of these continuation studies prior to entry into this study. Eligible participants on completion of 52-weeks entered Maintenance period and received belimumab 10 mg/kg every 4 weeks until Week 48 of subsequent years (Maintenance is Year 2, 3, 4). | Participants from BEL113750 (NCT01345253) and BEL114333 (NCT01597622) were part of this group. Eligible participants on completion of 52-weeks entered Maintenance period and received belimumab 10 mg/kg every 4 weeks until Week 48 of subsequent years (Maintenance is Year 2, 3, 4). | Participants from BEL113750 (NCT01345253) and BEL114333 (NCT01597622) were part of this group. Eligible participants on completion of 52-weeks entered Maintenance period and received belimumab 10 mg/kg every 4 weeks until Week 48 of subsequent years (Maintenance is Year 2, 3, 4). | ||||||
All Cause Mortality |
||||||||||||
| Treatment Phase: Long-term Discontinuation Group | Treatment Phase: Treatment Control Group | Treatment Phase: Treatment Holiday Group - Holiday Phase | Treatment Phase: Treatment Holiday Group - Re-start Phase | Maintenance Phase: Treatment Control | Maintenance Phase: Treatment Holiday | |||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/39 (0%) | 0/29 (0%) | 0/12 (0%) | 0/11 (0%) | 0/16 (0%) | 0/10 (0%) | ||||||
Serious Adverse Events |
||||||||||||
| Treatment Phase: Long-term Discontinuation Group | Treatment Phase: Treatment Control Group | Treatment Phase: Treatment Holiday Group - Holiday Phase | Treatment Phase: Treatment Holiday Group - Re-start Phase | Maintenance Phase: Treatment Control | Maintenance Phase: Treatment Holiday | |||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 6/39 (15.4%) | 2/29 (6.9%) | 0/12 (0%) | 1/11 (9.1%) | 0/16 (0%) | 0/10 (0%) | ||||||
| Cardiac disorders | ||||||||||||
| Pericarditis lupus | 1/39 (2.6%) | 1 | 0/29 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/10 (0%) | 0 |
| General disorders | ||||||||||||
| Generalised oedema | 1/39 (2.6%) | 1 | 0/29 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/10 (0%) | 0 |
| Infections and infestations | ||||||||||||
| Diarrhoea infectious | 1/39 (2.6%) | 1 | 0/29 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/10 (0%) | 0 |
| Pneumonia pseudomonal | 1/39 (2.6%) | 1 | 0/29 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/10 (0%) | 0 |
| Sepsis | 1/39 (2.6%) | 1 | 0/29 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/10 (0%) | 0 |
| Upper respiratory tract infection | 0/39 (0%) | 0 | 1/29 (3.4%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/10 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||||||||
| Lumbar vertebral fracture | 0/39 (0%) | 0 | 0/29 (0%) | 0 | 0/12 (0%) | 0 | 1/11 (9.1%) | 1 | 0/16 (0%) | 0 | 0/10 (0%) | 0 |
| Skin laceration | 0/39 (0%) | 0 | 1/29 (3.4%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/10 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||||||||
| Arthritis | 0/39 (0%) | 0 | 1/29 (3.4%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/10 (0%) | 0 |
| Renal and urinary disorders | ||||||||||||
| Lupus nephritis | 2/39 (5.1%) | 2 | 0/29 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/10 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||||
| Acute respiratory failure | 1/39 (2.6%) | 1 | 0/29 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/10 (0%) | 0 |
| Chronic obstructive pulmonary disease | 1/39 (2.6%) | 1 | 0/29 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/10 (0%) | 0 |
| Respiratory failure | 1/39 (2.6%) | 1 | 0/29 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/10 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||||||||
| Treatment Phase: Long-term Discontinuation Group | Treatment Phase: Treatment Control Group | Treatment Phase: Treatment Holiday Group - Holiday Phase | Treatment Phase: Treatment Holiday Group - Re-start Phase | Maintenance Phase: Treatment Control | Maintenance Phase: Treatment Holiday | |||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 30/39 (76.9%) | 18/29 (62.1%) | 7/12 (58.3%) | 9/11 (81.8%) | 4/16 (25%) | 8/10 (80%) | ||||||
| Blood and lymphatic system disorders | ||||||||||||
| Increased tendency to bruise | 2/39 (5.1%) | 2 | 0/29 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/10 (0%) | 0 |
| Lymphadenopathy | 2/39 (5.1%) | 2 | 0/29 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/10 (0%) | 0 |
| Iron deficiency anaemia | 1/39 (2.6%) | 1 | 0/29 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 1/10 (10%) | 1 |
| Ear and labyrinth disorders | ||||||||||||
| Deafness | 0/39 (0%) | 0 | 0/29 (0%) | 0 | 1/12 (8.3%) | 1 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/10 (0%) | 0 |
| Vertigo | 0/39 (0%) | 0 | 0/29 (0%) | 0 | 0/12 (0%) | 0 | 1/11 (9.1%) | 1 | 0/16 (0%) | 0 | 0/10 (0%) | 0 |
| Endocrine disorders | ||||||||||||
| Adrenal insufficiency | 0/39 (0%) | 0 | 0/29 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 1/10 (10%) | 1 |
| Eye disorders | ||||||||||||
| Chalazion | 0/39 (0%) | 0 | 0/29 (0%) | 0 | 1/12 (8.3%) | 1 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/10 (0%) | 0 |
| Ocular discomfort | 0/39 (0%) | 0 | 0/29 (0%) | 0 | 0/12 (0%) | 0 | 1/11 (9.1%) | 1 | 0/16 (0%) | 0 | 1/10 (10%) | 1 |
| Cataract | 0/39 (0%) | 0 | 0/29 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 1/10 (10%) | 1 |
| Gastrointestinal disorders | ||||||||||||
| Diarrhoea | 3/39 (7.7%) | 4 | 1/29 (3.4%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/10 (0%) | 0 |
| Abdominal pain upper | 2/39 (5.1%) | 2 | 1/29 (3.4%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/10 (0%) | 0 |
| Dental caries | 0/39 (0%) | 0 | 2/29 (6.9%) | 2 | 0/12 (0%) | 0 | 1/11 (9.1%) | 1 | 1/16 (6.3%) | 1 | 0/10 (0%) | 0 |
| Dyspepsia | 3/39 (7.7%) | 3 | 0/29 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/10 (0%) | 0 |
| Toothache | 2/39 (5.1%) | 2 | 1/29 (3.4%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 1/10 (10%) | 1 |
| Vomiting | 1/39 (2.6%) | 1 | 0/29 (0%) | 0 | 1/12 (8.3%) | 1 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/10 (0%) | 0 |
| Periodontal disease | 0/39 (0%) | 0 | 0/29 (0%) | 0 | 0/12 (0%) | 0 | 1/11 (9.1%) | 1 | 0/16 (0%) | 0 | 0/10 (0%) | 0 |
| Stomatitis | 0/39 (0%) | 0 | 1/29 (3.4%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 1/10 (10%) | 1 |
| Abdominal discomfort | 0/39 (0%) | 0 | 0/29 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 1/10 (10%) | 1 |
| General disorders | ||||||||||||
| Fatigue | 4/39 (10.3%) | 5 | 0/29 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/10 (0%) | 0 |
| Immune system disorders | ||||||||||||
| Seasonal allergy | 2/39 (5.1%) | 2 | 0/29 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/10 (0%) | 0 |
| Infections and infestations | ||||||||||||
| Nasopharyngitis | 10/39 (25.6%) | 16 | 5/29 (17.2%) | 16 | 1/12 (8.3%) | 2 | 4/11 (36.4%) | 4 | 2/16 (12.5%) | 5 | 4/10 (40%) | 7 |
| Upper respiratory tract infection | 5/39 (12.8%) | 5 | 2/29 (6.9%) | 4 | 2/12 (16.7%) | 4 | 1/11 (9.1%) | 1 | 2/16 (12.5%) | 2 | 1/10 (10%) | 1 |
| Sinusitis | 3/39 (7.7%) | 3 | 0/29 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/10 (0%) | 0 |
| Upper respiratory tract infection bacterial | 3/39 (7.7%) | 5 | 0/29 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 1/10 (10%) | 2 |
| Cystitis | 0/39 (0%) | 0 | 1/29 (3.4%) | 1 | 0/12 (0%) | 0 | 1/11 (9.1%) | 1 | 0/16 (0%) | 0 | 1/10 (10%) | 3 |
| Gastroenteritis | 1/39 (2.6%) | 1 | 0/29 (0%) | 0 | 0/12 (0%) | 0 | 1/11 (9.1%) | 1 | 0/16 (0%) | 0 | 1/10 (10%) | 1 |
| Otitis externa bacterial | 0/39 (0%) | 0 | 0/29 (0%) | 0 | 1/12 (8.3%) | 1 | 1/11 (9.1%) | 1 | 0/16 (0%) | 0 | 0/10 (0%) | 0 |
| Urinary tract infection | 2/39 (5.1%) | 2 | 0/29 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/10 (0%) | 0 |
| Viral upper respiratory tract infection | 0/39 (0%) | 0 | 2/29 (6.9%) | 2 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 1/10 (10%) | 1 |
| Tinea versicolour | 0/39 (0%) | 0 | 0/29 (0%) | 0 | 1/12 (8.3%) | 1 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/10 (0%) | 0 |
| Angular cheilitis | 0/39 (0%) | 0 | 0/29 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 1/10 (10%) | 1 |
| Viral myositis | 0/39 (0%) | 0 | 0/29 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 1/10 (10%) | 1 |
| Conjunctivitis | 0/39 (0%) | 0 | 1/29 (3.4%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 1/10 (10%) | 1 |
| Gingivitis | 0/39 (0%) | 0 | 1/29 (3.4%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 1/10 (10%) | 1 |
| Herpes zoster | 1/39 (2.6%) | 1 | 0/29 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 1/10 (10%) | 1 |
| Injury, poisoning and procedural complications | ||||||||||||
| Contusion | 2/39 (5.1%) | 2 | 0/29 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 1/10 (10%) | 1 |
| Joint injury | 1/39 (2.6%) | 1 | 0/29 (0%) | 0 | 0/12 (0%) | 0 | 1/11 (9.1%) | 1 | 0/16 (0%) | 0 | 0/10 (0%) | 0 |
| Head injury | 0/39 (0%) | 0 | 1/29 (3.4%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 1/10 (10%) | 1 |
| Limb injury | 1/39 (2.6%) | 1 | 0/29 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 1/10 (10%) | 1 |
| Chillblains | 0/39 (0%) | 0 | 0/29 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 1/10 (10%) | 1 |
| Investigations | ||||||||||||
| Gamma-glutamyltransferase increased | 0/39 (0%) | 0 | 0/29 (0%) | 0 | 1/12 (8.3%) | 2 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/10 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||||||||
| Hypokalaemia | 1/39 (2.6%) | 1 | 2/29 (6.9%) | 2 | 1/12 (8.3%) | 1 | 2/11 (18.2%) | 2 | 0/16 (0%) | 0 | 0/10 (0%) | 0 |
| Glucose tolerance impaired | 0/39 (0%) | 0 | 0/29 (0%) | 0 | 1/12 (8.3%) | 1 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/10 (0%) | 0 |
| Hypercholesterolaemia | 0/39 (0%) | 0 | 0/29 (0%) | 0 | 1/12 (8.3%) | 1 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/10 (0%) | 0 |
| Hyperglycaemia | 0/39 (0%) | 0 | 0/29 (0%) | 0 | 1/12 (8.3%) | 1 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/10 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||||||||
| Arthralgia | 4/39 (10.3%) | 10 | 2/29 (6.9%) | 3 | 1/12 (8.3%) | 1 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/10 (0%) | 0 |
| Back pain | 3/39 (7.7%) | 3 | 2/29 (6.9%) | 2 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 1/10 (10%) | 1 |
| Arthritis | 4/39 (10.3%) | 5 | 0/29 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/10 (0%) | 0 |
| Pain in extremity | 4/39 (10.3%) | 8 | 0/29 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/10 (0%) | 0 |
| Bursitis | 3/39 (7.7%) | 4 | 0/29 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/10 (0%) | 0 |
| Musculoskeletal chest pain | 1/39 (2.6%) | 1 | 1/29 (3.4%) | 1 | 0/12 (0%) | 0 | 1/11 (9.1%) | 1 | 0/16 (0%) | 0 | 0/10 (0%) | 0 |
| Systemic lupus erythematosus | 2/39 (5.1%) | 3 | 0/29 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/10 (0%) | 0 |
| Musculoskeletal stiffness | 1/39 (2.6%) | 1 | 0/29 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 1/10 (10%) | 1 |
| Myopathy | 0/39 (0%) | 0 | 0/29 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 1/10 (10%) | 1 |
| Intervertebral disc displacement | 0/39 (0%) | 0 | 0/29 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 1/10 (10%) | 1 |
| Osteoporosis | 0/39 (0%) | 0 | 0/29 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 1/10 (10%) | 1 |
| Polymyositis | 0/39 (0%) | 0 | 0/29 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 1/10 (10%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||
| Benign neoplasm of skin | 0/39 (0%) | 0 | 0/29 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 1/10 (10%) | 1 |
| Nervous system disorders | ||||||||||||
| Dizziness | 2/39 (5.1%) | 2 | 1/29 (3.4%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/10 (0%) | 0 |
| Headache | 2/39 (5.1%) | 2 | 0/29 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/10 (0%) | 0 |
| Psychiatric disorders | ||||||||||||
| Insomnia | 2/39 (5.1%) | 2 | 1/29 (3.4%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/10 (0%) | 0 |
| Renal and urinary disorders | ||||||||||||
| Proteinuria | 2/39 (5.1%) | 2 | 0/29 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/10 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||||
| Cough | 3/39 (7.7%) | 3 | 2/29 (6.9%) | 2 | 0/12 (0%) | 0 | 1/11 (9.1%) | 1 | 0/16 (0%) | 0 | 0/10 (0%) | 0 |
| Nasal congestion | 3/39 (7.7%) | 3 | 0/29 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/10 (0%) | 0 |
| Oropharyngeal pain | 0/39 (0%) | 0 | 1/29 (3.4%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 1/10 (10%) | 1 |
| Skin and subcutaneous tissue disorders | ||||||||||||
| Eczema | 2/39 (5.1%) | 2 | 2/29 (6.9%) | 2 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/10 (0%) | 0 |
| Acne | 1/39 (2.6%) | 1 | 0/29 (0%) | 0 | 1/12 (8.3%) | 1 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/10 (0%) | 0 |
| Rash pruritic | 2/39 (5.1%) | 2 | 0/29 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/10 (0%) | 0 |
| Dermatitis allergic | 0/39 (0%) | 0 | 0/29 (0%) | 0 | 1/12 (8.3%) | 1 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/10 (0%) | 0 |
| Dry skin | 0/39 (0%) | 0 | 0/29 (0%) | 0 | 1/12 (8.3%) | 1 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/10 (0%) | 0 |
| Drug eruption | 1/39 (2.6%) | 1 | 0/29 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 1/16 (6.3%) | 1 | 0/10 (0%) | 0 |
| Vascular disorders | ||||||||||||
| Hypertension | 3/39 (7.7%) | 3 | 1/29 (3.4%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/16 (0%) | 0 | 0/10 (0%) | 0 |
Limitations/Caveats
Study limitations include the small sample size and differences in Day 0 characteristics between Long-term Discontinuation and Treatment Control groups, which limits the ability to draw inferences.
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Results Point of Contact
| Name/Title | GlaxoSmithKline |
|---|---|
| Organization | GlaxoSmithKline |
| Phone | 866-435-7343 ext 1 |
| GSKClinicalSupportHD@gsk.com |
Responsible Party:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT02119156
Other Study ID Numbers:
- 116027
First Posted:
Apr 21, 2014
Last Update Posted:
Jan 31, 2020
Last Verified:
Jan 1, 2020