A Pooled Analysis of the HGS1006-C1056 (BLISS-52) and HGS1006-C1057 (BLISS-76) Studies
Primary Purpose
Lupus Erythematosus, Discoid
Status
Completed
Phase
Locations
Study Type
Observational
Intervention
Belimumab 1 mg/kg
Belimumab 10 mg/kg
Placebo
Sponsored by
About this trial
This is an observational trial for Lupus Erythematosus, Discoid
Eligibility Criteria
Inclusion Criteria:
- Clinical diagnosis of SLE by ACR criteria.
- Active SLE disease.
- Autoantibody-positive.
- On stable SLE treatment regimen.
Exclusion Criteria:
- Pregnant or nursing
- Have received treatment with any B cell targeted therapy.
- Have received treatment with a biological investigational agent in the past year.
- Have received IV cyclophosphamide within 180 days of Day 0.
- Have severe lupus kidney disease.
- Have active central nervous system (CNS) lupus.
- Have required management of acute or chronic infections within the past 60 days.
- Have current drug or alcohol abuse or dependence.
- Have a historically positive test or test positive at screening for HIV, hepatitis B, or hepatitis C.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Arm Label
Baseline Health-Related Quality of Life (HRQOL)
SLE Medication Usage at Baseline
Arm Description
Quality of life assessment tools were similar across the treatment groups and indicated that there was impairment in quality of life of subjects in the Low C+anti-dsDNA Population
All subjects in the Low C+anti-dsDNA Population
Outcomes
Primary Outcome Measures
SLE (systemic lupus erythematosus) Response Index (SRI) at Week 52
Composite endpoint resulting from the combination of three well-established tools for evaluating SLE disease activity which include an objective measure of the reduction in global disease activity for efficacy and two measures to ensure that the improvement in disease activity (score) is not offset by worsening of the subject's condition overall.
Secondary Outcome Measures
The response rate by visit modified to exclude anti-dsDNA and complement items in the determination of a 4-point reduction in SELENA SLEDAI (Safety of Oestrogen in Lupus National Assessment Systemic Lupus Erythematosus Disease Activity Index).
The percent of subjects with no new BILAG A (British Isles Lupus Assessment Group) organ domain score or 2 new BILAG B organ domain scores
Percent of subjects with greater than 4 point reduction from baseline in SELENA SLEDAI (Safety of Oestrogen in Lupus National Assessment Systemic Lupus Erythematosus Disease Activity Index)
Mean change in PGA (Physician's Global Assessment)
All Flares and Severe Flares will be assessed for population a
Number of subjects experiencing a flare/severe flare (Weeks 0-52 and Weeks 24-52). Time to 1st flare/severe flare (Weeks 0-52 and Weeks 24-52.) Flares/Severe flares per subject year (Weeks 0-52).
All BILAG A (British Isles Lupus Assessment Group) Flares will be assessed for population a
Number of subjects experiencing a BILAG A flare (Weeks 0-52 and Weeks 24-52). Time to 1st BILAG A flare (Weeks 0-52 and Weeks 24-52). BILAG A flares per subject year (Weeks 0-52).
Percent of Subjects with Daily Prednisone Dose Reduced to ≤ 7.5 mg/day from > 7.5 mg/day at Baseline by Visit
Mean change in SF-36 (Short Form 36 Health Survey questionnaire) domains (population a only), Physical Component Summary (PCS) and Mental Component Summary MCS (population a only)
Mean change in FACIT (Functional Assessment of Chronic Illness Therapy) Fatigue Scale score
EQ-5D (EuroQol five dimension self-reported health state questionnaire) individual item score (mobility, self-care, usual activities, pain/discomfort, anxiety/depression)
Improvement in each SELENA SLEDAI (Safety of Oestrogen in Lupus National Assessment Systemic Lupus Erythematosus Disease Activity Index) organ domain
Percent of subjects with no worsening in PGA (Physician's Global Assessment)
Percent of Subjects with Daily Prednisone Dose Increased to > 7.5 mg/day from ≤7.5 mg/day at Baseline by Visit
Percent of Subjects with Daily Prednisone Dose Reduced by ≥25% and to ≤ 7.5 mg/day from > 7.5 mg/day at Baseline by Visit
Time to first SELENA SLEDAI (Safety of Oestrogen in Lupus National Assessment Systemic Lupus Erythematosus Disease Activity Index) organ improvement by organ domain, among subjects with involvement at baseline
Time to first BILAG organ improvement by organ domain, among subjects with involvement at baseline
EQ-5D (EuroQol five dimension self-reported health state questionnaire) index score using value set for the UK
EQ-5D (EuroQol five dimension self-reported health state questionnaire) visual analogue scale (VAS) score using value set for the UK
The response rate calculated without allowable and prohibited medication rules applied (population a only).
Full Information
NCT ID
NCT01858792
First Posted
December 19, 2012
Last Updated
May 16, 2013
Sponsor
Human Genome Sciences Inc., a GSK Company
Collaborators
GlaxoSmithKline
1. Study Identification
Unique Protocol Identification Number
NCT01858792
Brief Title
A Pooled Analysis of the HGS1006-C1056 (BLISS-52) and HGS1006-C1057 (BLISS-76) Studies
Official Title
Efficacy and Safety of Belimumab in a Subgroup of Systemic Lupus Erythematosus (SLE) Patients With Higher Disease Activity (Anti-dsDNA Positive and Low Complement): A Pooled Analysis of the HGS1006-C1056 (BLISS-52) and HGS1006-C1057 (BLISS-76) Studies
Study Type
Observational
2. Study Status
Record Verification Date
May 2013
Overall Recruitment Status
Completed
Study Start Date
May 2011 (undefined)
Primary Completion Date
June 2011 (Actual)
Study Completion Date
June 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Human Genome Sciences Inc., a GSK Company
Collaborators
GlaxoSmithKline
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Efficacy and Safety of Belimumab in a Subgroup of Systemic Lupus Erythematosus (SLE) Patients with Higher Disease Activity (anti-dsDNA positive and low complement): A Pooled Analysis of the HGS1006-C1056 (BLISS-52) and HGS1006-C1057 (BLISS-76) Studies
Detailed Description
Studies C1056 and C1057 followed very similar protocols, were of nearly identical design, had common inclusion and exclusion criteria, and were conducted over the same time period. Nevertheless, given the heterogeneous presentation of SLE disease and the fact that the Phase III program was run globally, variation in the patient population, both within the studies (e.g., between different centres) and between the studies (analogous to differences between centres within the same study) should be expected.
Since it has been established that the conduct of the studies was effectively the same, it then must be determined whether the relative treatment effect is different in one study compared with the other study when evaluating whether two studies are similar enough to pool. Each of these Phase III studies achieved statistical significance for belimumab 10 mg/kg on the pre-specified primary endpoint of SRI response at Week 52; therefore, these nearly identical studies provide independent replication of results. While pooling is not necessary to establish the effectiveness of belimumab, it was considered appropriate in order to evaluate treatment effects in the high disease activity subgroup of interest, given that the individual studies were not designed to provide sufficient power to demonstrate effectiveness within subgroups. Thus, statistical evaluation pooling the studies and testing for a treatment-by-study interaction was undertaken. A significant treatment-by-study interaction would indicate that the relative treatment differences were statistically different in the two studies and pooling would not be justified. Conversely, the lack of a treatment-by-study interaction would indicate the studies resulted in a similar treatment response and pooling would be justified.
When the two Phase III studies were pooled for the SRI analysis, the treatment-by-study interaction was >0.5. Likewise, for the target population of high disease activity, the treatment-by-study interaction was >0.7 suggesting that the high disease activity subgroup may be more homogenous and therefore have a more similar treatment effect between the studies than the population as a whole.
Given these considerations, it is reasonable and valid to pool the two studies and allows better precision for evaluation of subgroups.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lupus Erythematosus, Discoid
7. Study Design
Enrollment
1 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Baseline Health-Related Quality of Life (HRQOL)
Arm Description
Quality of life assessment tools were similar across the treatment groups and indicated that there was impairment in quality of life of subjects in the Low C+anti-dsDNA Population
Arm Title
SLE Medication Usage at Baseline
Arm Description
All subjects in the Low C+anti-dsDNA Population
Intervention Type
Drug
Intervention Name(s)
Belimumab 1 mg/kg
Intervention Description
Belimumab 1 mg/kg IV plus standard therapy; belimumab 1 mg/kg administered on Days 0, 14, 28, and every 28 days thereafter through 72 weeks.
Intervention Type
Drug
Intervention Name(s)
Belimumab 10 mg/kg
Intervention Description
Belimumab 10 mg/kg IV plus standard therapy; belimumab 10 mg/kg administered on Days 0, 14, 28, and every 28 days thereafter through 72 weeks.
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Placebo IV plus standard therapy; placebo administered on Days 0, 14, 28, and every 28 days thereafter through 72 weeks.
Primary Outcome Measure Information:
Title
SLE (systemic lupus erythematosus) Response Index (SRI) at Week 52
Description
Composite endpoint resulting from the combination of three well-established tools for evaluating SLE disease activity which include an objective measure of the reduction in global disease activity for efficacy and two measures to ensure that the improvement in disease activity (score) is not offset by worsening of the subject's condition overall.
Time Frame
Response rate by visit through Week 52 for the pooled studies and through Week 76 for Study C1056
Secondary Outcome Measure Information:
Title
The response rate by visit modified to exclude anti-dsDNA and complement items in the determination of a 4-point reduction in SELENA SLEDAI (Safety of Oestrogen in Lupus National Assessment Systemic Lupus Erythematosus Disease Activity Index).
Time Frame
By visit up to Week 52 for pooled studies.
Title
The percent of subjects with no new BILAG A (British Isles Lupus Assessment Group) organ domain score or 2 new BILAG B organ domain scores
Time Frame
By visit up to Week 52 for pooled studies
Title
Percent of subjects with greater than 4 point reduction from baseline in SELENA SLEDAI (Safety of Oestrogen in Lupus National Assessment Systemic Lupus Erythematosus Disease Activity Index)
Time Frame
By visit up to Week 52
Title
Mean change in PGA (Physician's Global Assessment)
Time Frame
At Week 24, and by visit up to week 52 (population a only).
Title
All Flares and Severe Flares will be assessed for population a
Description
Number of subjects experiencing a flare/severe flare (Weeks 0-52 and Weeks 24-52). Time to 1st flare/severe flare (Weeks 0-52 and Weeks 24-52.) Flares/Severe flares per subject year (Weeks 0-52).
Time Frame
In periods of Weeks 0-52 and weeks 24-52
Title
All BILAG A (British Isles Lupus Assessment Group) Flares will be assessed for population a
Description
Number of subjects experiencing a BILAG A flare (Weeks 0-52 and Weeks 24-52). Time to 1st BILAG A flare (Weeks 0-52 and Weeks 24-52). BILAG A flares per subject year (Weeks 0-52).
Time Frame
In periods of Weeks 0-52 and Weeks 24-52
Title
Percent of Subjects with Daily Prednisone Dose Reduced to ≤ 7.5 mg/day from > 7.5 mg/day at Baseline by Visit
Time Frame
For pooled studies through Week 52
Title
Mean change in SF-36 (Short Form 36 Health Survey questionnaire) domains (population a only), Physical Component Summary (PCS) and Mental Component Summary MCS (population a only)
Time Frame
By visit up to Week 52
Title
Mean change in FACIT (Functional Assessment of Chronic Illness Therapy) Fatigue Scale score
Time Frame
By visit up to Week 52
Title
EQ-5D (EuroQol five dimension self-reported health state questionnaire) individual item score (mobility, self-care, usual activities, pain/discomfort, anxiety/depression)
Time Frame
Change from baseline by visit up to Week 52
Title
Improvement in each SELENA SLEDAI (Safety of Oestrogen in Lupus National Assessment Systemic Lupus Erythematosus Disease Activity Index) organ domain
Time Frame
At week 52
Title
Percent of subjects with no worsening in PGA (Physician's Global Assessment)
Time Frame
By visit up to Week 52
Title
Percent of Subjects with Daily Prednisone Dose Increased to > 7.5 mg/day from ≤7.5 mg/day at Baseline by Visit
Time Frame
For pooled studies through Week 52.
Title
Percent of Subjects with Daily Prednisone Dose Reduced by ≥25% and to ≤ 7.5 mg/day from > 7.5 mg/day at Baseline by Visit
Time Frame
For pooled studies through Week 52
Title
Time to first SELENA SLEDAI (Safety of Oestrogen in Lupus National Assessment Systemic Lupus Erythematosus Disease Activity Index) organ improvement by organ domain, among subjects with involvement at baseline
Time Frame
Over Weeks 0-52
Title
Time to first BILAG organ improvement by organ domain, among subjects with involvement at baseline
Time Frame
Over Weeks 0-52
Title
EQ-5D (EuroQol five dimension self-reported health state questionnaire) index score using value set for the UK
Time Frame
Change from baseline by visit up to Week 52
Title
EQ-5D (EuroQol five dimension self-reported health state questionnaire) visual analogue scale (VAS) score using value set for the UK
Time Frame
Change from baseline by visit up to Week 52
Title
The response rate calculated without allowable and prohibited medication rules applied (population a only).
Time Frame
By visit up to Week 52
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Clinical diagnosis of SLE by ACR criteria.
Active SLE disease.
Autoantibody-positive.
On stable SLE treatment regimen.
Exclusion Criteria:
Pregnant or nursing
Have received treatment with any B cell targeted therapy.
Have received treatment with a biological investigational agent in the past year.
Have received IV cyclophosphamide within 180 days of Day 0.
Have severe lupus kidney disease.
Have active central nervous system (CNS) lupus.
Have required management of acute or chronic infections within the past 60 days.
Have current drug or alcohol abuse or dependence.
Have a historically positive test or test positive at screening for HIV, hepatitis B, or hepatitis C.
Study Population Description
Subjects who were anti-dsDNA positive and had low C3 and/or C4 at baseline (Low C+anti-dsDNA Population) Subjects with baseline SELENA SLEDAI score >= 10 (SS >=10 Population)
Sampling Method
Non-Probability Sample
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GSK Clinical Trials
Organizational Affiliation
GlaxoSmithKline
Official's Role
Study Director
12. IPD Sharing Statement
Citations:
PubMed Identifier
22337213
Citation
van Vollenhoven RF, Petri MA, Cervera R, Roth DA, Ji BN, Kleoudis CS, Zhong ZJ, Freimuth W. Belimumab in the treatment of systemic lupus erythematosus: high disease activity predictors of response. Ann Rheum Dis. 2012 Aug;71(8):1343-9. doi: 10.1136/annrheumdis-2011-200937. Epub 2012 Feb 15.
Results Reference
background
Learn more about this trial
A Pooled Analysis of the HGS1006-C1056 (BLISS-52) and HGS1006-C1057 (BLISS-76) Studies
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