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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
Human Genome Sciences Inc., a GSK Company
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an observational trial for Lupus Erythematosus, Discoid

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

    First Posted
    December 19, 2012
    Last Updated
    May 16, 2013
    Sponsor
    Human Genome Sciences Inc., a GSK Company
    Collaborators
    GlaxoSmithKline
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    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
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    Learn more about this trial

    A Pooled Analysis of the HGS1006-C1056 (BLISS-52) and HGS1006-C1057 (BLISS-76) Studies

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