Lupus Erythematosus, DiscoidNCT01858792
A Pooled Analysis of the HGS1006-C1056 (BLISS-52) and HGS1006-C1057 (BLISS-76) Studies
An observational study of Lupus Erythematosus, Discoid, run by Human Genome Sciences Inc., a GSK Company.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lupus Erythematosus, Discoid
- What is being tested?
- Belimumab 1 mg/kg and Belimumab 10 mg/kg
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1 participants
- Where
- No sites listed yet
- Study dates
- May 2011to Jun 2011
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: 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)
Who may be able to join
- Clinical diagnosis of SLE by ACR criteria.
- Active SLE disease.
- Autoantibody-positive.
- On stable SLE treatment regimen.
Who cannot join
- 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.
Show all 9Show fewer
- 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.
About this study
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
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
Read the 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.
- Conditions
- Lupus Erythematosus, Discoid
- Being tested
- Belimumab 1 mg/kg, Belimumab 10 mg/kg, Placebo
- Medical subject headings
- Lupus Erythematosus, Discoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Belimumab 1 mg/kgDrug
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.
Belimumab 10 mg/kgDrug
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.
PlaceboOther
Placebo IV plus standard therapy; placebo administered on Days 0, 14, 28, and every 28 days thereafter through 72 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Baseline Health-Related Quality of Life (HRQOL) | 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 Receives: Drug: Belimumab 1 mg/kg; Drug: Belimumab 10 mg/kg; Other: Placebo | |
| SLE Medication Usage at Baseline | All subjects in the Low C+anti-dsDNA Population Receives: Drug: Belimumab 1 mg/kg; Drug: Belimumab 10 mg/kg; Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Response rate by visit through Week 52 for the pooled studies and through Week 76 for Study C1056
Secondary outcomes (19)
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).
Measured: By visit up to Week 52 for pooled studies.
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
Measured: By visit up to Week 52 for pooled studies
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)
Measured: By visit up to Week 52
Mean change in PGA (Physician's Global Assessment)
Measured: At Week 24, and by visit up to week 52 (population a only).
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).
Measured: In periods of Weeks 0-52 and weeks 24-52
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).
Measured: In periods of Weeks 0-52 and Weeks 24-52
Percent of Subjects with Daily Prednisone Dose Reduced to ≤ 7.5 mg/day from > 7.5 mg/day at Baseline by Visit
Measured: For pooled studies through Week 52
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)
Measured: By visit up to Week 52
Mean change in FACIT (Functional Assessment of Chronic Illness Therapy) Fatigue Scale score
Measured: By visit up to Week 52
EQ-5D (EuroQol five dimension self-reported health state questionnaire) individual item score (mobility, self-care, usual activities, pain/discomfort, anxiety/depression)
Measured: Change from baseline by visit up to Week 52
Improvement in each SELENA SLEDAI (Safety of Oestrogen in Lupus National Assessment Systemic Lupus Erythematosus Disease Activity Index) organ domain
Measured: At week 52
Percent of subjects with no worsening in PGA (Physician's Global Assessment)
Measured: By visit up to Week 52
Percent of Subjects with Daily Prednisone Dose Increased to > 7.5 mg/day from ≤7.5 mg/day at Baseline by Visit
Measured: For pooled studies through Week 52.
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
Measured: For pooled studies through Week 52
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
Measured: Over Weeks 0-52
Time to first BILAG organ improvement by organ domain, among subjects with involvement at baseline
Measured: Over Weeks 0-52
EQ-5D (EuroQol five dimension self-reported health state questionnaire) index score using value set for the UK
Measured: Change from baseline by visit up to Week 52
EQ-5D (EuroQol five dimension self-reported health state questionnaire) visual analogue scale (VAS) score using value set for the UK
Measured: Change from baseline by visit up to Week 52
The response rate calculated without allowable and prohibited medication rules applied (population a only).
Measured: By visit up to Week 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 May 2013 (estimated)
- Study startMay 2011
- Primary completionJun 2011
- Study completionJun 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Lupus Erythematosus, DiscoidStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Human Genome Sciences Inc., a GSK Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- GlaxoSmithKline
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01858792
- Sponsor's protocol ID
- 115030
- Status last verified
- May 2013
- First submitted
- 19 Dec 2012
- Last updated
- 21 May 2013
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 22337213
Study at a glance
From the registry record, last updated by the sponsor on 21 May 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01858792
- Acronym / sponsor ID
- 115030
- Conditions
- Lupus Erythematosus, Discoid
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Human Genome Sciences Inc., a GSK CompanyIndustry (pharma, biotech, devices)
- Collaborators
- GlaxoSmithKline
- Study start
- May 2011
- Primary completion
- Jun 2011 (actual)
- Study completion
- Jun 2011 (actual)
- First posted
- 21 May 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Baseline Health-Related Quality of Life (HRQOL) | – | Drug: Belimumab 1 mg/kg, Drug: Belimumab 10 mg/kg, Other: PlaceboQuality 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 |
| SLE Medication Usage at Baseline | – | Drug: Belimumab 1 mg/kg, Drug: Belimumab 10 mg/kg, Other: PlaceboAll subjects in the Low C+anti-dsDNA Population |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- 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)
Key inclusion criteria (4 listed)
- Clinical diagnosis of SLE by ACR criteria.
- Active SLE disease.
- Autoantibody-positive.
- On stable SLE treatment regimen.
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Belimumab 1 mg/kgBelimumab 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. | Drug | Baseline Health-Related Quality of Life (HRQOL), SLE Medication Usage at Baseline |
| Belimumab 10 mg/kgBelimumab 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. | Drug | Baseline Health-Related Quality of Life (HRQOL), SLE Medication Usage at Baseline |
| PlaceboPlacebo IV plus standard therapy; placebo administered on Days 0, 14, 28, and every 28 days thereafter through 72 weeks. | Other | Baseline Health-Related Quality of Life (HRQOL), SLE Medication Usage at Baseline |
Primary outcome
SLE (systemic lupus erythematosus) Response Index (SRI) at Week 52
Time frame: Response rate by visit through Week 52 for the pooled studies and through Week 76 for Study C1056
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.
19 secondary outcomes
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.
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
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
Mean change in PGA (Physician's Global Assessment)
Time frame: At Week 24, and by visit up to week 52 (population a only).
All Flares and Severe Flares will be assessed for population a
Time frame: In periods of Weeks 0-52 and weeks 24-52
All BILAG A (British Isles Lupus Assessment Group) Flares will be assessed for population a
Time frame: In periods of Weeks 0-52 and Weeks 24-52
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
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
Mean change in FACIT (Functional Assessment of Chronic Illness Therapy) Fatigue Scale score
Time frame: By visit up to Week 52
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
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
Percent of subjects with no worsening in PGA (Physician's Global Assessment)
Time frame: By visit up to Week 52
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.
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
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
Time to first BILAG organ improvement by organ domain, among subjects with involvement at baseline
Time frame: Over Weeks 0-52
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
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
The response rate calculated without allowable and prohibited medication rules applied (population a only).
Time frame: By visit up to Week 52
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 May 2013.
- Background: PubMed 22337213van 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
Questions about this trial
What is this clinical trial studying?
An observational study of Lupus Erythematosus, Discoid, run by Human Genome Sciences Inc., a GSK Company.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 May 2013. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
SLE (systemic lupus erythematosus) Response Index (SRI) at Week 52 (time frame: Response rate by visit through Week 52 for the pooled studies and through Week 76 for Study C1056). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01858792, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 May 2013.