ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 5 of 8 for:    belimumab BLISS | Lupus Erythematosus

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01858792
Recruitment Status : Completed
First Posted : May 21, 2013
Last Update Posted : May 21, 2013
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
GlaxoSmithKline ( Human Genome Sciences Inc., a GSK Company )

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

Condition or disease Intervention/treatment
Lupus Erythematosus, Discoid Drug: Belimumab 1 mg/kg Drug: Belimumab 10 mg/kg Other: Placebo

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 Type : Observational
Actual Enrollment : 1 participants
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 Start Date : May 2011
Actual Primary Completion Date : June 2011
Actual Study Completion Date : June 2011

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lupus
Drug Information available for: Belimumab

Group/Cohort Intervention/treatment
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
Drug: Belimumab 1 mg/kg
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.

Drug: Belimumab 10 mg/kg
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.

Other: Placebo
Placebo IV plus standard therapy; placebo administered on Days 0, 14, 28, and every 28 days thereafter through 72 weeks.

SLE Medication Usage at Baseline
All subjects in the Low C+anti-dsDNA Population
Drug: Belimumab 1 mg/kg
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.

Drug: Belimumab 10 mg/kg
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.

Other: Placebo
Placebo IV plus standard therapy; placebo administered on Days 0, 14, 28, and every 28 days thereafter through 72 weeks.




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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. ]
  2. 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 ]
  3. 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 ]
  4. Mean change in PGA (Physician's Global Assessment) [ Time Frame: At Week 24, and by visit up to week 52 (population a only). ]
  5. All Flares and Severe Flares will be assessed for population a [ Time Frame: In periods of Weeks 0-52 and weeks 24-52 ]
    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).

  6. 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 ]
    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).

  7. 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 ]
  8. 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 ]
  9. Mean change in FACIT (Functional Assessment of Chronic Illness Therapy) Fatigue Scale score [ Time Frame: By visit up to Week 52 ]
  10. 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 ]
  11. 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 ]
  12. Percent of subjects with no worsening in PGA (Physician's Global Assessment) [ Time Frame: By visit up to Week 52 ]
  13. 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. ]
  14. 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 ]
  15. 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 ]
  16. Time to first BILAG organ improvement by organ domain, among subjects with involvement at baseline [ Time Frame: Over Weeks 0-52 ]
  17. 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 ]
  18. 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 ]
  19. The response rate calculated without allowable and prohibited medication rules applied (population a only). [ Time Frame: By visit up to Week 52 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
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)
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01858792


Sponsors and Collaborators
Human Genome Sciences Inc., a GSK Company
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline

Publications:
R.F. van Vollenhoven,1 M.A. Petri,2 R. Cervera,3 D. Roth,4 B. Ji,5 C. Kleoudis,6 Z. John Zhong,7 W. Freimuth,7 for the BLISS-52 and BLISS-76 Study Groups. Response of Systemic Lupus Erythematosus Patients With High Disease Activity to Belimumab Treatment in the BLISS Trials . [Ann Rheum Dis]. 2012;71(8):1343-9.

Responsible Party: Human Genome Sciences Inc., a GSK Company
ClinicalTrials.gov Identifier: NCT01858792     History of Changes
Other Study ID Numbers: 115030
First Posted: May 21, 2013    Key Record Dates
Last Update Posted: May 21, 2013
Last Verified: May 2013

Additional relevant MeSH terms:
Lupus Erythematosus, Systemic
Lupus Erythematosus, Discoid
Lupus Erythematosus, Cutaneous
Belimumab
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Skin Diseases
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs