A Study of Belimumab Administered Subcutaneously in Subjects With Systemic Lupus Erythematosus (SLE) (BLISS-SC)

• ClinicalTrials.gov Identifier: NCT01484496
• Recruitment Status: Completed
• First Posted: December 2, 2011
• Results First Posted: July 25, 2017
• Last Update Posted: June 6, 2018
• Sponsor: Human Genome Sciences Inc., a GSK Company
• Collaborator: GlaxoSmithKline
• Information provided by (Responsible Party): GlaxoSmithKline ( Human Genome Sciences Inc., a GSK Company )

Tracking Information

• First Submitted Date: November 28, 2011
• First Posted Date: December 2, 2011
• Results First Submitted Date: January 30, 2017
• Results First Posted Date: July 25, 2017
• Last Update Posted Date: June 6, 2018
• Study Start Date: November 16, 2011
• Actual Primary Completion Date: February 13, 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 23, 2017)

Percentage of Par. Achieving a SLE Responder Index (SRI) Response Rate at Week 52 [ Time Frame: Week 52 ]

SRI response is defined as >=4 point reduction, from Baseline in safety of estrogen in lupus national assessment (SELENA) systemic lupus erythematosus disease activity index (SLEDAI) score, no worsening (increase of <0.30 points from Baseline) in physician's global assessment (PGA) and no new British Isles Lupus Assessment Group of SLE clinics (BILAG) A organ domain score or 2 new BILAG B organ domain scores compared with Baseline. Analysis was performed using a logistic regression model for the comparison between belimumab and placebo with covariates treatment group, Baseline SELENA SLEDAI score (<=9 vs. >=10), Baseline complement levels (low C3 and/or C4 vs. no low C3 or C4) and race (black vs. other).

Original Primary Outcome Measures (submitted: November 30, 2011)

SLE Responder Index (SRI) response rate [ Time Frame: Baseline, 52 Weeks ]

A patient that has an SRI response has all 3 of the following: • ≥4 point reduction from baseline in SELENA SLEDAI score, AND • No worsening (increase of <0.30 points from baseline) in Physician's Global Assessment (PGA), AND • No new British Isles Lupus Assessment Group (BILAG) A organ domain score or 2 new BILAG B organ domain scores compared with baseline at the time of assessment (ie, at Week 52).

Current Secondary Outcome Measures (submitted: July 23, 2017)

• Time to First Severe Flare (as Measured by the Modified SLE Flare Index) [ Time Frame: Baseline (Day 0, prior to dosing) to Week 52 ]
  Time to first severe SLE flare is defined as the number of days from treatment start date until the participant met an event (event date - treatment start date +1). Analyses of severe SLE flare was performed on modified SELENA SLEDAI SLE flare index that excludes severe flares that were triggered only by an increase in SELENA SLEDAI score to >12 (since this may only represent a modest increase in disease activity). Only post-baseline severe flares were considered.
• Percentage of Par. Whose Average Prednisone Dose Had Been Reduced by >=25% From Baseline to <=7.5 mg/Day During Weeks 40 Through 52 in Par. Receiving Greater Than 7.5 mg/Day at Baseline [ Time Frame: Baseline (Day 0, prior to dosing), Weeks 40 through Week 52 ]
  For the analysis of steroid use, all steroid dosages were converted to a prednisone equivalent in mg. The average daily prednisone dose was calculated taking into account all steroids taken intravenously, intramuscularly, SC, intradermally and orally for both SLE and non-SLE reasons. A responder was defined as having a prednisone reduction by >=25% from Baseline to <=7.5 mg/day during Weeks 40 through 52. At Baseline, the average daily prednisone dose was the sum of all prednisone doses over 7 consecutive days up to, but not including Day 0, divided by 7. For this analysis, the average prednisone dose was the total prednisone dose during weeks 40 through 52 divided by the number of days during Weeks 40 through 52. Analysis was performed using a logistic regression model with covariates treatment group, Baseline prednisone dose, Baseline SELENA SLEDAI score, (<=9 vs >=10), Baseline complement levels (low C3 and/or C4 vs. no low C3 or C4) and race (black vs. other).

Original Secondary Outcome Measures (submitted: November 30, 2011)

• Time to first severe flare (SLE Flare Index) [ Time Frame: Baseline to 52 weeks ]
• Reduction in prednisone dose [ Time Frame: Baseline, Weeks 40-52 ]
  Percent of subjects whose average prednisone dose has been reduced by ≥ 25% from baseline to ≤ 7.5 mg/day during Weeks 40 through 52 in subjects receiving greater than 7.5 mg/day at baseline.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of Belimumab Administered Subcutaneously in Subjects With Systemic Lupus Erythematosus (SLE)
• Official Title: A Phase 3, Multi-Center, Randomized, Double-Blind, Placebo-Controlled, 52-Week Study to Evaluate the Efficacy and Safety of Belimumab (HGS1006) Administered Subcutaneously (SC) to Subjects With Systemic Lupus Erythematosus (SLE)
• Brief Summary: The purpose of this study is to evaluate the efficacy, safety and tolerability of belimumab administered subcutaneously (SC) to adult subjects with Systemic Lupus Erythematosus (SLE).
• Detailed Description: This is a Phase 3, multi-center, international, randomized, double-blind, placebo-controlled, 52-week study to evaluate the efficacy, safety and tolerability of belimumab administered subcutaneously (SC) (200 mg weekly) in adult subjects with active Systemic Lupus Erythematosus (SLE). Approximately 816 SLE subjects will be randomized, with a target of about 544 subjects receiving belimumab and 272 subjects receiving placebo. Subjects completing the 52-week double-blind period can enter a 6-month open-label extension in which all subjects receive belimumab 200 mg SC weekly.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Systemic Lupus Erythematosus

Intervention

• Biological: Placebo
  Placebo
• Biological: Belimumab 200 mg SC
  Belimumab 200 mg SC
  Other Name: BENLYSTA™
• Drug: Standard therapy
  Standard therapy comprises any of the following (alone or in combination): corticosteroids, antimalarials, non-steroidal anti-inflammatory drugs (NSAIDs), and immunosuppressives; biologics and intravenous cyclophosphamide are not permitted.

Study Arms

• Placebo Comparator: Placebo plus standard therapy
  Placebo SC plus standard therapy; placebo administered on Day 0 and then weekly (ie, every 7 days) through Week 51, with final evaluation at Week 52 in the double-blind period. In the open-label extension period, placebo subjects who opt to participate will receive belimumab 200 mg SC weekly for an additional 6-months.
  Interventions:

  • Biological: Placebo
  • Drug: Standard therapy
• Experimental: Belimumab 200 mg SC plus standard therapy
  Belimumab 200 mg SC plus standard therapy; belimumab administered on Day 0 and then weekly (ie, every 7 days) through Week 51, with a final evaluation at Week 52 in the double-blind period. In the open-label extension period, subjects who opt to participate will continue on the same dose of belimumab for an additional 6-months.
  Interventions:

  • Biological: Belimumab 200 mg SC
  • Drug: Standard therapy

Publications *

• Brunner HI, Abud-Mendoza C, Mori M, Pilkington CA, Syed R, Takei S, Viola DO, Furie RA, Navarra S, Zhang F, Bass DL, Eriksson G, Hammer AE, Ji BN, Okily M, Roth DA, Quasny H, Ruperto N. Efficacy and safety of belimumab in paediatric and adult patients with systemic lupus erythematosus: an across-study comparison. RMD Open. 2021 Sep;7(3):e001747. doi: 10.1136/rmdopen-2021-001747.
• Hannon CW, McCourt C, Lima HC, Chen S, Bennett C. Interventions for cutaneous disease in systemic lupus erythematosus. Cochrane Database Syst Rev. 2021 Mar 9;3(3):CD007478. doi: 10.1002/14651858.CD007478.pub2.
• Maslen T, Bruce IN, D'Cruz D, Ianosev M, Bass DL, Wilkinson C, Roth DA. Efficacy of belimumab in two serologically distinct high disease activity subgroups of patients with systemic lupus erythematosus: post-hoc analysis of data from the phase III programme. Lupus Sci Med. 2021 Feb;8(1):e000459. doi: 10.1136/lupus-2020-000459.
• Lokhandwala T, Yue B, Coutinho AD, Bell CF. Within-trial economic analysis of flare data from the BLISS-SC trial of subcutaneous belimumab in systemic lupus erythematosus. Lupus Sci Med. 2021 Feb;8(1):e000438. doi: 10.1136/lupus-2020-000438.
• Doria A, Bass D, Schwarting A, Hammer A, Gordon D, Scheinberg M, Fox NL, Groark J, Stohl W, Kleoudis C, Roth D. A 6-month open-label extension study of the safety and efficacy of subcutaneous belimumab in patients with systemic lupus erythematosus. Lupus. 2018 Aug;27(9):1489-1498. doi: 10.1177/0961203318777634. Epub 2018 May 28.
• Doria A, Stohl W, Schwarting A, Okada M, Scheinberg M, van Vollenhoven R, Hammer AE, Groark J, Bass D, Fox NL, Roth D, Gordon D. Efficacy and Safety of Subcutaneous Belimumab in Anti-Double-Stranded DNA-Positive, Hypocomplementemic Patients With Systemic Lupus Erythematosus. Arthritis Rheumatol. 2018 Aug;70(8):1256-1264. doi: 10.1002/art.40511. Epub 2018 Jun 15.
• Stohl W, Schwarting A, Okada M, Scheinberg M, Doria A, Hammer AE, Kleoudis C, Groark J, Bass D, Fox NL, Roth D, Gordon D. Efficacy and Safety of Subcutaneous Belimumab in Systemic Lupus Erythematosus: A Fifty-Two-Week Randomized, Double-Blind, Placebo-Controlled Study. Arthritis Rheumatol. 2017 May;69(5):1016-1027. doi: 10.1002/art.40049. Epub 2017 Apr 7.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 7, 2016): 839
• Original Estimated Enrollment (submitted: November 30, 2011): 816
• Actual Study Completion Date: October 1, 2015
• Actual Primary Completion Date: February 13, 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. At least 18 years of age.
2. Clinical diagnosis of Systemic Lupus Erythematosus (SLE) by ACR criteria.
3. Active SLE disease.
4. Autoantibody-positive.
5. On stable SLE treatment regimen which may include corticosteroids (for example, prednisone), antimalarial (for example, hydroxychloroquine) and/or immunosuppressants (for example, azathioprine, methotrexate, mycophenolate, etc.)

Exclusion Criteria:

1. Pregnant or nursing.
2. Have received treatment with any B cell targeted therapy (for example, rituximab or belimumab).
3. Have received treatment an investigational biological agent in the past year.
4. Have received intravenous (IV) cyclophosphamide within 90 days of Day 0.
5. Have severe active lupus kidney disease.
6. Have severe active central nervous system (CNS) lupus.
7. Have required management of acute or chronic infections within the past 60 days.
8. Have current drug or alcohol abuse or dependence.
9. Have a positive test for human immunodeficiency virus (HIV), hepatitis B, or hepatitis C.
10. Have a history of hypersensitivity reactions to contrast agents or biological medicines.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Austria, Belgium, Brazil, Bulgaria, Chile, Colombia, Croatia, Czechia, Denmark, France, Germany, Hungary, Italy, Japan, Malaysia, Mexico, Philippines, Poland, Portugal, Romania, Russian Federation, Serbia, Singapore, Spain, Sweden, Taiwan, Thailand, Ukraine, United Kingdom, United States
• Removed Location Countries: Czech Republic

Administrative Information

• NCT Number: NCT01484496
• Other Study ID Numbers: 112341; 2011-003814-18; HGS1006-C1115
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

• Current Responsible Party: GlaxoSmithKline ( Human Genome Sciences Inc., a GSK Company )
• Original Responsible Party: Human Genome Sciences Inc.
• Current Study Sponsor: Human Genome Sciences Inc., a GSK Company
• Original Study Sponsor: Human Genome Sciences Inc.
• Collaborators: GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials; GlaxoSmithKline

• PRS Account: GlaxoSmithKline
• Verification Date: May 2018