Efficacy and Safety of Belimumab in Black Race Patients With Systemic Lupus Erythematosus (SLE)

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT01632241
• Date of registration: 28/06/2012
• Prospective Registration: Yes
• Primary sponsor: Human Genome Sciences Inc., a GSK Company
• Public title: Efficacy and Safety of Belimumab in Black Race Patients With Systemic Lupus Erythematosus (SLE) EMBRACE
• Scientific title: A Phase 3/4, Multi-Center, Randomized, Double-Blind, Placebo-Controlled, 52-Week Study to Evaluate the Efficacy and Safety of Belimumab (HGS1006) in Adult Subjects of Black Race With Systemic Lupus Erythematosus (SLE)
• Date of first enrolment: February 19, 2013
• Target sample size: 503
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01632241
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 4

Countries of recruitment

Brazil, Colombia, France, South Africa, United Kingdom, United States

Contacts

• Name: GSK Clinical Trials
• Affiliation: GlaxoSmithKline

Key inclusion & exclusion criteria

Inclusion criteria:

- At least 18 years of age.

- Self-identified black race.

- Have a clinical diagnosis of SLE according to the American College of Rheumatology
(ACR) criteria

- Have active SLE disease defined as a SELENA SLEDAI score >= 8 at screening

- Have 2 unequivocally positive autoantibody test results defined as a positive
antinuclear antibody (ANA) test [i.e., titer >= 1:80 by human epithelial cell line 2
(HEp-2) immunofluorescence assay (IFA) and/or positive enzyme immunoassay (EIA)]
and/or a positive anti- double stranded deoxyribonucleic acid (dsDNA) (>= 30
international units [IU]/milliliter [mL]) serum antibody test as follows:

- From 2 independent time points within the study screening period. Screening
results must be based on the study's central laboratory results, OR

- One positive historical test result and 1 positive test result during the
screening period.

Historical documentation of a positive ANA test (e.g., HEp-2 IFA or EIA) or anti-dsDNA (eg,
anti-dsDNA by any validated commercial assay) must include the date and type of the test,
the name of the testing laboratory, numerical reference range, and a key that explains
values provided as positive versus negative OR negative, equivocal/borderline positive).
Only unequivocally positive values as defined in the laboratory's reference range are
acceptable; borderline values will not be accepted.

- On a stable SLE treatment regimen consisting of any of the following medications
(alone or in combination) for a period of at least 30 days prior to Day 0 (i.e., day
of 1st dose of study agent):

- Corticosteroids (prednisone or prednisone equivalent, up to 40 mg/day): For
subjects on SLE combination therapy, their stable steroid dose must be fixed
within the range of 0 to 40 mg/day (prednisone or prednisone equivalent). For
subjects whose only SLE treatment is steroids, their stable steroid dose must be
fixed within the range of 7.5 to 40 mg/day (prednisone or prednisone equivalent).
For those subjects on alternating day doses of steroids, use the average of 2
daily doses to calculate the average daily steroid dose.

- Other immunosuppressive or immunomodulatory agents including methotrexate,
azathioprine, leflunomide, mycophenolate (including mycophenolate mofetil,
mycophenolate mofetil hydrochloride, and mycophenolate sodium), calcineurin
inhibitors (e.g., tacrolimus, cyclosporine), sirolimus, oral cyclophosphamide,
6-mercaptopurine, mizoribine, or thalidomide.

- Anti-malarials (e.g., hydroxychloroquine, chloroquine, quinacrine).

- Non-steroidal anti-inflammatory drugs (NSAIDs).

Note:

- Pre-existing SLE medications must be stable for at least 30 days prior to Day 0.

- Corticosteroids may be added as new medication or their doses adjusted only up to 30
days prior to Day 0.

- New SLE therapy other than corticosteroids must not be added within 60 days of Day 0.

- A female subject is eligible to enter the study if she is:

- Not pregnant or nursing;

- Of non-childbearing potential defined as: pre-menopausal females with a
documented tubal ligation, hysterectomy, documented hysteroscopic tubal occlusion
procedure with follow-up confirmation of bilateral tubal occlusion, or documented
bilateral oophorectomy, OR postmenopausal defined as 12 months of spontaneous
amenorrhea with an appropriate clinical profile [e.g., > 45 years, in the absence
of hormone replacement therapy or other cause for amenorrhea]; in questionable
cases obtain a blood sample for follicle stimulating hormone (FSH) and estradiol
simultaneously to confirm. Diagnostic levels for FSH and estradiol vary by
specific laboratories/assays;

- OR is of child-bearing potential with negative pregnancy test as determined by
serum human chorionic gonadotrophin (hCG) test at screening and urine hCG test
prior to dosing AND agrees to use one of the contraception methods for 2 weeks
prior to the day of dosing to sufficiently minimize the risk of pregnancy at that
point. Female subjects must agree to use contraception until 16 weeks following
the last dose of study agent.

- OR has only same-sex partners, when this is her preferred and usual lifestyle.

- Have the ability to understand the requirements of the study, provide written
informed consent (including consent for the use and disclosure of
research-related health information), and comply with the study protocol
procedures (including required study visits).

Exclusion criteria:

- Have received treatment with anti-B lymphocyte stimulator (BLyS) [belimumab] at any
time.

- Have received any of the following within 364 days of Day 0:

- Abatacept

- Other B cell targeted therapy (e.g., rituximab, other anti-cluster of
differentiation [CD] 20 agents, anti-CD22 [epratuzumab], anti-CD52 [alemtuzumab],
BLyS-receptor fusion protein [BR3], TACI-Fc, or anti-B-cell activating factor
[BAFF] (LY2127399).

- A biologic investigational agent other than B cell targeted therapy (e.g.,
abetimus sodium, anti-CD40L antibody [BG9588/IDEC-131]).

- Have required 3 or more courses of systemic corticosteroids for concomitant conditions
(e.g., asthma, atopic dermatitis) within 364 days of Day 0. (Topical or inhaled
steroids are permitted.)

- Have received any of the following within 90 days of Day 0:

- Anti-tumor necrosis factor (TNF) therapy (eg, adalimumab, certolizumab pegol,
etanercept, golimumab, infliximab).

- Intravenous (IV) cyclophosphamide

- Interleukin-1 receptor antagonist (anakinra).

- Intravenous immunoglobulin (IVIG).

- High dose prednisone or equivalent (> 100 mg/day).

- Plasmapheresis.

- Have received any of the following within 60 days of Day 0:

- A non-biologic investigational agent.

- Any new immunosuppressive/immunomodulatory agent, anti-malarial, or NSAID Note:
New inhaled and topical steroids and new topical immunosuppressive agents (e.g.,
eye drops, topical creams) are allowed. Any NSAID use for < 1 week is allowed.

- Any steroid injection (e.g., intramuscular, intraarticular, or intravenous).

- Have received any of the following within 30 days of Day 0:


Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Systemic Lupus Erythematosus

Intervention(s)

Biological: Belimumab 10 mg/kg plus standard therapy

Drug: Standard therapy

Biological: Placebo plus standard therapy

Primary Outcome(s)

Number of Participants With Non-serious Adverse Events (nSAEs) and Serious Adverse Event (SAEs) [OL Phase] [Time Frame: Week 52 to Week 84]

Number of Participants With Worst Toxicity Grade of 3 or 4 for Urinalysis Parameters [OL Phase] [Time Frame: Week 52 to Week 84]

Number of Participants With Severe AEs [OL Phase] [Time Frame: Week 52 to Week 84]

Number of Participants With Worst Toxicity Grade of 3 or 4 of Immunoglobulins [OL Phase] [Time Frame: Week 52 to Week 84]

Percentage of Participants Achieving a Systemic Lupus Erythematosus Responder Index (SRI) Response Rate With the Modified Systemic Lupus Erythematosus Disease Activity Index- 2K (SLEDAI-2K) Scoring for Proteinuria at Week 52 [DB Phase] [Time Frame: Week 52]

Number of Participants With Worst Toxicity Grade 3 or 4 for Hematology Parameters [OL Phase] [Time Frame: Week 52 to Week 84]

Number of Participants With Worst Toxicity Grade of 3 or 4 for Clinical Chemistry Parameters [OL Phase] [Time Frame: Week 52 to Week 84]

Percentage of Participants Achieving a SRI Response Rate With the Modified SLEDAI-2K Scoring for Proteinuria at Week 24 of OL Phase [Time Frame: Week 24 of OL phase (Week 76)]

Number of Participants With AEs Leading to Treatment Discontinuation [OL Phase] [Time Frame: Week 52 to Week 84]

Secondary Outcome(s)

Number of Participants With AEs Leading to Treatment Discontinuation [DB Phase] [Time Frame: Up to 52 Weeks]

Number of Participants With Severe AEs [DB Phase] [Time Frame: Up to 52 Weeks]

Number of Participants With Worst Toxicity Grade of 3 or 4 for Urinalysis Parameters [DB Phase] [Time Frame: Up to 52 weeks]

Percent of Participants Whose Average Prednisone Dose Had Been Reduced to <=7.5 mg/Day in Participants Receiving Greater Than 7.5 mg/Day at Pre-belimumab Baseline (at Week 28 of OL Phase) [Time Frame: OL Baseline and Week 28 of OL Phase (Week 80)]

Number of Participants With nSAEs and SAEs [DB Phase] [Time Frame: Up to 52 Weeks]

Number of Participants With Worst Toxicity Grade 3 or 4 for Hematology Parameters [DB Phase] [Time Frame: Up to 52 weeks]

Percentage of Participants Achieving SRI-SS Response Rate With the SELENA SLEDAI for Scoring of Proteinuria at Week 24 of OL Phase [Time Frame: Week 24 of OL phase (Week 76)]

Percentage of Participants Achieving SRI-SS Response Rate at Week 52 [DB Phase] [Time Frame: Week 52]

Number of Participants With Worst Toxicity Grade of 3 or 4 for Clinical Chemistry Parameters [DB Phase] [Time Frame: Up to 52 weeks]

Percent of Participants Whose Average Prednisone Dose Had Been Reduced by >=25% From Baseline to <=7.5 mg/Day During Week 40 Through 52, in Participants Receiving Greater Than 7.5 mg/Day at Baseline [DB Phase] [Time Frame: Baseline and Week 40 through Week 52]

Time to First Severe Flare (as Measured by the Modified SLE Flare Index) [OL Phase] [Time Frame: Up to Week 24 of OL Phase (Week 76)]

Time to First Severe Flare (as Measured by the Modified SLE Flare Index) up to 52 Weeks [DB Phase] [Time Frame: Up to 52 Weeks]

Secondary ID(s)

HGS1006-C1112

115471

2011-005672-42

U1111-1139-9723

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

GlaxoSmithKline

Results

• Results available: Yes
• Date Posted: 05/07/2019
• URL: https://clinicaltrials.gov/ct2/show/results/NCT01632241