A Phase 3 Study to Evaluate the Efficacy and Safety of Belimumab Administered in Combination with Rituximab to Adult Subjects with Systemic Lupus Erythematosus (SLE) – BLISS-BELIEVE

• Register: EUCTR
• Last refreshed on: 26 September 2023
• Main ID: EUCTR2016-003050-32-ES
• Date of registration: 01/12/2017
• Prospective Registration: Yes
• Primary sponsor: GlaxoSmithKline, S.A.
• Public title: A Phase 3 Study to Evaluate the Efficacy and Safety of Belimumab Administered in Combination with Rituximab to Adult Subjects with Systemic Lupus Erythematosus (SLE) – BLISS-BELIEVE
• Scientific title: A Phase 3, Multi-Center, Randomized, Double-Blind, Placebo- Controlled, 104-Week Study to Evaluate the Efficacy and Safety of Belimumab Administered in Combination with Rituximab to Adult Subjects with Systemic Lupus Erythematosus (SLE).
• Date of first enrolment: 05/12/2017
• Target sample size: 200
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-003050-32
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: yes Other: no Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Brazil, Canada, Germany, Korea, Republic of, Mexico, Netherlands, Russian Federation, South Africa, Spain, United States

Contacts

• Name: Centro de Información
• Affiliation: GlaxoSmithKline

• Name: Centro de Información
• Affiliation: GlaxoSmithKline

Key inclusion & exclusion criteria

Inclusion criteria:
1. Participant must be = 18 years of age at the time of signing the informed consent.
2. Have a clinical diagnosis of SLE according to the American College of Rheumatology (ACR) criteria.
3. Have a screening SLEDAI-2K score =6 (serological activity, i.e., anti-double stranded deoxyribonucleic acid [dsDNA]) positivity and/or hypocomplementemia, is scored in the SLEDAI-2K).
4. Have unequivocally positive autoantibody test results defined as an anti-nuclear (ANA) titer = 1:80 and/or a positive anti-dsDNA ( =30 IU/mL) serum antibody test from 2 independent time points as follows:
Positive test results 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.
NOTE: Historical documentation of a positive test of ANA (e.g., ANA by HEp-2 titer) and anti-dsDNA (e.g., anti-dsDNA by Farr assay) that 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 vs. negative. Only unequivocally positive values as defined in the laboratory's reference range are acceptable; borderline values will not be accepted.
5. Are 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 1 (i.e., day of first dose of study treatment) with the exception that switching one agent for another of the same class for tolerability or availability reasons, which will be allowed within 30 days of Day 1.
·Corticosteroids (prednisone or prednisone equivalent)
·For those subjects on alternating daily doses of steroids, use the average of 2 daily doses to calculate the average daily steroid dose.
·Any immunosuppressant 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).
NOTES: Corticosteroids may be added as a new medication or their doses adjusted up to 30 days prior to Day 1.
New SLE therapy other than corticosteroids must not be added within 60 days prior to Day 1.
6. Male and/or female
A female participant is eligible to participate if she is not pregnant (see Appendix 3 of the study protocol), not breastfeeding, and at least one of the following conditions applies:
(i) Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 (of the study protocol)
OR
(ii) A WOCBP who agrees to follow the contraceptive guidance in Appendix 3 (of the study protocol) during the treatment period and for at least 16 weeks after the last dose of belimumab, or at least 12 months after the last dose of rituximab or rituximab placebo, whichever is later.
7. Capable of giving signed informed consent as described in Appendix 4 (of the study protocol) which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 195
F.1
Exclusion criteria:
1. Symptomatic herpes zoster within 3 months prior to screening.
2. Evidence of active or latent tuberculosis (TB) as documented by medical history and examination, chest X-rays (posterior, anterior, and lateral), and TB testing
3. Significant allergies to humanized monoclonal antibodies.
4. Clinically significant multiple or severe drug allergies and/or history of hypersensitivity to belimumab and/or rituximab or known to have titers of human anti-mouse antibody or history of hypersensitivity reactions when treated with other diagnostic or therapeutic monoclonal antibodies.
5. Lymphoma, leukemia, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years.
6. Alanine transferase (ALT) >2x upper limit of normal (ULN).
7. Bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
8. IgA deficiency (IgA level < 10 mg/dL).
9. IgG < 250 mg/dL.
10. Neutrophils < 1.5 x 10 to the power of 9
11. Current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis.
12. Severe heart failure (New York Heart Association Class IV) or other severe, uncontrolled cardiac disease.
13. QTc >450 msec or QTc >480 msec in participants with bundle branch block.
14. Have a history of a major organ transplant or hematopoietic stem cell/marrow transplant.
15. Have clinical evidence of significant unstable or uncontrolled acute or chronic diseases not due to SLE which, in the opinion of the principal investigator, could confound the results of the study or put the subject at undue risk.
16. Have an acute or chronic infection requiring management as follows:
Currently on any suppressive therapy for a chronic infection
·Hospitalization for treatment of infection within 60 days of Day 1.
·Have had infection requiring treatment with parenteral (IV or IM) antibiotics within 60 days of Day 1. Prophylactic anti-infective treatment is allowed.
17. Have severe lupus kidney disease (defined by proteinuria >6 g/24 hour or equivalent using spot urine protein to creatinine ratio, or serum creatinine >2.5 mg/dL), or have severe active nephritis requiring induction therapy not permitted by protocol, or have required hemodialysis or high dose prednisone or equivalent (>100 mg/day) within 90 days of Day 1.
18. Have severe active central nervous system (CNS) lupus (including seizures, psychosis, organic brain syndrome, cerebrovascular accident (CVA), cerebritis, or CNS vasculitis) requiring therapeutic intervention within 60 days of Day 1.
19. Have a planned surgical procedure, laboratory abnormality, or condition that, in the opinion of the principal investigator, makes the subject unsuitable for the study.
20. Have evidence of serious suicide risk, including any history of suicidal behavior in the last 6 months and/or any suicidal ideation of type 4 or 5 on the C-SSRS in the last 2 months or who, in the investigator's opinion, pose a significant suicide risk.
21. Have a history of an anaphylaxis reaction to parenteral administration of contrast agents, human or murine proteins, or monoclonal antibodies.
22. Live vaccine(s) within 1 month prior to screening, or plans to receive such vaccines during the screening period or during the study.
23. Have

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Systemic Lupus Erythematosus (SLE) or Lupus
MedDRA version: 20.0 Level: PT Classification code 10042945 Term: Systemic lupus erythematosus System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Intervention(s)

Trade Name: MabThera (Rituximab)
Product Name: MabThera (Rituximab)
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: RITUXIMAB
CAS Number: 174722-31-7
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 500-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Trade Name: Benlysta (Belimumab)
Product Name: Benlysta (Belimumab)
Pharmaceutical Form: Solution for injection in pre-filled pen
INN or Proposed INN: BELIMUMAB
CAS Number: 356547-88-1
Current Sponsor code: GSK1550188
Other descriptive name: HGS1006, LymphoStat-B, monoclonal anti-BLyS, LSB, BENLYSTA
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 200-

Primary Outcome(s)

Secondary Objective: - To assess the safety and tolerability of belimumab and a single cycle of rituximab administered in a combination regimen to adult participants with SLE.
- To assess the impact of belimumab and a single cycle of rituximab administered in a combination regimen to adult participants with SLE on PROs.

Primary end point(s): Proportion of participants with a state of disease control defined as a SLEDAI- 2K score =2, achieved without immunosuppressants and with corticosteroids at a prednisone equivalent dose of =5mg/day at Week 52. (Serological activity, i.e., anti-dsDNA positivity and/or hypocomplementemia, is scored in the SLEDAI-2K endpoint.)

Main Objective: To evaluate the efficacy of belimumab and a single cycle of rituximab administered in a combination regimen to adult participants with SLE.

Timepoint(s) of evaluation of this end point: Week 52

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Semana 64, Semana 104

Secondary end point(s): Proportion of participants with a state of clinical remission defined as a Clinical
SLEDAI-2K score =0, achieved without immuno-suppressants and with
corticosteroids at a prednisone equivalent dose of 0 mg/day at Week 64. (Serological activity score, i.e., anti-dsDNA positivity and/or hypocomplementemia, is excluded from the Clinical SLEDAI-2K endpoint.)
Proportion of participants with a state of disease control defined as a SLEDAI-2K
score =2, achieved without immunosuppressants and withcorticosteroids at a prednisone equivalent dose of =5 mg/day at Week 104.

Secondary ID(s)

205646

2016-003050-32-DE

Source(s) of Monetary Support

GlaxoSmithKline LLC

Ethics review

Status: Approved
Approval date: 24/11/2017
Contact:

Results

• Results available: Yes
• Date Posted: 18/04/2022
• Date Completed: 07/07/2021
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2016-003050-32/results