A Study Describing the Efficacy and Safety of Belimumab Administered in Adult Participants With Early Systemic Lupus Erythematosus (SLE) (BE-EARLY)

A Phase 4, Multicenter, Prospective, Open-Label Study Describing the Efficacy and Safety of Belimumab Administered Subcutaneously in Adult Participants With Early Systemic Lupus Erythematosus

This is a prospective, open-label, single arm 3-year clinical study to describe the short-term and long-term efficacy and safety of belimumab in participants with autoantibody positive early SLE with ongoing disease activity despite stable initial SLE therapy.

Study Overview

• Status: Not yet recruiting
• Conditions: Systemic Lupus Erythematosus
• Intervention / Treatment: Drug: Belimumab (GSK1550188)

• Study Type: Interventional
• Enrollment (Estimated): 350
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: US GSK Clinical Trials Call Center; Phone Number: 877-379-3718; Email: GSKClinicalSupportHD@gsk.com
• Study Contact Backup: Name: EU GSK Clinical Trials Call Center; Phone Number: +44 (0) 20 89904466; Email: GSKClinicalSupportHD@gsk.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Documented clinical diagnosis of SLE within 2 years of signing the informed consent according to the American College of Rheumatology (ACR) SLE classification criteria 2019
• Have unequivocally positive autoantibody test results defined as an Anti-nuclear antibody (ANA) titer ≥1:80 and/or a positive anti-

Double stranded deoxyribonucleic acid (dsDNA) serum antibody test from 2 independent time points as follows:

• Active SLE defined as:

  • Clinical SLEDAI-2K (excluding anti-dsDNA and C3/C4) score greater than (>) 4, OR
  • Clinical SLEDAI-2K (excluding anti-dsDNA and C3/C4) ≤4 and prednisone or equivalent dose ≥10 milligram per day (mg/day)
• The Systematic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index (SDI) = 0 at Screening

• Male and/or female; a female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:

  • Not a Women of childbearing potential (WOCBP) OR
  • Is a WOCBP and using a contraceptive method that is highly effective
• Capable of giving signed informed consent

Exclusion Criteria:

• 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.
• Have clinical evidence of significant unstable or uncontrolled acute or chronic diseases not due to SLE (i.e., cardiovascular, pulmonary, hematologic, gastrointestinal (GI), hepatic, renal, neurological, psychiatric, malignancy, or infectious diseases) and/or a planned surgical procedure, which, in the opinion of the principal investigator (PI), could confound the results of the clinical study or put the participant at undue risk.

• Have an acute or chronic infection including requiring management as follows:

  • Currently on any suppressive therapy for a chronic infection such as pneumocystis, cytomegalovirus, herpes simplex virus, herpes zoster, or atypical mycobacteria.
  • A serious infection requiring treatment with intravenous or Intramuscular (IV/IM) antibiotics and/or hospitalization if the last dose of antibiotics or the hospital discharge date was within 60 days of the first day of dosing (Day 1). Prophylactic anti-infective treatment is allowed.
• Evidence of active or latent tuberculosis (TB) as documented by medical history and examination, chest X-rays (posterior, anterior, and lateral), and TB testing: either a positive tuberculin skin test (TST); defined as a skin induration ≥5millimeter (mm) at 48 to 72 hours, regardless of Bacillus Calmette-Guerin (BCG) or other vaccination history) or a positive (not indeterminate) interferon gamma release assay TB test.
• Confirmed Progressive multifocal leukoencephalopathy (PML) or unexplained new-onset or deteriorating neurologic signs and symptoms.
• 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 Screening.
• Lupus kidney disease defined by proteinuria >6 gram (g)/24 hour or equivalent using spot urine protein to creatinine ratio, or serum creatinine >2.5 milligram per decilitre (mg/dL) or have active LN requiring induction therapy within 35 days of Screening.
• Have evidence of serious suicide risk, defined as Patient Health Questionnaire (PHQ)-9 score ≥10, or any history of suicidal behavior in the last 6 months and/or any suicidal ideation in the last 2 months or who, in the investigator's opinion, pose a significant suicide risk.
• Known to have titers of human anti-mouse antibody or history of hypersensitivity reactions when treated with diagnostic or therapeutic monoclonal antibodies
• Live or live-attenuated vaccine(s) within 35 days prior to Screening or plans to receive such vaccines during the Screening period or during the clinical study
• Chronic oral steroid use for a non-SLE disorder at the Screening study visit (e.g., for asthma). Inhaled steroid use will be allowed.

• Treatment at or prior to Screening study visit:

  • Treatment at Screening study visit with any of the following:

• Azathioprine (AZA) >200 mg/day
• Methotrexate (MTX) (any formulation) >25 mg/week
• Mycophenolate mofetil (MMF) (PO)/MMF hydrochloride (IV) >2 g/day
• Mycophenolate acid/sodium (PO) >1.44 g/day
• Oral cyclophosphamide >2.5 mg/kg/day
• Tacrolimus >0.2 mg/kg/day

• Cyclosporine (PO) >2.5 mg/kg/day

  • Treatment at any time prior to Screening with any of the following:

• Second line use of conventional ISs or AMs
• Commercially available Belimumab (BEL)
• Anifrolumab
• Rituximab or other B cell depleting therapies
• Anti-TNF therapy (e.g., adalimumab, etanercept, infliximab)
• Other treatments with effects on the immune system (e.g., abatacept, interleukin-1 receptor antagonist [anakinra], Janus kinase (JAK) inhibitors)
• IV cyclophosphamide
• IV immunoglobulin
• Plasmapheresis
• Intra-articular, IM, or IV corticosteroids within 6 weeks of Day 1
• Daily use of >1 Nonsteroidal anti-inflammatory (NSAID) within 2 weeks prior to Day 1
• History of primary immunodeficiency, or hypogammaglobulinemia (Immunoglobulin G [IgG] <400 mg/dL) or Immunoglobulin A (IgA) deficiency (IgA <10 mg/dL)
• Have a Grade 3 or greater neutropenia, defined as absolute neutrophil count <1000/cubic millimetre (mm3) (<1.0 x109/L) based on the Common terminology criteria for adverse events (CTCAE) v5.0 Alanine aminotransferase >2 x upper limit of normal (ULN)
• Total bilirubin >1.5 x ULN (isolated bilirubin >1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin <35 percent [%])
• Have any other clinically significant abnormal laboratory value, that in the opinion of the investigator, is capable of significantly altering the absorption, metabolism, or elimination of the clinical study intervention; or constitutes a risk when taking the clinical study intervention or interferes with the interpretation of the clinical study data.
• Positive Human immunodeficiency virus (HIV) antibody test
• Presence of hepatitis B surface antigen (HBsAg) or Hepatitis B core antibody (HBcAb) at screening or within 3 months prior to first dose of study intervention.
• Positive Hepatitis C antibody test result at screening or within 3 months prior to starting study intervention. NOTE: Participants with positive Hepatitis C antibody due to prior resolved disease can be enrolled, only if a confirmatory negative Hepatitis C Ribonucleic acid (RNA) test is obtained.
• Positive Hepatitis C RNA test result at screening or within 3 months prior to first dose of study intervention. NOTE: Test is optional and participants with negative Hepatitis C antibody test are not required to also undergo Hepatitis C RNA testing.
• Sensitivity to the clinical study intervention, or components thereof, or monoclonal antibodies or drug or other allergy that, in the opinion of the investigator, contraindicates participation in the clinical study
• Current drug or alcohol dependence, or a history of drug or alcohol abuse or dependence within 364 days prior to Day 1
• Current enrolment or past participation in any other clinical study involving an investigational study intervention (including investigational vaccines) within 3 months or 5 half-lives of the investigational drug (whichever is longer) before enrolment
• Unable to administer clinical study intervention by subcutaneous (SC) auto-injector and has no other reliable resource to administer the study intervention.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Belimumab (GSK1550188); Participants will receive GSK1550188.	Drug: Belimumab (GSK1550188); GSK1550188 will be administered subcutaneously.; Other Names: BEL (BENLYSTA)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A: Percentage of Participants Achieving Lupus Low Disease Activity State (LLDAS) at Week 52	LLDAS is defined as Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) less than or equal to (≤) 4, with no activity in major organ systems (renal, central nervous system, cardiopulmonary, vasculitis, fever) and no new features of lupus disease activity compared with the previous assessment, Physician Global Assessment (PGA) ≤ 1, with a 7-day average oral prednisone equivalent dose for SLE reasons ≤7.5 milligram (mg)/day and stable treatment and without discontinuing due to lack of efficacy, dying, or taking prohibited medications.	At Week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A: Percentage of Participants Achieving SLE Responder Index 4 (SRI4) at Week 52	SRI4 is defined as greater than or equal to (≥) 4-point reduction from baseline in SLEDAI-2K score and no worsening (increase of < 0.30 points from baseline) in PGA and no new Easy- British Isles Lupus Assessment Group (BILAG) A organ domain score or 2 new Easy-BILAG B organ domain scores compared with baseline at the time of assessment without participants discontinuing due to lack of efficacy, dying, taking prohibited medications or meeting treatment failure criteria.	At Week 52
Part A: Percentage of Participants Achieving Lupus Low Disease Activity State (LLDAS) for ≥ 25 percent (%) of time from Day 1 to Week 52	LLDAS is defined as Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) less than or equal to (≤) 4, with no activity in major organ systems (renal, central nervous system, cardiopulmonary, vasculitis, fever) and no new features of lupus disease activity compared with the previous assessment, Physician Global Assessment (PGA) ≤ 1, with a 7-day average oral prednisone equivalent dose for SLE reasons ≤7.5 milligram (mg)/day and stable treatment and without discontinuing due to lack of efficacy, dying, or taking prohibited medications.	Day 1 and up to Week 52
Part A: Percentage of Participants Achieving Average Oral Prednisone Equivalent Dose ≤ 5 mg/day at Week 52	A seven-day average oral prednisone equivalent dose ≤5 mg/day at week 52, if oral prednisone equivalent dose is >5 mg/day at baseline without study intervention discontinuation due to lack of efficacy, serious AE , prohibited medication intake, or treatment failure by Week 52.	At Week 52
Part A: Estimate of Probability of Having a Severe Flare Defined as Modified SELENA-SLEDAI Flare Index (SFI) at Week 52	SFI Flare was defined as a mild/moderate or severe flare according to the modified Safety of Estrogen in Lupus National Assessment Systemic Lupus Erythematosus Disease Activity Index (SELENA SLEDAI) SLE Flare Index (modified excluded severe flares from the SELENA SLEDAI flare assessment that were triggered only by an increase in SLEDAI SLEDAI score to >12). Change in SELENA SLEDAI instrument score of greater than 12.	At Week 52

Collaborators and Investigators

• Sponsor: GlaxoSmithKline
• Investigators: Study Director: GSK Clinical Trials, GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Estimated): June 4, 2024
• Primary Completion (Estimated): April 19, 2027
• Study Completion (Estimated): May 29, 2029

Study Registration Dates

• First Submitted: May 8, 2024
• First Submitted That Met QC Criteria: May 8, 2024
• First Posted (Actual): May 13, 2024

Study Record Updates

• Last Update Posted (Actual): May 13, 2024
• Last Update Submitted That Met QC Criteria: May 8, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Safety; Efficacy; Systemic Lupus Erythematosus; Autoimmune Diseases; Belimumab; Benlysta; Early Use
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Connective Tissue Diseases; Lupus Erythematosus, Systemic; Physiological Effects of Drugs; Immunosuppressive Agents; Immunologic Factors; Belimumab
• Other Study ID Numbers: 219240; 2023-509146-35 (Other Identifier: EU CTR)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to anonymized individual patient-level data (IPD) and related study documents of the eligible studies via the Data Sharing Portal. Details on GSK's data sharing criteria can be found at: https://www.gsk.com/en-gb/innovation/trials/data-transparency/
• IPD Sharing Time Frame: Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or terminated asset(s) across all indications.
• IPD Sharing Access Criteria: Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension may be granted, when justified, for up to 6 months.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No