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

Systemic Lupus Erythematosus Clinical Trial

— BE-EARLY  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06411249
• Other study ID #: 219240
• Secondary ID: 2023-509146-35-0
• Status: Recruiting
• Phase: Phase 4
• Start date: June 4, 2024
• Est. completion date: May 29, 2029

Study information

• Verified date: May 2024
• Source: GlaxoSmithKline
• Contact: US GSK Clinical Trials Call Center
• Phone: 877-379-3718
• Email: GSKClinicalSupportHD[@]gsk.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 350
• Est. completion date: May 29, 2029
• Est. primary completion date: April 19, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Lupus Erythematosus, Systemic
• Systemic Lupus Erythematosus

Intervention

Drug:
• Belimumab (GSK1550188)
GSK1550188 will be administered subcutaneously.

Locations

Country	Name	City	State
Argentina	GSK Investigational Site	Berazategui	Buenos Aires
Argentina	GSK Investigational Site	Ciudad Autonoma Buenos Aires
Argentina	GSK Investigational Site	Ciudad Autonoma de Buenos Aires	Ciudad Autonoma Buenos Aires
Argentina	GSK Investigational Site	Ciudad Autonoma de Buenos Aires	Ciudad Autonoma Buenos Aires
Argentina	GSK Investigational Site	Ciudad Autónoma de Buenos Aires
Argentina	GSK Investigational Site	La Plata	Buenos Aires
Argentina	GSK Investigational Site	Mar del Plata	Buenos Aires
Argentina	GSK Investigational Site	Quilmes	Buenos Aires
Argentina	GSK Investigational Site	Rosario	Santa Fe
Argentina	GSK Investigational Site	San Miguel de Tucuman	Tucumán
Argentina	GSK Investigational Site	San Miguel de Tucuman	Tucumán
Brazil	GSK Investigational Site	Belo Horizonte	Minas Gerais
Brazil	GSK Investigational Site	Cuiaba	Mato Grosso
Brazil	GSK Investigational Site	Curitiba	Paraná
Brazil	GSK Investigational Site	Juiz de Fora	Minas Gerais
Brazil	GSK Investigational Site	Passo Fundo	Rio Grande Do Sul
Brazil	GSK Investigational Site	Porto Alegre	Rio Grande Do Sul
Brazil	GSK Investigational Site	Porto Alegre	Rio Grande Do Sul
Brazil	GSK Investigational Site	Porto Alegre	Rio Grande Do Sul
Brazil	GSK Investigational Site	Salvador	Bahia
Brazil	GSK Investigational Site	Sao Jose do Rio Preto	São Paulo
Brazil	GSK Investigational Site	São Paulo
Brazil	GSK Investigational Site	São Paulo	Sao Paulo
France	GSK Investigational Site	Angers
France	GSK Investigational Site	Lille	Nord
France	GSK Investigational Site	Pessac	Gironde
France	GSK Investigational Site	Rennes cedex 09	Ille Et Vilaine
France	GSK Investigational Site	Rennes cedex 09	Ille Et Vilaine
France	GSK Investigational Site	Toulouse	Haute Garonne
Germany	GSK Investigational Site	Herne	Nordrhein-Westfalen
Germany	GSK Investigational Site	Luebeck	Schleswig Holstein
Germany	GSK Investigational Site	Mainz	Rheinland-Pfalz
Greece	GSK Investigational Site	Athens
Greece	GSK Investigational Site	Athens
Greece	GSK Investigational Site	Athens
Greece	GSK Investigational Site	Athens
Greece	GSK Investigational Site	Heraklion
Greece	GSK Investigational Site	Thessaloniki
Italy	GSK Investigational Site	Milano
Italy	GSK Investigational Site	Pisa
Italy	GSK Investigational Site	Rome	Lazio
Italy	GSK Investigational Site	Rozzano	Milano
Japan	GSK Investigational Site	Kanagawa
Japan	GSK Investigational Site	Kitakyushu-shi	Fukuoka-Ken
Japan	GSK Investigational Site	Osakasayama-shi	Osaka-Fu
Japan	GSK Investigational Site	Sendai-shi	Miyagi-Ken
Japan	GSK Investigational Site	Tokyo
Mexico	GSK Investigational Site	Ciudad de México	Distrito Federal
Mexico	GSK Investigational Site	Guadalajara	Jalisco
Mexico	GSK Investigational Site	Leon	Guanajuato
Mexico	GSK Investigational Site	León	Guanajuato
Mexico	GSK Investigational Site	Merida	Yucatán
Mexico	GSK Investigational Site	Mexico
Mexico	GSK Investigational Site	Mexico
Mexico	GSK Investigational Site	Monterrey	Nuevo León
Mexico	GSK Investigational Site	San Luis Potosí
Mexico	GSK Investigational Site	Torreon	Coahuila
Portugal	GSK Investigational Site	Almada
Portugal	GSK Investigational Site	Coimbra
Portugal	GSK Investigational Site	Lisboa
Portugal	GSK Investigational Site	Porto
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Córdoba
Spain	GSK Investigational Site	Sevilla
Spain	GSK Investigational Site	Valladolid	Cantabria
Spain	GSK Investigational Site	Vigo	Pontevedra
Spain	GSK Investigational Site	Vilajoyosa
United States	GSK Investigational Site	Anniston	Alabama
United States	GSK Investigational Site	Apple Valley	California
United States	GSK Investigational Site	Austin	Texas
United States	GSK Investigational Site	Aventura	Florida
United States	GSK Investigational Site	Baton Rouge	Louisiana
United States	GSK Investigational Site	Baytown	Texas
United States	GSK Investigational Site	Beverly Hills	California
United States	GSK Investigational Site	Brooklyn	New York
United States	GSK Investigational Site	Chicago	Illinois
United States	GSK Investigational Site	Clearwater	Florida
United States	GSK Investigational Site	Colleyville	Texas
United States	GSK Investigational Site	Covina	California
United States	GSK Investigational Site	Danville	Virginia
United States	GSK Investigational Site	Denver	Colorado
United States	GSK Investigational Site	Detroit	Michigan
United States	GSK Investigational Site	Duncansville	Pennsylvania
United States	GSK Investigational Site	Elgin	Illinois
United States	GSK Investigational Site	Flagstaff	Arizona
United States	GSK Investigational Site	Fontana	California
United States	GSK Investigational Site	Fort Worth	Texas
United States	GSK Investigational Site	Fullerton	California
United States	GSK Investigational Site	Glendale	Wisconsin
United States	GSK Investigational Site	Hinsdale	Illinois
United States	GSK Investigational Site	Houston	Texas
United States	GSK Investigational Site	Katy	Texas
United States	GSK Investigational Site	Lansing	Michigan
United States	GSK Investigational Site	Los Angeles	California
United States	GSK Investigational Site	Marietta	Georgia
United States	GSK Investigational Site	Menifee	California
United States	GSK Investigational Site	Mesa	Arizona
United States	GSK Investigational Site	Miami	Florida
United States	GSK Investigational Site	Minot	North Dakota
United States	GSK Investigational Site	Mission Hills	California
United States	GSK Investigational Site	New Orleans	Louisiana
United States	GSK Investigational Site	Pearland	Texas
United States	GSK Investigational Site	Philadelphia	Pennsylvania
United States	GSK Investigational Site	Plano	Texas
United States	GSK Investigational Site	Shreveport	Louisiana
United States	GSK Investigational Site	Sparta	New Jersey
United States	GSK Investigational Site	Sugar Hill	Georgia
United States	GSK Investigational Site	Tamarac	Florida
United States	GSK Investigational Site	Tucson	Arizona
United States	GSK Investigational Site	Tujunga	California
United States	GSK Investigational Site	Waco	Texas
United States	GSK Investigational Site	Whittier	California
United States	GSK Investigational Site	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  France,  Germany,  Greece,  Italy,  Japan,  Mexico,  Portugal,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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