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NCT06411249PHASE4Recruiting

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

GlaxoSmithKline

Start Date

6/6/2024

Completion Date

5/29/2029

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 first-line SLE therapy.

Eligibility Criteria

Age Range: 18 years to No maximum

Inclusion Criteria: * Documented diagnosis of systemic lupus erythematosus (SLE) within 2 years of signing the informed consent according to the European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) SLE classification criteria 2019 * Have unequivocally positive autoantibody test results defined as an Anti-nuclear antibody (ANA) titer greater than or equal to (\>=) 1:80 and/or a positive anti-Double stranded deoxyribonucleic acid (dsDNA) serum antibody test from 2 independent time points * 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) score 1 to 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 Woman 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. * Participants with history of major organ transplant or hematopoietic stem cell/marrow transplant or renal transplant. * 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. * Confirmed active or untreated latent tuberculosis (TB): * Diagnosis of active TB confirmed by: 1) evidence of active TB disease from chest imaging (posterior anterior and lateral x-rays or chest computed tomography \[CT\]), 2) medical history and physical examination, and 3) either positive microscopy smear/culture for mycobacteria or positive TB polymerase chain reaction (PCR), i.e., Xpert. A tuberculin skin test (TST) or an interferon gamma release assay (IGRA) will be done for all participants. A positive TST or a positive (not indeterminate) IGRA TB test such as QuantiFERON-TB Gold Plus test is indicative but not required for diagnosis of active TB. A positive TST is defined as a skin induration \>=5 millimeter (mm) at 48 to 72 hours (regardless of Bacillus Calmette-Guerin or other vaccination history). * Untreated latent tuberculosis infection (LTBI) confirmed by: 1) no evidence of active TB based on chest imaging, medical history and physical examination and laboratory evaluation of sputum; and 2) a positive TST, defined as a skin induration \>5 mm at 48 to 72 hours, regardless of Bacillus Calmette-Guerin or other vaccination history); or a positive (not indeterminate) IGRA TB test such as QuantiFERON-TB Gold Plus test. Those with IGRA positive tests or positive TST who can document ongoing LTBI treatment for at least 4 weeks may be enrolled. Those with IGRA positive tests with documentation of the following may also be enrolled: * Successful completion of treatment for active TB. * Completion of treatment for LTBI (with treatment as per local practice, for example: 3 months of isoniazid and rifampin or 4 months of rifampin or 3 months weekly isoniazid and rifapentine, or 9 months of isoniazid). * 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. * Active Lupus Nephritis defined as active urinary sediment and/or proteinuria \>500 milligrams (mg) per 24 hours, or equivalent using spot urine protein to creatinine ratio, requiring induction therapy not permitted by protocol. * Participants with patient health questionnaire (PHQ)-9 score \>=10 that in the opinion of a mental healthcare professional pose a serious suicide risk, 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 judgment, poses a significant suicide risk. NOTE: For participants with a PHQ-9 score \>=10, at the Screening visit or at the day 1 visit before the first administration of the study drug, it is required that they be referred for an assessment by a mental healthcare professional (e.g., locally licensed psychiatrist, psychologist, or master's level therapist) before the investigator makes a final decision regarding suitability for enrollment. * 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) (oral \[PO\])/MMF hydrochloride (IV) \>2 grams (g)/day * Mycophenolate acid/sodium (PO) \>1.44 g/day * Oral cyclophosphamide \>2.5 mg/kilograms (kg)/day * Tacrolimus \>0.2 mg/kg/day * Cyclosporine (PO) \>2.5 mg/kg/day * Treatment within specified timeframe prior to Screening: * 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 * Treatment at any time prior to Screening with any of the following: * Second line use of conventional immunosuppressants (ISs) or anti-malarials (AMs) * Commercially available Belimumab (BEL) * Anifrolumab * Rituximab or other B cell depleting therapies * Anti-tumor necrosis factor (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 Any addition of a new IS or AM, or IS or AM switch, performed more than 3 months after initiating first line therapy in response to inadequate disease control is considered second-line therapy and is therefore exclusionary. Therapy changes made due to intolerance or toxicity are not considered second-line, provided that the intolerance/toxicity is clearly documented. Any therapy changes after initiating first line therapy considered to be due to intolerance/toxicity must be reviewed and confirmed by the EAC prior to determining eligibility. * History of primary immunodeficiency, or hypogammaglobulinemia (Immunoglobulin G \[IgG\] \<400 mg/deciliter \[dL\]) or Immunoglobulin A (IgA) deficiency (IgA \<10 mg/dL) at Screening * Have a Grade 3 or greater neutropenia, defined as absolute neutrophil count \<1000/cubic millimeter (mm3) (\<1.0 x10\^9/liter \[L\]) based on the Common terminology criteria for adverse events (CTCAE) version (v) 5.0 * Alanine aminotransferase \>2 x upper limit of normal (ULN) * Total bilirubin \>1.5 x ULN; For participants with Gilbert's syndrome can be included with total bilirubin \>1.5xULN if direct bilirubin is ≤1.5xULN. Cirrhosis or current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice. NOTE: Stable non-cirrhotic chronic liver disease (including Gilbert's syndrome), asymptomatic gallstones, and chronic stable hepatitis B (in whom Hepatitis D \[HDV\] has been excluded) or C are acceptable if participant otherwise meets entry criteria. * 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 * Serologic evidence of Hepatitis B (HB) infection based on the results of testing for hepatitis B surface antigen (HBsAg), anti-hepatitis B core (HBc) and anti-HBs will be excluded as follows: * Participants positive for HBsAg. * Participants negative for HBsAg but positive for Anti-HBc and detectable hepatitis B virus (HBV) DNA, regardless of Anti-HBs antibody status. * 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 at home and has no other reliable resource to administer the study intervention at home.

Interventions

BIOLOGICAL

Belimumab (GSK1550188)

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Conditions

Systemic Lupus Erythematosus

Locations

GSK Investigational Site

Anniston, Alabama 36207

United States

GSK Investigational Site

Flagstaff, Arizona 86001

United States

GSK Investigational Site

Mesa, Arizona 85210

United States

GSK Investigational Site

Tucson, Arizona 85748

United States

GSK Investigational Site

Covina, California 91722

United States

GSK Investigational Site

Fontana, California 92335

United States

GSK Investigational Site

Fullerton, California 92835

United States

GSK Investigational Site

Long Beach, California 90720

United States

GSK Investigational Site

Los Angeles, California 90211

United States

GSK Investigational Site

Mission Hills, California 91345

United States

GSK Investigational Site

San Diego, California 92128

United States

GSK Investigational Site

Temecula, California 92592

United States

GSK Investigational Site

Tujunga, California 91042

United States

GSK Investigational Site

Van Nuys, California 92307-2333

United States

GSK Investigational Site

Van Nuys, California 92586

United States

GSK Investigational Site

Whittier, California 90602

United States

GSK Investigational Site

Aventura, Florida 33180

United States

GSK Investigational Site

Clearwater, Florida 33765

United States

GSK Investigational Site

Miami, Florida 33126

United States

GSK Investigational Site

Tamarac, Florida 33321

United States

GSK Investigational Site

Tampa, Florida 33606

United States

GSK Investigational Site

Atlanta, Georgia 30152

United States

GSK Investigational Site

Sugar Hill, Georgia 30518

United States

GSK Investigational Site

Morton Grove, Illinois 60521

United States

GSK Investigational Site

Rockford, Illinois 60123

United States

GSK Investigational Site

Baton Rouge, Louisiana 70836

United States

GSK Investigational Site

New Orleans, Louisiana 70112

United States

GSK Investigational Site

Shreveport, Louisiana 71115

United States

GSK Investigational Site

Detroit, Michigan 48202

United States

GSK Investigational Site

Lansing, Michigan 48910

United States

GSK Investigational Site

Sparta, New Jersey 07871

United States

GSK Investigational Site

Brooklyn, New York 11201

United States

GSK Investigational Site

Charlotte, North Carolina 28202

United States

GSK Investigational Site

Winston-Salem, North Carolina 27157

United States

GSK Investigational Site

Duncansville, Pennsylvania 16635

United States

GSK Investigational Site

Philadelphia, Pennsylvania 19140

United States

GSK Investigational Site

Austin, Texas 78745

United States

GSK Investigational Site

Baytown, Texas 77521

United States

GSK Investigational Site

Colleyville, Texas 76034

United States

GSK Investigational Site

Fort Worth, Texas 76109

United States

GSK Investigational Site

Houston, Texas 77089

United States

GSK Investigational Site

Katy, Texas 77494

United States

GSK Investigational Site

Plano, Texas 75024

United States

GSK Investigational Site

Waco, Texas 76710

United States

GSK Investigational Site

Danville, Virginia 24541

United States

GSK Investigational Site

Glendale, Wisconsin 53217

United States

GSK Investigational Site

Berazategui, 1884

Argentina

GSK Investigational Site

Buenos Aires, C1121ABE

Argentina

GSK Investigational Site

Buenos Aires, C1406AGA

Argentina

GSK Investigational Site

Ciudad Autonoma Buenos Aires, C1015ABO

Argentina

GSK Investigational Site

Ciudad Autonoma de Buenos Aire, 1425

Argentina

GSK Investigational Site

La Plata, B1900AX

Argentina

GSK Investigational Site

Mar del Plata, 7600

Argentina

GSK Investigational Site

Quilmes, B1878GEG

Argentina

GSK Investigational Site

San Miguel de Tucumán, CP 4000

Argentina

GSK Investigational Site

Santa Fe, S2000DSV

Argentina

GSK Investigational Site

Belo Horizonte, 30150-221.

Brazil

GSK Investigational Site

Cuiabá, 78020-840

Brazil

GSK Investigational Site

Juiz de Fora, 36010-570

Brazil

GSK Investigational Site

Passo Fundo, 99010-080

Brazil

GSK Investigational Site

Porto Alegre, 90035-001

Brazil

GSK Investigational Site

Porto Alegre, 90430-001

Brazil

GSK Investigational Site

Porto Alegre, 90610-000

Brazil

GSK Investigational Site

Salvador, 41820-020

Brazil

GSK Investigational Site

São José do Rio Preto, 15090-000

Brazil

GSK Investigational Site

São Paulo, 01323-001

Brazil

GSK Investigational Site

São Paulo, 05403-000

Brazil

GSK Investigational Site

Angers, 49933

France

GSK Investigational Site

Lille, 59800

France

GSK Investigational Site

Pessac, 33604

France

GSK Investigational Site

Rennes, 35200

France

GSK Investigational Site

Saint-Priest-en-Jarez, 42270

France

GSK Investigational Site

Toulouse, 31400

France

GSK Investigational Site

Herne, 44649

Germany

GSK Investigational Site

Lübeck, 23538

Germany

GSK Investigational Site

Mainz, 55131

Germany

GSK Investigational Site

Mainz, 55131

Germany

GSK Investigational Site

Meerbusch, 40668

Germany

GSK Investigational Site

Athens, 11 527

Greece

GSK Investigational Site

Athens, 11527

Greece

GSK Investigational Site

Athens, 12462

Greece

GSK Investigational Site

Heraklion, 71500

Greece

GSK Investigational Site

Thessaloniki, 54642

Greece

GSK Investigational Site

Brescia, 25123

Italy

GSK Investigational Site

Ferrara, 44124

Italy

GSK Investigational Site

Milan, 20132

Italy

GSK Investigational Site

Pisa, 56100

Italy

GSK Investigational Site

Reggio Emilia, 42123

Italy

GSK Investigational Site

Rome, 00168

Italy

GSK Investigational Site

Rozzano, 20089

Italy

GSK Investigational Site

Fukuoka, 807-8556

Japan

GSK Investigational Site

Kanagawa, 252-0375

Japan

GSK Investigational Site

Miyagi, 980-8574

Japan

GSK Investigational Site

Osaka, 590-0197

Japan

GSK Investigational Site

Tokyo, 104-8560

Japan

GSK Investigational Site

Cuauhtémoc, Mexico City 06090

Mexico

GSK Investigational Site

DF, 14000

Mexico

GSK Investigational Site

Guadalajara Jalisco, 44950

Mexico

GSK Investigational Site

León, 37000

Mexico

GSK Investigational Site

Mexico City, 06700

Mexico

GSK Investigational Site

Mexico City, 06726

Mexico

GSK Investigational Site

Mérida, 97000

Mexico

GSK Investigational Site

Monterrey Nuevo LeOn, 64000

Mexico

GSK Investigational Site

San Luis Potosí City, 78200

Mexico

GSK Investigational Site

Torreón, 27000

Mexico

GSK Investigational Site

Almada, 2805-267

Portugal

GSK Investigational Site

Barcelona, 08003

Spain

GSK Investigational Site

Castellon, 12004

Spain

GSK Investigational Site

Córdoba, 14004

Spain

GSK Investigational Site

Murcia, 30120

Spain

GSK Investigational Site

Seville, 41014

Spain

GSK Investigational Site

Valladolid, 47012

Spain

GSK Investigational Site

VigoPontevedra, 36213

Spain

GSK Investigational Site

Villajoyosa, 3570

Spain