Clinical trial NCT06411249: A Study Describing the Efficacy and Safety of Belimumab Administered in Adult Participants With Early Systemic Lupus Erythematosus (SLE)
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Systemic Lupus Erythematosus
Keywords: Belimumab
Benlysta
Efficacy
Safety
Early Use
Systemic Lupus Erythematosus
Autoimmune Diseases
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2024-05-13
Enrollment: 350
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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) less than or equal 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
* 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 x109/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 (isolated bilirubin \>1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin \<35 percent \[%\]). Participants with Gilbert's syndrome can be included with total bilirubin \>1.5xULN as long as 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.

Primary outcomes:
measure: Part A: Percentage of Participants Achieving Lupus Low Disease Activity State (LLDAS) at Week 52
timeFrame: At Week 52
Secondary outcomes:
measure: Part A: Percentage of Participants Achieving SLE Responder Index 4 (SRI4) at Week 52
timeFrame: At Week 52
measure: Part A: Percentage of Participants Achieving Lupus Low Disease Activity State (LLDAS) for ≥ 25 percent (%) of time from Day 1 to Week 52
timeFrame: Day 1 and up to Week 52
measure: Part A: Percentage of Participants Achieving Average Oral Prednisone Equivalent Dose ≤ 5 mg/day at Week 52
timeFrame: At Week 52
measure: Part A: Estimate of probability of having a Severe Flare defined as modified SELENA-SLEDAI Flare Index (SFI) at Week 52
timeFrame: At Week 52
measure: Part A: Percentage of Participants Achieving a ≥ 50% Improvement in Cutaneous Lupus Disease Area and Severity Index (CLASI) Activity Score at Week 52
timeFrame: At Week 52
measure: Part A: Change from Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) -Fatigue at Week 52
timeFrame: Baseline (Day 1) and at Week 52
measure: Part A: Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), and AEs of Special Interest (AESIs) up to Week 52
timeFrame: Up to Week 52
measure: Part B: Percentage of Participants Achieving Definition of Remission in SLE (DORIS) Remission at Week 104
timeFrame: At Week 104
measure: Part B: Percentage of Participants Maintaining Systematic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) of 0 up to Week 156
timeFrame: Up to Week 156
measure: Part B: Number of Participants With AEs, SAEs, and AESIs up to Week 104 and Week 156
timeFrame: Up to Week 104 and Week 156
Other outcomes:
Locations:
city: Anniston
country: United States
facility: GSK Investigational Site
state: Alabama
city: Flagstaff
country: United States
facility: GSK Investigational Site
state: Arizona
city: Mesa
country: United States
facility: GSK Investigational Site
state: Arizona
city: Tucson
country: United States
facility: GSK Investigational Site
state: Arizona
city: Covina
country: United States
facility: GSK Investigational Site
state: California
city: Fontana
country: United States
facility: GSK Investigational Site
state: California
city: Fullerton
country: United States
facility: GSK Investigational Site
state: California
city: Long Beach
country: United States
facility: GSK Investigational Site
state: California
city: Los Angeles
country: United States
facility: GSK Investigational Site
state: California
city: Mission Hills
country: United States
facility: GSK Investigational Site
state: California
city: San Diego
country: United States
facility: GSK Investigational Site
state: California
city: Tujunga
country: United States
facility: GSK Investigational Site
state: California
city: Van Nuys
country: United States
facility: GSK Investigational Site
state: California
city: Van Nuys
country: United States
facility: GSK Investigational Site
state: California
city: Whittier
country: United States
facility: GSK Investigational Site
state: California
city: Aventura
country: United States
facility: GSK Investigational Site
state: Florida
city: Clearwater
country: United States
facility: GSK Investigational Site
state: Florida
city: Miami
country: United States
facility: GSK Investigational Site
state: Florida
city: Tamarac
country: United States
facility: GSK Investigational Site
state: Florida
city: Tampa
country: United States
facility: GSK Investigational Site
state: Florida
city: Atlanta
country: United States
facility: GSK Investigational Site
state: Georgia
city: Sugar Hill
country: United States
facility: GSK Investigational Site
state: Georgia
city: Morton Grove
country: United States
facility: GSK Investigational Site
state: Illinois
city: Rockford
country: United States
facility: GSK Investigational Site
state: Illinois
city: Baton Rouge
country: United States
facility: GSK Investigational Site
state: Louisiana
city: Shreveport
country: United States
facility: GSK Investigational Site
state: Louisiana
city: Lansing
country: United States
facility: GSK Investigational Site
state: Michigan
city: Sparta
country: United States
facility: GSK Investigational Site
state: New Jersey
city: Charlotte
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Duncansville
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Austin
country: United States
facility: GSK Investigational Site
state: Texas
city: Baytown
country: United States
facility: GSK Investigational Site
state: Texas
city: Colleyville
country: United States
facility: GSK Investigational Site
state: Texas
city: Fort Worth
country: United States
facility: GSK Investigational Site
state: Texas
city: Houston
country: United States
facility: GSK Investigational Site
state: Texas
city: Katy
country: United States
facility: GSK Investigational Site
state: Texas
city: Plano
country: United States
facility: GSK Investigational Site
state: Texas
city: Waco
country: United States
facility: GSK Investigational Site
state: Texas
city: Danville
country: United States
facility: GSK Investigational Site
state: Virginia
city: Glendale
country: United States
facility: GSK Investigational Site
state: Wisconsin
city: Berazategui
country: Argentina
facility: GSK Investigational Site
city: Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Ciudad Autonoma de Buenos Aire
country: Argentina
facility: GSK Investigational Site
city: La Plata
country: Argentina
facility: GSK Investigational Site
city: Mar del Plata
country: Argentina
facility: GSK Investigational Site
city: Quilmes
country: Argentina
facility: GSK Investigational Site
city: Santa Fe
country: Argentina
facility: GSK Investigational Site
city: Tucuman
country: Argentina
facility: GSK Investigational Site
city: Belo Horizonte
country: Brazil
facility: GSK Investigational Site
city: Cuiaba
country: Brazil
facility: GSK Investigational Site
city: Juiz de Fora
country: Brazil
facility: GSK Investigational Site
city: Passo Fundo
country: Brazil
facility: GSK Investigational Site
city: Porto Alegre
country: Brazil
facility: GSK Investigational Site
city: Porto Alegre
country: Brazil
facility: GSK Investigational Site
city: Porto Alegre
country: Brazil
facility: GSK Investigational Site
city: Salvador
country: Brazil
facility: GSK Investigational Site
city: Sao Jose Do Rio Preto
country: Brazil
facility: GSK Investigational Site
city: Sao Paulo
country: Brazil
facility: GSK Investigational Site
city: SAo Paulo
country: Brazil
facility: GSK Investigational Site
city: Angers Cedex 9
country: France
facility: GSK Investigational Site
city: Lille cedex
country: France
facility: GSK Investigational Site
city: Pessac
country: France
facility: GSK Investigational Site
city: Rennes
country: France
facility: GSK Investigational Site
city: Saint-Priest en Jarez
country: France
facility: GSK Investigational Site
city: Toulouse Cedex 9
country: France
facility: GSK Investigational Site
city: Herne
country: Germany
facility: GSK Investigational Site
city: Luebeck
country: Germany
facility: GSK Investigational Site
city: Mainz
country: Germany
facility: GSK Investigational Site
city: Mainz
country: Germany
facility: GSK Investigational Site
city: Meerbusch
country: Germany
facility: GSK Investigational Site
city: Brescia
country: Italy
facility: GSK Investigational Site
city: Ferrara
country: Italy
facility: GSK Investigational Site
city: Rome
country: Italy
facility: GSK Investigational Site
city: Fukuoka
country: Japan
facility: GSK Investigational Site
city: Kanagawa
country: Japan
facility: GSK Investigational Site
city: Miyagi
country: Japan
facility: GSK Investigational Site
city: Osaka
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: LeOn Guanajuato
country: Mexico
facility: GSK Investigational Site
city: Merida
country: Mexico
facility: GSK Investigational Site
city: Mexico DF
country: Mexico
facility: GSK Investigational Site
city: Monterrey Nuevo LeOn
country: Mexico
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: COrdoba
country: Spain
facility: GSK Investigational Site
city: Murcia
country: Spain
facility: GSK Investigational Site
city: Sevilla
country: Spain
facility: GSK Investigational Site
city: Valladolid
country: Spain
facility: GSK Investigational Site
city: VigoPontevedra
country: Spain
facility: GSK Investigational Site
city: Villajoyosa
country: Spain
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: