Efficacy and Safety of Subcutaneous Belimumab in Adults with Early Systemic Lupus Erythematosus: A Phase 4 Multicenter Prospective Study

Trial ID: 2023-509146-35-00
Protocol: 219240
Sponsor: Glaxosmithkline Research & Development Limited

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Diseases & Conditions

Systemic lupus erythematosus

Objectives

The primary objective of this study is to evaluate the efficacy of **belimumab** (BEL) in achieving low disease activity state (LLDAS) at week 52 in adult participants with early **Systemic Lupus Erythematosus** (SLE). Achieving LLDAS is clinically significant as it indicates a state of controlled disease activity, which can lead to improved patient outcomes and quality of life.

Secondary objectives include:

Describing the efficacy of BEL in achieving the Systemic Lupus Erythematosus Responder Index 4 (SRI4) at week 52 in participants with early SLE who have a SLE Disease Activity Index 2000 (SLEDAI-2K) score of ≥4 at baseline.
Evaluating the efficacy of BEL in achieving and maintaining LLDAS in participants with early SLE.
Assessing the efficacy of BEL in reducing corticosteroid use in participants with early SLE who are taking an average oral prednisone equivalent dose of >5 mg/day at baseline.
Describing the efficacy of BEL in managing severe flare-ups in participants with early SLE.

Participants

The clinical trial involves a total of **257 participants** diagnosed with **Systemic Lupus Erythematosus** (SLE). The study population includes both male and female subjects, aged 18 years and older, who have been clinically diagnosed with SLE within two years prior to the trial. Participants were selected based on specific inclusion criteria, including a documented positive autoantibody test and active disease status as defined by the Clinical SLEDAI-2K score. The trial population is characterized by individuals who have shown an incomplete response to stable initial SLE therapy, which may include antimalarials, oral prednisone, or conventional immunosuppressive treatments. Participants are required to be capable of providing informed consent and, if female, must not be pregnant or breastfeeding and must adhere to effective contraceptive measures if of childbearing potential. The trial does not exclude vulnerable populations, ensuring a comprehensive assessment of the treatment's efficacy across a diverse group of individuals.

Plans and Procedures

The clinical trial is a **Phase IV** multicenter, prospective, open-label study designed to evaluate the efficacy and safety of **belimumab** administered subcutaneously in adult participants with early **systemic lupus erythematosus** (SLE). The trial aims to assess the achievement of low lupus disease activity state (LLDAS) at week 52 as the primary endpoint. Secondary endpoints include achieving SRI4 at week 52, maintaining LLDAS for at least 25% of the time from Day 1 to Week 52, and achieving an average oral prednisone equivalent dose of ≤5 mg/day at Week 52. The trial also evaluates the incidence of severe flare and other safety outcomes up to Week 156.

The study follows a structured sequence of visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, documented SLE diagnosis, and positive autoantibody test results. Participants must have an active SLE as defined by specific clinical criteria and an incomplete response to stable initial SLE therapy. The trial includes follow-up visits at regular intervals to monitor the participants' response to treatment and any adverse events. The end-of-study visit marks the conclusion of the participant's involvement, which is expected to last up to 156 weeks.

Participants are expected to remain in the study for the full duration unless specific conditions necessitate early termination. These conditions include significant adverse events, withdrawal of consent, or non-compliance with the study protocol. The trial is not categorized as low intervention and is conducted under rigorous scientific and ethical standards to ensure the validity and reliability of the results. The estimated recruitment start date is October 14, 2024, with an anticipated end date of April 20, 2029.

Treatment

The clinical trial involves the administration of **Benlysta**, a **200 mg solution for injection** in a pre-filled pen, developed by GlaxoSmithKline (Ireland) Limited. The active substance in Benlysta is **belimumab**, classified as a biological product with a protein origin. The pharmaceutical form is a solution for injection, specifically designed for subcutaneous administration. The maximum daily and total dose is 200 mg, with a treatment period extending up to 156 weeks. The pre-filled pen is a customized version of the Scandinavian Health Limited (SHL) MollyTM platform, which includes a prefilled syringe with additional functional components. This device does not have a CE mark.

In this study, Benlysta is the experimental medication, and no additional non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are specified. The administration schedule and participant compliance are monitored according to the study protocol, ensuring adherence to the dosing regimen. The trial aims to evaluate the efficacy and safety of belimumab in adult participants with early systemic lupus erythematosus, focusing on achieving low disease activity status at week 52.

Efficacy

The efficacy of **belimumab** in the clinical trial will be assessed primarily by evaluating the achievement of Low Lupus Disease Activity State (LLDAS) at Week 52 in participants with early systemic lupus erythematosus (SLE). Secondary endpoints include achieving the Systemic Lupus Erythematosus Responder Index 4 (SRI4) at Week 52, maintaining LLDAS for at least 25% of the time from Day 1 to Week 52, achieving an average oral prednisone equivalent dose of ≤5 mg/day at Week 52, and assessing the incidence of severe flare using a modified Systemic Flare Index (SFI) at Week 52. Additionally, Part B of the study will evaluate achieving DORIS remission at Week 104, maintaining an SDI of 0 at Week 156, and the incidence of adverse events (AEs), serious adverse events (SAEs), and adverse events of special interest (AESI) up to Week 104 and Week 156.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Adults ≥18 years of age at the time of signing the informed consent.
Documented diagnosis of SLE within 2 years of signing the informed consent according to the EULAR/ACR SLE classification criteria 2019.
Have unequivocally positive autoantibody test results defined as an ANA titer ≥1:80 and/or a positive anti-dsDNA serum antibody test from 2 independent time points as follows: • Positive test results from 2 independent time points within the study screening period based on the study's central laboratory results OR • One positive historical test result and 1 positive test result during the screening period, based on the study’s central laboratory results.
Eligibility Adjudication Committee confirmation of active SLE defined as: • Clinical SLEDAI-2K (excluding anti-dsDNA and C3/C4) score >4, OR • Clinical SLEDAI-2K (excluding anti-dsDNA and C3/C4) score 1 to 4 and prednisone or equivalent dose ≥10 mg/day.
SDI = 0 at Screening
Stable, first-line SLE therapy which includes any of the following or combination of the following: • AMs started at least 12 weeks prior to Screening study visit and on a stable dose for a minimum of 4 weeks prior to Day 1. • Oral prednisone or equivalent at a dose of ≤20 mg/day. If oral prednisone or equivalent is the sole therapy for SLE at the screening visit it should have been initiated at least 8 weeks prior to Screening study visit. If a participant is not on oral prednisone prior to the Screening study visit, oral prednisone at a dose of ≤20 mg/day may be introduced during Screening. No change in oral prednisone dose may occur during the last 2 weeks during Screening prior to Day 1. • Conventional IS treatment for least 12 weeks prior to Screening study visit, and at a stable dose for a minimum of 4 weeks prior to Day 1.
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 WOCBP OR • Is a WOCBP and using a contraceptive method that is highly effective, with a failure rate of <1%.
Capable of giving signed informed consent.

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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, GI, hepatic, renal, neurological, psychiatric, malignancy, or infectious diseases) and/or a planned surgical procedure, which, in the opinion of the 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 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 tubercolosis (TB).
Confirmed PML or unexplained new-onset or deteriorating neurologic signs and symptoms.
Have severe active CNS lupus (including seizures, psychosis, organic brain syndrome, 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 mg/24 hours or equivalent using spot urine protein to creatinine ratio, requiring induction therapy not permitted by protocol.
Participants with 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 judgement, 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 enrolment.
Known to have titers of human anti-mouse antibody or history of hypersensitivity reactions when treated with diagnostic or therapeutic monoclonal antibodies.
Participants with history of major organ transplant or hematopoietic stem cell/marrow transplant or renal transplant.

Trial Status by Country

Country	Status	Start of Recruitment	Planned Patients
France	Not Recruiting	14 Oct 2024	11
Germany	Not Recruiting	14 Oct 2024	7
Greece	Not Recruiting	14 Oct 2024	15
Italy	Not Recruiting	14 Oct 2024	17
Portugal	Not Recruiting	14 Oct 2024	10
Spain	Not Recruiting	14 Oct 2024	16