A study describing the efficacy and safety of belimumab administered subcutaneously in adult participants with early systemic lupus erythematosus

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Glaxosmithkline Research & Development Limited

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

30 Jan 2025 → ongoing

Decision date (initial)

2024-10-10

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

GlaxoSmithKline Research & Development Limited

External identifiers

EU CT number

2023-509146-35-00

ClinicalTrials.gov

NCT06411249

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Safety, Efficacy

To describe the efficacy of BEL on achieving LLDAS at week 52 in participants with early SLE.

Secondary objectives 4

1. To describe the efficacy of BEL on achieving SRI4 at wk 52 in participants with early SLE who have a SLEDAI-2K ≥4 at baseline.
2. To describe the efficacy of BEL on achieving and maintaining LLDAS in participants with early SLE.
3. To describe the efficacy of BEL on corticosteroid reduction in participants with early SLE who are taking an average oral prednisone equivalent dose >5 mg/day at baseline.
4. To describe the efficacy of BEL on severe flare in participants with early SLE.

Conditions and MedDRA coding

Systemic Lupus Erythematosus

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. ≥18 years of age at the time of signing the informed consent.
2. Documented diagnosis of SLE within 2 years of signing the informed consent according to the EULAR/ACR SLE classification criteria 2019.
3. 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. Screening results must be based on the study's central laboratory results OR • One positive historical test result and 1 positive test result during the screening period.
4. 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) ≤4 and prednisone or equivalent dose ≥10 mg/day.
5. SDI = 0 at Screening
6. Stable, initial 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 at a dose of ≤20 mg/day. 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.
7. 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%.
8. Capable of giving signed informed consent.

Exclusion criteria 10

1. 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.
2. 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.
3. 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.
4. Confirmed active or untreated latent tubercolosis (TB).
5. Confirmed PML or unexplained new-onset or deteriorating neurologic signs and symptoms.
6. Have severe active CNS lupus (including seizures, psychosis, organic brain syndrome, CVA, cerebritis, or CNS vasculitis) requiring therapeutic intervention within 60 days of Screening.
7. 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.
8. 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.
9. Known to have titers of human anti-mouse antibody or history of hypersensitivity reactions when treated with diagnostic or therapeutic monoclonal antibodies.
10. Participants with history of major organ transplant or hematopoietic stem cell/marrow transplant or renal transplant.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Achieving LLDAS at Week 52.

Secondary endpoints 7

1. Achieving SRI4 at Week 52.
2. Achieving LLDAS for ≥25% of time from Day 1 to Week 52.
3. Achieving average oral prednisone equivalent dose ≤5 mg/day at Week 52.
4. Incidence of severe flare (modified SFI) as assessed at Week 52.
5. Part B: Achieving DORIS remission at Week 104.
6. Part B: Maintaining an SDI of 0 at Week 156.
7. Part B: Incidence of AEs, SAEs and AESI up to Week 104 and up to Week 156.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Glaxosmithkline Research & Development Limited

Sponsor organisation

Glaxosmithkline Research & Development Limited

Address

G S K House, 980 Great West Road 980 Great West Road

City

Brentford

Postcode

TW8 9GS

Country

United Kingdom

Scientific contact point

Organisation

Glaxosmithkline Research & Development Limited

Contact name

EU GSK Clinical Trials Call Center

Public contact point

Organisation

Glaxosmithkline Research & Development Limited

Contact name

EU GSK Clinical Trials Call Center

Third parties 10

Locations

6 EU/EEA countries · 36 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 166 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

14 submissions — initial application plus substantial / non-substantial modifications