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

JRCT ID: jRCT2071240068

Registered date:08/10/2024

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Systemic Lupus Erythematosus
• Date of first enrollment: 25/10/2024
• Target sample size: 12
• Countries of recruitment: Argentina,Japan,Belgium,Japan,Brazil,Japan,Canada,Japan,France,Japan,Germany,Japan,Italy,Japan,Mexico,Japan,Slovakia,Japan,Spain,Japan,United States,Japan
• Study type: Interventional
• Intervention(s): Belimumab(Genetical Recombination). The recommended dosage is 200 mg once weekly as subcutaneous Administration.

Outcome(s)

• Primary Outcome: Achieving LLDAS at Week 52

Secondary Outcome

- Achieving SRI4 at Week 52
- Achieving LLDAS for >-25% of time from Day 1 to Week 52
- Achieving average oral prednisone equivalent dose =<5 mg/day2 at Week 52
- Incidence of severe flare (modified SFI)3 as assessed at Week 52
- Achieving a >-50% improvement in CLASI activity score at Week 52
- Change from baseline in FACIT-Fatigue at Week 52
- Incidence of AEs, SAEs and AESI up to Week 52
- Achieving DORIS remission1 at Week 104
- Maintaining an SDI of 0 at Week 156
- Incidence of AEs, SAEs and AESI up to Week 104 and up to Week 156

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1. >=18 years of age at the time of signing the informed consent
2. 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
3. Have unequivocally positive autoantibody test results defined as an Anti-nuclear antibody (ANA) titer >=1:80 and/or a positive anti-dsDNA (>=30 IU/mL) 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. Disease Activity Inclusion Criteria Adjudication Group confirmation of 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 mg/day
5. SDI = 0 at Screening
6. Incomplete response to 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%, as described in Contraceptive and Barrier Guidance during the study intervention period and for at least 4 months after the last dose of study intervention. The investigator should evaluate potential for contraceptive method failure in relationship to the first dose of study intervention.
A WOCBP must have a negative highly sensitive pregnancy test (urine or serum, as required by local regulations) within 24 hours before the first dose of study intervention.
- If a urine test cannot be confirmed as negative, a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
- The investigator is responsible for review of medical history, menstrual history,
and recent sexual activity to decrease the risk for inclusion of a woman with an
early undetected pregnancy.
- A WOCBP who agrees to follow the contraceptive guidance during the
treatment period and for at least 16 weeks after the last dose of BEL
8. Capable of giving signed informed consent

Exclude criteria

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. Evidence of active or latent 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 >=5 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.
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. Lupus kidney disease defined by proteinuria >6 g/24 hour or equivalent using spot urine protein to creatinine ratio, or serum creatinine >2.5 mg/dL, or have active LN requiring induction therapy within 35 days of Screening.
8. Have evidence of serious suicide risk, defined as 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.
9. Known to have titers of human anti-mouse antibody or history of hypersensitivity reactions when treated with diagnostic or therapeutic monoclonal antibodies.
10. 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
11. Chronic oral steroid use for a non-SLE disorder at the Screening study visit (e.g., for asthma). Inhaled steroid use will be allowed.
12. Treatment at or prior to Screening study visit:
- Treatment at Screening study visit with any of the following:
AZA >200 mg/day, MTX (any formulation) >25 mg/week, 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 BEL, Anifrolumab, Rituximab or other B cell depleting therapies, Anti-TNF therapy, Other treatments with effects on the immune system, IV cyclophosphamide, IV immunoglobulin, Plasmapheresis, Intra-articular, IM, or IV corticosteroids within 6 weeks of Day 1, Daily use of >1 NSAID within 2 weeks prior to Day 1
13. History of primary immunodeficiency, or hypogammaglobulinemia (IgG <400 mg/dL) or IgA deficiency (IgA <10 mg/dL)
14. Have a Grade 3 or greater neutropenia, defined as absolute neutrophil count <1000/mm3
(<1.0 x10^9/L) based on the CTCAE v5.0
15. Alanine aminotransferase >2 x ULN
16. Total bilirubin >1.5 x ULN (isolated bilirubin >1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%)
17. 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.
18. Positive HIV antibody test
19. Presence of HBsAg or HBcAb at screening or within 3 months prior to first dose of study intervention.
20. Positive Hepatitis C antibody test result at screening or within 3 months prior to starting study intervention.
21. Positive Hepatitis C RNA test result at screening or within 3 months prior to first dose of study intervention.

Related Information

• Primary Sponsor: Assudani Deepak
• Secondary ID(s): NCT06411249