Systemic Lupus Erythematosus
Conditions
Brief summary
This study will evaluate the efficacy, safety, pharmacokinetics(PK), pharmacodynamics(PD) and ADA of MIL62 compared with placebo in participants with systemic lupus erythematosus.
Interventions
DRUGMIL62
MIL62 will be administered by intravenous (IV) infusion at a dose of 1000 mg on Week (W) 1 Day (D) 1, W3D1, W25D1, W27D1, W53D1, and W55D1.
DRUGplacebo
Placebo will be administered by intravenous (IV) infusion at a dose of 1000 mg on Week (W) 1 Day (D) 1, W3D1, W25D1, W27D1, W53D1, and W55D1.
Sponsors
Beijing Mabworks Biotech Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Age 18-80 ; 2. Diagnosis of systemic lupus erythematosus according to European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) SLE classification criteria ; 3. Positive antinuclear antibodies (ANA) ≥ 1:80 at screening or positive anti- dsDNA ; 4. Low C3 and/or low C4 complement at screening ; 5. High disease activity at screening ; 6. On a stable SLE treatment regimen for at least 30 days prior to the first administration； 7. Able and willing to provide written informed consent and to comply with the study protocol.
Exclusion criteria
1. Unsufficient organ function; 2. Received rituximab or any B-cell depleting drug within 9 months prior to the first dose; 3. Subjects with CD4+ T lymphocyte count \< 200 cells/μL; 4. Received cyclophosphamide within 8 weeks prior to the first dose; received calcineurin inhibitors (cyclosporine, tacrolimus, etc., except for topical use) or plasma exchange therapy within 4 weeks prior to the first dose; 5. Received a B-cell stimulating factor inhibitor such as Belimumab, and Telitacicept within 12 weeks prior to the first administration; TNF inhibitor, interleukin monoclonal antibody, JAK inhibitor, BTK inhibitor, TYK2 inhibitor, or thalidomide within 4 weeks prior to the first administration; 6. Received live or attenuated vaccination within 28 days prior to the first administration; 7. Participated in other clinical trials within 28 days prior to the first administration; 8. Concomitant with other serious diseases; 9. Positive for hepatitis B surface antigen (HBsAg) and/or hepatitis B core antibody (HBcAb) with HBV DNA titer above the normal range; positive for hepatitis C virus (HCV) antibody; positive for human immunodeficiency virus (HIV); 10. Subjects with known history of severe allergic reactions to humanized monoclonal antibodies MIL62 ; 11. Breastfeeding or pregnant women; 12. Childbearing potential and unwillingness or impossibility to comply with a scientifically acceptable birth-control method; 13. Other conditions unsuitable for participation in this study determined by the Investigator.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part A and Part B:Percentage of participants achieving SRI-4 at Week 12 | at Week 12 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part A and Part B:Proportion of participants achieving SRI-4 at Week 24 | at Week 24 | — |
| Part A and Part B:Proportion of participants achieving SRI-4 at Week76 | at Week 76 | — |
| Part A and Part B:Change From Baseline in 24-hour urine protein in participants with elevated baseline urine protein (24-hour urine protein ≥ 0.5g) at Week 24,52,76 | up to 76 weeks after randomization | — |
| Part A and Part B:Percentage of participants who achieved or maintained a prednisone dose of ≤7.5 mg/day (or equivalent dose) during Weeks 40 to 52 | from Week 40 to Week 52 after randomization | — |
| Part A and Part B:Change From Baseline in EuroQol- 5 Dimension (EQ-5D) at Week 24, 52, 76 | up to 76 weeks after randomization | — |
| Part A and Part B:Change From Baseline in Serum Immunoglobulin Levels at Week 24 Change from baseline in the serum levels of IgG, IgA, IgM | up to 76 weeks after randomization | — |
| Part A and Part B:Proportion of participants achieving SRI-4 at Week 52 | at Week 52 | — |
| Part A and Part B:Percentage of Participants with Adverse Events | up to 76 weeks after randomization | — |
| Part A: Pharmacokinetic(PK) Parameters: AUC | up to 76 weeks after randomization | The area under the curve (AUC) of serum concentration of the drug after the administration |
| Part A: Pharmacokinetic(PK) Parameters:Cmax | up to 76 weeks after randomization | Maximum concentration(Cmax) of the drug after administration |
| Part A and Part B: Pharmacodynamics(PD) characteristics：summarizing the changes in the absolute counts and percentages of peripheral blood CD19⁺ B cells, CD3⁺CD4⁺ T cells, CD3⁺CD8⁺ T cells, NK cells, CD19⁺CD27⁺ B cells, and CD19⁺CD27- naïve B cells | up to 76 weeks after randomization | — |
| Part Aand Part B: Anti-Drug Antibodies (ADA) will be tested and percentage of ADA positive patients will be calculated to evaluate immunogenicity of MIL62 | up to 76 weeks after randomization | — |
| Part A and Part B:Change From Baseline in biomarkers associated with disease anti-dsDNA ,complement component 3 (C3), and complement component 4 (C4) | up to 76 weeks after randomization | — |
Countries
China
Outcome results
None listed