This study is a randomized, parallel, double-blind, placebo-controlled, subcutaneous administration Phase II dose-exploration clinical trial aimed at evaluating the efficacy, safety, PK, PD, and immunogenicity characteristics of SLN12140 at different doses in IgA nephropathy subjects who have previously received standard treatment (the standard treatment drugs allowed in this study include: angiotensin-converting enzyme inhibitors \[ACEi\], angiotensin II receptor blockers \[ARB\], and sodium-glucose co-transporter 2 inhibitors \[SGLT2i\]) but have poor control. The study is divided into four stages, including a screening period of up to 8 weeks, an introduction period of up to 12 weeks, a 40-week double-blind period (including a 36-week treatment period and a 4-week safety follow-up period; all subjects in the three dose groups who are willing to continue treatment and are judged by the investigator to potentially benefit from subsequent treatment will enter the open-label extension period for continued treatment after completing the double-blind period), and a 56-week open-label extension period (all subjects in the three dose groups who are willing to continue treatment and are judged by the investigator to potentially benefit from subsequent treatment will continue SLN12140 at the same dose group \[the optimal dose\], including a 52-week open treatment period and a 4-week safety follow-up period).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
48
SLN12140 by subcutaneous (sc) injection:100mg QW for 36 weeks in blind treatment period; SLN12140 by subcutaneous (sc) injection:200mg QW for 36 weeks in blind treatment period; SLN12140 by subcutaneous (sc) injection:600mg Q4W for 36 weeks in blind treatment period; after 36 weeks of blind treatment period, all of subjects will receive SLN12140 treatment for 52 weeks as open-label extension period with one optimal dosage.
Placebo (0.9% sodium chloride solution) will be provided as an injectable solution without active ingredient for 36 weeks in blind treatment period.
Beijing University 1st hospital
Beijing, Beijing Municipality, China
Mean change from baseline in urine protein-to-creatinine ratio (UPCR)at Week 36
Change from baseline in Urine protein-to-creatinine ratio (UPCR) by visit.
Time frame: Week 36
Mean change from baseline in urine protein-to-creatinine ratio (UPCR)at Week 24
Change from baseline in Urine protein-to-creatinine ratio (UPCR) by visit.
Time frame: Week 24
Mean change from baseline in urine albumin-to-creatinine ratio (UACR) at Weeks 24, 36;
Change from baseline in Urine albumin-to-creatinine ratio (UACR) by visit.
Time frame: Weeks 24, 36
Mean change from baseline in estimated glomerular filtration rate (eGFR) at Weeks 12, 24, 36
Change from baseline in eGFR by visit
Time frame: Weeks 12, 24, 36
Mean changes from baseline in 24-hour urinary protein excretion (24h-UPE) at weeks 24 and 36.
Time frame: Weeks 24 and 36
Mean changes from baseline in 24-hour urinary albumin excretion (24h-UAE) at weeks 24 and 36.
Time frame: Weeks 24 and 36
Mean changes from baseline in quantitative first morning void (FMV) UPCR at weeks 2, 4, 8, 12, 24, and 36.
Time frame: Weeks 2, 4, 8, 12, 24, and 36.
Mean changes from baseline in quantitative FMV-UACR at weeks 2, 4, 8, 12, 24, and 36.
Time frame: Weeks 2, 4, 8, 12, 24, and 36.
Number and severity of treatment-emergent adverse events
Number and intensity of adverse events
Time frame: 106 weeks
Incidence of treatment-induced anti-drug antibodies
Anti-drug antibody (ADA), incidence, titers and duration
Time frame: Weeks 4、8、12、24、36 and 40
Pharmacokinetics (PK)parameters of SLN12140: Area Under The Plasma Concentration-time Curve
Time frame: Baseline through week 92 (predose and postdose)
PK: Maximum Plasma Concentration (Cmax)
To characterize the pharmacokinetics of SLN12140 in participants with IgAN
Time frame: Baseline through week 92( predose and postdose)
PK: Time To Maximum Concentration (Tmax)
To characterize the pharmacokinetics of SLN12140 in participants with IgAN
Time frame: Baseline through week 92( predose and postdose)
Complement Alternative Pathway (AP) Functional Activity
Serum AP functional activity was measured by the Wieslab functional immunoassay method.
Time frame: Baseline through week 92( predose and post dose)
Complement FP
Plasma FP was measured by enzyme-linked immunosorbent assay (ELISA).
Time frame: Baseline through week 92(predose and postdose)
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.