Randomized Phase 2 Trial of Telitacicept in Patients With IgA Nephropathy With Persistent Proteinuria

Abstract

Introduction: To date, no specific therapies have been approved for immunoglobulin A nephropathy (IgAN) treatment. Telitacicept is a fusion protein composed of transmembrane activator and calcium-modulating cyclophilin ligand interactor and fragment crystallizable portion of immunoglobulin G (IgG), which neutralizes the B lymphocyte stimulator and a proliferation-inducing ligand.

Methods: This phase 2 randomized placebo-controlled trial aimed to evaluate the efficacy and safety of telitacicept in patients with IgAN. Participants with an estimated glomerular filtration rate (eGFR) >35 ml/min per 1.73 m² and proteinuria ≥0.75 g/d despite optimal supportive therapy, were randomized 1:1:1 to receive subcutaneous telitacicept 160 mg, telitacicept 240 mg, or placebo weekly for 24 weeks. The primary end point was the change in 24-hour proteinuria at week 24 from baseline.

Results: Forty-four participants were randomized into placebo (n = 14), telitacicept 160 mg (n = 16), and telitacicept 240 mg (n = 14) groups. Continuous reductions in serum IgA, IgG, and IgM levels were observed in the telitacicept group. Telitacicept 240 mg therapy reduced mean proteinuria by 49% from baseline (change in proteinuria vs. placebo, 0.88; 95% confidence interval, -1.57 to -0.20; P = 0.013), whereas telitacicept 160 mg reduced it by 25% (-0.29; 95% confidence interval, -0.95 to 0.37; P = 0.389). The eGFR remained stable over time. Adverse events (AEs) were similar in all groups. Treatment-emergent AEs were mild or moderate, and no severe AEs were reported.

Conclusion: Telitacicept treatment led to a clinically meaningful reduction in proteinuria in patients with IgAN in the present phase 2 clinical trial. This effect is indicative of a reduced risk for future kidney disease progression.

Keywords: BLyS/APRIL inhibitors; IgA Nephropathy; TACI-Fc fusion protein; proteinuria; telitacicept.

Figure 1

Participant enrollment, randomization, and follow-up. eGFR, estimated glomerular filtration rate.

Figure 2

Mean changes in proteinuria from baseline. Data are expressed as mean values (bars indicate the standard error of the mean). (a) Absolute mean changes in 24-hour proteinuria from baseline in patients receiving placebo or telitacicept (160 mg/week or 240 mg/week) at each visit. (b) Mean change (%) in 24-hour proteinuria from baseline in patients receiving placebo or telitacicept (160 mg/week or 240 mg/week) at each visit.

Figure 3

Mean changes in eGFR from baseline. Data are expressed as mean values (bars indicate the standard error of the mean). (a) Absolute mean changes in eGFR from baseline in patients receiving placebo or telitacicept (160 or 240 mg/week) at each visit. (b) Mean change (%) in eGFR from baseline in patients receiving placebo or telitacicept (160 or 240 mg/week) at each visit. eGFR indicates the estimated glomerular filtration rate calculated using CKD-EPI. CKD-EPI, chronic kidney disease epidemiology collaboration; eGFR, estimated glomerular filtration rate.

Figure 4

Median and IQR of immunoglobulins among patients before and after treatment. Data are expressed as median and IQR. (a) Absolute values of IgA in patients receiving placebo or telitacicept (160 mg/week or 240 mg/week) at baseline and week 24. (b) Absolute values of IgG in patients receiving placebo or telitacicept (160 mg/week or 240 mg/week) at baseline and week 24. (c) Absolute values of IgM in patients receiving placebo or telitacicept (160 mg/week or 240 mg/week) at baseline and week 24. IgA, immunoglobulin A; IgM, immunoglobulin M; IgG, immunoglobulin G; IQR, interquartile range.