Phase 2 Trial of Cemdisiran in Adult Patients with IgA Nephropathy: A Randomized Controlled Trial.
An injectable RNA-based drug that switches off liver production of a key immune protein cut urine protein levels by about a third in IgA nephropathy over eight months, and was generally well tolerated.
Background
IgA nephropathy is the most common primary glomerulonephritis, and proteinuria is the strongest known surrogate for progression to kidney failure. Complement pathway activation is a recognised driver of inflammation and tissue injury in the disease, providing the rationale for targeting complement component 5.
Study design
In this phase 2, 36-week, double-blind study, adult patients with IgA nephropathy and urine protein at least 1 g/24 hours were randomized 2:1 to subcutaneous cemdisiran 600 mg or placebo every 4 weeks alongside standard of care. The primary endpoint was percentage change from baseline at week 32 in 24-hour urine protein-to-creatinine ratio (UPCR); additional endpoints included spot UPCR, serum C5 level and safety.
Key findings
Thirty-one patients were randomized (cemdisiran n=22, placebo n=9). At week 32 the placebo-adjusted geometric mean change in 24-hour UPCR was -37.4%, with spot UPCR consistent at -45.8%. Mean change in serum C5 from baseline at week 32 was -98.7% with cemdisiran versus +25.2% with placebo, confirming near-complete target engagement.
Safety
Over 36 weeks most adverse events were mild or moderate and transient. The most common adverse event with cemdisiran was injection-site reaction, occurring in 41% of treated patients.
Clinical implications
The trial establishes proof of mechanism for hepatic C5 knockdown in IgA nephropathy but is far too small and too short to inform treatment decisions. Its practical significance is in supporting phase 3 development and in reinforcing complement as a tractable target in a disease where several complement-directed agents are now advancing in parallel.
Category
Research
Source
Clinical Journal of the American Society of Nephrology
More from ASNRT News
Browse the latest news, society announcements, KDIGO guideline updates, and AJNT issue releases on the ASNRT newsroom.