Advancing Treatment for C3G; Targeting the Complement System for Personalized Kidney Care - Episode 7
Ongoing Clinical Trials in C3G: Safety, Efficacy, and Future Directions
Panelists discuss how improved understanding of C3 glomerulopathy (C3G) pathobiology has led to multiple clinical trials targeting complement pathways, with considerations for efficacy measurement through proteinuria reduction and kidney biopsies, while emphasizing the importance of vaccination and patient education to manage safety concerns associated with complement inhibitors.
Video content above is prompted by the following:
Clinical Update: C3G Treatment Options and Ongoing Trials
Key Points for Physicians
Current Clinical Trials in C3G
- Multiple clinical trials are investigating complement pathway inhibitors targeting different components:
- C5a receptor antagonism (avacopan)
- C3 and C3b inhibition (pegcetacoplan)
- Anti-factor D and anti-factor B agents
- Phase 3 trials include repeat kidney biopsies as an important measure of treatment efficacy
Evaluating Treatment Efficacy
- Current biomarkers for monitoring response remain limited:
- Proteinuria/albuminuria
- Serum creatinine/estimated glomerular filtration rate
- Hematuria
- C3 normalization (applicable only in patients with low baseline C3)
- Repeat kidney biopsy is considered valuable for directly assessing glomerular health and complement activation at the tissue level
- Several experimental biomarkers (urinary C5b-9, inflammatory markers) show promise but are not yet ready for clinical practice
Safety Considerations
- Primary safety concern: Increased susceptibility to encapsulated bacterial infections (Neisseria, Haemophilus, Streptococci)
- Mandatory vaccination against Neisseria meningitidis prior to treatment
- Some protocols may require prophylactic antibiotics depending on regional guidelines
- Patient education about infection risk and warning signs is critical
- Medical identification (cards, bracelets) indicating complement inhibitor use is recommended
Practical Implementation Challenges
- Most nephrologists (>95%) have limited experience with complement inhibitors
- Specialized glomerular disease clinics may be better equipped to manage patients on these therapies
- Pediatric patients present unique challenges regarding education and infection risk
- Vaccine hesitancy issues may complicate treatment eligibility
- Current phase 3 data suggests theoretical infection concerns may not be as pronounced as initially feared
This emerging class of targeted therapies represents a significant paradigm shift in C3G management, requiring nephrologists to develop new expertise in complement biology and patient monitoring.
