C3 Glomerulopathy (C3G) Clinical Trials and Treatments

C3 glomerulopathy results from dysregulation of the alternative complement pathway, a branch of the innate immune system that normally provides rapid defense against pathogens. In C3G, genetic mutations (in complement factor H, complement factor I, C3, complement factor B, or CFHR genes) or acquired autoantibodies (C3 nephritic factors, anti-factor H antibodies) cause the alternative pathway to remain constitutively active, generating excessive C3 convertase activity. This leads to continuous C3 cleavage and deposition of C3 breakdown products (C3b, iC3b, C3dg) in the glomerular basement membrane and mesangium.

The most common symptoms of C3 Glomerulopathy include Blood in the urine (hematuria), sometimes visible, often detected on urinalysis, Excess protein in the urine (proteinuria) causing foamy urine, Swelling in the face, hands, and legs (edema) from protein loss, High blood pressure that may be difficult to control, Fatigue and general malaise as kidney function declines, among others. C3 Glomerulopathy affects approximately 1 to 2 new cases per million per year; approximately 5,000 to 10,000 affected individuals in the U.S.. Symptoms can range from mild to severe and may vary between individuals.

Trial Friend lists all active clinical trials for C3 Glomerulopathy from ClinicalTrials.gov, with eligibility criteria translated into plain English. Patients can filter by trial phase and recruitment status, search by location, and use the Match Me tool to score trials against their profile. The approval of two complement-targeted therapies in 2025 has transformed the C3G treatment landscape, but clinical questions remain open. Trials are comparing factor B inhibition versus C3 inhibition, studying combination complement blockade, evaluating treatment in post-transplant C3G recurrence, and investigating whether early complement-targeted therapy can prevent progression to end-stage kidney disease.

Two FDA-approved targeted therapies are now available for C3 glomerulopathy. Iptacopan (Fabhalta), approved March 20, 2025, is an oral pill that blocks the alternative complement pathway at an upstream step (the factor B protein) and reduced protein in urine by about 35 percent in pivotal trials. Pegcetacoplan (Empaveli), approved July 28, 2025, is a subcutaneous (under-the-skin) injection that blocks the central amplification step of the complement cascade (the C3 protein itself) and reduced protein in urine by 68 percent in the Phase 3 VALIANT trial — the largest study ever conducted in C3G. Eculizumab (Soliris) and ravulizumab (Ultomiris) are older complement drugs that target a different step (C5) and are sometimes used off-label. ACE inhibitors and ARBs remain foundational for proteinuria reduction. Always consult a nephrologist about whether iptacopan or pegcetacoplan is more appropriate for your biopsy findings, complement profile, and ability to keep up with the required vaccinations.

C3 glomerulopathy results from dysregulation of the alternative complement pathway, a branch of your immune system that normally helps fight infections quickly. Genetic variants in complement factor H (CFH), complement factor I (CFI), C3, complement factor B (CFB), or the related CFHR genes (the CFHR3-CFHR1 deletion is particularly common), or autoantibodies — antibodies your body mistakenly makes against itself, like C3 nephritic factor, anti-factor H, and anti-factor B — cause this pathway to remain stuck "on." The result is excessive activity that continuously cleaves the C3 protein and dumps breakdown products in the kidney's filtering units. The deposits trigger inflammation and progressive scarring. C3G has two subtypes that look different under a microscope: dense deposit disease (DDD), where deposits sit inside the kidney's basement membrane, and C3 glomerulonephritis (C3GN), where they sit in different layers. Roughly half of patients reach kidney failure within 10 years, and the disease frequently comes back after a kidney transplant.

Genetic and antibody testing is recommended for most C3G patients because it influences treatment choice and transplant planning. Comprehensive complement-pathway panels test for variants in CFH, CFI, C3, CFB, and the CFHR1 to CFHR5 genes — the CFHR3-CFHR1 deletion is particularly common in C3G. Antibody panels test for C3 nephritic factor (C3NeF), anti-factor H antibodies, and anti-factor B antibodies, which are present in roughly half of patients and may predict which complement therapy will work best. Identifying the specific genetic or antibody driver of your disease can guide whether factor B blockade (iptacopan) or C3 blockade (pegcetacoplan) makes more sense. The University of Iowa Molecular Otolaryngology and Renal Research Laboratories (MORL) operates the most comprehensive complement panel in the U.S.; Mayo Clinic, GeneDx, and PreventionGenetics also offer testing. Genetic counseling — meeting with a specialist who explains test results in plain English — is recommended for affected families.

Eligibility for C3 Glomerulopathy clinical trials depends on factors like age, diagnosis, treatment history, and overall health. Each trial sets its own inclusion and exclusion criteria. Trial Friend translates these requirements from medical language into plain English so patients can review them more easily. The Match Me tool can score your profile against active trials to help identify studies that may be a fit.

Participating in a C3 Glomerulopathy clinical trial typically involves scheduled visits, medical tests, and close monitoring by a research team. Depending on the study phase, you may receive an investigational treatment, a placebo, or the current standard of care. Trials may last from a few weeks to several years. Study participation is voluntary, and you can withdraw at any time.

C3 glomerulopathy clinical trials commonly exclude prior or current complement therapy with washouts of 3 to 6 months, because these drugs have long-lasting effects on the immune system. Trials also typically require encapsulated-bacteria vaccinations (meningococcal, pneumococcal, and Haemophilus influenzae type b — three families of bacteria that complement normally helps fight) at least 2 weeks before enrollment, because blocking complement raises the risk of these infections. Trial Friend's medication conflict checker scans each trial's exclusion criteria against common C3G medications including iptacopan (Fabhalta), pegcetacoplan (Empaveli), eculizumab (Soliris), ravulizumab (Ultomiris), ACE inhibitors, ARBs, corticosteroids, mycophenolate mofetil, rituximab, and cyclophosphamide. The checker flags the specific drug, the trial's exclusion language, and a confidence level so you can discuss timing, washout planning, and vaccination scheduling with your nephrologist.

Key questions to ask your nephrologist about C3G clinical trials: Was my biopsy classified as dense deposit disease (DDD) or C3 glomerulonephritis (C3GN)? Have we tested the genetic and antibody drivers of my disease — the complement gene panel (CFH, CFI, C3, CFB, CFHR genes) and the autoantibody panel (C3 nephritic factor, anti-factor H, anti-factor B)? Now that both iptacopan and pegcetacoplan are FDA-approved, which one is right for me, and why — blocking factor B upstream or blocking C3 in the middle of the cascade? Have I completed the meningococcal, pneumococcal, and Haemophilus type b vaccinations at least 2 weeks before starting complement therapy? If I have a kidney transplant or am being evaluated for one, what is my recurrence risk and how should complement-targeted therapy be timed around it?