Phase III Study Assessing the Efficacy and Safety of Pegcetacoplan in Patients With C3 Glomerulopathy or Immune-Complex Membranoproliferative Glomerulonephritis

Inclusion Criteria

• Aged at least 18 years; where approved, adolescents (aged 12-17 years) weighing at least 30 kg may also be enrolled.
• A diagnosis of primary C3G or IC-MPGN (with or without previous renal transplant).
• Evidence of active renal disease, based on one or more of the following:
• In adults or adolescents with a baseline renal biopsy (either one collected during screening or a historic biopsy collected within 28 weeks prior to randomization), at least 2+ C3c staining on the baseline renal biopsy.
• In adolescents not providing a baseline renal biopsy, at least one of the following:
• Plasma sC5b-9 level above the upper limit of normal during screening
• Serum C3 below the LLN during screening
• Presence of an active urine sediment during screening, as evidenced by hematuria with at least 5 red blood cells (RBCs) per high-power field (HPF) and/or red blood cell casts on local or central microscopic analysis of urine.
• Presence of C3 nephritic factor within 6 months of screening, based on central laboratory results or medical history.
• No more than 50% global glomerulosclerosis or interstitial fibrosis on the baseline biopsy for adult participants or adolescent participants providing a baseline biopsy.
• At least 1 g/day of proteinuria on a screening 24-hour urine collection and a uPCR of at least 1000 mg/g in at least 2 first-morning spot urine samples collected during screening.
• eGFR ≥30 mL/min/1.73 m2 calculated by the Chronic Kidney Disease-Epidemiology Collaboration creatinine equation for adults or the Bedside Schwartz equation for adolescents.
• Stable regimen for C3G/IC-MPGN treatment, as described below:
• Angiotensin-converting enzyme inhibitor/, angiotensin receptor blocker, and/or sodium-glucose cotransporter-2 inhibitor therapy that is stable and optimized, in the opinion of the investigator, for at least 12 weeks prior to randomization
• Stable doses of other medications that can affect proteinuria (eg, steroids, mycophenolate mofetil, and/or other allowed immunosuppressants that the participant is receiving for treatment of C3G or IC-MPGN) for at least 12 weeks prior to the baseline renal biopsy and randomization.
• If a participant is on prednisone (or other systemic corticosteroid) for C3G or IC-MPGN treatment, the dosage is stable and no higher than 20 mg/day (or equivalent dosage of a corticosteroid other than prednisone) for at least 12 weeks prior to randomization.
• Have received vaccinations against S pneumoniae, N meningitidis (types A, C, W, Y, and B), and H influenzae (type B) within 5 years prior to randomization or agree to receive vaccinations during screening.

Exclusion Criteria

• Previous exposure to pegcetacoplan.
• C3G/IC-MPGN secondary to another condition (eg, infection, malignancy, monoclonal gammopathy, a systemic autoimmune disease such as systemic lupus erythematosus, chronic antibody-mediated rejection, or a medication), in the opinion of the investigator.
• Current or prior diagnosis of human immunodeficiency virus (HIV), hepatitis B (HBV), or hepatitis C (HCV) infection or positive serology during screening that is indicative of infection with any of these viruses.
• Body weight greater than 100 kg at screening.
• Hypersensitivity to pegcetacoplan or to any of the excipients.
• History of meningococcal disease.
• Malignancy, except for the following:
• Cured basal or squamous cell skin cancer
• Curatively treated in situ disease
• Malignancy-free and off treatment for ≥5 years
• Severe infection (eg, requiring IV antibiotic therapy) within 14 days prior to the first dose of pegcetacoplan.
• An absolute neutrophil count <1000 cells/mm3 at screening.
• Use of rituximab, belimumab, or any approved or investigational anticomplement therapy other than pegcetacoplan within 5 half-lives of that product prior to the screening period.
• Female participants who are pregnant or who are currently breastfeeding and are unwilling to discontin