Real‑World Effectiveness and Safety of Pegcetacoplan in Patients with C3 Glomerulopathy or Primary Immune Complex MPGN: Multi‑Country Observational Study

Primary objective: To evaluate the real‑world clinical effectiveness of pegcetacoplan in patients diagnosed with C3 Glomerulopathy or primary immune complex membranoproliferative glomerulonephritis, thereby informing its therapeutic impact in routine practice.

Secondary objectives:

• Characterize baseline demographics, clinical features (including biomarkers), and concomitant medication use among individuals initiating therapy.
• Assess renal function trends, disease progression, and biomarker dynamics before and during treatment.
• Examine renal outcomes, disease trajectory, and biomarker changes in subgroups experiencing alterations in treatment patterns.
• Determine incidence rates of key safety events occurring during exposure to the study drug.
• Capture patient‑reported outcomes throughout the treatment period.
• Analyze healthcare resource utilization related to C3G and primary IC‑MPGN before and while on therapy.

The trial enrolled a total of 60 participants diagnosed with either primary immune complex membranoproliferative glomerulonephritis or C3 Glomerulopathy. Both female and male patients were included, encompassing a broad age spectrum from early childhood through adulthood as indicated by age‑range codes 2, 3, and 4. All subjects were classified as patients and were considered a vulnerable population. Eligibility required that participants had already received or were planning to receive pegcetacoplan for the indicated conditions and that a signed, dated informed consent (or, for minors, consent from a legally authorized representative with assent as appropriate) was obtained. No additional lifestyle restrictions such as specific diet or physical activity requirements were specified.

The study is a prospective, multi‑country, low‑interventional observational trial evaluating the real‑world effectiveness and safety of pegcetacoplan in patients diagnosed with C3 glomerulopathy or primary immune complex membranoproliferative glomerulonephritis. Participants are enrolled after a screening (inclusion) visit confirming eligibility and receipt of a signed informed consent form. Baseline data are collected at the start of pegcetacoplan therapy, followed by scheduled assessments at 1, 3, 6, and 12 months and subsequently every 6 months for the duration of the study. The primary endpoint—achievement of a urine protein‑to‑creatinine ratio (UPCR) < 1 g/g at 6 months—is measured alongside a comprehensive set of secondary outcomes including proteinuria reductions, renal function changes, biomarker trends, adverse event rates, and health‑resource utilization. Participant involvement may extend up to the estimated study end date of 30 June 2032, resulting in a maximum follow‑up of approximately five years. Early termination may occur if the investigator discontinues pegcetacoplan, if the participant withdraws consent, is lost to follow‑up, or experiences a serious adverse event that precludes continued observation. All data are recorded in accordance with the protocol while treatment decisions remain at the discretion of the treating physician.

The investigational product is ASPAVELI 1080 mg solution for infusion, containing the active substance pegcetacoplan. The formulation is a sterile solution for infusion administered by the subcutaneous route at a dose of 308.6 mg per administration. The dosing schedule, including the interval between doses, follows the protocol‑specified regimen for each participant.

No comparator, placebo, or standard‑of‑care therapy is detailed in the provided information; therefore, no non‑experimental treatments are described for this study.

Administration of the investigational product is performed under clinical supervision to ensure accurate dosing. Compliance monitoring includes documentation of each administered dose in the study record and verification of the subcutaneous injection technique by qualified personnel.

Efficacy assessment focuses on proteinuria reduction, renal function preservation, and related clinical outcomes. The primary efficacy parameter is the proportion of participants achieving a urine protein‑to‑creatinine ratio (UPCR) of less than 1 g/g at 6 months after initiation of pegcetacoplan. Secondary efficacy parameters include ≥50 % reduction in proteinuria, achievement of UPCR thresholds of <1 g/g, <0.5 g/g (or <0.2 g/g for participants younger than 18 years), resolution of nephrotic syndrome, sustained doubling of serum creatinine, progression to CKD stage 5 or end‑stage renal disease, receipt of a new kidney transplant, initiation of maintenance dialysis for at least 4 weeks, and death attributable to kidney failure. Additional secondary measures comprise longitudinal changes in UPCR and estimated glomerular filtration rate (eGFR) at 1, 3, 6, and 12 months and subsequently every 6 months, the proportion of participants with an annualised eGFR decline ≤5 mL/min/1.73 m², changes in laboratory parameters, kidney biopsy findings, and serial biomarker levels, as well as patient‑reported outcomes such as FACIT‑Fatigue, WPAI, and TSQM scores.

Proteinuria and eGFR are quantified using standard laboratory assays on spot urine samples and serum creatinine measurements, respectively, with eGFR calculated from creatinine and height where applicable. UPCR values are collected at baseline and at each scheduled visit (1, 3, 6, 12 months, then every 6 months). eGFR is assessed at the same intervals and additionally on an annual basis. Kidney biopsy specimens are evaluated for C3c staining and other histologic changes at baseline and during follow‑up as clinically indicated. Patient‑reported outcomes are captured using validated questionnaires (FACIT‑Fatigue, WPAI, TSQM) at baseline, study enrolment, and every 6 months thereafter. Incidence rates of serious adverse events and adverse events of special interest are calculated on an exposure‑adjusted basis throughout the treatment period. Data analyses will employ descriptive statistics for proportions achieving predefined thresholds, time‑to‑event analyses for clinical outcomes, and longitudinal mixed‑effects models to evaluate changes over time.