Evaluation of Pegcetacoplan for Reducing Proteinuria in Adults and Adolescents with Focal Segmental Glomerulosclerosis

The primary objective is to evaluate the efficacy of twice‑weekly subcutaneous Pegcetacoplan in reducing proteinuria in adults with Focal segmental glomerulosclerosis during the Phase 2 segment, and to compare this reduction with placebo in the Phase 3 segment.

Secondary objectives include:

• Assessment of the effect on albuminuria (Phase 2).
• Evaluation of complete remission of proteinuria and change in eGFR (Phase 3).

The trial enrolled a total of 141 participants diagnosed with focal segmental glomerulosclerosis. Eligible individuals were adults aged ≥ 18 years, with inclusion of adolescents aged 12–17 years in the Phase 3 cohort where regulatory approval permitted. Both male and female subjects were represented, and the population included participants classified as vulnerable. Inclusion required a body weight between 30 kg and 100 kg, an estimated glomerular filtration rate of at least 25 mL/min/1.73 m², and a stable regimen for FSGS treatment for a minimum of 12 weeks prior to dosing. Participants also needed to demonstrate persistent proteinuria of ≥1.5 g/day (or a urine protein‑creatinine ratio ≥1.5 g/g in at least two screening samples). Selection was based on confirmed primary, genetic, or otherwise undetermined FSGS by kidney biopsy (or recognized podocyte genetic mutation in Phase 3). No specific lifestyle restrictions such as diet or physical activity were stipulated in the eligibility criteria.

The investigation consists of a sequential Phase 2/3 program evaluating twice‑weekly subcutaneous administrations of pegcetacoplan versus matching placebo in participants with Focal segmental glomerulosclerosis. Phase 2 is a single‑arm, open‑label study enrolling adults (≥18 years) who meet predefined inclusion criteria; efficacy and safety data are collected before the initiation of Phase 3. Phase 3 is a multicenter, randomized, double‑blind, placebo‑controlled trial that includes adults and, where approved, adolescents (12–17 years). The overall trial period extends from the projected recruitment start on 15 September 2026 to an estimated completion date of 31 December 2029.

Study visits are scheduled as follows: a screening visit to confirm eligibility, baseline assessments on Day 1 of dosing, regular follow‑up visits (typically every 2 weeks) to monitor urine protein/creatinine ratios, renal function, and adverse events, and a final end‑of‑study visit after the designated treatment period. Participants remain in the study from the screening visit through the end‑of‑study visit, completing all required assessments during this interval.

The investigational product, ASPAVELI 1080 mg solution for infusion, contains the active substance pegcetacoplan and is supplied as a sterile solution for subcutaneous administration. Each dose delivers 1080 mg of pegcetacoplan in a single-use vial. Participants receive the medication twice weekly by subcutaneous injection throughout the treatment period.

The matching placebo consists of a sterile solution of 10 mM acetate buffer (pH 5.0) with 4.1 % sorbitol, provided in a single-use glass vial. The placebo is administered subcutaneously on the same twice‑weekly schedule as the active product to maintain blinding.

Dosing occurs on non‑consecutive days each week, with each administration performed by qualified personnel following aseptic technique. Compliance is monitored through dosing logs, vial counts, and electronic records of injection times. Any missed or delayed doses are documented and reported according to protocol‑specified procedures.

The efficacy of pegcetacoplan will be evaluated in participants with focal segmental glomerulosclerosis by assessing changes from baseline in quantitative urinary biomarkers. The primary efficacy endpoint for both the phase 2 single‑arm portion and the phase 3 randomized, placebo‑controlled portion is the change in log‑transformed urine protein‑to‑creatinine ratio (uPCR). Secondary efficacy assessments include the change from baseline in log‑transformed urine albumin‑to‑creatinine ratio (uACR), the proportion of participants achieving complete remission of proteinuria, and the slope of estimated glomerular filtration rate (eGFR) over the treatment period.

Urine protein and albumin concentrations will be measured using laboratory assays performed on spot urine samples collected at predefined study visits. Creatinine concentrations will be determined in parallel to calculate the respective ratios. eGFR will be estimated from serum creatinine using a validated equation at the same time points. All efficacy parameters will be analyzed by comparing the baseline values to values obtained during treatment, applying log‑transformation where specified, and using appropriate statistical methods to assess differences between the pegcetacoplan and placebo groups in phase 3.