A Sequential Phase 2/3 Study of APL2 in Patients With Focal Segmental Glomerulosclerosis

A Sequential Phase 2/3, Single-Arm, Open-Label Study in Adults Followed by a Randomized, Placebo-Controlled, Double-Blind, Multicenter Study to Evaluate the Efficacy and Safety of APL2 in Adults and Adolescents With Focal Segmental Glomerulosclerosis

This is a sequential phase 2/3 study to evaluate the efficacy and safety of twice-weekly subcutaneous (SC) infusions of APL2 in patients diagnosed with FSGS. The initial phase 2 portion is a single-arm, open-label study in adults diagnosed with FSGS. Phase 2 will commence prior to randomizing for phase 3. The phase 3 portion of the study is a randomized, placebo-controlled, double-blinded, multicenter study in adults and adolescents diagnosed with FSGS.

Study Overview

• Status: Suspended
• Conditions: FSGS
• Intervention / Treatment: Other: Placebo; Drug: APL2

• Study Type: Interventional
• Enrollment (Estimated): 270
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60643
      • Investigator Site 1
  • New York
    • New York, New York, United States, 10032
      • Investigator Site 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age

  • Phase 2: adults aged ≥18 years
  • Phase 3: adults aged ≥18 years; if and where approved, adolescents (aged 12--17 years) at the time of signing the informed consent and assent form
• Weight ≥30 kg and ≤100 kg at screening

• FSGS diagnosis

  • Phase 2: primary, genetic, or undetermined FSGS diagnosed by kidney biopsy
  • Phase 3: primary, genetic, or undetermined FSGS diagnosed by kidney biopsy or by recognized podocyte genetic mutation
• At least 1.5 g/day of proteinuria on a screening 24-hour urine collection and a uPCR of at least 1.5 g/g in at least 2 FMU samples collected during screening
• Estimated glomerular filtration rate (eGFR) ≥25 mL/min/1.73 m2
• Stable regimen for FSGS treatment for at least 12 weeks prior to randomization, with no planned or anticipated adjustments or dose changes to the stable treatment regimen

Exclusion Criteria:

• Previous exposure to APL2
• Evidence of improving kidney disease in the 8 weeks prior to screening or during the screening period according to available data
• FSGS secondary to another condition (eg, infectious, diabetic, drug-induced, obesity, prematurity, sickle-cell, vesicoureteral reflux, congenital anomalies of the kidney, and urinary tract)
• Type 1 or uncontrolled (HbA1C ≥8%) type 2 diabetes mellitus
• History of kidney transplant
• Current or prior diagnosis of HIV, hepatitis B, or hepatitis C infection or positive serology or viral load during screening that is indicative of active infection with any of these viruses
• Hypersensitivity to APL2 or to any of the excipients
• Significant other kidney disease that would, in the opinion of the investigator, confound interpretation of study results
• Use of rituximab, belimumab, or any approved or investigational anticomplement therapy within 5 half-lives of that product prior to the screening period

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 2 - APL2; Sub-cutaneous infusions of APL2 (1080 mg / 20mL) twice weekly	Drug: APL2; Complement (C3) Inhibitor
Experimental: Phase 3 - APL2; Adults: Sub-cutaneous infusions of APL2 (1080 mg / 20mL) twice weekly Adolescents: ≥50 Kg: Sub-cutaneous infusions of APL2 (1080 mg / 20mL) twice weekly 35 to <50kg: First sub-cutaneous infusion of 648mg (12 mL) followed by 810mg (15 mL) every infusion thereafter (i.e. twice weekly) 30 to <35kg: First & Second sub-cutaneous infusion of 540mg (10mL) followed by 648mg (12 mL) every infusion thereafter (twice weekly)	Drug: APL2; Complement (C3) Inhibitor
Placebo Comparator: Phase 3 - Placebo; Subcutaneous infusions of a sterile solution, twice-weekly, and equivalent in volume to the active arm based on participant's age and weight	Other: Placebo; Sterile solution of equal volume to active arm

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 2: Evaluate the efficacy of APL2 in terms of change from baseline in log-transformed urine protein to creatinine ratio (uPCR)	Change from Baseline in Log-Transformed uPCR will be based on triplicate first morning urine (FMU)	Baseline to Week 12
Phase 3: Change from baseline in log-transformed urine protein to creatinine ratio (uPCR)	Change from baseline in log-transformed uPCR will be based on triplicate first morning urine (FMU)	Baseline to Week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 2: Evaluate the efficacy of APL2 in terms of change from baseline in log-transformed urine albumin to creatinine ratio (uACR)	Change From Baseline in Log-Transformed uACR will be based on first morning urine (FMU)	Baseline to Week 12
Phase 3: Change from Baseline in log-transformed urine protein to creatinine ratio (uPCR)	Change from baseline in log-transformed uPCR will be based on triplicate first morning urine (FMU)	Baseline to Week 104
Phase 3: Proportion of participants achieving Complete Remission	Complete Remission is defined as participants who have achieved uPCR <0.3 g/g	Week 104
Phase 3: Slope of estimated Glomerular Filtration Rate (eGFR)	The annualized eGFR slope	Baseline to Week 104

Collaborators and Investigators

• Sponsor: Apellis Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2026
• Primary Completion (Estimated): October 1, 2029
• Study Completion (Estimated): December 1, 2029

Study Registration Dates

• First Submitted: September 15, 2025
• First Submitted That Met QC Criteria: October 2, 2025
• First Posted (Actual): October 9, 2025

Study Record Updates

• Last Update Posted (Actual): June 22, 2026
• Last Update Submitted That Met QC Criteria: June 17, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Child; Adult; Peptides; Glomerulosclerosis; Cyclic; Focal Segmental; Complement Inactivator Proteins
• Other Study ID Numbers: APL2-FSG-319

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No