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.

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