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

NCT07213960 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: APL2-FSG-319
• Study Type: interventional
• Target: 270
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

FSGS

Keywords

Glomerulosclerosis; Focal Segmental; Child; Adult; Peptides; Cyclic; Complement Inactivator Proteins

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (4)

• Phase 2: Evaluate the efficacy of APL2 in terms of change from baseline in log-transformed urine albumin to creatinine ratio (uACR)

  Baseline to Week 12

• Phase 3: Change from Baseline in log-transformed urine protein to creatinine ratio (uPCR)

  Baseline to Week 104

• Phase 3: Proportion of participants achieving Complete Remission

  Week 104

• Phase 3: Slope of estimated Glomerular Filtration Rate (eGFR)

  Baseline to Week 104

Study Arms (3)

Phase 2 - APL2

EXPERIMENTAL

Sub-cutaneous infusions of APL2 (1080 mg / 20mL) twice weekly

Drug: APL2

Phase 3 - APL2

EXPERIMENTAL

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

Phase 3 - Placebo

PLACEBO COMPARATOR

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

Interventions

APL2 DRUG

Complement (C3) Inhibitor

Phase 2 - APL2; Phase 3 - APL2

Placebo OTHER

Sterile solution of equal volume to active arm

Phase 3 - Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Apellis Pharmaceuticals, Inc.: lead

Study Sites (2)

Investigator Site 1

Chicago, Illinois, 60643, United States

Location

Investigator Site 2

New York, New York, 10032, United States

Location

Central Study Contacts

Apellis Clinical Trial Information Line

CONTACT

833-284-6361; clinicaltrials@apellis.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 15, 2025
• First Posted: October 9, 2025
• Study Start: December 1, 2025
• Primary Completion (Estimated): October 1, 2029
• Study Completion (Estimated): December 1, 2029
• Last Updated: October 9, 2025

Record last verified: 2025-10

Locations

US (2)