A Sequential Phase 2/3 Study of APL2 in Patients With Focal Segmental Glomerulosclerosis
- Registration Number
- NCT07213960
- Lead Sponsor
- Apellis Pharmaceuticals, Inc.
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 270
-
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
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Estimated glomerular filtration rate (eGFR) ≥25 mL/min/1.73 m2
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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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Phase 2 - APL2 APL2 Sub-cutaneous infusions of APL2 (1080 mg / 20mL) twice weekly Phase 3 - APL2 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) Phase 3 - Placebo Placebo Subcutaneous infusions of a sterile solution, twice-weekly, and equivalent in volume to the active arm based on participant's age and weight
- Primary Outcome Measures
Name Time Method Phase 2: Evaluate the efficacy of APL2 in terms of change from baseline in log-transformed urine protein to creatinine ratio (uPCR) Baseline to Week 12 Change from Baseline in Log-Transformed uPCR will be based on triplicate first morning urine (FMU)
Phase 3: Change from baseline in log-transformed urine protein to creatinine ratio (uPCR) Baseline to Week 52 Change from baseline in log-transformed uPCR will be based on triplicate first morning urine (FMU)
- Secondary Outcome Measures
Name Time Method 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 Change From Baseline in Log-Transformed uACR will be based on first morning urine (FMU)
Phase 3: Slope of estimated Glomerular Filtration Rate (eGFR) Baseline to Week 104 The annualized eGFR slope
Phase 3: Change from Baseline in log-transformed urine protein to creatinine ratio (uPCR) Baseline to Week 104 Change from baseline in log-transformed uPCR will be based on triplicate first morning urine (FMU)
Phase 3: Proportion of participants achieving Complete Remission Week 104 Complete Remission is defined as participants who have achieved uPCR \<0.3 g/g
Trial Locations
- Locations (2)
Investigator Site 1
🇺🇸Chicago, Illinois, United States
Investigator Site 2
🇺🇸New York, New York, United States
Investigator Site 1🇺🇸Chicago, Illinois, United States