FSGS
Conditions
Keywords
Glomerulosclerosis, Focal Segmental, Child, Adult, Peptides, Cyclic, Complement Inactivator Proteins
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.
Interventions
DRUGAPL2
Complement (C3) Inhibitor
OTHERPlacebo
Sterile solution of equal volume to active arm
Sponsors
Apellis Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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: 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 |
| Phase 3: Slope of estimated Glomerular Filtration Rate (eGFR) | Baseline to Week 104 | The annualized eGFR slope |
Countries
United States
Contacts
CONTACTApellis Clinical Trial Information Line
Outcome results
None listed