Phase II Study Assessing Safety and Efficacy of APL-2 in Glomerulopathies

Study Overview
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Brief Summary
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This is a Phase II trial assessing the safety and preliminary efficacy of daily APL-2 subcutaneous infusion administered for 16 weeks with a 6 month safety follow up, in patients with glomerulopathies

Official Title
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A Phase 2 Study to Evaluate the Safety and Biologic Activity of APL- 2 in Patients With IgA Nephropathy, Lupus Nephritis, Primary Membranous Nephropathy, or C3 Glomerulopathy (C3 Glomerulonephritis and Dense Deposit Disease)

Conditions
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IgA Nephropathy, Lupus Nephritis, Membranous Nephropathy, C3 Glomerulonephritis, Dense Deposit Disease

Intervention / Treatment
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* Drug: APL-2


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients of at least 18 years of age at screening (16 years of age for C3G), able to provide written informed consent, and able to understand and comply with all scheduled procedures and other requirements of the study by the opinion of Principal Investigator (PI) Patients must have a diagnosis of IgAN, LN, Primary MN, or C3G confirmed by renal biopsy and required measurements performed prior to study participation IgAN: Prior biopsy results for C3 and C4d staining should be made available LN: Diagnostic biopsy showing proliferative focal, diffuse, or membranous lesions (Class III, IV or V, respectively) by renal biopsy. Subject should have either a biopsy in the last 6 months, or evidence of disease activity (nephritic changes on urinalysis or nephrotic changes) Primary MN: PLA2R positive titer plus nephrotic range proteinuria (defined as uPCR >2350 mg/g) C3G plus one of the following: Low serum C3 level or historical renal biopsy within the last 3 years Have proteinuria >750 mg/g (calculated by uPCR on 24 hour urine collection) collected during the first screening visit (Visit 3a). eGFR≥30mL/min/1.73 m2 calculated by CKD-EPI creatinine equation at screening visit 3a and currently not on dialysis Must have stable or worsening renal disease, on stable and optimized treatment, in the opinion of the PI, for at least 2 months prior to the first dose of APL-2 (Visit 4); treatments may include, but are not limited to, immunosuppressive agents, anti-hypertensives and/or anti-proteinurics. Willing to receive vaccinations against Neisseria meningitidis at least 2 weeks prior to dosing on Day 1 with a booster on Day 56 (for both vaccinations) and Pneumococcal and Hib vaccines at least 2 weeks prior to dosing on Day 1. Exclusion Criteria: Absolute neutrophil count <1000 cells/mm3 at screening Visits 3a and 3b ALT or AST >3.0 x the upper limit of normal at screening Visits 3a and 3b Previous treatment with APL-2 History of solid organ transplant Diagnosis of human immunodeficiency virus (HIV), hepatitis B, or hepatitis C infection, or positive serology at screening Visits 3a and 3b (previous HBV or HCV diagnosis cleared by treatment is allowed) Renal disease secondary to another condition (e.g. infection, malignancy, monoclonal gammopathy, or a medication) Presence or suspicion of active bacterial or viral infection or severe recurrent bacterial infections Participation in any other investigational drug trial or exposure to other investigational agent, device, or procedure within 30 days prior to screening period Unwillingness to receive or intolerant of SC infusions of study medication or known allergy to ingredients in APL-2.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: APL-2<br>Open Label, Study Drug, APL-2 | Drug: APL-2<br>* APL-2 administered as a daily subcutaneous infusion for 48 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proteinuria | Proteinuria reduction from baseline to Week 48, based on urinary protein-to-creatinine ratio (uPCR). | 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes of Disease Specific Biomarkers (serum C3 levels, AH50 and C3a concentrations, serum albumin levels) |  | Week 48 | 
| Complete clinical remission defined as normalization of proteinuria as defined by <200 mg/g uPCR at Week 48 |  | Week 48 | 
| Stabilization or improvement in estimated Glomerular Filtration Rate (eGFR) from baseline to Week 48 |  | Week 48 |