Safety Study of IgAN, LN, MN, & C3 Glomerulopathy Including Dense Deposit Disease Treated With OMS721

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and tolerability of OMS721 (narsoplimab) in subjects with Immunoglobulin A Nephropathy (IgAN), Lupus Nephritis (LN), Membranous Nephropathy (MN), and Complement Component 3 (C3) Glomerulopathy including Dense Deposit Disease. The study will also evaluate Pharmacokinetics (PK), Pharmacodynamics (PD), anti-drug antibody response (ADA), and neutralizing antibodies (NAb) of OMS721 when administered intravenously and when administered both intravenously and subcutaneously in subjects of Asian descent with IgA Nephropathy.

Official Title
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A Phase 2 Study to Evaluate the Safety and Effect on Proteinuria of OMS721 in Subjects With IgA Nephropathy, Lupus Nephritis, Membranous Nephropathy, or C3 Glomerulopathy Including Dense Deposit Disease

Conditions
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IgAN, Lupus Nephritis, MN, C3 Glomerulopathy

Intervention / Treatment
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* Biological: OMS721 (narsoplimab)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: At least 18 years of age at screening and competent to provide informed consent; For Cohort 4 only, participants are of Asian descent Have a diagnosis of one of the following: IgAN on kidney biopsy LN, MN and C3 Glomerulopathy including Dense Deposit Disease on kidney biopsy and 24-hour Urine Protein Excretion (UPE) > 1000 mg/24 hours (for Cohort 1 only) IgAN diagnosis is confirmed by biopsy within 8 years of screening for Asian descent (for Cohort 4 only) For Cohort 4 only: subjects with IgAN of Asian descent, documented history of 24-hour UPE > 1 g within 6 months prior to Screening or Urine Protein-Creatinine Ratio (uPCR) > 0.75 by spot urine at screening Screening Estimated Glomerular Filtration Rate (eGFR) >= 30 mL/min/1.73 m^2 Are on physician-directed, stable, optimized treatment with angiotensin converting enzyme inhibitors (ACEI) and/or angiotensin receptor blockers (ARB) and have a systolic blood pressure of < 150 mmHg and a diastolic blood pressure of < 90 mmHg at rest Exclusion Criteria: Have a hemoglobin less than 9.0 g/dL Have a platelet count =less than 100,000/mm^3 Have an absolute neutrophil count <500 cells/mm^3 Have an Alanine aminotransferase (ALT) or Aspartate Aminotransferase (AST) greater than 5.0 x the upper limit of normal (ULN) Have systemic manifestations of Henoch-Schonlein purpura within 2 years prior to Screening Have used: belimumab, eculizumab, or rituximab within 6 months prior to Screening Have a history of renal transplant History of human immunodeficiency virus (HIV), evidence of immune suppression, active hepatitis C virus (HCV) infection (subjects with positive anti-HCV antibody Have a malignancy except for adequately treated and cured basal or squamous cell skin cancer, curatively treated in situ disease, or other cancer from which the patient has been disease-free for 5 years or more

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
Interventional Model Description: Cohort 2 and 3 subjects are randomized in a 1:1 fashion during the first 12 weeks of treatment. Cohort 1 and 4 are non-randomized.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: OMS721 (narsoplimab)<br>Administration of OMS721 (narsoplimab) | Biological: OMS721 (narsoplimab)<br>* Biological: OMS721 (narsoplimab)<br>* Other names: narsoplimab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cohort 1-3: Proportion of IgAN, LN, MN, C3 Glomerulopathy subjects with treatment related adverse events (AE). |  | up to 104 weeks | 
| Cohort 4: Proportion of IgAN patients of Asian descent with treatment related AEs. |  | 38 weeks | 
| Cohort 4: Change from baseline in serum and urine complement component levels. |  | 38 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cohort 1-3: Change from baseline in serum narsoplimab concentrations. |  | up to 104 weeks | 
| Cohort 4: Change from baseline in serum narsoplimab concentrations. |  | 38 weeks | 
| Cohort1-3: Change from baseline in proteinuria. |  | up to 104 weeks | 
| Cohort1-3: Change from baseline in urine albumin/creatinine ratio. |  | up to 104 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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IgAN, Lupus Nephritis, MN, C3 Glomerulopathy