Safety Study of of Intravenous CCL2-LPM in Patients With IgA Nephropathy

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety of several dose levels of CCL2-LPM in patients with IgA Nephropathy who have high levels of protein in the urine.

Detailed Description
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In spite of adequate blood pressure control and diet, 30 percent of patients with IgA nephropathy continue to secrete large amounts of protein in the urine and have a high likelihood of progressing to end-stage renal disease over 5-10 years and eventually requiring dialysis or kidney transplant. In IgA nephropathy, the injured kidney tissue secretes a messenger that recruits white blood cells (leukocytes) into the kidney. This messenger is the chemokine, CCL2. As a consequence CCL2 also is excreted into the urine and can be measured as evidence of inflammation in the kidney. This study evaluates the safety of a new potential therapy,CCL2-LPM (leukocyte population modulator), for IgA nephropathy. CCL2-LPM is composed of the messenger chemokine, CCL2, fused to an enzyme that inhibits protein production by the leukocytes and prevents the leukocytes from migrating into the kidney. The CCL2 end of the molecule targets only a small subset of leukocytes that have the corresponding receptor for CCL2 on the surface. After CCL2 binds to its receptor it is drawn inside the cell and carries the enzyme into the cell. The targeted cells are prevented from entering the kidney and causing further damage. Thus, CCL2-LPM may interrupt the ongoing cycle of inflammation that leads to end-stage renal disease.

Official Title
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A Dose-Escalating Phase I Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of Intravenous OPL-CCL2-LPM in Patients With IgA Nephropathy

Conditions
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IGA Nephropathy, Proteinuria

Intervention / Treatment
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* Biological: OPL-CCL2-LPM


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Biopsy proven IgA nephropathy GFR > 30 mL/min Urinary protein > 700 mg/day Stable serum creatinine Urine CCL2/creatinine > 250 pg/mg Stable doses of medications ACEI and/or ARB maximized to control hypertension and proteinuria Exclusion Criteria: Other causes of nephropathy Pregnant or nursing females Prednisone > 10 mg/day Other prohibited medications BP > 140/90 BMI > 35 Concurrent infection requiring treatment Clinical significant concurrent medical conditions Known allergy or sensitivity to formulation ingredients

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

| Intervention/Treatment |
| --- |
|Biological: OPL-CCL2-LPM|CCL2-LPM intravenous 0.001 mg/kg, 0.01 mg/kg, 0.05 mg/kg, 0.1 mg/kg, 0.5 mg/kg, 1 mg/kg 2 doses one week apart|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose limiting toxicity |  | 30 days after last dose of study drug | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics: urine protein/creatinine, urine CCL2/creatinine, sCRP change, change in leukocyte subsets by flow cytometry analysis |  | over 30 day period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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IgA nephropathy, chemokine fusion protein, leukocyte population modulator, phase-1