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Study terminated due to resources and slow enrollment; not due to safety
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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.
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.
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| OPL-CCL2-LPM | Biological | 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 |
|
| Measure | Description | Time Frame |
|---|---|---|
| Dose limiting toxicity | 30 days after last dose of study drug |
| 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 |
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Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Vincent Pichette, M.D., Ph.D. | Hopital Maisonneuve-Rosemont, Univeristy of Montreal | Principal Investigator |
| Michelle Hladunewich, M.D. | Sunnybrook Health Sciences Centre | Principal Investigator |
| Bryan Curtis, M.D. | Eastern Health, HSC, Memorial University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Eastern Health, HSC, Memorial University | St. John's | Newfoundland and Labrador | A1B 3V6 | Canada | ||
| Sunnybrook Health Sciences Centre |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 16015483 | Background | McDonald JR, McManaman JL, Yong VW. The therapeutic potential of chemokine-toxin fusion proteins. IDrugs. 2001 Apr;4(4):427-42. | |
| 16609683 | Background | Eardley KS, Zehnder D, Quinkler M, Lepenies J, Bates RL, Savage CO, Howie AJ, Adu D, Cockwell P. The relationship between albuminuria, MCP-1/CCL2, and interstitial macrophages in chronic kidney disease. Kidney Int. 2006 Apr;69(7):1189-97. doi: 10.1038/sj.ki.5000212. |
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| ID | Term |
|---|---|
| D005922 | Glomerulonephritis, IGA |
| D011507 | Proteinuria |
| ID | Term |
|---|---|
| D005921 | Glomerulonephritis |
| D009393 | Nephritis |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
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| Toronto |
| Ontario |
| M4N 3M5 |
| Canada |
| Hoptial Maisonneuve-Rosemont | Montreal | Quebec | H1T 2M4 | Canada |
| 19040610 | Background | McIntosh LM, Barnes JL, Barnes VL, McDonald JR. Selective CCR2-targeted macrophage depletion ameliorates experimental mesangioproliferative glomerulonephritis. Clin Exp Immunol. 2009 Feb;155(2):295-303. doi: 10.1111/j.1365-2249.2008.03819.x. Epub 2008 Nov 25. |
| 17978307 | Background | Reich HN, Troyanov S, Scholey JW, Cattran DC; Toronto Glomerulonephritis Registry. Remission of proteinuria improves prognosis in IgA nephropathy. J Am Soc Nephrol. 2007 Dec;18(12):3177-83. doi: 10.1681/ASN.2007050526. Epub 2007 Oct 31. |
| 12803507 | Background | Morii T, Fujita H, Narita T, Koshimura J, Shimotomai T, Fujishima H, Yoshioka N, Imai H, Kakei M, Ito S. Increased urinary excretion of monocyte chemoattractant protein-1 in proteinuric renal diseases. Ren Fail. 2003 May;25(3):439-44. doi: 10.1081/jdi-120021156. |
| 17981599 | Background | Rovin BH. The chemokine network in systemic lupus erythematous nephritis. Front Biosci. 2008 Jan 1;13:904-22. doi: 10.2741/2731. |
| 16531983 | Background | Nair R, Walker PD. Is IgA nephropathy the commonest primary glomerulopathy among young adults in the USA? Kidney Int. 2006 Apr;69(8):1455-8. doi: 10.1038/sj.ki.5000292. |
| D052776 |
| Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| D014555 | Urination Disorders |
| D020924 | Urological Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |