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

Proteinuria Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00856674
• Other study ID #: OPL01-CCL2
• Status: Terminated
• Phase: Phase 1
• First received: March 4, 2009
• Last updated: June 1, 2010
• Start date: March 2009
• Est. completion date: June 2010

Study information

• Verified date: June 2010
• Source: Osprey Pharmaceuticals USA, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 30
• Est. completion date: June 2010
• Est. primary completion date: June 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Glomerulonephritis, IGA
• IGA Nephropathy
• Kidney Diseases
• Proteinuria

Intervention

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

Locations

Country	Name	City	State
Canada	Hoptial Maisonneuve-Rosemont	Montreal	Quebec
Canada	Eastern Health, HSC, Memorial University	St. John's	Newfoundland and Labrador
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
Osprey Pharmaceuticals USA, Inc.

Country where clinical trial is conducted

Canada, 

References & Publications (7)

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. — View Citation

McDonald JR, McManaman JL, Yong VW. The therapeutic potential of chemokine-toxin fusion proteins. IDrugs. 2001 Apr;4(4):427-42. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. Epub 2007 Oct 31. — View Citation

Rovin BH. The chemokine network in systemic lupus erythematous nephritis. Front Biosci. 2008 Jan 1;13:904-22. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose limiting toxicity		30 days after last dose of study drug	Yes
Secondary	Pharmacokinetics: urine protein/creatinine, urine CCL2/creatinine, sCRP change, change in leukocyte subsets by flow cytometry analysis		over 30 day period	No