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

NCT ID: NCT00856674

Last Updated: 2010-06-02

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-03-31
• Study Completion Date: 2010-06-30

Brief 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.

Detailed 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.

Conditions

IGA Nephropathy; Proteinuria

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

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

Intervention Type: BIOLOGICAL

Other Intervention Names

CCL2-LPM; CCL2-SA1 fusion protein

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Osprey Pharmaceuticals USA, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Osprey Pharmaceuticals USA, Inc.

Principal Investigators

Vincent Pichette, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Hopital Maisonneuve-Rosemont, Univeristy of Montreal

Michelle Hladunewich, M.D.

Role: PRINCIPAL_INVESTIGATOR

Sunnybrook Health Sciences Centre

Bryan Curtis, M.D.

Role: PRINCIPAL_INVESTIGATOR

Eastern Health, HSC, Memorial University

Locations

Eastern Health, HSC, Memorial University

St. John's, Newfoundland and Labrador, Canada

Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada

Hoptial Maisonneuve-Rosemont

Montreal, Quebec, Canada

Countries

Canada

References

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Reference Type: BACKGROUND

PMID: 16015483 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 16609683 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 19040610 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 17978307 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 12803507 (View on PubMed)

Rovin BH. The chemokine network in systemic lupus erythematous nephritis. Front Biosci. 2008 Jan 1;13:904-22. doi: 10.2741/2731.

Reference Type: BACKGROUND

PMID: 17981599 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 16531983 (View on PubMed)

Other Identifiers

OPL01-CCL2

Identifier Type: -

Identifier Source: org_study_id