Clinical trial NCT00856674: Safety Study of of Intravenous CCL2-LPM in Patients With IgA Nephropathy
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: IGA Nephropathy
Proteinuria
Keywords: IgA nephropathy
chemokine fusion protein
leukocyte population modulator
phase-1
Lead sponsor: Osprey Pharmaceuticals USA, Inc.
Sponsor class: INDUSTRY
First posted: 2009-03-06
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Dose limiting toxicity
timeFrame: 30 days after last dose of study drug
Secondary outcomes:
measure: Pharmacokinetics: urine protein/creatinine, urine CCL2/creatinine, sCRP change, change in leukocyte subsets by flow cytometry analysis
timeFrame: over 30 day period
Other outcomes:
Locations:
city: St. John's
country: Canada
facility: Eastern Health, HSC, Memorial University
state: Newfoundland and Labrador
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Montreal
country: Canada
facility: Hoptial Maisonneuve-Rosemont
state: Quebec
Study officials:
affiliation: Hopital Maisonneuve-Rosemont, Univeristy of Montreal
name: Vincent Pichette, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Sunnybrook Health Sciences Centre
name: Michelle Hladunewich, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Eastern Health, HSC, Memorial University
name: Bryan Curtis, M.D.
role: PRINCIPAL_INVESTIGATOR
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