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

This study has been terminated.
(Study terminated due to resources and slow enrollment; not due to safety)
Sponsor:
Information provided by:
Osprey Pharmaceuticals USA, Inc.
ClinicalTrials.gov Identifier:
NCT00856674
First received: March 4, 2009
Last updated: June 1, 2010
Last verified: June 2010
  Purpose

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.


Condition Intervention Phase
IGA Nephropathy
Proteinuria
Biological: OPL-CCL2-LPM
Phase 1

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

Resource links provided by NLM:


Further study details as provided by Osprey Pharmaceuticals USA, Inc.:

Primary Outcome Measures:
  • Dose limiting toxicity [ Time Frame: 30 days after last dose of study drug ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Pharmacokinetics: urine protein/creatinine, urine CCL2/creatinine, sCRP change, change in leukocyte subsets by flow cytometry analysis [ Time Frame: over 30 day period ] [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: March 2009
Estimated Study Completion Date: June 2010
Estimated Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Intervention Details:
    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

    Other Names:
    • CCL2-LPM
    • CCL2-SA1 fusion protein
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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00856674

Locations
Canada, Newfoundland and Labrador
Eastern Health, HSC, Memorial University
St. John's, Newfoundland and Labrador, Canada, A1B 3V6
Canada, Ontario
Sunnybrook Health Sciences Centre
Toronto, Ontario, Canada, M4N 3M5
Canada, Quebec
Hoptial Maisonneuve-Rosemont
Montreal, Quebec, Canada, H1T 2M4
Sponsors and Collaborators
Osprey Pharmaceuticals USA, Inc.
Investigators
Principal Investigator: 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
  More Information

Publications:
Responsible Party: Barbara K. Finck, M.D., Senior Vice President and Chief Medical Officer, Osprey Pharmaceuticals USA, Inc.
ClinicalTrials.gov Identifier: NCT00856674     History of Changes
Other Study ID Numbers: OPL01-CCL2
Study First Received: March 4, 2009
Last Updated: June 1, 2010
Health Authority: Canada: Health Canada

Keywords provided by Osprey Pharmaceuticals USA, Inc.:
IgA nephropathy
chemokine fusion protein
leukocyte population modulator
phase-1

Additional relevant MeSH terms:
Glomerulonephritis, IGA
Kidney Diseases
Proteinuria
Glomerulonephritis
Nephritis
Urologic Diseases
Autoimmune Diseases
Immune System Diseases
Urination Disorders
Urological Manifestations
Signs and Symptoms

ClinicalTrials.gov processed this record on April 21, 2014