A Study of Fresolimumab in Patients With Steroid-Resistant Primary Focal Segmental Glomerulosclerosis (FSGS) (FSGS)

A Phase 2, Multicenter, Double-Blind, Parallel Dosing, Randomized Study of Fresolimumab or Placebo in Patients With Steroid-Resistant Primary Focal Segmental Glomerulosclerosis

The primary objectives of this trial are as follows:

• to compare the achievement of a partial remission (PR) or complete remission (CR) in urinary protein: creatinine ratio (Up/c ratio) in patients treated with fresolimumab versus placebo
• to compare the safety profile of patients treated with fresolimumab versus placebo

The secondary objectives are as follows:

• To compare the reduction in proteinuria in patients treated with fresolimumab versus placebo
• To evaluate fresolimumab dose-dependent reduction in proteinuria
• To compare the change in renal function (estimated glomerular filtration rate [eGFR]) in patients treated with fresolimumab versus placebo
• To evaluate the multiple-dose pharmacokinetics of fresolimumab

Study Overview

• Status: Completed
• Conditions: Primary Focal Segmental Glomerulosclerosis
• Intervention / Treatment: Drug: fresolimumab; Drug: fresolimumab; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 2

Contacts and Locations

Study Locations

• Brazil
  • Porto Alegre, Brazil, 90035 003
    • Investigational Site Number 4104
• Germany
  • Aachen, Germany, 52074
    • Investigational Site Number 4302
  • Düsseldorf, Germany, 40225
    • Investigational Site Number 4301
  • Hamburg, Germany, 20246
    • Investigational Site Number 4304
• Italy
  • Bari, Italy, 70124
    • Investigational Site Number 4401
  • Bergamo, Italy, 24127
    • Investigational Site Number 4404
  • Montichiari, Italy, 25018
    • Investigational Site Number 4403
  • Reggio Calabria, Italy, 89124
    • Investigational Site Number 4405
• Spain
  • Barcelona, Spain, 08025
    • Investigational Site Number 4503
  • Madrid, Spain, 28040
    • Investigational Site Number 4504
  • Madrid, Spain, 28041
    • Investigational Site Number 4502
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
      • Investigational Site Number 4008
  • Arizona
    • Phoenix, Arizona, United States, 85032
      • Investigational Site Number 4029
  • California
    • San Francisco, California, United States, 94143
      • Investigational Site Number 4009
    • Stanford, California, United States, 94305
      • Investigational Site Number 4023
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Investigational Site Number 4005
  • Illinois
    • Springfield, Illinois, United States, 01107
      • Investigational Site Number 4019
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Investigational Site Number 4004
    • Bethesda, Maryland, United States, 20892
      • Investigational Site Number 4002
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Investigational Site Number 4022
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Investigational Site Number 4012
    • Detroit, Michigan, United States, 48202
      • Investigational Site Number 4025
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Investigational Site Number 4006
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Investigational Site Number 4024
  • New York
    • New York, New York, United States, 10029
      • Investigational Site Number 4016
    • New York, New York, United States, 10032
      • Investigational Site Number 4003
    • Rosedale, New York, United States, 11422
      • Investigational Site Number 4014
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Investigational Site Number 4018
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Investigational Site Number 4001
  • Texas
    • Dallas, Texas, United States, 75390
      • Investigational Site Number 4020
    • Houston, Texas, United States, 77030
      • Investigational Site Number 4027
  • Washington
    • Seattle, Washington, United States, 98195
      • Investigational Site Number 4013

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• The patient's renal biopsy is consistent with the diagnosis of primary Focal Segmental Glomerulosclerosis (FSGS) including all histological subtypes.
• The patient has an eGFR ≥ 30 mL/min/1.73 m2
• The patient has a urinary total protein:creatinine ratio ≥ 3 mg protein/mg creatinine
• In the opinion of the Investigator, the patient has steroid-resistant FSGS. The patient must have been treated for FSGS with a course of high-dose steroid therapy for a minimum of 4 weeks
• The patient has been treated with an ACEi (angiotensin converting enzyme inhibitor) and/or ARB (angiotensin receptor blocker) at a stable dose for a minimum of 4 weeks prior to Visit 2 (treatment start)

Exclusion Criteria:

• The patient has FSGS which in the Investigator's opinion is secondary to another condition
• The patient has been taking prednisone at a dose > 10 mg/day (or equivalent dose of an alternative glucocorticoid) within 4 weeks prior to Visit 1 (Screening Visit).
• The patient has received any other systemically administered immunosuppressive drugs (other than glucocorticoids) within 8 weeks prior to Visit 1.
• The patient has received rituximab within 6 months prior to Visit 1.
• The patient has a history of organ transplantation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Placebo administered to match active treatment group
Experimental: fresolimumab 1 mg/kg total body weight	Drug: fresolimumab; 1 mg/kg total body weight administered intravenous (IV); Drug: fresolimumab; 4 mg/kg total body weight administered intravenous (IV)
Experimental: fresolimumab 4 mg/kg total body weight	Drug: fresolimumab; 1 mg/kg total body weight administered intravenous (IV); Drug: fresolimumab; 4 mg/kg total body weight administered intravenous (IV)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of patients achieving partial remission (PR) or complete remission (CR) in urinary protein: creatinine ratio (Up/c ratio)	Up to Day 112
Number of patients reporting adverse events (AEs), serious adverse events (SAEs), and medical events of interest (MEOIs)	Up to Day 112

Secondary Outcome Measures

Outcome Measure	Time Frame
Percentage of patients achieving CR in Up/c ratio	Up to Day 112
Percentage of patients achieving PR in Up/c ratio	Up to Day 112
Change from baseline in Up/c ratio and urinary protein excretion rate	Up to Day 112
Time to first PR or CR	Up to Day 112
Change from baseline in eGFR (estimated glomerular filtration rate)	Up to Day 112
Percentage of patients achieving PR or CR with stable eGFR (estimated glomerular filtration rate)	Up to Day 112
Mean Fresolimumab serum concentration at each sample collection time point	Up to Day 252

Collaborators and Investigators

• Sponsor: Genzyme, a Sanofi Company

Publications and helpful links

General Publications

• Hodson EM, Sinha A, Cooper TE. Interventions for focal segmental glomerulosclerosis in adults. Cochrane Database Syst Rev. 2022 Feb 28;2(2):CD003233. doi: 10.1002/14651858.CD003233.pub3.

Study record dates

Study Major Dates

• Study Start: August 1, 2012
• Primary Completion (Actual): June 1, 2014
• Study Completion (Actual): November 1, 2014

Study Registration Dates

• First Submitted: August 13, 2012
• First Submitted That Met QC Criteria: August 13, 2012
• First Posted (Estimate): August 15, 2012

Study Record Updates

• Last Update Posted (Estimate): August 26, 2015
• Last Update Submitted That Met QC Criteria: August 12, 2015
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Nephritis; Glomerulonephritis; Glomerulosclerosis, Focal Segmental; Physiological Effects of Drugs; Immunologic Factors; Antibodies, Monoclonal
• Other Study ID Numbers: GC1008FSGS03110; 2010-019545-25 (EudraCT Number); U1111-1139-9082 (Other Identifier: World Health Organization Universal Trial Number (UTN)); DRI12792 (Other Identifier: Sanofi)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No