Clinical trial NCT01665391: A Study of Fresolimumab in Patients With Steroid-Resistant Primary Focal Segmental Glomerulosclerosis (FSGS)
Official title: A Phase 2, Multicenter, Double-Blind, Parallel Dosing, Randomized Study of Fresolimumab or Placebo in Patients With Steroid-Resistant Primary Focal Segmental Glomerulosclerosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Primary Focal Segmental Glomerulosclerosis
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2012-08-15
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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


Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of patients achieving partial remission (PR) or complete remission (CR) in urinary protein: creatinine ratio (Up/c ratio)
timeFrame: Up to Day 112
measure: Number of patients reporting adverse events (AEs), serious adverse events (SAEs), and medical events of interest (MEOIs)
timeFrame: Up to Day 112
Secondary outcomes:
measure: Percentage of patients achieving CR in Up/c ratio
timeFrame: Up to Day 112
measure: Percentage of patients achieving PR in Up/c ratio
timeFrame: Up to Day 112
measure: Change from baseline in Up/c ratio and urinary protein excretion rate
timeFrame: Up to Day 112
measure: Time to first PR or CR
timeFrame: Up to Day 112
measure: Change from baseline in eGFR (estimated glomerular filtration rate)
timeFrame: Up to Day 112
measure: Percentage of patients achieving PR or CR with stable eGFR (estimated glomerular filtration rate)
timeFrame: Up to Day 112
measure: Mean Fresolimumab serum concentration at each sample collection time point
timeFrame: Up to Day 252
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Investigational Site Number 4008
state: Alabama
city: Phoenix
country: United States
facility: Investigational Site Number 4029
state: Arizona
city: San Francisco
country: United States
facility: Investigational Site Number 4009
state: California
city: Stanford
country: United States
facility: Investigational Site Number 4023
state: California
city: Atlanta
country: United States
facility: Investigational Site Number 4005
state: Georgia
city: Springfield
country: United States
facility: Investigational Site Number 4019
state: Illinois
city: Baltimore
country: United States
facility: Investigational Site Number 4004
state: Maryland
city: Bethesda
country: United States
facility: Investigational Site Number 4002
state: Maryland
city: Boston
country: United States
facility: Investigational Site Number 4022
state: Massachusetts
city: Ann Arbor
country: United States
facility: Investigational Site Number 4012
state: Michigan
city: Detroit
country: United States
facility: Investigational Site Number 4025
state: Michigan
city: Rochester
country: United States
facility: Investigational Site Number 4006
state: Minnesota
city: St Louis
country: United States
facility: Investigational Site Number 4024
state: Missouri
city: New York
country: United States
facility: Investigational Site Number 4016
state: New York
city: New York
country: United States
facility: Investigational Site Number 4003
state: New York
city: Rosedale
country: United States
facility: Investigational Site Number 4014
state: New York
city: Philadelphia
country: United States
facility: Investigational Site Number 4018
state: Pennsylvania
city: Chattanooga
country: United States
facility: Investigational Site Number 4001
state: Tennessee
city: Dallas
country: United States
facility: Investigational Site Number 4020
state: Texas
city: Houston
country: United States
facility: Investigational Site Number 4027
state: Texas
city: Seattle
country: United States
facility: Investigational Site Number 4013
state: Washington
city: Porto Alegre
country: Brazil
facility: Investigational Site Number 4104
city: Aachen
country: Germany
facility: Investigational Site Number 4302
city: Düsseldorf
country: Germany
facility: Investigational Site Number 4301
city: Hamburg
country: Germany
facility: Investigational Site Number 4304
city: Bari
country: Italy
facility: Investigational Site Number 4401
city: Bergamo
country: Italy
facility: Investigational Site Number 4404
city: Montichiari
country: Italy
facility: Investigational Site Number 4403
city: Reggio Calabria
country: Italy
facility: Investigational Site Number 4405
city: Barcelona
country: Spain
facility: Investigational Site Number 4503
city: Madrid
country: Spain
facility: Investigational Site Number 4504
city: Madrid
country: Spain
facility: Investigational Site Number 4502
Study officials:
affiliation: Genzyme, a Sanofi Company
name: Medical Monitor
role: STUDY_DIRECTOR
References:
citation: 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.