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

Study Overview
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Brief Summary
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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

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

Conditions
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Primary Focal Segmental Glomerulosclerosis

Intervention / Treatment
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* Drug: fresolimumab
* Drug: fresolimumab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 |