Fresolimumab FSGS

Overview

Status: Not yet recruiting
Keywords: FSGS , Kidney disease , Fresolimumab
IRB Number: 00063244
Specialty: Nephrology and Hypertension
Sub Specialties:

Brief Summary

 

STUDY OBJECTIVES
In patients with steroid-resistant, primary FSGS and nephrotic-range proteinuria:
 
Primary Objectives
• 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
 
Secondary Objective
• 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
 
Exploratory Objectives
In patients treated with fresolimumab versus placebo:
• To compare the signs and symptoms of nephrotic syndrome
• To compare the effect on blood and urine biomarkers

Principal Investigator: Jo Abraham
Department: Nephrology
Co Investigator:

Contact Information

Name:Nala Rogers
Phone: 801-213-4009
Email: nala.rogers@carma.utah.edu

Inclusion Criteria

 

A patient must meet all of the following criteria to be eligible for this study:
 
1. The patient is willing and able to provide signed informed consent.
 
2. The patient is a man or woman 18 years of age or above at time of giving consent.
 
3. The patient’s renal biopsy has been evaluated by the central reader and is consistent
with the diagnosis of primary FSGS including all histological subtypes.
 
4. The patient has an eGFR ≥ 30 mL/min/1.73 m2 as calculated by the central laboratory
at Visit 1.
 
5. The patient has a urinary total protein:creatinine ratio ≥ 3 mg protein/mg creatinine in
at least 1 of the urine samples collected during the Screening Period and a urinary
total protein:creatinine ratio ≥ 2 mg protein/mg creatinine in 2 samples during the
Screening Period.
 
6. 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 in duration or have been found to be intolerant to steroids prior
to the Screening visit.
 
7. The patient has been treated with an ACEi and/or ARB at a stable dose for a
minimum of 4 weeks prior to Visit 2 (treatment start) unless intolerant or
contraindicated.

Exclusion Criteria

 

A patient who meets any of the following criteria will be excluded from this study:
 
1. The patient has FSGS which in the Investigator’s opinion is secondary to another
condition, such as diabetes Type II (pre-dating FSGS), morbid obesity, or drug use
(e.g., heroin, interferon A, lithium, pamidronate). Patients with known genetic
mutations that may predispose them or lead to FSGS are not excluded.
 
2. 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).
 
3. The patient has received any other systemically administered immunosuppressive
drugs (other than glucocorticoids) within 8 weeks prior to Visit 1.
 
4. The patient has received rituximab within 6 months prior to Visit 1.
 
5. The patient has a history of systemic autoimmune disease such as lupus
erythematosus or rheumatoid arthritis for which they received any systemic
immunosuppressive therapy.
 
6. The patient has a history of organ transplantation.
 
7. The patient is reactive for HIV at Visit 1.
 
8. The patient has positive viral hepatitis B or hepatitis C serologies at Visit 1. Patients
with a positive hepatitis B surface antibody (HBsAb) test with a history of prior
hepatitis B immunization are eligible as long as other criteria are met (i.e. negative
tests for hepatitis B surface antigen [HBsAg], hepatitis B core antibody [HBcAb], and
hepatitis C virus antibody [HCVAb]).
 
9. The patient has a clinically significant infection.
 
10. The patient is a woman who is pregnant or lactating.
 
11. The patient is a sexually active man or woman with reproductive potential who is not
willing to use 2 forms of birth control including a barrier method during the study.
 
12. The patient has unstable angina (characterized by increasingly frequent episodes with
modest exertion or at rest, worsening severity, and/or prolonged duration) or has had
a myocardial infarction within 3 months of Visit 1.
 
13. The patient has a known history of cancer or precancerous condition (e.g., familial
polyposis), other than curatively treated cervical intraepithelial neoplasia or nonmelanomatous
skin cancer, within 5 years prior to Visit 1.
 
14. The patient, during the Screening Period, is found to have a skin lesion (such as
suspected keratoacanthoma or actinic keratosis) requiring a biopsy to exclude a
malignant lesion except where a biopsy confirms the lesion to be non-malignant prior
to Visit 2.
 
15. The patient uses non-steroidal inflammatory agents (NSAIDS) more than
occasionally (once or twice weekly).
 
16. The patient has any of the following central laboratory values at Visit 1:
• hemoglobin level of < 9.0 g/dL
• total bilirubin > 1.5 x upper limit of normal (ULN)
(Patients with an indirect hyperbilirubinemia due to Gilbert’s Disease may
be included if their total bilirubin is ≤ 3.0 mg/dL)
• alanine aminotransferase (ALT) > 2.5 x ULN
• aspartate aminotransferase (AST) > 2.5 x ULN
 
17. The patient has active bleeding not due to a benign, self-limited cause.
 
18. The patient has any clinically significant unstable medical condition or other
condition which, in the Investigator’s opinion, will prohibit the patient’s inclusion in
and completion of the study.
 
19. The patient actively abuses ethanol or drugs, excluding tobacco use.
 
20. The patient is known to be allergic to fresolimumab or its components.
 
21. The patient has used an investigational drug administered as part of a clinical trial
within 30 days of Visit 1.
 
22. The patient, in the opinion of the Investigator, is unable to adhere to the requirements
of the study.