6803: A Pilot Study to Assess the Efficacy of Rituximab Therapy in Patients with Treatment Resistant Idiopathic Focal Segmental Glomerulosclerosis (FSGS): Integrating an Assessment of suPAR and Activation of Podocyte β3 Integrin

Status: Recruiting

For Diseases:

  • Focal Segmental Glomerulosclerosis (FSGS)

Background

FSGS stands for Focal Segmental Glomerulosclerosis. The incidence of FSGS has increased and it is now the most common cause of nephrotic syndrome (a disorder where the kidneys are damaged causing them to leak large amounts of protein into the urine) in North American adults and children. Although there are several known risk factors, we don’t yet know why most people develop FSGS. In order to be diagnosed with FSGS, you must undergo a kidney biopsy.

FSGS is named for the scarring, or “sclerosis”, that can be found in the kidney of people with this disease. When looked at under a microscope, everyone’s kidneys contain millions of tiny filters called “glomeruli”. When these filters are damaged they become scarred and they are no longer able to filter blood appropriately. This is called “glomerulosclerosis”. The word “focal” is added because in FSGS, only some of the filters are damaged. “Segmental” is included because often only parts of the filters are scarred.

Since the waste from blood isn’t filtered completely with FSGS, people affected by the disease can experience protein in the urine, high blood pressure, and swelling (edema). If the disease is not treated or if it does not respond well to attempts at treatment, FSGS can progress to cause kidney damage or failure in 50% of patients. Physicians have previously been unable to predict which patients will progress to these outcomes, however new research has identified biological markers (measurable characteristics) (suPAR and podocyte β3 integrin activation) that may be linked to disease activity and outcomes. Current treatments that suppress the immune system of patients with FSGS have been shown to improve protein leakage and slow the progression of the disease, but side effects of the current options are common and can be serious and rates of treatment failure and relapses are common. This study will look at Rituximab as a new option to treat FSGS and its impact on these biological markers.

The research aims are:

  1. Does Rituximab therapy cause the following changes in urine protein levels and kidney function at 1, 3, 6 and 12 months after treatment?
    • Complete remission
    • Partial remission
    • Incomplete remission
    • Worsening of kidney function without significant improvement in proteinuria or no improvement in proteinuria
  2. Does Rituximab therapy cause changes in levels of the following secondary outcomes after 1, 3, 6 and 12 months after treatment as measured by blood and urine tests:
    • suPAR level
    • podocyte β3 integrin

This is a pilot study testing the use of Rituximab therapy in 20 people with FSGS who are either resistant or intolerant to current treatments (steroid and/or calcineurin inhibitors). Study participants will complete a screening and enrollment visit to see if they are eligible to participate. If they are eligible, they will receive two doses of Rituximab approximately 2 weeks apart. Participants will then be evaluated for one year, with study visits at 1, 3, 6 and 12 months after-treatment. All study visits will take place at one of the clinical sites (see the list of participating sites below).

For each visit, you will be asked to:

  • Have a physical exam
  • Update the study staff of any changes to your health or medications
  • Give blood (up to 70 mL/volume, or about 5 tablespoons, to be based on weight for children)
  • Give a urine sample
  • Complete a 24 hour urine sample before each visit

We will look at your medical records from your local doctor’s office so that we can collect information about your medical history.

Targeted Enrollment

To be eligible to participate, you must:

  • You must have been diagnosed with FSGS , with no prior kidney transplant
  • Be between 6 years and 80 years of age
  • Urine protein levels within the study-required range
    • ≥ 3.0 grams per day (24 hour urine collection) for adults
    • ≥ 1.0 urine protein: creatinine ratio (first morning urine sample) for children
  • Patients must have a minimal washout period before initiating Rituximab to avoid over immunosuppression and consequent risk of morbidity.
  • UuPAR (biomarker) blood and urine levels within the study-required range (>3500 pg mL-1)
  • Meet blood pressure targets (may require treatment with blood pressure medications)
    •       Target blood pressure for adults (at least 75% of readings) ≤ 140/90 mmHg
    •       Target blood pressure for children (at least 75% of readings) ≤ 120/80 mmHg
  • Negative serum pregnancy test (for women of child bearing age)
  • Men and women of reproductive potential must agree to use acceptable method of birth control during treatment and 1 year after completion of trial.

You are not eligible to participate if you have:

  • You must have estimated GFR < 40 mL/min per 1.73m2
  • You have collapsing-variant FSGS
  • You are currently using immunosuppressive therapy (with the exception of prednisone 10mg/day)
  • You have a medical condition that may cause FSGS (such as HIV, lymphoma or heroin use)
  • You have a secondary form of FSGS due to massive obesity, renal mass reduction or vesicoureteral reflux
  • You have Type 1 or 2 Diabetes Mellitus
  • You have a history of a serious or recurrent chronic infection (including but not limited to Hepatitis B, C, HIV, tuberculosis, HCV)
  • Your blood test results to not meet the study-required range
  • You have been diagnosed with cancer within the last 5 years
  • You have an allergy to the type of medication being used or have been previously treated with this medication (Rituximab)
  • You have been treated with any investigational medication (‘study drug’) within 4 weeks
  • You have a history of a major psychiatric disorder, drug or alcohol abuse within 6 months

In order to participate in a study, you must personally contact the study coordinator of the participating institution closest to you by phone or e-mail. Please use the information below to inquire about participation.

United States

Minnesota

Mayo Clinic, Rochester
Fernando Fervenza, MD, PhD
Principal Investigator
Email: fervenza.fernando@mayo.edu

Julie A. E. Ray, MPH, MEM
Coordinator
Email: ray.julie@mayo.edu

Canada

Ontario

University Health Network (UHN), Toronto
Dr. Daniel C. Cattran, MD, FRCP(C)
Principal Investigator
Email: daniel.cattran@uhn.ca

Paul Ling
Coordinator
Email: pling@uhnresearch.ca



Please Note: The Rare Diseases Clinical Research Network will make every effort to enroll all the patients we can, but we cannot make any guarantees that we will be able to enroll everyone in a particular study who wants to participate.