A Pilot Study to Assess the Efficacy of Rituximab Therapy in Treatment Resistant FSGS

NCT01573533 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 12-005640U54DK083912
• Study Type: interventional
• Target: 9
• Locations: 2 countries
• Sites: 4

Brief Summary

The purpose of this study is to determine whether Rituximab therapy is safe and effective in treating patients with the kidney condition, focal segmental glomerulosclerosis (FSGS), that is no longer responsive to traditional therapies.

Conditions

Primary Focal Segmental Glomerulosclerosis

Keywords

Treatment Resistant Idiopathic FSGS; Glomerulosclerosis; Proteinuria; Rituximab

Outcome Measures

Primary Outcomes (1)

• Changes in Proteinuria (With Stable Renal Function)

  The amount of protein in excreted urine measured by grams per day (g/day). Remission status defined by the following criteria at 12 months: * Complete Remission - Proteinuria \< 0.5 g/day * Partial Remission - Improvement in proteinuria by \> 50% and to a level between 0.5-3.5g/day * Incomplete Remission - Improvement in proteinuria equal to or \>50%, but residual proteinuria still \>3.5g/day

  Baseline, 12 months

Secondary Outcomes (3)

• Change in suPAR Levels

  Baseline, 1, 3, 6 and 12 months

• Change in Activation of Podocyte β3 Integrin

  Baseline, 1, 3, 6, 12 months

• Number of Subjects With Complete or Partial Remission Following Treatment

  12 months

Study Arms (1)

Rituximab

EXPERIMENTAL

Biological: Rituximab

Interventions

Rituximab BIOLOGICAL

Rituximab will be infused intravenously on Day 1 and Day 15 at a dose of 375 mg/m2 up to a maximum of 1000mg per dose in children and at a dose of 1000 mg on Day 1 and Day 15 in adults.

Also known as: Rituxan®

Rituximab

Eligibility Criteria

• Age: 6 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• FSGS involving native kidneys with a diagnostic biopsy performed within the last 3 years
• Patients \>6 years of age and \< 80 years of age
• suPAR \> 3500 pg ml-1
• Treatment with an ACEI and/or ARB as tolerated for at least 3 months prior to enrollment to with a target a systolic blood pressure ≤ 140 mmHg and a diastolic pressure ≤ 90 mmHg in adults and blood pressure readings less than the 95th percentile for age, gender and height in children in at least 75% of readings
• Proteinuria ≥ 3.0 grams as measured by 24-hour urine collection in adults and urine protein:creatinine ratio ≥ 1.0 in the first morning urine in children, despite ACE inhibitor / ARB treatment as tolerated and a minimum of 8 weeks of prednisone therapy at ≥ 1 mg/kg/day, a trial of calcineurin inhibitor for=\> 3 months or a contraindication/intolerance to such therapy (diabetes, osteoporosis/osteonecrosis, age \>60, BMI ≥35)
• Negative serum pregnancy test (for women of child bearing age)
• Men and women of reproductive potential must agree to use an acceptable method of birth control during treatment and for twelve months (1 year) after completion of the trial
• Able and willing to give written informed consent and comply with study requirements

You may not qualify if:

• Estimated GFR \< 40 ml/min per1.73m2. The rationale is that patients with advanced renal failure may progress rapidly towards ESRD.
• Collapsing variant of FSGS, as it is rare and has been associated with an aggressive course
• Concurrent use of immunosuppressive therapy with the exceptions of prednisone 10 mg/day. Patients who are taking other immunosuppressive therapy, must be off immunosuppressive medications for equal to or \> 3 months prior to enrollment into the study with the exception of patients demonstrating significant worsening of proteinuria (of \>30% above baseline) during the washout period. These resistant patients can be treated after 1 month of washout due to the high likelihood of progression and/or lack of delayed (previous) immunosuppression effect.
• Patients with medical conditions that may cause FSGS (e.g. HIV, lymphoma, heroin use) or have a secondary form of FSGS due to hyperfiltration injury (massive obesity, vesicoureteral reflux, or renal mass reduction)
• Type 1 or type 2 diabetes mellitus as diabetic glomerulosclerosis may be contributing to proteinuria in these patients
• History of serious recurrent or chronic infection
• Presence or suspicion of active infection including TB, HIV, Hepatitis B and HCV with positive tests for Hepatitis B surface antigen (HBsAg), Hepatitis B core antibody (HBcAb), Hepatitis B virus (HBV), Hepatitis C serology, HIV serology or a positive TB skin test, which require further investigation to rule out active disease (ie. chest x-ray)
• Known active infection requiring hospitalization or treatment with intravenous antibiotics within 4 weeks or oral antibiotics within 2 weeks of the study initiation
• Low immunoglobulins (level to be based on age)
• Absolute neutrophil count \< 1.5 x103/mL
• Patients in receipt of a live vaccine within 4 weeks of the study initiation
• Concomitant malignancies or previous malignancies within the last five years, with the exception of adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix
• Previous Treatment with a B-cell depleting antibody
• History of severe allergic reactions to humanized or murine monoclonal antibodies
• Treatment with any investigational agent within 4 weeks of the study initiation

Sponsors & Collaborators

• Mayo Clinic: lead
• University Health Network, Toronto: collaborator
• National Institutes of Health (NIH): collaborator
• Genentech, Inc.: collaborator
• Rush University Medical Center: collaborator
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (4)

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Mayo Clinic College of Medicine

Rochester, Minnesota, 55905, United States

Location

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

Location

University Health Network

Toronto, Ontario, M5G 2N2, Canada

Location

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Proteinuria

Interventions

Rituximab

Condition Hierarchy (Ancestors)

Urination Disorders; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Fernando C. Fervenza, M.D., Ph.D.
• Organization: Mayo Clinic

Fervenza.Fernando@mayo.edu

507-266-1045

Study Officials

• Michelle Hladunewich, MD, MSc, BSc

  University Health Network, Sunnybrook Health Sciences Centre

  PRINCIPAL INVESTIGATOR

• Fernando C Fervenza, MD, PhD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PI

Study Record Dates

• First Submitted: April 5, 2012
• First Posted: April 9, 2012
• Study Start: October 1, 2013
• Primary Completion: November 15, 2018
• Study Completion: November 15, 2018
• Last Updated: February 10, 2020
• Results First Posted: February 10, 2020

Record last verified: 2020-01

Locations

CA (2); US (2)