Using Rituximab and Plasmapheresis to Prevent Kidney Graft Failure in FSGS Patients

PRI-VENT FSGS: Preemptive Rituximab to Prevent Recurrent Focal Segmental Glomerulosclerosis Post-Transplant

This study is testing whether giving rituximab and plasmapheresis before or during kidney transplants can help prevent kidney problems in patients with FSGS.

Quick facts

• Phase: Early Phase 1
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 1 Year to 65 Years
• Sex: All
• Sponsor: University of Minnesota (Academic / other)
• Drugs / interventions: rituximab
• Locations: 12 sites (Tuscaloosa, Alabama and 11 other locations)
• Trial ID: NCT03763643 on ClinicalTrials.gov

What this trial studies

This pilot clinical trial aims to evaluate the effectiveness of preemptive treatment with plasmapheresis and rituximab in preventing the recurrence of focal segmental glomerulosclerosis (FSGS) in patients undergoing kidney transplantation. The study will involve a multicenter, randomized, open-label design, enrolling both children and adults who have a biopsy-proven diagnosis of FSGS or minimal change disease. By administering these treatments prior to or at the time of transplantation, the researchers hope to reduce the risk of immediate graft dysfunction and improve long-term graft survival rates. The trial will also assess the safety and feasibility of this approach in a diverse patient population.

Who should consider this trial

Good fit: Ideal candidates include individuals aged 1-65 years with a biopsy-proven diagnosis of primary FSGS or minimal change disease who are undergoing their first or subsequent kidney transplant.

Not a fit: Patients who do not have a history of nephrotic syndrome or those with other forms of kidney disease unrelated to FSGS may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve kidney transplant outcomes and reduce the need for multiple transplants in patients with FSGS.

How similar studies have performed: While there have been small studies exploring similar approaches, this trial represents a novel application of preemptive treatment strategies specifically for FSGS in the context of kidney transplantation.

Eligibility criteria

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

1. Age 1-65 years at the time of kidney transplant
2. Biopsy proven diagnosis of primary FSGS or minimal change disease
3. History of nephrotic syndrome (proteinuria, edema, hypoalbuminemia)
4. First kidney transplant or second or third transplant with a history of recurrent FSGS in the first or second kidney transplant.
5. The patient (if ≥18 years old) or the child's parent or guardian must be able and willing to give written informed consent and comply with the requirements of the study protocol. Patient assent if \<18 years old will be required per local IRB requirements.
6. Negative urine pregnancy test prior to randomization (for females who are post-menarche).
7. Males and females of reproductive potential (sexually active in boys or post-menarche in girls) must agree to use an acceptable method of birth control during treatment and for twelve months (1 year) after completion of treatment with rituximab.

An individual who meets any of the following criteria will be excluded from participation in this study:

1. Known genetic cause of FSGS 2. Patients with FSGS secondary to another condition (obesity, viral infection, medications, etc.) 3. 4. Received rituximab within 1 year prior to transplant 5. Known hypersensitivity to rituximab, to any of its excipients, or to murine proteins 6. History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies 7. Known active bacterial, viral (e.g. HIV, hepatitis B, hepatitis C), fungal, mycobacterial, or other infection (including tuberculosis or atypical mycobacterial disease, but excluding fungal infections of nail beds) or any major episode of infection requiring hospitalization or treatment with iv antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks prior to screening visit.

8. Participation in another therapeutic trial within 30 days of enrollment or 5 half-lives of the investigational drug (whichever is longer) 9. ANC \< 1.5 x 103 10. Hemoglobin: \< 8.0 gm/dL 11. Platelets: \< 100,000/mm 12. AST or ALT \>2.5 x Upper Limit of Normal at the local institution's laboratory 13. History of drug, alcohol, or chemical abuse within 6 months prior to screening visit.

14. Pregnant, lactating, or refusal of birth control in an adolescent of child-bearing potential 15. Concomitant malignancies or previous malignancies 16. History of psychiatric disorder that would interfere with normal participation in this protocol 17. History of significant cardiac (including arrhythmias) or pulmonary disease (including obstructive pulmonary disease) 18. Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications 19. Inability to comply with study and follow-up procedures

Where this trial is running

Tuscaloosa, Alabama and 11 other locations

• University of Alabama — Tuscaloosa, Alabama, United States (Recruiting)
• University of California at Davis — Davis, California, United States (Recruiting)
• Lurie Children's Hospital — Chicago, Illinois, United States (Recruiting)
• University of Iowa — Iowa City, Iowa, United States (Recruiting)
• Children's Hospital of Colorado — Aurora, Minnesota, United States (Recruiting)
• University of Minnesota — Minneapolis, Minnesota, United States (Recruiting)
• Mayo Clinic — Rochester, Minnesota, United States (Recruiting)
• Duke University — Durham, North Carolina, United States (Recruiting)
• University of Cincinnati — Cincinnati, Ohio, United States (Recruiting)
• Cincinnati Children's Hospital — Cincinnati, Ohio, United States (Recruiting)
• Children's Hospital of Philadelphia — Philadelphia, Pennsylvania, United States (Recruiting)
• Seattle Children's Hospital — Seattle, Washington, United States (Recruiting)

Study contacts

• Principal investigator: Michelle Rheault, MD — University of Minnesota
• Study coordinator: Amy Hanson

Conditions Focal Segmental Glomerulosclerosis