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

NCT03763643 | Completed Early Phase 1 DMC FDA Drug

• 1 other identifier: PEDS-2018-25868
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 12

Brief Summary

This is a pilot/feasibility, multicenter, randomized, open label, clinical trial to test that hypothesis that plasmapheresis plus rituximab prior to or at the time of kidney transplantation can prevent recurrent FSGS in children and adults.

Conditions

Focal Segmental Glomerulosclerosis

Outcome Measures

Primary Outcomes (1)

• Feasibility assessment

  quantifying the number and proportion of patients who can undergo the steps of recruitment, informed consent, enrollment, randomization, and follow-ups within the time frame of interest.

  through study completion, an average of 1 year

Secondary Outcomes (5)

• Patient and graft survival at 1 year post-transplant

  through study completion, an average of 1 year

• Graft function at 1 year post-transplant

  through study completion, an average of 1 year

• Proportion with acute rejection at 1 year post-transplant

  through study completion, an average of 1 year

• Proportion with CD19+ <1%

  1 month, 6 months, and 12 months

• Recurrent FSGS free survival

  after 1 year post-transplant

Study Arms (2)

Rituximab + plasmapharesis

EXPERIMENTAL

This is a phase III, multicenter, randomized, open-label clinical trial. Participants with FSGS will be randomized 1:1 to receive rituximab or placebo on day -1, 0 and +1 prior to or after kidney transplantation in addition to standard plasmapheresis.

Drug: Rituximab; Procedure: Plasmapheresis

Placebo + plasmapharesis

PLACEBO COMPARATOR

This is a phase III, multicenter, randomized, open-label clinical trial. Participants with FSGS will be randomized 1:1 to receive rituximab or placebo on day -1, 0 and +1 prior to or after kidney transplantation in addition to standard plasmapheresis.

Procedure: Plasmapheresis

Interventions

Rituximab DRUG

Rituximab 375mg/m2 intravenous on day 0 or -1 prior to kidney transplant

Rituximab + plasmapharesis

Plasmapheresis PROCEDURE

1.5 volume exchange plasmapheresis with fresh frozen plasma replacement

Placebo + plasmapharesis; Rituximab + plasmapharesis

Eligibility Criteria

• Age: 1 Year - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• University of Minnesota: lead
• United States Department of Defense: collaborator

Study Sites (12)

University of Alabama

Tuscaloosa, Alabama, 35487, United States

Location

University of California at Davis

Davis, California, 95616, United States

Location

Lurie Children's Hospital

Chicago, Illinois, 60611, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

Children's Hospital of Colorado

Aurora, Minnesota, 80045, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Duke University

Durham, North Carolina, 27708, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45221, United States

Location

Cincinnati Children's Hospital

Cincinnati, Ohio, 45229, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

Related Publications (1)

• Rheault MN, Amaral S, Bock M, Chambers ET, Chavers B, Ters ME, Garro R, Gbadegesin R, Govil A, Harshman L, Amer H, Hooper DK, Israni AK, Riad S, Sageshima J, Shapiro R, Seifert M, Smith J, Sung R, Thomas CP, Wang Q, Verghese PS. A randomized controlled trial of preemptive rituximab to prevent recurrent focal segmental glomerulosclerosis post-kidney transplant (PRI-VENT FSGS): protocol and study design. Front Nephrol. 2023 May 15;3:1181076. doi: 10.3389/fneph.2023.1181076. eCollection 2023.

  PMID: 37675355 DERIVED

MeSH Terms

Conditions

Glomerulosclerosis, Focal Segmental

Interventions

Rituximab; Plasmapheresis

Condition Hierarchy (Ancestors)

Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Blood Component Removal; Therapeutics; Sorption Detoxification; Extracorporeal Circulation; Surgical Procedures, Operative

Study Officials

• Michelle Rheault, MD

  University of Minnesota

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Control group and treatment/intervention group. Pilot/feasibility study.

Study Record Dates

• First Submitted: August 7, 2018
• First Posted: December 4, 2018
• Study Start: July 1, 2019
• Primary Completion: February 7, 2025
• Study Completion: February 7, 2025
• Last Updated: September 10, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (12)