Plasmapheresis + Rituximab for FSGS

No longer recruiting at 13 trial locations

Overseen By Lyndsay Harshman, MD, MS

Age: Any Age

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Minnesota

Must not be taking: Rituximab

Disqualifiers: Genetic FSGS, Secondary FSGS, Infections, others

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether combining plasmapheresis (a process that removes certain substances from the blood) with rituximab (a medication that affects the immune system) can prevent the return of FSGS (Focal Segmental Glomerulosclerosis) after a kidney transplant. FSGS can cause serious kidney damage. Participants will receive either rituximab or a placebo, along with standard plasmapheresis, around the time of their kidney transplant. This trial suits individuals with a confirmed FSGS diagnosis who have experienced symptoms like protein in urine and swelling and are undergoing their first, second, or third kidney transplant. As an Early Phase 1 trial, this research aims to understand how the treatment works in people, offering participants a chance to be among the first to receive this innovative approach.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that using rituximab with plasmapheresis (a process to remove certain proteins from the blood) might be safe for treating recurring FSGS, a kidney condition. One study found that this treatment did not lead to a high rate of infections, indicating a positive safety profile. However, another study found that adding rituximab to plasmapheresis did not significantly prevent FSGS from recurring after a kidney transplant.

In summary, while the safety results are encouraging, this treatment remains under investigation. The combination has been used in other situations without major safety issues, but more research is needed to fully understand its effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the use of rituximab for FSGS because it offers a different approach than the typical immunosuppressive therapies and corticosteroids currently used. Rituximab is a monoclonal antibody that specifically targets CD20-positive B cells, which play a role in the immune response associated with FSGS. This targeted action could potentially lead to more effective management of the condition with fewer side effects. Additionally, combining rituximab with plasmapheresis, a process that filters the blood to remove harmful substances, may enhance its therapeutic effects, offering hope for improved outcomes in patients undergoing kidney transplantation.

What evidence suggests that plasmapheresis and rituximab could be effective for preventing recurrent FSGS?

Research has shown mixed results on using rituximab with plasmapheresis to treat recurrent FSGS, a kidney disease, after a transplant. In this trial, participants will receive either rituximab with plasmapheresis or a placebo with plasmapheresis. Some studies have found that this combination can help prevent the disease from returning within a year after the transplant. However, other research suggests that adding rituximab might not significantly impact outcomes. Despite these mixed results, the treatment is considered safe and well-tolerated in both children and adults. Overall, current findings suggest potential benefits, but more research is needed to confirm its effectiveness. ^{6 7 8 9 10}

Who Is on the Research Team?

Michelle Rheault, MD

Principal Investigator

University of Minnesota

Are You a Good Fit for This Trial?

This trial is for children and adults aged 1-65 with a confirmed diagnosis of primary FSGS or minimal change disease, who are undergoing their first to third kidney transplant. Participants must not have genetic causes of FSGS, known allergies to rituximab or murine proteins, active infections, recent drug abuse, significant heart or lung disease, other trials within the last 30 days or certain blood disorders.

Inclusion Criteria

I have had nephrotic syndrome.

I have been diagnosed with FSGS or minimal change disease through a biopsy.

I am between 1 and 65 years old and need a kidney transplant.

Exclusion Criteria

My FSGS is caused by another condition like obesity or an infection.

I haven't been in another drug trial recently.

History of drug, alcohol, or chemical abuse within 6 months prior to screening visit

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-transplant Treatment

Participants receive rituximab or placebo on day -1, 0, and +1 prior to kidney transplantation in addition to standard plasmapheresis

1 week

3 visits (in-person)

Post-transplant Monitoring

Participants are monitored for graft function and survival, as well as for acute rejection and recurrent FSGS

1 year

Regular follow-up visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Plasmapheresis
• Rituximab

Trial Overview The PRI-VENT FSGS trial is testing if plasmapheresis combined with rituximab before or at the time of kidney transplantation can prevent recurrent FSGS. It's an open label study where participants will be randomly assigned to receive these interventions around the time they get their new kidney.

How Is the Trial Designed?

Group I: Rituximab + plasmapharesis Experimental Treatment 2 Interventions

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.

Group II: Placebo + plasmapharesis Placebo Group 1 Intervention

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.

Rituximab is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Rituxan for:

• Non-Hodgkin's lymphoma
• Chronic lymphocytic leukemia
• Rheumatoid arthritis
• Granulomatosis with polyangiitis
• Microscopic polyangiitis

Approved in European Union as MabThera for:

• Non-Hodgkin's lymphoma
• Chronic lymphocytic leukemia
• Rheumatoid arthritis
• Granulomatosis with polyangiitis
• Microscopic polyangiitis

Approved in Canada as Rituxan for:

• Non-Hodgkin's lymphoma
• Chronic lymphocytic leukemia
• Rheumatoid arthritis
• Granulomatosis with polyangiitis
• Microscopic polyangiitis

Who Is Running the Clinical Trial?

University of Minnesota

Lead Sponsor

Trials

1,459

Recruited

1,623,000+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Published Research Related to This Trial

A 22-year-old patient with focal segmental glomerulosclerosis (FSGS) experienced severe proteinuria after kidney transplantation, but treatment with rituximab and plasmapheresis led to a significant reduction in protein levels and improved kidney function.

The combination of rituximab and plasmapheresis resulted in sustained remission of nephrotic syndrome for over 2 years post-transplant, with no notable adverse effects, suggesting this approach may be effective for managing recurrent FSGS after transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful treatment of recurrent focal segmental glomerulosclerosis after kidney transplantation by plasmapheresis and rituximab. Hristea, D., Hadaya, K., Marangon, N., et al.[2022]

Rituximab therapy was successfully used in an adolescent patient with recurrent focal segmental glomerulosclerosis (FSGS) after renal transplantation, allowing for the rapid elimination of plasmapheresis treatment.

The patient maintained excellent kidney function for 12 months post-transplant, suggesting that rituximab may be an effective addition to standard therapies for recurrent FSGS in pediatric patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Case report: successful treatment of recurrent focal segmental glomerulosclerosis with a novel rituximab regimen. Stewart, ZA., Shetty, R., Nair, R., et al.[2021]

In a study of eight pediatric patients with recurrent focal segmental glomerulosclerosis (recFSGS) treated with rituximab after minimal response to plasmapheresis, complete response was achieved in 25% of patients, while 50% showed partial response, indicating variable efficacy of the treatment.

Despite some positive outcomes, significant complications were noted, including rituximab-associated lung injury and acute tubular necrosis, highlighting the need for caution and further long-term studies to assess both efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab in post-transplant pediatric recurrent focal segmental glomerulosclerosis. Kumar, J., Shatat, IF., Skversky, AL., et al.[2021]

In a study of 3 adult renal transplant recipients with recurrent focal segmental glomerulosclerosis (FSGS), rituximab therapy combined with chronic plasmapheresis did not lead to remission of proteinuria, despite some reductions in protein levels.

All patients tolerated the treatment well, with no infectious complications or graft loss observed during the 1-month follow-up, indicating that while rituximab was ineffective for remission, it was safe to use in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab and chronic plasmapheresis therapy of nephrotic syndrome in renal transplantation patients with recurrent focal segmental glomerulosclerosis. Rodríguez-Ferrero, M., Ampuero, J., Anaya, F.[2015]

In a study of four pediatric patients with recurrent focal segmental glomerulosclerosis (FSGS) after kidney transplantation, rituximab combined with plasmapheresis led to complete remission in three out of four cases, demonstrating its efficacy as a treatment option.

Rituximab was found to be safe and well-tolerated, with no reported adverse side effects during a follow-up period averaging 22.5 months, indicating its potential as a reliable therapy for this complication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of recurrent focal segmental glomerulosclerosis in pediatric kidney transplant recipients: effect of rituximab. Sethna, C., Benchimol, C., Hotchkiss, H., et al.[2021]

In a study of eight adult patients with biopsy-proven FSGS treated with rituximab, only three showed a positive response, indicating that the treatment may not be effective for the majority.

The patients who responded positively received additional doses of rituximab, suggesting that the dosage regimen may play a crucial role in the treatment's efficacy, highlighting the need for further research to determine optimal dosing and mechanisms of action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab treatment of adult patients with steroid-resistant focal segmental glomerulosclerosis. Fernandez-Fresnedo, G., Segarra, A., González, E., et al.[2023]

In a meta-analysis of eight observational studies involving 85 patients with focal segmental glomerulosclerosis in transplanted kidneys, the combination therapy of rituximab and plasmapheresis/plasma exchange achieved an overall remission rate of 72.7%, significantly reducing proteinuria and serum creatinine levels over a median follow-up of 18 months.

The therapy demonstrated a complete remission rate of 41.0% and a partial remission rate of 31.7%, with a low incidence of serious adverse events at 0.12 events per year, suggesting it is a relatively safe treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined rituximab and plasmapheresis or plasma exchange for focal segmental glomerulosclerosis in adult kidney transplant recipients: a meta-analysis. Hansrivijit, P., Ghahramani, N.[2021]

A multicenter clinical trial is underway to evaluate the effectiveness of combining plasmapheresis with rituximab in preventing recurrent focal segmental glomerulosclerosis (FSGS) in kidney transplant recipients, addressing a significant gap in treatment options.

This combination therapy is promising as it may offer a new approach to prevent recurrence of FSGS, which affects 30-80% of kidney transplant recipients and currently lacks established prevention guidelines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized controlled trial of preemptive rituximab to prevent recurrent focal segmental glomerulosclerosis post-kidney transplant (PRI-VENT FSGS): protocol and study design. Rheault, MN., Amaral, S., Bock, M., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5820165/

Rituximab and Therapeutic Plasma Exchange in Recurrent ... In this study, we sought to assess the efficacy of rituximab and TPE for the prevention and treatment of recurrent FSGS post kidney transplantation.

2. academic.oup.com academic.oup.com/ckj/article/18/3/sfaf058/8026877

Use of rituximab and plasma exchange in treatment and ... We conclude that rituximab did not add significant benefit to plasma exchange when used as initial therapeutic intervention in post-transplant recurrent FSGS.

3. journals.lww.com journals.lww.com/transplantationdirect/fulltext/2025/03000/impact_of_therapeutic_plasma_exchange_and.13.aspx

Impact of Therapeutic Plasma Exchange and Rituximab for... This study aimed to assess the efficacy of therapeutic plasma exchange (TPE) combined with rituximab (RTX) in preventing early FSGS recurrence within 1 y post- ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/29189487/

Rituximab and Therapeutic Plasma Exchange in Recurrent ... In this study, we sought to assess the efficacy of rituximab and TPE for the prevention and treatment of recurrent FSGS after kidney transplantation.

5. withpower.com withpower.com/trial/phase-2-glomerulosclerosis-focal-segmental-6-2019-f598e

Plasmapheresis + Rituximab for FSGS · Info for Participants The combination of plasmapheresis and rituximab has been reported as safe and well-tolerated in both children and adults with recurrent focal segmental ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11875572/

Impact of Therapeutic Plasma Exchange and Rituximab for ... Conclusions. TPE combined with RTX may prevent early FSGS recurrence without significant rates of infection. Focal segmental glomerulosclerosis (FSGS) is a ...

7. academic.oup.com academic.oup.com/ckj/advance-article/doi/10.1093/ckj/sfaf058/8026877

Use of rituximab and plasma exchange in treatment and ... We conclude that rituximab did not add significant benefit to plasma exchange when used as initial therapeutic intervention in post-transplant recurrent FSGS.

8. sciencedirect.com sciencedirect.com/science/article/pii/S1568997225001983

Rituximab in glomerular diseases: Indications, long-term ... Radin, et al. High-dose rituximab ineffective for focal segmental glomerulosclerosis: a long-term observation study. Am J Nephrol, 46 (2) ...

9. researchgate.net researchgate.net/publication/340741150_Combined_rituximab_and_plasmapheresis_or_plasma_exchange_for_focal_segmental_glomerulosclerosis_in_adult_kidney_transplant_recipients_a_meta-analysis

Combined rituximab and plasmapheresis or plasma ... PurposeTo demonstrate the efficacy of combined rituximab and plasmapheresis (PP)/plasma exchange (PE) therapy for focal segmental ...

10. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8291000/

Rituximab or plasmapheresis for prevention of recurrent ... Prevention of recurrent FSGS using rituximab and/or plasmapheresis has been evaluated in multiple small studies with conflicting results.