Multiple Drugs for Focal Segmental Glomerulosclerosis and Minimal Change Disease

(RESULT Trial)

Recruiting at 40 trial locations

Overseen By Trial Transparency email recommended (Toll free for US & Canada)

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Sanofi

Must be taking: RAAS inhibitors, SGLT2 inhibitors

Disqualifiers: Genetic FSGS, Secondary MCD, ESKD, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 18

Duration: 24 weeks

84 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a parallel, Phase 2a, double-blind, 6-arm study for the treatment of primary focal segmental glomerulosclerosis (FSGS) or primary minimal change disease (MCD). The purpose of this study is to measure the change in proteinuria and its impact on the rates of remission of nephrotic syndrome with frexalimab, SAR442970, or rilzabrutinib compared with placebo in participants with primary FSGS or primary MCD aged 16 to 75 years. Study details for each participant include: The study duration will be up to 76 weeks. The treatment duration will be 24 weeks. There will be up to 18 visits.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop your current medications. However, you must be on a stable dose of RAAS inhibitors and SGLT2 inhibitors for at least 4 weeks before screening, and you cannot start these treatments during the trial. You should also be on a stable dose of prednisone or equivalent for at least 1 week before randomization.

What data supports the idea that Multiple Drugs for Focal Segmental Glomerulosclerosis and Minimal Change Disease is an effective treatment?

The available research shows that rituximab, a drug used for treating focal segmental glomerulosclerosis (FSGS), has shown some promise. In several case reports, patients with FSGS who did not respond to other treatments were successfully treated with rituximab, leading to remission of symptoms. However, the data is limited, and more extensive studies are needed to confirm its effectiveness. Compared to other treatments, rituximab has been effective in cases where steroids and other drugs failed, but it is not yet clear if it is better than other options like calcineurin inhibitors, which also show good results. ^{1 2 3 4 5}

What safety data exists for the treatment of FSGS and MCD with these drugs?

The provided research does not contain specific safety data for the drugs Frexalimab, INX 021, SAR-441344, XC 01129, Rilzabrutinib, PRN 1008, SAR-444671, or SAR442970. However, it includes safety data for fresolimumab and rituximab in the context of FSGS and MCD. Fresolimumab was well tolerated in a phase I study with only pustular rash reported as an adverse event in two patients. Rituximab was evaluated in several studies, showing it can be effective in reducing recurrence and aiding in the reduction or discontinuation of glucocorticoids, with some adverse events reported. Further studies are needed for comprehensive safety data on the specific drugs mentioned. ^{6 7 8 9 10}

Is the drug Frexalimab, Rilzabrutinib, SAR442970 a promising treatment for Focal Segmental Glomerulosclerosis and Minimal Change Disease?

The drug Frexalimab, Rilzabrutinib, SAR442970 could be promising because it is being considered for treating Focal Segmental Glomerulosclerosis (FSGS), a disease with high unmet clinical needs. While the research articles focus on another drug, Rituximab, for FSGS, the interest in new treatments like Frexalimab, Rilzabrutinib, SAR442970 suggests potential for addressing this challenging condition. ^{1 3 10 11 12}

Eligibility Criteria

This trial is for people aged 16-75 with primary FSGS or MCD, proven by biopsy. Participants must be on a stable dose of certain medications like prednisone and RAAS inhibitors, weigh between 45 to 120 kg, have had a significant drop in proteinuria from past treatments, and have an eGFR (a kidney function test) of at least 45.

Inclusion Criteria

I have been diagnosed with FSGS or MCD through a biopsy.

My urine protein to creatinine ratio is 3 or higher.

My kidney function is good, with an eGFR of 45 or higher.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either frexalimab, SAR442970, rilzabrutinib, or placebo for 24 weeks

24 weeks

Up to 18 visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

52 weeks

Treatment Details

Interventions

• Frexalimab
• Rilzabrutinib
• SAR442970

Trial Overview The study compares the effects of three drugs—frexalimab, SAR442970, rilzabrutinib—and placebo on proteinuria and remission rates in nephrotic syndrome due to FSGS or MCD. It's double-blind (neither doctors nor patients know who gets which treatment), has six groups, lasts up to 76 weeks with a treatment phase of 24 weeks.

Participant Groups

Group I: SAR442970 Experimental Treatment 1 Intervention

SAR442970 active dose

Group II: Rilzabrutinib Experimental Treatment 1 Intervention

Rilzabrutinib active dose

Group III: Frexalimab Experimental Treatment 1 Intervention

Frexalimab active dose

Group IV: Placebo Placebo Group 1 Intervention

Matching placebo

Who Is Running the Clinical Trial?

Sanofi

Lead Sponsor

Trials

2,246

Recruited

4,085,000+

Paul Hudson

Sanofi

Chief Executive Officer since 2019

Degree in Economics from Manchester Metropolitan University

Christopher Corsico

Sanofi

Chief Medical Officer

MD from Cornell University, MPH in Chronic Disease Epidemiology from Yale University

Findings from Research

In a study of 108 patients with focal segmental glomerulosclerosis (FSGS) treated with sparsentan over a median follow-up of 47 months, 43% achieved complete remission (CR) of proteinuria, which was linked to a slower decline in kidney function.

Sparsentan was found to be safe for long-term use, showing sustained antiproteinuric effects, and achieving CR—even if not maintained—was associated with better kidney outcomes, suggesting it could be a valuable treatment indicator.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Implications of Complete Proteinuria Remission at any Time in Focal Segmental Glomerulosclerosis: Sparsentan DUET Trial. Trachtman, H., Diva, U., Murphy, E., et al.[2023]

A 76-year-old male with steroid-resistant focal segmental glomerulosclerosis (FSGS) was successfully treated with rituximab, achieving remission after six months, suggesting its potential efficacy for this condition.

Current literature on rituximab for steroid-resistant FSGS is limited, indicating a need for larger controlled studies to better understand its effectiveness and role in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of steroid-resistant focal segmental glomerulosclerosis with rituximab: A case report and review of literature. Varwani, MH., Sokwala, A.[2019]

In a case series of four adults with primary focal segmental glomerulosclerosis (FSGS) resistant to conventional immunosuppressive treatments, all patients responded positively to rituximab, achieving sustained remission.

A literature review identified 29 additional cases of adults with immunosuppressive-resistant FSGS treated with rituximab, resulting in an overall response rate of 58%, indicating that rituximab may be an effective treatment option for this challenging condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab for Adults With Multi-Drug Resistant Focal Segmental Glomerulosclerosis: A Case Series and Review of the Literature. Zhong, E., Ghadiri, S., Pai, A., et al.[2022]

An 11-month-old boy with steroid-resistant nephrotic syndrome due to focal and segmental glomerulosclerosis (FSGS) was successfully treated with rituximab alone, marking a novel use of this medication without the need for calcineurin inhibitors.

Rituximab treatment resulted in complete remission of the child's symptoms after four weekly infusions, demonstrating its potential as a safe and effective standalone therapy for cases of SRNS where conventional treatments have failed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Remission of steroid-resistant nephrotic syndrome due to focal and segmental glomerulosclerosis using rituximab. Suri, M., Tran, K., Sharma, AP., et al.[2021]

Steroid treatment remains the standard first-line therapy for adult primary focal segmental glomerulosclerosis (FSGS), achieving an overall remission rate of 50% or higher, but optimal strategies for steroid-resistant (SR) and steroid-dependent/multirelapsing (SD/MR) cases need further definition.

Calcineurin inhibitors have shown good efficacy in treating both SR and SD/MR FSGS, while mycophenolate mofetil and rituximab are less effective in SR cases, indicating a need for alternative treatments like extracorporeal options or alkylating agents for resistant patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment Strategies of Adult Primary Focal Segmental Glomerulosclerosis: A Systematic Review Focusing on the Last Two Decades. Beer, A., Mayer, G., Kronbichler, A.[2022]

Rituximab (RTX) showed a high complete remission (CR) rate of 84.2% in adult patients with frequent-relapsing or steroid-dependent nephrotic syndrome, with even higher rates of 91.6% for minimal change disease (MCD) and 43% for focal segmental glomerulosclerosis (FSGS) based on a meta-analysis of 21 studies involving 382 subjects.

The treatment was associated with a relatively low relapse rate of 27.4% and minimal adverse events, suggesting that RTX is a safe and effective alternative to traditional treatments like calcineurin inhibitors or prednisone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of rituximab in adult frequent-relapsing or steroid-dependent minimal change disease or focal segmental glomerulosclerosis: a systematic review and meta-analysis. Xue, C., Yang, B., Xu, J., et al.[2022]

Fresolimumab, a monoclonal antibody targeting TGF-β, was well tolerated in a phase I study involving 16 patients with treatment-resistant primary FSGS, with only mild adverse effects reported.

Despite a slight decline in kidney function (eGFR) and fluctuating protein levels in urine, the safety profile and pharmacokinetics of fresolimumab suggest it may be a promising treatment, warranting further investigation in larger studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1, single-dose study of fresolimumab, an anti-TGF-β antibody, in treatment-resistant primary focal segmental glomerulosclerosis. Trachtman, H., Fervenza, FC., Gipson, DS., et al.[2022]

In a study involving 29 children with frequently relapsing or steroid-dependent nephrotic syndrome, low-dose rituximab (200 mg/m2) was found to be as effective as the standard dose (375 mg/m2) in reducing relapses and glucocorticoid use.

Both dosing regimens were safe, with no serious adverse reactions reported, but the low-dose group had significantly lower hospital costs, making it a promising option for clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy and safety of low-dose rituximab in treatment of pediatric nephrotic syndrome: a prospective randomized controlled trial]. Zhu, Y., Wu, L., Wang, Y., et al.[2023]

In a retrospective study of 14 adults with primary focal segmental glomerulosclerosis (FSGS) treated with rituximab (RTX), 7 patients achieved complete remission, demonstrating RTX's efficacy in managing glucocorticoid-dependent or frequently relapsing nephrotic syndrome.

After 6 months, most patients were able to discontinue glucocorticoids, indicating that RTX not only helps in achieving remission but also reduces reliance on traditional immunosuppressive treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab treatment of adults with primary focal segmental glomerulosclerosis. Wang, L., Yu, L., Wang, Y., et al.[2023]

In a study involving five children with steroid-resistant nephrotic syndrome (SRNS) due to focal segmental glomerulosclerosis (FSGS), the combination therapy of rituximab and low-dose cyclosporine led to a significant reduction in CD19-positive B cells, which was maintained for an average of about 260 days.

All patients achieved remission after treatment, allowing for the discontinuation of prednisolone, and the overall doses of steroids and cyclosporine were lower post-treatment, suggesting that this combination therapy may reduce the side effects associated with traditional immunosuppressive treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab and low-dose cyclosporine combination therapy for steroid-resistant focal segmental glomerulosclerosis. Suyama, K., Kawasaki, Y., Miyazaki, K., et al.[2023]

Rituximab was effective in treating recurrent focal segmental glomerular sclerosis (FSGS) in one patient, leading to complete remission of nephrotic syndrome after two infusions, and he maintained this remission for 10 months post-transplant.

In contrast, another patient with recurrent FSGS did not respond to rituximab after multiple treatments, highlighting the variability in response and the need for further research on rituximab's efficacy in preventing and treating nephritic syndrome in kidney transplant patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of focal segmental glomerular sclerosis with rituximab: 2 case reports. Kamar, N., Faguer, S., Esposito, L., et al.[2019]

In a study of 31 patients with primary focal segmental glomerular sclerosis (FSGS) treated with rituximab (RTX) over a median follow-up of 17 months, the response rates were 39% at 3 months, 52% at 6 months, and 42% at 12 months, indicating RTX can be effective in managing this condition.

The treatment was particularly beneficial for steroid-dependent patients and those with lower proteinuria levels (<5 g/24 h), suggesting that RTX may be a viable option for specific subgroups of FSGS patients, although long-term management strategies remain uncertain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Role of Rituximab in Primary Focal Segmental Glomerular Sclerosis of the Adult. Tedesco, M., Mescia, F., Pisani, I., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Implications of Complete Proteinuria Remission at any Time in Focal Segmental Glomerulosclerosis: Sparsentan DUET Trial. [2023]

2. Saudi Arabia pubmed.ncbi.nlm.nih.gov

Treatment of steroid-resistant focal segmental glomerulosclerosis with rituximab: A case report and review of literature. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Rituximab for Adults With Multi-Drug Resistant Focal Segmental Glomerulosclerosis: A Case Series and Review of the Literature. [2022]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Remission of steroid-resistant nephrotic syndrome due to focal and segmental glomerulosclerosis using rituximab. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Treatment Strategies of Adult Primary Focal Segmental Glomerulosclerosis: A Systematic Review Focusing on the Last Two Decades. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of rituximab in adult frequent-relapsing or steroid-dependent minimal change disease or focal segmental glomerulosclerosis: a systematic review and meta-analysis. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

A phase 1, single-dose study of fresolimumab, an anti-TGF-β antibody, in treatment-resistant primary focal segmental glomerulosclerosis. [2022]

8. China pubmed.ncbi.nlm.nih.gov

[Efficacy and safety of low-dose rituximab in treatment of pediatric nephrotic syndrome: a prospective randomized controlled trial]. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Rituximab treatment of adults with primary focal segmental glomerulosclerosis. [2023]

10. Australia pubmed.ncbi.nlm.nih.gov

Rituximab and low-dose cyclosporine combination therapy for steroid-resistant focal segmental glomerulosclerosis. [2023]

11. Germany pubmed.ncbi.nlm.nih.gov

Treatment of focal segmental glomerular sclerosis with rituximab: 2 case reports. [2019]

12. United States pubmed.ncbi.nlm.nih.gov

The Role of Rituximab in Primary Focal Segmental Glomerular Sclerosis of the Adult. [2022]