LIPOSORBER® LA-15 System for Focal Segmental Glomerulosclerosis

(FSGSALLAGE Trial)

Recruiting at 9 trial locations

Overseen By Ayaka Kitamura

Age: Any Age

Sex: Any

Trial Phase: Academic

Sponsor: Kaneka Medical America LLC

Must not be taking: Ace inhibitors, Arbs, Vitamin K antagonists

Disqualifiers: Pregnancy, Cardiac impairments, Infections, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 17

Duration: 9 weeks

35 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the LIPOSORBER® LA-15 System, a treatment for nephrotic syndrome caused by focal segmental glomerulosclerosis (FSGS). The trial aims to determine if this system can help when standard treatments, like steroids, are ineffective or cause adverse side effects. The treatment involves a process similar to dialysis, performed several times over a few weeks. Individuals with this kidney disease who have not responded to other treatments or have had a kidney transplant might be suitable candidates. As an unphased trial, it offers patients the opportunity to explore new treatment options when other therapies have failed.

Will I have to stop taking my current medications?

You may need to stop taking certain medications. Specifically, ACE inhibitors must be stopped at least 24 hours before each treatment, and other blood pressure medications should not be taken on the day of the procedure until after it is done.

What prior data suggests that the LIPOSORBER® LA-15 System is safe for treating nephrotic syndrome associated with primary focal segmental glomerulosclerosis?

Research has shown that the LIPOSORBER® LA-15 System is generally well-tolerated by people with nephrotic syndrome, a kidney disorder related to focal segmental glomerulosclerosis (FSGS). In past studies, this treatment did not raise major safety concerns. Most participants experienced mild side effects, such as low blood pressure during the procedure, but these were manageable and short-lived.

The LIPOSORBER® LA-15 System has been used in both adults and children with FSGS and holds FDA approval for this condition. This approval indicates that the treatment is reasonably safe. Additionally, studies examining the system's safety over several months found it to be generally safe, with few serious side effects reported.

Overall, while minor side effects may occur, the LIPOSORBER® LA-15 System is considered safe for most patients with FSGS. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the LIPOSORBER® LA-15 System because it offers a novel approach to treating Focal Segmental Glomerulosclerosis (FSGS). Unlike the standard treatments for FSGS, which often include medications like corticosteroids and immunosuppressants that work by suppressing the immune system, the LIPOSORBER® LA-15 System uses an extracorporeal treatment process. This method involves removing harmful substances directly from the blood, potentially reducing kidney damage more effectively and with fewer systemic side effects. The unique approach of targeting the problem outside the body could offer hope for those who haven't responded well to existing therapies.

What evidence suggests that the LIPOSORBER® LA-15 System is effective for focal segmental glomerulosclerosis?

Research has shown that the LIPOSORBER® LA-15 System can aid patients with focal segmental glomerulosclerosis (FSGS) who do not respond well to standard treatments like steroids. Approximately half of the patients with steroid-resistant FSGS experienced complete or partial improvement two years after using this treatment. The system removes harmful substances from the blood, which can enhance kidney function. In some cases, all patients treated with this method fully recovered, even if they had not responded to other medications before. These findings suggest that the LIPOSORBER® LA-15 System could be an effective treatment for FSGS. ^{2 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for adults and children with a kidney disease called primary FSGS who haven't improved on standard treatments or can't handle their side effects. Participants need to have a certain level of kidney function (GFR ≥ 45 ml/min/1.73m2) and can be post-kidney transplant patients. It's not for those over 75, under 22, with severe health issues that could affect the study, or women who are pregnant.

Inclusion Criteria

I have FSGS with unsuccessful standard treatments and my kidney function is still okay.

I have had a kidney transplant.

Exclusion Criteria

I do not have serious heart problems like uncontrolled irregular heartbeat or severe heart failure.

Medical condition or disorder that would limit life expectancy to less than the primary clinical study endpoint or that may cause noncompliance with the study plan or confound the data analysis

You are pregnant, breastfeeding, or planning to get pregnant before the study is finished. If you have the potential to become pregnant, you should avoid getting pregnant while using the LIPOSORBER device and during the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive extracorporeal treatment using the LIPOSORBER® LA-15 System, twice weekly for 3 weeks and then once weekly for 6 weeks

9 weeks

12 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment at 1, 3, 6, 12, and 24 months

24 months

5 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• LIPOSORBER® LA-15

Trial Overview The LIPOSORBER® LA-15 System is being tested in this study. It's designed for people whose focal segmental glomerulosclerosis hasn't responded to usual treatments like steroids or calcineurin inhibitors, or if these treatments caused severe side effects.

How Is the Trial Designed?

Group I: LIPOSORBER® LA-15 System Experimental Treatment 1 Intervention

All study patients who meet the study eligibility criteria will undergo the extracorporeal treatment using LIPOSORBER® LA-15 System. The participants are to be treated with the system twice weekly for the 3weeks and then once weekly for the following 6 weeks.

LIPOSORBER® LA-15 is already approved in United States for the following indications:

Approved in United States as LIPOSORBER LA-15 System for:

• Nephrotic syndrome associated with primary focal segmental glomerulosclerosis (FSGS)
• Familial Hypercholesterolemia (FH)

Who Is Running the Clinical Trial?

Kaneka Medical America LLC

Lead Sponsor

Trials

13

Recruited

720+

Published Research Related to This Trial

The Liposorber LA-40 is an effective treatment for familial hypercholesterolemia, selectively adsorbing low-density and very low-density lipoproteins, which helps lower cholesterol levels significantly, as demonstrated in two clinical cases.

After seven months of bi-weekly treatments, patients maintained total cholesterol levels under 300 mg/dl without the need for replacement fluids, indicating both the efficacy and safety of this apheresis system.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adsorption of lipoprotein containing apolipoprotein-B through plasma separation for treatment of familial hypercholesterolemia. Odaka, M., Kobayashi, H., Soeda, K., et al.[2017]

In a study of seven obese African American adolescents, obesity-associated proteinuria was linked to severe obesity and specific kidney changes, including focal segmental glomerulosclerosis, highlighting the need for monitoring in this population.

Treatment options such as weight reduction and angiotensin-converting enzyme inhibitors showed promise, with one patient experiencing a significant decrease in proteinuria, indicating potential for effective management of this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proteinuria and focal segmental glomerulosclerosis in severely obese adolescents. Adelman, RD., Restaino, IG., Alon, US., et al.[2022]

In a study of 142 obese adolescents, increased levels of cholesterol, triglycerides, and uric acid, along with elevated urine concentrations of neutrophil gelatinase-associated lipocalin (NGAL), were identified as potential predictors for the development of chronic kidney disease (CKD).

The research highlighted that all participants with decreased glomerular filtration rate (GFR) showed increased urine levels of NGAL, indicating a link between kidney damage markers and the risk of CKD in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronic kidney disease predictors in obese adolescents. Mackowiak-Lewandowicz, K., Ostalska-Nowicka, D., Zaorska, K., et al.[2022]

In a multicenter study involving 17 patients with drug-resistant primary FSGS, lipoprotein apheresis using the Liposorber® LA-15 system showed promising results, with partial or complete remission of nephrotic syndrome observed in 66.7% of patients at the 6-month follow-up.

All patients demonstrated improved or stable kidney function (eGFR) over the follow-up period, indicating that lipoprotein apheresis may enhance the effectiveness of standard treatments for resistant cases of primary FSGS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dextran-Sulfate Plasma Adsorption Lipoprotein Apheresis in Drug Resistant Primary Focal Segmental Glomerulosclerosis Patients: Results From a Prospective, Multicenter, Single-Arm Intervention Study. Raina, R., Krishnappa, V., Sanchez-Kazi, C., et al.[2020]

In a study of 168 patients with primary focal segmental glomerulosclerosis (FSGS), factors such as high proteinuria levels, low baseline eGFR, and severe glomerular sclerosis were identified as risk factors for worsening kidney function, indicating the importance of monitoring these parameters for prognosis.

Patients treated with steroids who achieved stable remission had better renal function and less severe glomerular sclerosis compared to those who were steroid-dependent, suggesting that early intervention with steroids may lead to improved outcomes in FSGS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment and prognosis of primary focal segmental glomerulosclerosis. Ren, H., Shen, P., Li, X., et al.[2013]

In a study of 72 patients with focal segmental glomerulosclerosis (FSGS), including 65 African Americans, treatment with steroids did not improve renal survival, indicating that steroids may not be effective for this population.

Complications from steroid treatment were noted in about one third of patients, including diabetes and significant weight gain, highlighting potential safety concerns associated with prolonged steroid use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of steroids in focal segmental glomerulosclerosis in a predominantly African-American population. Crook, ED., Habeeb, D., Gowdy, O., et al.[2022]

LDL-apheresis therapy using the Liposorber LA-15 System significantly reduces LDL cholesterol levels in patients with familial hypercholesterolemia (FH), achieving mean acute reductions of 76% in heterozygous FH and 81% in homozygous FH patients.

The procedure is generally safe, with hypotension being the most common side effect occurring in only 3% of treatments, and it is FDA-approved for specific patient groups with high LDL cholesterol levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-density lipoprotein apheresis using the Liposorber dextran sulfate cellulose system for patients with hypercholesterolemia refractory to medical therapy. Gordon, BR., Saal, SD.[2005]

In a study of five African-American patients aged 11-18 with severe focal segmental glomerulosclerosis (FSGS) and chronic renal insufficiency, aggressive treatment with intravenous methylprednisolone, with or without chlorambucil, led to significant improvements in three patients, including normalization of kidney function.

These results suggest that even in advanced cases of FSGS, particularly in African-American patients who typically have a more aggressive disease course, there is potential for positive treatment outcomes with intensive therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aggressive treatment of severe idiopathic focal segmental glomerulosclerosis. Aviles, DH., Irwin, KC., Dublin, LS., et al.[2022]

In a multicenter trial involving 120 patients with severe hypercholesterolemia, LDL apheresis using the Liposorber LA-15 system resulted in significant reductions in total cholesterol (TC) by 52.6% and LDL-cholesterol (LDL-C) by 63.1% during treatment, demonstrating its efficacy for patients unresponsive to diet and maximum drug therapy.

The treatment was generally well tolerated, with adverse events primarily related to hypotension occurring in only 1% of treatments, indicating that LDL apheresis is a safe option for managing severe hypercholesterolemia, although caution is advised for patients on ACE inhibitors due to potential severe reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-density lipoprotein apheresis for prevention and regression of atherosclerosis: clinical results. Bambauer, R., Olbricht, CJ., Schoeppe, E.[2019]

Liposorber effectively purifies plasma by selectively adsorbing low-density lipoproteins, making it useful for treating conditions like familial hypercholesterolemia, peripheral arterial disease, and focal segmental glomerulosclerosis.

Selesorb targets and removes specific antibodies and immune complexes, providing a treatment option for patients with systemic lupus erythematosus, especially those who do not respond to standard medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blood purification therapies using dextran sulfate cellulose columns Liposorber and Selesorb. Asahi, T., Yamamoto, T., Kutsuki, H.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02235857?cond=Focal%20segmental%20glomerulosclerosis%20OR%20%22FGS%22%20OR%20%22%20FGS%20(focal%20glomerular%20sclerosis)%22%20OR%20%22%20focal%20glomerular%20sclerosis%22%20OR%20%22%20focal%20glomerulosclerosis%22%20OR%20%22%20FSGS%22%20OR%20%22%20FSGS%20-%20focal%20segmental%20glomerulosclerosis%22&aggFilters=status:not%20rec&viewType=Table&rank=7

Post Approval Study of Liposorber LA-15 System for the ... Liposorber® LA-15 System is a blood purification therapy that selectively removes malignant lipoproteins including low density lipoprotein from circulating ...

2. liposorber.com liposorber.com/kidney-disease/liposorber-for-fsgs/

FSGS Treatment | LIPOSORBER® LIPOSORBER therapy has enabled nearly 50% of steroid-resistant primary FSGS patients to attain complete or partial remission, 2 years after treatment.

3. fda.gov fda.gov/media/169211/download

H120005 Liposorber® LA-15 System The Agency also conducted an analysis of the outcomes of data for the eleven (11) subjects who ... Liposorber, Child, Focal Segmental Glomerulosclerosis. 3.

4. journals.lww.com journals.lww.com/jasn/fulltext/2024/10001/successful_treatment_of_primary_fsgs_with_ldl.947.aspx

Successful Treatment of Primary FSGS with LDL Apheresis:... All 4 of our patients were able to achieve complete remission of primary FSGS despite a lengthy history of multi-drug resistance.

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34453196/

Liposorber® LA-15 system for LDL apheresis in resistant ... LDL-A was able to significantly decrease the lipid levels in these patients and induce CR and PR in the majority. The current study confirms ...

6. accessdata.fda.gov accessdata.fda.gov/cdrh_docs/pdf17/H170002D.pdf

LIPOSORBER® LA-15 The LIPOSORBER® LA-15 System is indicated for use in the treatment of adult and pediatric patients with nephrotic syndrome associated with primary focal ...

7. clinicaltrials.cedars-sinai.edu clinicaltrials.cedars-sinai.edu/view/H170002

Treatment of Adult and Pediatric FSGS Using the ... The purpose of the study is to evaluate a device called the LIPOSORBER LA-15 System in relieving kidney problems associated with primary FSGS or post- ...

8. kireports.org kireports.org/article/S2468-0249(19)30624-2/fulltext

SUN-034 Liposorber® LA-15 system for LDL apheresis in ... The objective of this study is to examine the safety and probable benefit at 1, 3, 6, 12 and 24 months following completion of apheresis treatment using ...

9. accessdata.fda.gov accessdata.fda.gov/cdrh_docs/pdf17/H170002B.pdf

summary of safety and probable benefit (sspb) Clinical Data. Clinical data to support the safety and probable benefit of LIPOSORBER® LA-15 System for FSGS in adults can be divided to pre ...