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

Trial Summary

What is the purpose of this trial?

This trial tests a blood-filtering device called the LIPOSORBER® LA-15 System in adults with kidney issues from FSGS who haven't had success with other treatments or have had severe side effects. The device helps by cleaning the blood to protect the kidneys.

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 data supports the effectiveness of the LIPOSORBER LA-15 treatment for Focal Segmental Glomerulosclerosis?

The LIPOSORBER LA-15 treatment showed some effectiveness in patients with drug-resistant Focal Segmental Glomerulosclerosis, with partial or complete remission of symptoms in several patients over a follow-up period. Additionally, the treatment has been effective in lowering cholesterol levels in patients with familial hypercholesterolemia, indicating its potential in managing conditions related to lipid imbalances. ^{1 2 3 4 5}

How is the LIPOSORBER® LA-15 treatment different from other treatments for focal segmental glomerulosclerosis?

The LIPOSORBER® LA-15 treatment is unique because it uses a process called apheresis, which involves filtering the blood to remove harmful substances, unlike traditional treatments that often rely on medications like steroids. This approach can be particularly beneficial for patients who do not respond well to standard drug therapies. ^{6 7 8 9 10}

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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 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 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 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 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]

References

1. Switzerland 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. [2020]

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

Low-density lipoprotein apheresis for prevention and regression of atherosclerosis: clinical results. [2019]

3. Australia pubmed.ncbi.nlm.nih.gov

Blood purification therapies using dextran sulfate cellulose columns Liposorber and Selesorb. [2022]

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

Adsorption of lipoprotein containing apolipoprotein-B through plasma separation for treatment of familial hypercholesterolemia. [2017]

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

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

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

Proteinuria and focal segmental glomerulosclerosis in severely obese adolescents. [2022]

7. Germany pubmed.ncbi.nlm.nih.gov

Aggressive treatment of severe idiopathic focal segmental glomerulosclerosis. [2022]

8. Germany pubmed.ncbi.nlm.nih.gov

Chronic kidney disease predictors in obese adolescents. [2022]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Treatment and prognosis of primary focal segmental glomerulosclerosis. [2013]

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

Effects of steroids in focal segmental glomerulosclerosis in a predominantly African-American population. [2022]