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| General |
| Study Status |
Delayed |
Application Number /
Requirement Number |
H170002 / PAS001 |
| Date Original Protocol Accepted |
03/04/2019
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| Date Current Protocol Accepted |
12/05/2022
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| Study Name |
New Enroll PAS LIPOSORBER LA-15 Adults
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| Device Name |
LIPOSORBER LA-15 System
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| General Study Protocol Parameters |
| Study Design |
Prospective Cohort Study
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| Data Source |
New Data Collection
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| Comparison Group |
No Control
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| Analysis Type |
Descriptive
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| Study Population |
Infant: 29 days-2 yrs,
Child: 2-12 yrs,
Adolescent: 13-18 yrs,
Transit. Adolescent A (distinctively) : 18-21 yrs,
Transit. Adolescent B (as adults) : 18-21 yrs,
Adult: >21
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| Detailed Study Protocol Parameters |
| Study Objectives |
Design: multicenter, prospective, single-arm, new enrollment clinical study to evaluate the probable benefit and safety of the LIPOSORBER® LA-15 System
Objectives:
The primary objectives of this study are to evaluate the safety and probable benefit of the LIPOSORBER® LA-15 System in relieving nephrotic syndrome associated with primary FSGS at 1 month after the final apheresis treatment.
The secondary objectives are to evaluate safety and probable benefit of the LIPOSORBER® LA-15 System in relieving nephrotic syndrome associated with primary FSGS at 3 months, 6 months, 12 months, and 24 months after the final apheresis treatment.
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| Study Population |
Adult and pediatric patients with nephrotic syndrome associated with primary focal segmental glomerulosclerosis, when the standard treatment options, including corticosteroid and/or calcineurin inhibitors treatments, have been unsuccessful or not well tolerated, and the patient has a GFR greater than or equal to 60 ml/min/1.73m2, or the patient is post renal transplantation. No comparator group is included.
Inclusion Criteria:
Patient eligibility for enrollment shall be based on known information at the time of the procedure. Patients will be selected in accordance with the Manufacturer’s Instructions for Use, the Operator’s Manual and this study protocol. Information obtained at a later date may contradict these criteria, but this will not be considered a violation of the study plan. A patient is deemed suitable for inclusion in the study if the patient has nephrotic syndrome associated with primary FSGS when: Standard treatment options, including corticosteroid and/or calcineurin inhibitors, are unsuccessful or not well tolerated and the patient’s glomerular filtration rate (GFR) greater than or equal to 60 ml/min/1.73 m2. or The patient is post renal transplantation. Exclusion Criteria A patient is excluded from enrollment into the study if any of the following are true:
General Exclusion Criteria 1. Patient is greater than 75 years of age at the start of the treatment period 2. Parent or patient is unwilling or unable to sign and date the informed consent (Note: Patients 18 years of age or older sign the informed consent on their own behalf) 3. Pregnant, lactating, or planning to become pregnant prior to completing the study (Note: The safety of the use of LIPOSORBER® in pregnant women has not been studied. There may be unknown risks to an embryo/fetus. Sexually active women of child bearing potential should avoid pregnancy during the use of the LIPOSORBER device and throughout the study duration.) 4. Unable or unwilling to comply with the follow-up schedule 5. Simultaneously participating in another investigational drug or device study 6. Body weight < 18 kg (39.7 lbs) Medical Exclusion Criteria 1. Currently being administered ACE inhibitors that cannot be withheld for at least 24 hours prior to each apheresis treatment (Note: The time period to withhold ACE inhibitors should be prolonged, if determined by the treating physician, considering each individual’s renal function and the biological half-life of the ACE-inhibitor currently in use.) 2. Currently being administered antihypertensive drugs other than ACE inhibitors (e.g., ARBs) that cannot be withheld on the day of apheresis until after the procedure 3. 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 4. Hypersensitivity to dextran sulfate, heparin, or ethylene oxide
5. Adequate anticoagulation cannot be achieved due to severe hemophilia, severe hemorrhage diathesis, severe gastrointestinal ulcers, or are recipients of vitamin K antagonist medications 6. Extracorporeal circulation therapy with LIPOSORBER® LA-15 System cannot be tolerated due to severe cardiac insufficiency, acute myocardial infarction, severe cardiac arrhythmia, acute apoplexy, severe uncontrollable hypertension, or severe uncontrollable hypotension Note: Severe uncontrollable hypotension/hypertension indicates the cases with systolic and/or diastolic blood pressure less than or equal to 5th percentile for age, gender, and height. Cardiac impairments such as uncontrolled arrhythmia, unstable angina, decompensated congestive heart failure, or valvular disease 2. Thyroid disease or liver abnormalities 3. Unresolved systemic or local infection that could affect the clinical study outcomes
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| Sample Size |
35 adults and 35 children at 3 to 10 clinical sites. Sample size was calculated considering both the primary safety and the primary probable benefit objectives.
The primary probable benefit endpoint will be assessed using a 95% confidence interval. The assumption for sample size calculation was that 50% of patients would achieve a 50% reduction in urine protein at 1 month. Optimal conservative medical therapy would be expected to be approximately 10% based on the collected data in Glomerular Disease Collaborative Network (University of North Carolina, Chapel Hill, NC) as stated in the FONT study protocol which include both adults and pediatrics (age 1 to 51 years at time of randomization).11 The reported clinical results in steroid-resistant FSGS treated with the LIPOSORBER® LA-15 System suggest the incidence of favorable cases is at least 25%, implying that the probable benefit of the system is superior to that of ordinary medical therapies. With a performance goal of 25%, an expected rate of 50% of patients, a one-sided exact binomial test, and a type I error rate of 0.025 (corresponding to a 95% one-sided confidence interval), 30 patients provides a power of 0.82.
The primary safety endpoint will be assessed using a 95% confidence interval. An incidence rate of serious device-related and procedure-related adverse events of less than or equal to 10% is considered clinically acceptable in both adults and pediatrics. The rate of device-related and procedure-related SAE during the 9-week treatment period for patients receiving LIPOSORBER® apheresis treatments up to including the first follow-up visit after the last treatment was assumed to be 3%; the error rate for the confidence interval was set to be 7% resulting in a hypothesized upper bound of 10%. With a type I error of 0.025, corresponding to a 95% one-sided confidence interval, the enrollment of 11 patients, each having 12 procedures, is required.
Thus, the primary probable benefit requires the largest sample size (n = 30). To account for patient attrition and loss to follow-up, 35 each of adult and pediatric patients will be enrolled.
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| Key Study Endpoints |
Primary Endpoints
The primary probable benefit endpoint is the percent of patients who show complete or partial remission at 1 month after the final apheresis treatment.
The primary safety endpoint is the rate of device-related and procedure-related serious adverse events (SAEs) occurring during the period in which the apheresis procedures are administered and up to at the 1-month follow-up visit.
Secondary Endpoints
The secondary endpoints will be to measure the following:
Nephrotic condition (complete remission, partial remission, and nephrotic state) at 1, 3, 6, 12, and 24 months after the final apheresis treatment, including the percentage of patients who obtain complete or partial remission at 3, 6, 12, and 24 months
Incidence of adverse events encountered during the period in which apheresis treatments are given
Incidence of all AEs and SAEs occurring within 3, 6, 12, and 24 months after the final apheresis treatment
Laboratory values, including eGFR, at baseline, after the last treatment, and at 1, 3, 6, 12, and 24 months after the final apheresis treatment, including percent change from baseline and percentage of patients showing an increase or decrease in each value
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| Follow-up Visits and Length of Follow-up |
1, 3, 6, 12, and 24 months after the final apheresis treatment.
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| Interim or Final Data Summary |
| Interim Results |
Safety:
There were 14 adverse events, including 3 serious adverse events, reported for the pediatric cohort and 17, including 3 serious adverse events, for the adult cohort. All but 2 adverse events were resolved. All events were categorized as not related to the treatments.
Effectiveness:
The proportion of pediatric patients in complete or partial remission ranged from 53.3% at 1 month follow-up to 80% at 24 months follow-up.
The proportion of adult patients in complete or partial remission ranged from 30% at 1 month follow-up to 0% at 24 months. However, the small number of patients being followed makes it impossible to evaluate the effectiveness in adults at this time.
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| Actual Number of Patients Enrolled |
27 pediatric and 19 adult enrollments
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| Actual Number of Sites Enrolled |
16 sites
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| Patient Follow-up Rate |
Pediatric: 63% at 1 month, 48% at 3 months, 41% at 6 months, 33% at 12 months, and 26% at 24 months.
Adults: 58% at 1 month, 58% at 3 months, 53% at 6 months, 37% at 12 months, and 21% at 24 months.
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