Clinical trial NCT02235857: Post Approval Study of Liposorber LA-15 System for the Treatment of Focal Segmental Glomerulosclerosis in Children
Official title: Treatment of Drug-resistant Pediatric Primary Focal Segmental Glomerulosclerosis Using the Liposorber® LA-15 System
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Focal Segmental Glomerulosclerosis
Keywords: pediatric, renal transplantation, recurrence, drug-resistant
Lead sponsor: Kaneka Medical America LLC
Sponsor class: INDUSTRY
First posted: 2014-09-10
Enrollment: 35
Sex: ALL
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Patients with focal segmental glomerulosclerosis treated by LIPOSORBER® LA-15 system
Primary purpose: TREATMENT

Brief summary: Liposorber® LA-15 System is a blood purification therapy that selectively removes malignant lipoproteins including low density lipoprotein from circulating blood flow and rapidly reduces the plasma cholesterol level. The system was originally developed for the treatment of patients with serious dyslipidemia such as familial hypercholesterolemia and then applied to improve the dyslipidemia, a common complication of nephrotic syndrome and found to bring about improvement not only with the dyslipidemic condition but the nephrotic condition (e.g, proteinuria and hypoproteinemia).

Although the definitive mechanism by which the system may relieve nephrotic syndrome is unknown, it has been recognized as one of alternative therapies for refractory nephrotic syndrome including focal segmental glomerulosclerosis (FSGS) in Japan and referred in the Guidelines for the Treatment of Nephrotic Syndrome endorsed by The Japanese Society of Nephrology.

This study is conducted as a post approval study imposed by Humanitarian Device Exemption (HDE) order to confirm the safety and efficacy of the Liposorber® LA-15 System in the treatment of drug-resistant pediatric primary FSGS.


Eligibility criteria: Inclusion Criteria:

* A pediatric patient is deemed suitable for inclusion in the study if the patient has FSGS with a GFR ≥ 45 ml/min/1.73 m 2 and any of the following:

  * Refractory nephrotic syndrome in which standard treatment options are unsuccessful (i.e., patient is unresponsive to standard corticosteroid and/or calcineurin inhibitor therapy for at least 8 weeks resulting in failure to achieve complete or partial remission);
  * Refractory nephrotic syndrome in which standard treatment options are not well tolerated (i.e., patients intolerant to standard therapies due to severe side effects that negatively affect quality of life without providing an acceptable level of clinical benefit);
  * Refractory or recurrent nephrotic syndrome in which standard therapy is contraindicated.

or

- Pediatric post renal transplant patients with nephrotic syndrome associated with primary FSGS.

Exclusion Criteria:

* General Exclusion Criteria

  * Patient is greater than 21 years of age
  * Parent or patient is unwilling or unable to sign and date the informed consent (Note: Only patients 18-21 years of age may sign the informed consent on their own behalf)
  * 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.)
  * Unable or unwilling to comply with the follow-up schedule
  * Simultaneously participating in another investigational drug or device study
  * Body weight \< 15 kg (33.1 lbs)
* Medical Exclusion Criteria

  * 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.)
  * Currently being administered antihypertensive drugs other than ACE inhibitors (e.g., Angiotensin II receptor blockers (ARBs) that cannot be withheld on the day of apheresis until after the procedure
  * 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
  * Hypersensitivity to dextran sulfate, heparin, or ethylene oxide
  * Adequate anticoagulation cannot be achieved due to severe hemophilia, severe hemorrhage diathesis, severe gastrointestinal ulcers, or are recipients of vitamin K antagonist medications
  * 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
  * Cardiac impairments such as uncontrolled arrhyth¬mia, unstable angina, decompensated congestive heart failure, or valvular disease
  * Functional thyroid disease or liver abnormalities
  * Unresolved systemic or local infection that could affect the clinical study outcomes

Primary outcomes:
measure: The percent of patients who show complete or partial remission
timeFrame: 1 month after the final treatment
measure: the rate of device-related and procedure-related serious adverse events
timeFrame: During the period in which the apheresis procedures are administered and up to at the 1-month follow-up visit
Secondary outcomes:
measure: Nephrotic Condition
timeFrame: 1, 3, 6, 12, and 24 months after the final treatment
measure: The percent of patients who obtain complete or partial remission
timeFrame: 3, 6, 12, and 24 months after the final treatment
measure: Incidence of adverse events
timeFrame: From the initiation of the first apheresis session until the termination of the last (usually 12th) apheresis session, standad period of 9 weeks for a total of 12 aoheresis sessions
measure: Incidence of adverse events and severe adverse events
timeFrame: From 1 months to 24 months after the final aphresis
measure: Various laboratory values
timeFrame: 1,3, 6, 12, and 24 months after the final apheresis
Other outcomes:
Locations:
city: Loma Linda
country: United States
facility: Loma Linda University Children's Hospital
state: California
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center
state: California
city: Wilmington
country: United States
facility: Nemours/A.I. duPont Hospital for Children
state: Delaware
city: Orlando
country: United States
facility: Nemours Children's Health
state: Florida
city: Grand Rapids
country: United States
facility: Helen DeVos Children's Hospital
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: New York
country: United States
facility: Weill Cornell Medical Center / NewYork-Presbyterian
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Akron
country: United States
facility: Akron Children's Hospital
state: Ohio
city: Philadelphia
country: United States
facility: St. Christopher's Hospital for Children
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina Children's Hospital
state: South Carolina
city: Richmond
country: United States
facility: Children's Hospital of Richmond at VCU
state: Virginia
Study officials:
affiliation: Weill Medical College of Cornell University
name: Jeffrey I Silberzweig, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Reidy K, Kaskel FJ. Pathophysiology of focal segmental glomerulosclerosis. Pediatr Nephrol. 2007 Mar;22(3):350-4. doi: 10.1007/s00467-006-0357-2. Epub 2007 Jan 10.
citation: Franceschini N, North KE, Kopp JB, McKenzie L, Winkler C. NPHS2 gene, nephrotic syndrome and focal segmental glomerulosclerosis: a HuGE review. Genet Med. 2006 Feb;8(2):63-75. doi: 10.1097/01.gim.0000200947.09626.1c.
citation: Korbet SM. The treatment of primary focal segmental glomerulosclerosis. Ren Fail. 2000 Nov;22(6):685-96. doi: 10.1081/jdi-100101956.
citation: Tarshish P, Tobin JN, Bernstein J, Edelmann CM Jr. Cyclophosphamide does not benefit patients with focal segmental glomerulosclerosis. A report of the International Study of Kidney Disease in Children. Pediatr Nephrol. 1996 Oct;10(5):590-3. doi: 10.1007/s004670050167.
citation: Fine RN. Recurrence of nephrotic syndrome/focal segmental glomerulosclerosis following renal transplantation in children. Pediatr Nephrol. 2007 Apr;22(4):496-502. doi: 10.1007/s00467-006-0361-6. Epub 2006 Dec 21.
citation: Schwartz GJ, Munoz A, Schneider MF, Mak RH, Kaskel F, Warady BA, Furth SL. New equations to estimate GFR in children with CKD. J Am Soc Nephrol. 2009 Mar;20(3):629-37. doi: 10.1681/ASN.2008030287. Epub 2009 Jan 21.
citation: Trachtman H, Vento S, Gipson D, Wickman L, Gassman J, Joy M, Savin V, Somers M, Pinsk M, Greene T. Novel therapies for resistant focal segmental glomerulosclerosis (FONT) phase II clinical trial: study design. BMC Nephrol. 2011 Feb 10;12:8. doi: 10.1186/1471-2369-12-8.