Post Approval Study of Lixelle for the Treament of Dialysis-Related Amyloidosis

NCT02952144 | Recruiting

• 1 other identifier: KPA-Lixelle-001
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Dialysis-related amyloidosis (DRA) is a serious complication of long-term hemodialysis (HD). Its pathogenic mechanism involves accumulation of β2-microglobulin (β2M) in the blood. β2M is produced by most cells in the body and is metabolized in the kidney in healthy individuals. However, in HD patients with renal dysfunction, β2M which is not removed entirely by HD accumulates excessively in the blood. Then it forms amyloid fibrils that are deposited in bones, joints, and soft tissues. The fibrils are further modified by advanced glycation end products (AGE), inducing local macrophage infiltration and production of cytokines leading to chronic inflammation and activation of osteoclasts. Consequently, severe complications with various symptoms are developed, which are collectively referred to as DRA. Lixelle® is a whole-blood β2M apheresis column developed to adsorb and eliminate β2M selectively from the blood of DRA patients. The treatment is performed with Lixelle® connected upstream of the dialyzer in series on a HD circuit in every session. The Lixelle® column contains porous cellulose beads with covalently linked hexadecyl alkyl chain ligands, which selectively adsorb β2M, via a molecular sieving effect because of its porous structure and hydrophobic interaction with ligands. Lixelle® has been used to relieve symptoms and prevent the progression of DRA in Japan since 1996, when health insurance coverage and reimbursement for the treatment were approved by Japanese Ministry of Health, Labor, and Welfare. Improvement of the activities of daily living (ADL) and remission of arthralgia by Lixelle® treatment has been shown in several clinical studies.

Conditions

Dialysis Amyloidosis

Outcome Measures

Primary Outcomes (1)

• the rate of SAE

  comparison of incidence of SAE between between the Lixelle® treatment group and the natural history during treatment period (2 years)

  through 2 years of Lixelle® treatment during the study period

Secondary Outcomes (2)

• β2M reduction rate in Lixelle® treatment (2 year)

  comparison between baseline and 2 years (104 weeks) after Lixelle® treatment

• comparison of β2M reduction rate between Lixelle® treatment and natural history

  comparison between baseline and 2 years (104 weeks) after Lixelle® treatment

Study Arms (2)

Lixelle® treatment

EXPERIMENTAL

2 years of Lixelle® treatment in the patients with dialysis related amyloidosis (DRA)

Device: Lixelle® treatment

natural history

NO INTERVENTION

2 years of natural history in the patients with dialysis related amyloidosis (DRA)

Interventions

Lixelle® treatment DEVICE

The treatment will be performed with the Lixelle® column connected to upstream of the dialyzer in series on the routine HD circuit according to the description in the IFU. The dialyzer and the Kt/V urea in the conventional HD for each patient will be kept equal in Lixelle®-treatment. Since the maximum blood flow rate for Lixelle® is 250 ml/min, the dialysis time will be extended to achieve the target Kt/V urea. The study will not restrict the type of hemodialyzer and other conditions of HD as specified by the physician. However, any changes to the HD procedure should be recorded properly, and the Kt/V urea should be kept equal to that at the enrollment.

Lixelle® treatment

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients receiving thrice-weekly HD and diagnosed as DRA by one or more of the following 1 to 4 will be included.
• Biopsy of any tissue, showing Congo-red positive amyloid fibrils and immunohistochemical stains consistent with β2M
• Shoulder ultrasonography showing rotator cuffs greater than 8 mm in thickness, and /or echogenic pads between muscle groups of the rotator cuff
• Two or more diagnoses of the following (1) to (5) (1) Polyarthralgia (2) Carpal tunnel syndrome (3) Trigger finger (4) Dialysis-associated spondylosis ((i) or (ii)) (i) Destructive spondyloarthropathy (DSA) (ii) Spinal stenosis (5) Bone cysts (Bone cysts considered to be caused by other diseases such as osteoarthritis, aneurysmal bone cysts and unicameral bone cysts should be excluded.)
• Biopsy of any tissue, showing Congo-red positive amyloid fibrils, and one diagnosis or surgical history of criterion 3- (1) to (5)

You may not qualify if:

• Patient who meets any of the following 1 to 7 will be excluded from the study.
• Patient diagnosed with rheumatoid arthritis
• Patient diagnosed with osteoporosis
• Patient diagnosed with osteoarthritis
• Patient planning to receive renal transplantation during the study
• Patient for whom adequate anticoagulation cannot be achieved
• Patient for whom extracorporeal circulation therapy is contraindicated, such as those with severe cardiac insufficiency, acute myocardial infarction, severe cardiac arrhythmia, acute seizure disorder, or severe uncontrolled hypertension or hypotension
• Patient planning to become pregnant, pregnant, or breast-feeding
• Patient unable to understand or answer the questionnaires even with a proper assistance

Sponsors & Collaborators

• Kaneka Medical America LLC: lead

Study Sites (1)

The Rogosin Institute

New York, New York, 10021, United States

RECRUITING

Related Publications (11)

• Argiles A, Mourad G, Kerr PG, Garcia M, Collins B, Demaille JG. Cells surrounding haemodialysis-associated amyloid deposits are mainly macrophages. Nephrol Dial Transplant. 1994;9(6):662-7. doi: 10.1093/ndt/9.6.662.

  PMID: 7970093 BACKGROUND

• Inoue H, Saito I, Nakazawa R, Mukaida N, Matsushima K, Azuma N, Suzuki M, Miyasaka N. Expression of inflammatory cytokines and adhesion molecules in haemodialysis-associated amyloidosis. Nephrol Dial Transplant. 1995 Nov;10(11):2077-82.

  PMID: 8643171 BACKGROUND

• Chertow GM, Trimbur T, Karlson EW, Lazarus JM, Kay J. Performance characteristics of a dialysis-related amyloidosis questionnaire. J Am Soc Nephrol. 1996 Aug;7(8):1235-40. doi: 10.1681/ASN.V781235.

  PMID: 8866418 BACKGROUND

• Carmichael P, Popoola J, John I, Stevens PE, Carmichael AR. Assessment of quality of life in a single centre dialysis population using the KDQOL-SF questionnaire. Qual Life Res. 2000 Mar;9(2):195-205. doi: 10.1023/a:1008933621829.

  PMID: 10983483 BACKGROUND

• Kutsuki H. beta(2)-Microglobulin-selective direct hemoperfusion column for the treatment of dialysis-related amyloidosis. Biochim Biophys Acta. 2005 Nov 10;1753(1):141-5. doi: 10.1016/j.bbapap.2005.08.007. Epub 2005 Sep 6.

  PMID: 16168723 BACKGROUND

• Gejyo F, Yamada T, Odani S, Nakagawa Y, Arakawa M, Kunitomo T, Kataoka H, Suzuki M, Hirasawa Y, Shirahama T, et al. A new form of amyloid protein associated with chronic hemodialysis was identified as beta 2-microglobulin. Biochem Biophys Res Commun. 1985 Jun 28;129(3):701-6. doi: 10.1016/0006-291x(85)91948-5.

  PMID: 3893430 RESULT

• Gejyo F, Odani S, Yamada T, Honma N, Saito H, Suzuki Y, Nakagawa Y, Kobayashi H, Maruyama Y, Hirasawa Y, et al. Beta 2-microglobulin: a new form of amyloid protein associated with chronic hemodialysis. Kidney Int. 1986 Sep;30(3):385-90. doi: 10.1038/ki.1986.196.

  PMID: 3537446 RESULT

• Gejyo F, Homma N, Arakawa M. Carpal tunnel syndrome and beta 2-microglobulin-related amyloidosis in chronic hemodialysis patients. Blood Purif. 1988;6(2):125-31. doi: 10.1159/000169494. No abstract available.

  PMID: 3293616 RESULT

• Miyata T, Oda O, Inagi R, Iida Y, Araki N, Yamada N, Horiuchi S, Taniguchi N, Maeda K, Kinoshita T. beta 2-Microglobulin modified with advanced glycation end products is a major component of hemodialysis-associated amyloidosis. J Clin Invest. 1993 Sep;92(3):1243-52. doi: 10.1172/JCI116696.

  PMID: 8376584 RESULT

• Abe T, Uchita K, Orita H, Kamimura M, Oda M, Hasegawa H, Kobata H, Fukunishi M, Shimazaki M, Abe T, Akizawa T, Ahmad S. Effect of beta(2)-microglobulin adsorption column on dialysis-related amyloidosis. Kidney Int. 2003 Oct;64(4):1522-8. doi: 10.1046/j.1523-1755.2003.00235.x.

  PMID: 12969174 RESULT

• Gejyo F, Kawaguchi Y, Hara S, Nakazawa R, Azuma N, Ogawa H, Koda Y, Suzuki M, Kaneda H, Kishimoto H, Oda M, Ei K, Miyazaki R, Maruyama H, Arakawa M, Hara M. Arresting dialysis-related amyloidosis: a prospective multicenter controlled trial of direct hemoperfusion with a beta2-microglobulin adsorption column. Artif Organs. 2004 Apr;28(4):371-80. doi: 10.1111/j.1525-1594.2004.47260.x.

  PMID: 15084199 RESULT

Study Officials

• Jeffrey Silberzweig, MD

  The Rogosin Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Joanne McLaughlin

CONTACT

(646) 202-3566; joanne.mclaughlin@kaneka.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 30, 2016
• First Posted: November 2, 2016
• Study Start: October 1, 2015
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: April 30, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)