LCAT-trial-24 weeks: Protocol for a clinical study to evaluate the safety of regenerative medicine and gene therapy by the autologous transplantation of human lecithin:cholesterol acyltransferase gene-transduced human pre-adipocytes

Masayuki Kuroda; Makoto Hori; Yoshiro Maezawa; Yoshitaka Kubota; Nobuyuki Mitsukawa; Yuki Shiko; Yoshihito Ozawa; Yohei Kawasaki; Yasushi Saito; Hideki Hanaoka; Koutaro Yokote

doi:10.1016/j.conctc.2022.100946

LCAT-trial-24 weeks: Protocol for a clinical study to evaluate the safety of regenerative medicine and gene therapy by the autologous transplantation of human lecithin:cholesterol acyltransferase gene-transduced human pre-adipocytes

Contemp Clin Trials Commun. 2022 Jun 9:28:100946. doi: 10.1016/j.conctc.2022.100946. eCollection 2022 Aug.

Authors

Affiliations

¹ Center for Advanced Medicine, Chiba University Hospital, Chiba University, 1-8-1 Inohana Chuo-ku, Chiba, 260-8677, Japan.
² Clinical Research Center, Chiba University Hospital, Chiba University, 1-8-1 Inohana Chuo-ku, Chiba, 260-8677, Japan.
³ Department of Endocrinology, Hematology and Gerontology, Chiba University Graduate School of Medicine, Chiba University, 1-8-1 Inohana Chuo-ku, Chiba, 260-0856, Japan.
⁴ Department of Plastic, Reconstructive, And Aesthetic Surgery, Chiba University Graduate School of Medicine, Chiba University, 1-8-1 Inohana Chuo-ku, Chiba, 260-0856, Japan.
⁵ Chiba University, 1-8-1 Inohana Chuo-ku, Chiba, 260-0856, Japan.

Abstract

Backgrounds: Despite the absolute need for life-long treatment of inherited and genetic diseases, there has been little effort to develop such treatments for most of these conditions due to their rarity. Familial lecithin:cholesterol acyltransferase (LCAT) deficiency is recognized as one such orphan disease. We have been developing an adipocyte-based ex vivo gene therapy/regenerative medicine, a novel methodology that differs from the adeno-associated virus-mediated in vivo gene therapy or ex vivo gene-transduced hematopoietic cell therapy, to treat familial LCAT deficiency. Recently, a first-in-human (FIH) clinical study was conducted under the Act on Securement of Safety of Regenerative Medicine, wherein a patient with familial LCAT deficiency was treated. To obtain approval to put this treatment into practical use, a clinical trial has been designed with reference to the FIH clinical study.

Methods: An interventional, open-label, unblinded dose-escalation trial was planned, referring to previous FIH clinical study. The trial aims to evaluate the safety of the investigational product in relation to the characteristics of the investigational product (ex vivo gene/cell therapy product by retroviral vector-mediated LCAT gene transduction) using two doses, and the efficacy of the treatment will be evaluated exploratively. A total of three patients will be enrolled sequentially and followed for 24 weeks after administration. This study is designed as a multicenter trial, with Chiba University Hospital administering and evaluating the safety/efficacy of the investigational products at the prescribed visit.

Conclusion: This clinical trial is expected to facilitate the provision of lifelong treatment to many patients with LCAT deficiency.

Trial registration number: Japan Registry of Clinical Trials (jRCT2033200096).

Keywords: Adipocytes; Enzyme replacement therapy; Familial lecithin:cholesterol acyltransferase deficiency; Regenerative medicine; ex vivo gene therapy.