OC 26.2 - A dose-escalation phase 1 clinical trial of autologous iPSC-derived platelets (iPLAT1)

Sunday, July 10, 2022

3:00 PM – 3:15 PM

Location: ExCel Center, ICC Capital Suite Room 10&11

Presentation Format: Virtual

Presenting Author(s)

NS

Naoshi Sugimoto

Program-Specific Junior Associate Professor
Center for iPS Cell Research and Application, Kyoto University
Kyoto, Kyoto, Japan

Co-Author(s)

JK

Junya Kanda

Associate Professor
Department of Hematology, Kyoto University Hospital
Kyoto, Kyoto, Japan
SN

Sou Nakamura

Program-Specific Assistant Professor
Kyoto University
Kyoto, Kyoto, Japan
TK

Toshiyuki Kitano

Assistant Professor
Kyoto University Hospital
Kyoto, Kyoto, Japan
SS

Shin Shimizu

Researcher
Center for iPS Cell Research and Application, Kyoto University
Kyoto, Kyoto, Japan
AS

Akiko Shigemasa

Researcher
Center for iPS Cell Research and Application, Kyoto University
Kyoto, Kyoto, Japan
HH

Hideyo Hirai

Assistant Professor
Kyoto University Hospital
Kyoto, Kyoto, Japan
MM

Manabu Minami

Associate Professor
Kyoto University Hospital
Kyoto, Kyoto, Japan
HT

Harue Tada

Associate Professor
Kyoto University Hospital
Kyoto, Kyoto, Japan
DM

Dai Momose

Doctor
Osaka General Hospital of West Japan Railway Company
Osaka, Osaka, Japan
KK

Ki-Ryang Koh

Head of Department
Osaka General Hospital of West Japan Railway Company
Osaka, Osaka, Japan
MN

Masayuki Nogawa

Researcher
Keio University School of Medicine
Tokyo, Tokyo, Japan
NW

Naohide Watanabe

Associate Professor
Keio University School of Medicine
Tokyo, Tokyo, Japan
MH

Makoto Handa

Professor
Keio University School of Medicine
Tokyo, Tokyo, Japan
AS

Akira Sawaguchi

Professor
Department of Anatomy, Faculty of Medicine, University of Miyazaki
Miyazaki, Miyazaki, Japan
MT

Mitsunobu Tanaka

Section Chief
Japanese Red Cross Society
Osaka, Osaka, Japan
TH

Tomoya Hayashi

Researcher
Japanese Red Cross Society
Osaka, Osaka, Japan
YT

Yoshihiko Tani

Director
Japanese Red Cross Society
Osaka, Osaka, Japan
AT

Akifumi Takaori-Kondo

Professor
Department of Hematology, Kyoto University Hospital
Kyoto, Kyoto, Japan
KE

Koji Eto

professor
Center for iPS Cell Research and Application, Kyoto University
Kyoto, Kyoto, Japan

Background: Platelet products are provided from blood banks which collect blood from healthy donors. However, approximately 5% of platelet transfusion patients are complicated with alloimmune platelet transfusion refractoriness (allo-PTR) due to alloantibodies against class I human leukocyte antigens (HLA-I) or human platelet antigens (HPA). In these cases, platelets from compatible donors are transfused, but for patients with rare HLA-I or HPA, donors are difficult to find. Aiming to ultimately solve this issue, we had developed ex vivo production system of iPSC-derived platelet products (iPSC-PLTs).

Aims: We aimed to assess the safety and efficacy of autologous iPSC-PLTs in an aplastic anemia patient with allo-PTR due to rare HPA-1 mismatch in Japan.

Methods: The iPSC-PLTs were produced from megakaryocyte cell lines (imMKCLs) established from patient iPSCs using turbulent flow bioreactors and new drugs. In preclinical studies, iPSC-PLTs were confirmed for quality, safety, and efficacy, including hemostasis in animal models. We then performed the first-in-human clinical trial of iPSC-PLTs as a phase I study of autologous transfusion. Three escalating doses of 0.1 x 1011, 0.3 x 1011 and 1 x 1011 iPSC-PLTs were sequentially administered.

Results: The primary endpoint was safety, and no significant adverse event was observed over one year. The secondary endpoint of corrected count increment showed no significant change in all dose cohorts. Circulation of larger size possibly iPSC-PLTs was observed, but there was also a slight increase in d-dimer.

Conclusion(s): This first-in-human clinical trial provides extensive resource of successful GMP-based production of iPSC-PLTs with no significant adverse event profile, as well as issues that needs to be overcome, thereby marking a first benchmark in realizing iPSC-PLTs as a clinical measure. (Funded by the Japan Agency for Medical Research and Development; This trial was registered at Japan Registry of Clinical Trials as jRCTa050190117)