Shigeru Saito1, Kenichi Takagi2, Junji Moriya3, Takao Kobayashi4, Naohiro Kanayama5, Hiroshi Sameshima6, Mamoru Morikawa7, Haruhiko Sago8, Tomoko Adachi9, Akihide Ohkuchi10, Satoru Takeda11, Hisashi Masuyama12, Hiroyuki Seki13. 1. University of Toyama, Toyama, Japan. Electronic address: s30saito@med.u-toyama.ac.jp. 2. Clinical Development Center, R&D Division, Kyowa Kirin Co., Ltd., Tokyo, Japan. 3. Biometrics Group, R&D Division, Kyowa Kirin Co., Ltd., Tokyo, Japan. 4. Hamamatsu Medical Center, Shizuoka, Japan. 5. Shizuoka College of Medical Care Science, Shizuoka, Japan. 6. University of Miyazaki, Miyazaki, Japan. 7. Department of Obstetrics and Gynecology, Kansai Medical University, Osaka, Japan. 8. Center for Maternal-Fetal, Neonatal and Reproductive Medicine, National Center for Child Health and Development, Tokyo, Japan. 9. Imperial Gift Foundation, Aiiku Maternal and Child Health Center, Aiiku Hospital, Tokyo, Japan. 10. Department of Obstetrics and Gynecology, Jichi Medical University, Tochigi, Japan. 11. Department of Obstetrics and Gynecology, Graduate School of Medicine, Juntendo University, Tokyo, Japan. 12. Department of Obstetrics and Gynecology, Okayama University Hospital, Okayama, Japan. 13. Center for Maternal, Fetal and Neonatal Medicine, Saitama Medical Center, Saitama Medical University, Saitama, Japan.
Abstract
INTRODUCTION: Preeclampsia is a leading cause of maternal and perinatal morbidity and mortality. Several studies have demonstrated the beneficial effects of antithrombin replacement in patients with preeclampsia. Here, we describe the study protocol of KOUNO-TORI (KW-3357 randOmized, mUlti-center, double-bliNd, placebO-controlled phase 3 sTudy in patients with early Onset pReeclampsIa) to evaluate recombinant human antithrombin gamma (rhAT-gamma) for the treatment of early-onset severe de novo preeclampsia. MATERIAL AND METHODS: Patients with early-onset severe de novo preeclampsia who are ≥24 to <32 weeks pregnant at the time of registration and have an antithrombin activity of ≤100% at screening are included. The target population is selected based on a reanalysis of the data of a previous plasma-derived antithrombin phase 3 study. Primary endpoint is the prolongation of pregnancy from the initiation of rhAT-gamma treatment to the pregnancy termination. Secondary endpoints include gestational age in terms of achievement of 32- and 34-weeks'gestation, and gestational age in terms of achievement of 28 weeks' gestation for patients enrolled at <28 weeks' gestation. Maternal, fetal, and neonatal outcomes will be assessed. DISCUSSION: As we have selected a specifically defined target population based on reanalysis of data of a previous plasma-derived antithrombin phase 3 study, the results of our study are expected to provide efficacy and safety data concerning rhAT-gamma treatment in Japanese patients. This study could help identify an effective novel treatment for such patients with early-onset severe preeclampsia for whom appropriate treatment is unavailable.
INTRODUCTION: Preeclampsia is a leading cause of maternal and perinatal morbidity and mortality. Several studies have demonstrated the beneficial effects of antithrombin replacement in patients with preeclampsia. Here, we describe the study protocol of KOUNO-TORI (KW-3357 randOmized, mUlti-center, double-bliNd, placebO-controlled phase 3 sTudy in patients with early Onset pReeclampsIa) to evaluate recombinant human antithrombin gamma (rhAT-gamma) for the treatment of early-onset severe de novo preeclampsia. MATERIAL AND METHODS: Patients with early-onset severe de novo preeclampsia who are ≥24 to <32 weeks pregnant at the time of registration and have an antithrombin activity of ≤100% at screening are included. The target population is selected based on a reanalysis of the data of a previous plasma-derived antithrombin phase 3 study. Primary endpoint is the prolongation of pregnancy from the initiation of rhAT-gamma treatment to the pregnancy termination. Secondary endpoints include gestational age in terms of achievement of 32- and 34-weeks'gestation, and gestational age in terms of achievement of 28 weeks' gestation for patients enrolled at <28 weeks' gestation. Maternal, fetal, and neonatal outcomes will be assessed. DISCUSSION: As we have selected a specifically defined target population based on reanalysis of data of a previous plasma-derived antithrombin phase 3 study, the results of our study are expected to provide efficacy and safety data concerning rhAT-gamma treatment in Japanese patients. This study could help identify an effective novel treatment for such patients with early-onset severe preeclampsia for whom appropriate treatment is unavailable.