- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04182373
KW-3357 Study in Patients With Early Onset Severe Preeclampsia
A Phase 3, Randomized, Placebo-controlled, Double Blind Study of KW-3357 in Patients With Early Onset Severe Preeclampsia
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Contact
- Name: Kyowa Kirin Co., Ltd
- Phone Number: +81-3-5205-7200
- Email: clinical.info.jp@kyowakirin.com
Study Locations
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Aomori, Japan
- Aomori Prefectural Central Hospital
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Fukuoka, Japan
- Fukuoka University Hospital
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Kagoshima, Japan
- Kagoshima City Hospital
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Kumamoto, Japan
- Kumamoto University Hospital
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Kyoto, Japan
- Kyoto University Hospital
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Kyoto, Japan
- University Hospital Kyoto Prefectural University of Medicine
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Miyazaki, Japan
- Faculty of Medicine, University of Miyazaki Hospital
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Nagasaki, Japan
- Nagasaki University Hospital
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Nara, Japan
- Nara Prefecture General Medical Center
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Niigata, Japan
- Niigata University Medical & Dental Hospital
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Oita, Japan
- Oita Prefectural Hospital
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Okayama, Japan
- Okayama University Hospital
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Osaka, Japan
- Osaka City General Hospital
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Toyama, Japan
- Toyama University Hospital
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Aichi
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Nagoya, Aichi, Japan
- Japanese Red Cross Aichi Medical Center Nagoya Daiichi Hospital
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Toyoake, Aichi, Japan
- Fujita Health University Hospital
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Toyota, Aichi, Japan
- Toyota Memorial Hospital
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Chiba
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Urayasu, Chiba, Japan
- Juntendo University Urayasu Hospital
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Yachiyo, Chiba, Japan
- Tokyo Women's Medical University Yachiyo Medical Center
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Ehime
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Toon, Ehime, Japan
- Ehime University Hospital
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Fukuoka
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Kitakyushu, Fukuoka, Japan
- National Hospital Organization Kokura Medical Center
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Kurume, Fukuoka, Japan
- Kurume University Hospital
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Kurume, Fukuoka, Japan
- Our Lady of the Snow Social Medical Corporation St. Mary's Hospital
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Hokkaido
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Hakodate, Hokkaido, Japan
- Hakodate Central General Hospital
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Obihiro, Hokkaido, Japan
- Obihiro Kosei General Hospital
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Sapporo, Hokkaido, Japan
- Hokkaido University Hospital
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Sapporo, Hokkaido, Japan
- Sapporo City General Hospital
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Hyogo
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Himeji, Hyogo, Japan
- Japanese Red Cross Society Himeji Hospital
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Kobe, Hyogo, Japan
- Kobe University Hospital
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Ishikawa
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Kanazawa, Ishikawa, Japan
- Ishikawa Prefectural Central Hospital
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Iwate
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Shiwa, Iwate, Japan
- Iwate Medical University Hospital
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Kagawa
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Zentsuji, Kagawa, Japan
- National Hospital Organization Shikoku Medical Center for Children and Adults
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Kanagawa
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Kawasaki, Kanagawa, Japan
- St. Marianna University School of Medicine
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Sagamihara, Kanagawa, Japan
- The Kitasato Institute Kitasato University Hospital
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Yokohama, Kanagawa, Japan
- Yokohama City University Medical Center
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Mie
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Tsu, Mie, Japan
- Mie University Hospital
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Miyagi
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Sendai, Miyagi, Japan
- Sendai Red Cross Hospital
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Nagano
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Matsumoto, Nagano, Japan
- Shinshu University Hospital
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Nagasaki
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Omura, Nagasaki, Japan
- National Hospital Organization Nagasaki Medical Center
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Nara
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Kashihara, Nara, Japan
- Nara Medical University Hospital
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Okinawa
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Uruma, Okinawa, Japan
- Okinawa prefectural Chubu Hospital
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Osaka
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Abeno-ku, Osaka, Japan
- Osaka Metropolitan University Hospital
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Hirakata, Osaka, Japan
- Kansai Medical University Hospital
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Izumi, Osaka, Japan
- Osaka Women's and Children's Hospital
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Izumisano, Osaka, Japan
- Rinku General Medical Center
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Suita, Osaka, Japan
- National Cerebral and Cardiovascular Center
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Saitama
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Kawagoe, Saitama, Japan
- Saitama Medical Center
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Shizuoka
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Hamamatsu, Shizuoka, Japan
- Hamamatsu University Hospital
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Hamamatsu, Shizuoka, Japan
- Hamamatsu Medical Center
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Izunokuni, Shizuoka, Japan
- Juntendo University Shizuoka Hospital
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Tochigi
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Mibu, Tochigi, Japan
- Dokkyo Medical University Hospital
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Shimotsuke, Tochigi, Japan
- Jichi Medical University Hospital
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Tokyo
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Bunkyo, Tokyo, Japan
- The University of Tokyo Hospital
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Bunkyo-ku, Tokyo, Japan
- Juntendo University Hospital
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Fuchu, Tokyo, Japan
- Tokyo Metropolitan Tama Medical Center
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Minato, Tokyo, Japan
- Aiiku Hospital
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Mitaka, Tokyo, Japan
- Kyorin University Hospital
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Setagaya, Tokyo, Japan
- National Center for Child Health and Development
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Shibuya, Tokyo, Japan
- Japanese Red Cross Medical Center
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Shinagawa, Tokyo, Japan
- Showa University Hospital
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Sumida, Tokyo, Japan
- Tokyo Metropolitan Bokutoh Hospital
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Yamaguchi
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Ube, Yamaguchi, Japan
- Yamaguchi University Hospital
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Yamanashi
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Kofu, Yamanashi, Japan
- Yamanashi Prefectural Central Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Patients who gave written consent to participate in the clinical trial by their own free will.
- Patients aged 18 years or older at the time of obtaining informed consent
Patients with early-onset PE* 24 weeks 0 days to 31 weeks 6 days of gestation at the time of enrollment
*: Determine the definition of gestational age based on the ""Guidelines for Obstetrics and Gynecology, Obstetrics, 2020""
Patients diagnosed with severe PE*
*: Follow the diagnostic criteria of the Japan Society for the Study of Hypertension in Pregnancy
- Patients with AT activity of 100% or less in the preliminary examination
Exclusion Criteria:
Patients who are judged to require immediate delivery*
*""Best Practice Guide 2015 for Care and Treatment of Hypertension in Pregnancy"" Requirements for Considering Pregnancy Termination Regardless of Pregnancy Weeks in Pregnancy-induced Hypertension Syndrome Cases will be consulted for judgment.
- Patients with right hypochondralgia or epigastralgia
- Patients with HELLP syndromes
- Patients with pulmonary edema
- Patients with severe pleural effusion, severe ascites, or serous retinal detachment
- Patients with central nervous system disorders (eclampsia, stroke) or visual disorders (cortical blindness)
- Patients with severe headache or urge eclampsia
- Patients with abruptio placentae
- Suspected patients with 8 or more obstetric DIC scores
- Patients with a definitive diagnosis of congenital AT deficiency
- Patients with diseases or symptoms other than the primary disease requiring immediate delivery
- Patients on ongoing treatment with nonsteroidal anti-inflammatory drugs (NSAIDs, e.g., aspirin) or who require NSAIDs use during the course of the study.
- Patients who have received the following drugs within 72 hours before administration of the investigational product, etc., or who require administration of the following drugs during the study period (from the start of administration of the investigational product, etc., until the date of termination of pregnancy); heparin, low-molecular-weight heparin (e.g., enoxaparin ordalteparin), fondaparinux, antiplatelet drugs (e.g., clopidogrel, prasugrel, aspirin), direct thrombin inhibitors (e.g., dabigatran), or anticoagulants (e.g., AT preparations).
- Patients with a current or past history of serious drug allergy
- Patients with a history or complication of drug dependence or alcoholism
- Patients with hypersensitivity to AT preparations
- Patients who are pregnant with a fetus with a chromosomal abnormality or a fetus suspected of having a serious malformation syndrome
- Patients with multiple pregnancies
- Patients with a history or complication of antiphospholipid antibody syndrome
- Patients with diabetes complicated pregnancy or obvious diabetes mellitus
Patients with uncontrollable or significant complications, including the following
- Clinically significant cardiovascular diseases, etc. (New York Heart Association cardiac function classifications Class III or higher)
- Serious hepatic disease
- Serious renal disease
- Pneumonia, interstitial lung disease or other severe respiratory disease
- Blood disorders such as idiopathic thrombocytopenic purpura
- Psycho-central nervous system disorders that may affect informed consent
- Endocrine disorders such as hyperthyroidism
- Autoimmune diseases such as systemic lupus erythematosus
- Patients with active malignancy or patients with a history of onset or treatment of malignancy within 5 years before pregnancy (excluding excised or surgically cured basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or ductal carcinoma of the breast, and excluding cervical intraepithelial neoplasia regardless of excised or surgically cured or not)
- Patients with active infections (e.g., toxoplasma infection, genital chlamydia, genital herpes, cytomegalovirus infection)
- Patients with a positive history for HIV antibody. Patients with a positive history for HBs antigen and HCV antibody and with active infection presenting with hepatitis symptoms.
Patients with any of the following laboratory abnormalities in preliminary examinations
- Patients with AST or ALT 2 times the upper limit of the reference level of the trial site
- Cr >=1.1 mg/dL
- Patients who have participated in a clinical trial or equivalent study of a drug or medical device within 4 months before pregnancy (within 6 months for biologics) and have received the investigational drug or used an unapproved medical device
- Other patients whom the principal investigator or the subinvestigator judges to be unfavorable for participation in the clinical trial
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: placebo
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Intravenous infusion, once a day, 7 days
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Experimental: KW-3357
72 IU/kg
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Intravenous infusion, once a day, 7 days
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Days of maintaining pregnancy
Time Frame: Subjects will be observed until maternal and/or fetal indications for delivery necessitate cessation of expectant management or until approximately 34 0/7 weeks of gestation.
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Subjects will be observed until maternal and/or fetal indications for delivery necessitate cessation of expectant management or until approximately 34 0/7 weeks of gestation.
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Presence or absence of achievement of 32 weeks of gestation
Time Frame: 28 days before the end of study
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28 days before the end of study
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Presence or absence of achievement of 34 weeks of gestation
Time Frame: 28 days before the end of study
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28 days before the end of study
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Presence or absence of achievement of 28 weeks of gestation in subjects enrolled in the period of less than 28 weeks of gestation
Time Frame: 28 days before the end of study
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28 days before the end of study
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Change in AT activity
Time Frame: From baseline to Day 8 at all time points and 3 days after termination of pregnancy
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From baseline to Day 8 at all time points and 3 days after termination of pregnancy
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Change in PLT concentration
Time Frame: From baseline to Day 8 at all time points and 3 days after termination of pregnancy
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From baseline to Day 8 at all time points and 3 days after termination of pregnancy
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Change on D-dimer concentration
Time Frame: From baseline to Day 8 at all time points
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From baseline to Day 8 at all time points
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Change in FDP concentration
Time Frame: From baseline to Day 8 at all time points
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From baseline to Day 8 at all time points
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Sitting systolic blood pressure and sitting diastolic blood pressure
Time Frame: From baseline to Day 8 at each time point, 3 days after termination of pregnancy, and 28 days after termination of pregnancy
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From baseline to Day 8 at each time point, 3 days after termination of pregnancy, and 28 days after termination of pregnancy
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Proteinuria/creatinine ratio
Time Frame: From baseline to Day 8 at each time point, 3 days after termination of pregnancy, and 28 days after termination of pregnancy
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From baseline to Day 8 at each time point, 3 days after termination of pregnancy, and 28 days after termination of pregnancy
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Amount of blood lost during delivery
Time Frame: 28 days before the end of study
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28 days before the end of study
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Biophysical Profile Score
Time Frame: From baseline to Day 8 at each time point
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Minimum is 0, max is 10.
Higher score means better condition.
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From baseline to Day 8 at each time point
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Fetal growth rate
Time Frame: 28 days before the end of study
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28 days before the end of study
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Apgar score
Time Frame: At 1 minute and 5 minutes after birth
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Minimum is 0, max is 10.
Higher score means better condition.
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At 1 minute and 5 minutes after birth
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Presence or absence of neonatal asphyxia
Time Frame: At 1 minute and 5 minutes after birth
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At 1 minute and 5 minutes after birth
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Birth weight
Time Frame: 28 days before the end of study
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28 days before the end of study
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Neonatal growth
Time Frame: 28 days before the end of study
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Fetal growth is classified into small for gestational age (SGA), appropriate for gestational age (AGA), and large for gestational age (LGA).
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28 days before the end of study
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Head and chest circumferences at birth
Time Frame: 28 days before the end of study
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28 days before the end of study
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Short-term prognosis of neonates (incidence of bronchopulmonary dysplasia, intraventricular hemorrhage, periventricular leukolame, retinopathy of prematurity, sepsis, necrotizing enteritis, death, etc)
Time Frame: 28 days after termination of pregnancy
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28 days after termination of pregnancy
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The number of neonates who was hospitalized in the NICU
Time Frame: 28 days after termination of pregnancy
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28 days after termination of pregnancy
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The number of days in the NICU
Time Frame: 28 days after termination of pregnancy
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28 days after termination of pregnancy
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The number of neonates with respiratory management at the time of admission to the NICU
Time Frame: 28 days after termination of pregnancy
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28 days after termination of pregnancy
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The number of days of respiratory management at the time of admission to the NICU
Time Frame: 28 days after termination of pregnancy
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28 days after termination of pregnancy
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Other Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Change in TNF-alpha at the time of examination
Time Frame: From baseline to Day 8
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From baseline to Day 8
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Change in interleukin (IL)-6 at the time of examination
Time Frame: From baseline to Day 8
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From baseline to Day 8
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Change in IL-10 at the time of examination
Time Frame: From baseline to Day 8
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From baseline to Day 8
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Change in hs-CRP at the time of examination
Time Frame: From baseline to Day 8
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From baseline to Day 8
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Change in sFlt-1 at the time of examination
Time Frame: From baseline to Day 8
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From baseline to Day 8
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Change in PlGF at the time of examination
Time Frame: From baseline to Day 8
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From baseline to Day 8
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Change in sFlt-1/PlGF at the time of examination
Time Frame: From baseline to Day 8
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From baseline to Day 8
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Pulsatility index of the umbilical artery and middle cerebral artery
Time Frame: At the time of examination from baseline to Day 8
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At the time of examination from baseline to Day 8
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Change in findings of the umbilical artery and middle cerebral artery
Time Frame: At the time of examination from baseline to Day 8
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At the time of examination from baseline to Day 8
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Distribution of reasons for termination of pregnancy
Time Frame: 28 days before the end of study
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28 days before the end of study
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Prolongation days of pregnancy by reason of termination of pregnancy
Time Frame: 28 days before the end of study
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28 days before the end of study
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Mode of delivery
Time Frame: 28 days before the end of study
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28 days before the end of study
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Presence or absence of stillbirth
Time Frame: 28 days before the end of study. Neonates will be assessed after delivery.
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28 days before the end of study. Neonates will be assessed after delivery.
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Placental weight
Time Frame: 28 days before the end of study
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28 days before the end of study
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Presence or absence of placental infarction
Time Frame: 28 days before the end of study
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28 days before the end of study
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Umbilical arterial blood gas at termination of pregnancy
Time Frame: 28 days before the end of study
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28 days before the end of study
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Presence or absence of HELLP syndromes and onset of symptoms
Time Frame: During the course of the clinical trial. Period from the day of commencement of administration of the investigational drug to Day 28 after the delivery
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During the course of the clinical trial. Period from the day of commencement of administration of the investigational drug to Day 28 after the delivery
|
Collaborators and Investigators
Sponsor
Collaborators
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pregnancy Complications
- Hypertension, Pregnancy-Induced
- Female Urogenital Diseases and Pregnancy Complications
- Urogenital Diseases
- Pre-Eclampsia
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Protease Inhibitors
- Serine Proteinase Inhibitors
- Anticoagulants
- Antithrombins
- Antithrombin III
Other Study ID Numbers
- 3357-101
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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