KW-3357 Study in Patients With Early Onset Severe Preeclampsia

November 13, 2023 updated by: Kyowa Kirin Co., Ltd.

A Phase 3, Randomized, Placebo-controlled, Double Blind Study of KW-3357 in Patients With Early Onset Severe Preeclampsia

The purpose of this study is to evaluate the efficacy of intravenous KW-3357 in patients with early-onset severe preeclampsia by comparing the prolongation days of pregnancy with that of placebo.

Study Overview

Status

Completed

Conditions

Study Type

Interventional

Enrollment (Actual)

181

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

      • Aomori, Japan
        • Aomori Prefectural Central Hospital
      • Fukuoka, Japan
        • Fukuoka University Hospital
      • Kagoshima, Japan
        • Kagoshima City Hospital
      • Kumamoto, Japan
        • Kumamoto University Hospital
      • Kyoto, Japan
        • Kyoto University Hospital
      • Kyoto, Japan
        • University Hospital Kyoto Prefectural University of Medicine
      • Miyazaki, Japan
        • Faculty of Medicine, University of Miyazaki Hospital
      • Nagasaki, Japan
        • Nagasaki University Hospital
      • Nara, Japan
        • Nara Prefecture General Medical Center
      • Niigata, Japan
        • Niigata University Medical & Dental Hospital
      • Oita, Japan
        • Oita Prefectural Hospital
      • Okayama, Japan
        • Okayama University Hospital
      • Osaka, Japan
        • Osaka City General Hospital
      • Toyama, Japan
        • Toyama University Hospital
    • Aichi
      • Nagoya, Aichi, Japan
        • Japanese Red Cross Aichi Medical Center Nagoya Daiichi Hospital
      • Toyoake, Aichi, Japan
        • Fujita Health University Hospital
      • Toyota, Aichi, Japan
        • Toyota Memorial Hospital
    • Chiba
      • Urayasu, Chiba, Japan
        • Juntendo University Urayasu Hospital
      • Yachiyo, Chiba, Japan
        • Tokyo Women's Medical University Yachiyo Medical Center
    • Ehime
      • Toon, Ehime, Japan
        • Ehime University Hospital
    • Fukuoka
      • Kitakyushu, Fukuoka, Japan
        • National Hospital Organization Kokura Medical Center
      • Kurume, Fukuoka, Japan
        • Kurume University Hospital
      • Kurume, Fukuoka, Japan
        • Our Lady of the Snow Social Medical Corporation St. Mary's Hospital
    • Hokkaido
      • Hakodate, Hokkaido, Japan
        • Hakodate Central General Hospital
      • Obihiro, Hokkaido, Japan
        • Obihiro Kosei General Hospital
      • Sapporo, Hokkaido, Japan
        • Hokkaido University Hospital
      • Sapporo, Hokkaido, Japan
        • Sapporo City General Hospital
    • Hyogo
      • Himeji, Hyogo, Japan
        • Japanese Red Cross Society Himeji Hospital
      • Kobe, Hyogo, Japan
        • Kobe University Hospital
    • Ishikawa
      • Kanazawa, Ishikawa, Japan
        • Ishikawa Prefectural Central Hospital
    • Iwate
      • Shiwa, Iwate, Japan
        • Iwate Medical University Hospital
    • Kagawa
      • Zentsuji, Kagawa, Japan
        • National Hospital Organization Shikoku Medical Center for Children and Adults
    • Kanagawa
      • Kawasaki, Kanagawa, Japan
        • St. Marianna University School of Medicine
      • Sagamihara, Kanagawa, Japan
        • The Kitasato Institute Kitasato University Hospital
      • Yokohama, Kanagawa, Japan
        • Yokohama City University Medical Center
    • Mie
      • Tsu, Mie, Japan
        • Mie University Hospital
    • Miyagi
      • Sendai, Miyagi, Japan
        • Sendai Red Cross Hospital
    • Nagano
      • Matsumoto, Nagano, Japan
        • Shinshu University Hospital
    • Nagasaki
      • Omura, Nagasaki, Japan
        • National Hospital Organization Nagasaki Medical Center
    • Nara
      • Kashihara, Nara, Japan
        • Nara Medical University Hospital
    • Okinawa
      • Uruma, Okinawa, Japan
        • Okinawa prefectural Chubu Hospital
    • Osaka
      • Abeno-ku, Osaka, Japan
        • Osaka Metropolitan University Hospital
      • Hirakata, Osaka, Japan
        • Kansai Medical University Hospital
      • Izumi, Osaka, Japan
        • Osaka Women's and Children's Hospital
      • Izumisano, Osaka, Japan
        • Rinku General Medical Center
      • Suita, Osaka, Japan
        • National Cerebral and Cardiovascular Center
    • Saitama
      • Kawagoe, Saitama, Japan
        • Saitama Medical Center
    • Shizuoka
      • Hamamatsu, Shizuoka, Japan
        • Hamamatsu University Hospital
      • Hamamatsu, Shizuoka, Japan
        • Hamamatsu Medical Center
      • Izunokuni, Shizuoka, Japan
        • Juntendo University Shizuoka Hospital
    • Tochigi
      • Mibu, Tochigi, Japan
        • Dokkyo Medical University Hospital
      • Shimotsuke, Tochigi, Japan
        • Jichi Medical University Hospital
    • Tokyo
      • Bunkyo, Tokyo, Japan
        • The University of Tokyo Hospital
      • Bunkyo-ku, Tokyo, Japan
        • Juntendo University Hospital
      • Fuchu, Tokyo, Japan
        • Tokyo Metropolitan Tama Medical Center
      • Minato, Tokyo, Japan
        • Aiiku Hospital
      • Mitaka, Tokyo, Japan
        • Kyorin University Hospital
      • Setagaya, Tokyo, Japan
        • National Center for Child Health and Development
      • Shibuya, Tokyo, Japan
        • Japanese Red Cross Medical Center
      • Shinagawa, Tokyo, Japan
        • Showa University Hospital
      • Sumida, Tokyo, Japan
        • Tokyo Metropolitan Bokutoh Hospital
    • Yamaguchi
      • Ube, Yamaguchi, Japan
        • Yamaguchi University Hospital
    • Yamanashi
      • Kofu, Yamanashi, Japan
        • Yamanashi Prefectural Central Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Patients who gave written consent to participate in the clinical trial by their own free will.
  2. Patients aged 18 years or older at the time of obtaining informed consent
  3. 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""

  4. Patients diagnosed with severe PE*

    *: Follow the diagnostic criteria of the Japan Society for the Study of Hypertension in Pregnancy

  5. Patients with AT activity of 100% or less in the preliminary examination

Exclusion Criteria:

  1. 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.

  2. Patients with right hypochondralgia or epigastralgia
  3. Patients with HELLP syndromes
  4. Patients with pulmonary edema
  5. Patients with severe pleural effusion, severe ascites, or serous retinal detachment
  6. Patients with central nervous system disorders (eclampsia, stroke) or visual disorders (cortical blindness)
  7. Patients with severe headache or urge eclampsia
  8. Patients with abruptio placentae
  9. Suspected patients with 8 or more obstetric DIC scores
  10. Patients with a definitive diagnosis of congenital AT deficiency
  11. Patients with diseases or symptoms other than the primary disease requiring immediate delivery
  12. Patients on ongoing treatment with nonsteroidal anti-inflammatory drugs (NSAIDs, e.g., aspirin) or who require NSAIDs use during the course of the study.
  13. 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).
  14. Patients with a current or past history of serious drug allergy
  15. Patients with a history or complication of drug dependence or alcoholism
  16. Patients with hypersensitivity to AT preparations
  17. Patients who are pregnant with a fetus with a chromosomal abnormality or a fetus suspected of having a serious malformation syndrome
  18. Patients with multiple pregnancies
  19. Patients with a history or complication of antiphospholipid antibody syndrome
  20. Patients with diabetes complicated pregnancy or obvious diabetes mellitus
  21. 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
  22. 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)
  23. Patients with active infections (e.g., toxoplasma infection, genital chlamydia, genital herpes, cytomegalovirus infection)
  24. 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.
  25. 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
  26. 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
  27. Other patients whom the principal investigator or the subinvestigator judges to be unfavorable for participation in the clinical trial

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

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
Intravenous infusion, once a day, 7 days
Experimental: KW-3357
72 IU/kg
Intravenous infusion, once a day, 7 days

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.
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.

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
28 days before the end of study
Presence or absence of achievement of 34 weeks of gestation
Time Frame: 28 days before the end of study
28 days before the end of study
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
28 days before the end of study
Change in AT activity
Time Frame: From baseline to Day 8 at all time points and 3 days after termination of pregnancy
From baseline to Day 8 at all time points and 3 days after termination of pregnancy
Change in PLT concentration
Time Frame: From baseline to Day 8 at all time points and 3 days after termination of pregnancy
From baseline to Day 8 at all time points and 3 days after termination of pregnancy
Change on D-dimer concentration
Time Frame: From baseline to Day 8 at all time points
From baseline to Day 8 at all time points
Change in FDP concentration
Time Frame: From baseline to Day 8 at all time points
From baseline to Day 8 at all time points
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
From baseline to Day 8 at each time point, 3 days after termination of pregnancy, and 28 days after termination of pregnancy
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
From baseline to Day 8 at each time point, 3 days after termination of pregnancy, and 28 days after termination of pregnancy
Amount of blood lost during delivery
Time Frame: 28 days before the end of study
28 days before the end of study
Biophysical Profile Score
Time Frame: From baseline to Day 8 at each time point
Minimum is 0, max is 10. Higher score means better condition.
From baseline to Day 8 at each time point
Fetal growth rate
Time Frame: 28 days before the end of study
28 days before the end of study
Apgar score
Time Frame: At 1 minute and 5 minutes after birth
Minimum is 0, max is 10. Higher score means better condition.
At 1 minute and 5 minutes after birth
Presence or absence of neonatal asphyxia
Time Frame: At 1 minute and 5 minutes after birth
At 1 minute and 5 minutes after birth
Birth weight
Time Frame: 28 days before the end of study
28 days before the end of study
Neonatal growth
Time Frame: 28 days before the end of study
Fetal growth is classified into small for gestational age (SGA), appropriate for gestational age (AGA), and large for gestational age (LGA).
28 days before the end of study
Head and chest circumferences at birth
Time Frame: 28 days before the end of study
28 days before the end of study
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
28 days after termination of pregnancy
The number of neonates who was hospitalized in the NICU
Time Frame: 28 days after termination of pregnancy
28 days after termination of pregnancy
The number of days in the NICU
Time Frame: 28 days after termination of pregnancy
28 days after termination of pregnancy
The number of neonates with respiratory management at the time of admission to the NICU
Time Frame: 28 days after termination of pregnancy
28 days after termination of pregnancy
The number of days of respiratory management at the time of admission to the NICU
Time Frame: 28 days after termination of pregnancy
28 days after termination of pregnancy

Other Outcome Measures

Outcome Measure
Time Frame
Change in TNF-alpha at the time of examination
Time Frame: From baseline to Day 8
From baseline to Day 8
Change in interleukin (IL)-6 at the time of examination
Time Frame: From baseline to Day 8
From baseline to Day 8
Change in IL-10 at the time of examination
Time Frame: From baseline to Day 8
From baseline to Day 8
Change in hs-CRP at the time of examination
Time Frame: From baseline to Day 8
From baseline to Day 8
Change in sFlt-1 at the time of examination
Time Frame: From baseline to Day 8
From baseline to Day 8
Change in PlGF at the time of examination
Time Frame: From baseline to Day 8
From baseline to Day 8
Change in sFlt-1/PlGF at the time of examination
Time Frame: From baseline to Day 8
From baseline to Day 8
Pulsatility index of the umbilical artery and middle cerebral artery
Time Frame: At the time of examination from baseline to Day 8
At the time of examination from baseline to Day 8
Change in findings of the umbilical artery and middle cerebral artery
Time Frame: At the time of examination from baseline to Day 8
At the time of examination from baseline to Day 8
Distribution of reasons for termination of pregnancy
Time Frame: 28 days before the end of study
28 days before the end of study
Prolongation days of pregnancy by reason of termination of pregnancy
Time Frame: 28 days before the end of study
28 days before the end of study
Mode of delivery
Time Frame: 28 days before the end of study
28 days before the end of study
Presence or absence of stillbirth
Time Frame: 28 days before the end of study. Neonates will be assessed after delivery.
28 days before the end of study. Neonates will be assessed after delivery.
Placental weight
Time Frame: 28 days before the end of study
28 days before the end of study
Presence or absence of placental infarction
Time Frame: 28 days before the end of study
28 days before the end of study
Umbilical arterial blood gas at termination of pregnancy
Time Frame: 28 days before the end of study
28 days before the end of study
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
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

This is where you will find people and organizations involved with this study.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 19, 2019

Primary Completion (Actual)

May 17, 2023

Study Completion (Actual)

June 16, 2023

Study Registration Dates

First Submitted

October 10, 2019

First Submitted That Met QC Criteria

November 27, 2019

First Posted (Actual)

December 2, 2019

Study Record Updates

Last Update Posted (Actual)

November 15, 2023

Last Update Submitted That Met QC Criteria

November 13, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

The datasets generated and/or analyzed during the study sponsored by Kyowa Kirin will be available in the Vivli repository, https://vivli.org/ourmember/kyowa-kirin/ as long as conditions of data disclosure specified in the policy section of the Vivli website are satisfied.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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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