KW-3357 Study in Patients With Early Onset Severe Preeclampsia

Overview

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.

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

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Double (Participant, Investigator)
  • Study Primary Completion Date: May 2022

Interventions

  • Drug: Antithrombin gamma
    • Intravenous infusion, once a day, 7 days
  • Drug: physiological saline
    • Intravenous infusion, once a day, 7 days

Arms, Groups and Cohorts

  • Experimental: KW-3357
    • 72 IU/kg
  • Placebo Comparator: placebo

Clinical Trial Outcome Measures

Primary Measures

  • 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.

Secondary Measures

  • Presence or absence of achievement of 32 weeks of gestation
    • Time Frame: 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
  • 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
  • Change in AT activity
    • Time Frame: 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
  • Change on D-dimer concentration
    • Time Frame: From baseline to Day 8 at all time points
  • Change in FDP concentration
    • Time Frame: 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
  • 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
  • Amount of blood lost during delivery
    • Time Frame: 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.
  • Fetal growth rate
    • Time Frame: 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.
  • Presence or absence of neonatal asphyxia
    • Time Frame: At 1 minute and 5 minutes after birth
  • Birth weight
    • Time Frame: 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).
  • Head and chest circumferences at birth
    • Time Frame: 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
  • The number of neonates who was hospitalized in the NICU
    • Time Frame: 28 days after termination of pregnancy
  • The number of days in the NICU
    • Time Frame: 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
  • The number of days of respiratory management at the time of admission to the NICU
    • Time Frame: 28 days after termination of pregnancy

Participating in This Clinical Trial

Inclusion Criteria

1. Patients who gave written consent to participate in the clinical trial by their own free will.

2. Patients aged 20 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, 2017"

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 or dalteparin), 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, obvious diabetes mellitus, or insulin use

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)

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

Gender Eligibility: Female

Minimum Age: 20 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Kyowa Kirin Co., Ltd.
  • Collaborator
    • Japan Blood Products Organization
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Contact(s)
    • Kyowa Kirin Co., Ltd, +81-3-5205-7200, clinical.info.jp@kyowakirin.com

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