A Feasibility Study to Evaluate the Safety of the KNP-1000 Apheresis System in Severe Preeclampsia

A Feasibility Study to Evaluate the Safety of the KNP-1000 Apheresis System in Patients With Preeclampsia With Severe Features

The study will primarily evaluate safety of the KNP-1000 apheresis system for pregnant women and their fetuses diagnosed with preeclampsia with severe features between 23- and 32-weeks' gestation (very preterm).

Study Overview

• Status: Not yet recruiting
• Conditions: Pre-Eclampsia, Severe
• Intervention / Treatment: Device: KNP-1000 Apheresis System

• Study Type: Interventional
• Enrollment (Estimated): 13
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Takashi Shimai; Phone Number: 5105988423; Email: Takashi.Shimai@kaneka.com
• Study Contact Backup: Name: Takuji Nishide; Phone Number: 5102030212; Email: Takuji.Nishide@kaneka.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

A participant is deemed suitable for inclusion in the investigation if she meets the following criteria:

1. Pregnant woman ≥ 23 0/7 and < 32 0/7 weeks gestation, aged 18 to 45 years, hospitalized for preeclampsia at time of enrollment.
2. Severe hypertension ever defined by resting systolic BP ≥ 160 mm Hg and/or diastolic BP ≥ 110 mm Hg on two occasions measured at least 4 hours apart.
3. Proteinuria, defined as ≥ 300 mg protein in a 24-hour urine collection or ≥ 0.3 protein/creatinine ratio.
4. Provision of signed and dated informed consent form.

Exclusion Criteria:

A participant will be excluded from the investigation if any of the following maternal or fetal criteria are met.

Maternal Exclusion Criteria:

1. Documented history of chronic hypertension, defined as systolic BP ≥ 140mmHg and/or systolic BP ≥ 90 mmHg before pregnancy or prior to 20 weeks of gestation.
2. Documented history of proteinuria prior to pregnancy or prior to 20 weeks of gestation.
3. Taking any form of angiotensin cascade blocker or angiotensin-converting enzyme (ACE) inhibitor at time of enrollment.
4. Documented history of cardiac impairments including uncontrolled arrhythmia, unstable angina, decompensated congestive heart failure, or valvular disease.
5. Actively receiving therapeutic anticoagulation therapy or within the therapeutic window after ceasing anticoagulation therapy at the time of enrollment.
6. Any condition which, in the opinion of the Investigator, would necessitate immediate delivery within 24 hours.
7. Signs or history of cerebral nervous system dysfunction, including seizures, cerebral edema (previously confirmed by computed tomography scan or magnetic resonance imaging per medical records).
8. Confirmed or suspected diagnosis of pulmonary edema at time of enrollment.
9. Diagnosis of HELLP syndrome.
10. Thrombocytopenia (platelet count < 100,000/mm3) at time of enrollment.
11. Anemia defined as hemoglobin < 8 g/dL at time of enrollment.
12. Absent or reverse flow on umbilical Doppler ultrasound exam at the time of screening, or documented history of negative or reverse flow during the current gestation period.
13. Diagnosis of placenta previa during the current gestation period.
14. Preterm labor at or before time of screening.
15. Documented medical history of active hepatitis B virus, hepatitis C virus (HCV), syphilis, tuberculosis infection, or human immunodeficiency virus (HIV) positive status.
16. Any condition that the Investigator deems a risk to the study participant or fetus in completing the investigation.
17. Hypersensitivity to dextran sulfate cellulose or heparin.
18. Multiple gestation.
19. Documented history of familial hypercholesterolemia.
20. Suspicion or diagnosis of placental abruption during the current gestation.
21. Patients who have received the drug treatment not recommended by the American College of Obstetricians and Gynecologists (ACOG) practice bulletin Gestational Hypertension and Preeclampsia (the clinical management guidelines) within 6 months prior to enrollment.
22. Patients who have participated in another clinical trial within 6 months prior to enrollment.

Fetal Exclusion Criteria:

1. Documented record of chromosomal anomalies.
2. Identifiable structural fetal abnormalities present at time of screening or a record of such abnormalities prior to enrollment.
3. Oligohydramnios, defined as Amniotic fluid index (AFI) less than 5 cm when measured using the four-quadrant method at time of enrollment.
4. Fetal growth restriction (FGR) defined as estimated fetal weight (EFW) below the 5th percentile for gestational age.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: KNP-1000 Apheresis System; Participants are to be treated with the system up to 2 times per week, continuing through delivery or 34 weeks of pregnancy, whichever comes first.	Device: KNP-1000 Apheresis System; sFlt-1 is removed from the participants' plasma through treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Antepartum maternal and fetal device-related serious adverse events	Rate of antepartum maternal and fetal device-related serious adverse events	Until date of delivery
Postpartum maternal and neonatal device-related serious adverse events	Rate of postpartum maternal and neonatal device-related serious adverse events	Following delivery until end of follow-up (2 years)
Maternal, fetal, and neonatal mortality	Rate of maternal, fetal, and neonatal mortality	Until end of follow-up (2 years)
Obstetric complication	Incidence rate of obstetric complication	Until discharge or 6 weeks after delivery, whichever occurs first
Fetal complications	Incidence rate of fetal complications	Until date of delivery
Neonatal morbidities associated with premature delivery	Incidence rate of neonatal morbidities associated with premature delivery	Following delivery until discharge or 6 weeks after delivery, whichever occurs first
Neonatal intensive care unit (NICU) admissions	Rate of NICU admissions and length of stay	From date of NICU admission until the date of NICU discharge, assessed up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prolongation of pregnancy	Number of days from enrollment to delivery	Until date of delivery
Maternal systolic blood pressure	Change in maternal systolic blood pressure over the duration of the investigation	Until discharge or 6 weeks after delivery, whichever occurs first
Maternal diastolic blood pressure	Change in maternal diastolic blood pressure over the duration of the investigation	Until discharge or 6 weeks after delivery, whichever occurs first
Maternal proteinuria	Change in maternal proteinuria before and after each procedure	Until discharge or 6 weeks after delivery, whichever occurs first, an average of 4 months
Gestational age of the neonate at delivery	Gestational age of the neonate at delivery	At date of delivery
Weight of neonate at delivery	Weight of neonate at delivery	At date of delivery
Amniotic fluid volume	Change in amniotic fluid volume before and after each procedure	Until the date of delivery, an average of 3 months
Fetal umbilical artery flow	Change in fetal umbilical artery flow before and after each procedure	Until the date of delivery, an average of 3 months
Uterine artery flow	Change in uterine artery flow before and after each procedure	Until the date of delivery, an average of 3 months
Maternal low-density lipoprotein cholesterol (LDL-C) levels	Change in LDL-C levels in maternal serum before and after each procedure	Until discharge or 6 weeks after delivery, whichever occurs first, an average of 4 months
Fetal growth restriction	Incidence rate of fetal growth restriction	Until date of delivery
APGAR scores	Neonatal APGAR scores	At date of delivery
Umbilical artery and vein blood gases	Umbilical artery and vein blood gases	At date of delivery
Bayley Scales	Bayley Scales of Infant and Toddler Development, Fourth Edition assessment at 6, 12, and 24 months after delivery. Standard score (Composite score) range from 40 to 160, with higher scores indicating higher performance.	At 6, 12, and 24 months after delivery
Body weight of infant	Body weight (grams) of infant at birth and during extended follow-up	Following delivery until end of follow-up (2 years)
Body length and head circumference of infant	Body length and head circumference (centimeters) of infant at birth and during extended follow-up	Following delivery until end of follow-up (2 years)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Soluble fms-like tyrosine kinase-1 (sFlt-1)/ placental growth factor (PlGF) ratio in maternal serum	sFlt-1/PlGF ratio in maternal serum	Until discharge or 6 weeks after delivery, whichever occurs first
Percentage reduction of sFlt-1 levels in maternal serum	Percentage reduction of sFlt-1 levels in maternal serum after each apheresis treatment	Until the date of delivery, an average of 3 months
Change in sFLT-1 levels	Change in sFLT-1 levels between the inlet and outlet of the apheresis system	During each apheresis procedure
Change in PlGF levels	Change in PlGF levels between the inlet and outlet of the apheresis system	During each apheresis procedure

Collaborators and Investigators

• Sponsor: Kaneka Medical America LLC

Study record dates

Study Major Dates

• Study Start (Estimated): May 31, 2025
• Primary Completion (Estimated): April 30, 2026
• Study Completion (Estimated): June 30, 2028

Study Registration Dates

• First Submitted: August 23, 2024
• First Submitted That Met QC Criteria: August 28, 2024
• First Posted (Actual): August 30, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 3, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Pregnancy Complications; Hypertension, Pregnancy-Induced; Eclampsia; Pre-Eclampsia
• Other Study ID Numbers: KNP-1000-US01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No