Proof-of-Concept Trial on Selective Removal of sFlt-1 in Pregnant Women With Preeclampsia Via Apheresis

Overview

This clinical investigation is a medical device trial to examine the safety and efficacy of TheraSorb sFlt-1 adsorber treatment of pregnant patients with preeclampsia.

Full Title of Study: “Proof-of-Concept Trial on Selective Removal of the Antiangiogenic Factor Soluble Fms-like Tyrosine Kinase-1 (sFlt-1) in Pregnant Women With Preeclampsia Via Apheresis Utilizing the Flt-1 Adsorption Column”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Non-Randomized
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: December 2024

Interventions

  • Device: TheraSorb sFlt-1 adsorber
    • Removal of excessive sFlt-1 from the plasma of subjects/ patients with therapeutic apheresis.

Arms, Groups and Cohorts

  • Experimental: Phase 0 – healthy volunteers
    • Phase 0 is an initial safety phase where subjects will undergo one single TheraSorb sFlt-1 adsorber apheresis procedure.
  • Experimental: Phase A – preeclampsia patients
    • Phase A is a safety and dose-finding phase during which pregnant women diagnosed with preeclampsia will undergo one single TheraSorb sFlt-1 adsorber apheresis procedure.
  • Experimental: Phase B – preeclampsia patients
    • Phase B is a safety and efficacy phase during which pregnant women diagnosed with preeclampsia will undergo TheraSorb sFlt-1 adsorber apheresis procedures up to twice weekly.

Clinical Trial Outcome Measures

Primary Measures

  • Occurrence of AEs and SAEs in healthy volunteers until the 2 weeks follow-up (Phase 0)
    • Time Frame: until 2 weeks post treatment
  • Occurrence of AEs and SAEs in pregnant subjects and the fetus or infant until the 6 weeks post-delivery visit is reached (Phase A-B).
    • Time Frame: until 6 weeks post delivery

Secondary Measures

  • Phase 0: Determine changes of sFlt-1 levels.
    • Time Frame: until 2 weeks post treatment
  • Phase 0: Complement activation levels pre-, during and post apheresis.
    • Time Frame: Before, during and directly following the performance of the single apheresis treatment (1 day)
  • Phase 0: Concentration of antibody leaching during an apheresis procedure
    • Time Frame: During an apheresis procedure (1 day)
  • Phase 0: Change of HAMA levels in pre- and post apheresis blood
    • Time Frame: until 2 weeks post treatment
  • Phase 0: Evaluate blood pressure values
    • Time Frame: until 2 weeks post treatment
  • Phase 0: Evaluate spot urine values
    • Time Frame: until 2 weeks post treatment
  • Phase A/B: Occurrence of SAEs in the one year follow-up period
    • Time Frame: until end of FU, (1 year)
  • Phases A/B: Evaluate antibody leaching in phase A.
    • Time Frame: During the performance of the single apheresis treatment in Phase A (1 day) as well as pre and 3hrs post apheresis
  • Phases A and B: Evaluate maternal sFlt-1 levels.
    • Time Frame: Constant measures throughout the trial until delivery (up to 19 weeks)
  • Phases A/B: Evaluate the sFlt-1/PlGF ratio.
    • Time Frame: Constant measures throughout the trial until delivery (up to 19 weeks)
  • Phases A/B:Evaluate neonatal umbilical cord blood sFlt-1 levels at birth.
    • Time Frame: at birth
  • Phases A/B: Determine HAMA levels
    • Time Frame: until 6 week FU visit
  • Phases A/B: Time and method of delivery, and anesthesia administered
    • Time Frame: at birth
  • Phases A and B: Determine the post-partum maternal and neonatal length of hospitalization.
    • Time Frame: Following birth up to one year
  • Phases A/B: Evaluate standard markers of fetal development throughout pregnancy.
    • Time Frame: From start of trial until delivery (up to 19 weeks)
  • Phases A/B: Evaluate standard markers of neonatal development.
    • Time Frame: Directly following delivery until end of FU (1 year)

Participating in This Clinical Trial

Reduced criteria! Phase 0 Inclusion Criteria:

  • Age ≥18 and ≤45 years; – Male or female; – Female subjects of childbearing potential must have a negative serum pregnancy test result at screening and practice two reliable methods of contraception throughout the study. Exclusion Criteria:

  • Dysfunction of cerebral nervous system and/or heart disease; – History of preexisting chronic renal disease; – Treatment with ACE inhibitors; – Therapeutic full anticoagulation therapy prior to trial entry; – Liver abnormalities; – Clinically significant pulmonary edema and/or thrombocytopenia and/or anemia; – Active hepatitis B, C, or tuberculosis infection or HIV infection – Hypersensitivity to heparin and/or citrate; – Indications that prohibit transient anticoagulation using heparin and/or ACD-A-solutions; – Known intolerance to extracorporeal procedures in general or towards one of the individual excipients or towards other supporting agents; – Drug or alcohol abuse within the last 2 years; – Lack of compliance of subject; – History or diagnosis of severe periodontitis; Phase A and B Inclusion Criteria:

  • Age >18 and ≤45 years ; – Pregnant woman with pre-term preeclampsia – sFlt-1/PlGF ratio ≥85 ; – sFlt-1 level of ≥ 8000pg/mL Exclusion Criteria:

Maternal exclusion criteria

  • History of cardiac impairments including uncontrolled arrhythmia, unstable angina, decompensated congestive heart failure or valve disease; – History of preexisting chronic renal disease (CKD stage >3a, eGFR ≤45ml/min/1.73m²); – Treatment with ACE inhibitors; – Therapeutic full anticoagulation therapy prior to trial entry; – Signs or history of clinically significant cerebral nervous system dysfunction; – History of clinically significant liver abnormalities; – Clinically significant pulmonary edema and/or thrombocytopenia and/or anemia; – Active hepatitis B, C, tuberculosis infection or HIV-positive status; – Any condition that the investigator deems a risk to the patient or fetus in completing the trial; – Indications that prohibit transient anticoagulation using heparin and/or ACD-A-solutions; – Drug or alcohol abuse within the last 2 years; – Lack of compliance of patient; – Known intolerance to extracorporeal procedures in general or to one of the excipients or other supporting agents; – Hypersensitivity to heparin and/or citrate; – < 30 0/7 weeks of gestation and abnormal CTG and/or abnormal Ductus venosus Doppler flow, – ≥30 0/7 weeks of gestation and Doppler evidence of umbilical artery Absent or Reversed End-Diastolic Velocity (AREDV); – Various Placental exclusion criteria; – Multiple pregnancy – History or diagnosis of severe periodontitis Fetal exclusion criteria – Any known trisomy; – Amniotic fluid index <5cm (greatest single pocket <2cm); – Estimated fetal weight <3rd percentile for gestational age; – Fetus which are at high risk of heart disease; – Fetus with congenital heart defect; – Fetal signs of bleeding; – Hydrops fetalis; – Pathological fetal Doppler flow of the ductus venosus (absent A-wave in two measurements); – Evidence of severe fetal malformations; – Known infection of fetus; – Known severe anemia.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 45 Years

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

  • Lead Sponsor
    • Miltenyi Biomedicine GmbH
  • Collaborator
    • Cromsource
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Contact(s)
    • Jörg Liebmann, PhD, joergli@miltenyi.com

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