Study of the Efficacy and Safety of AMAG-423 (Digoxin Immune Fab) in Antepartum Subjects With Severe Preeclampsia

A Phase 2b/3a, Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study of the Efficacy and Safety of AMAG-423, a Digoxin Immune Fab, in Antepartum Subjects With Severe Preeclampsia

This study evaluates the use of AMAG-423 (Digoxin Immune Fab) in addition to expectant management in the treatment of severe preeclampsia as compared to placebo.

Study Overview

• Status: Terminated
• Conditions: Severe Preeclampsia
• Intervention / Treatment: Biological: AMAG-423 (digoxin immune fab); Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 59
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Poland
  • Pomorskie
    • Gdansk, Pomorskie, Poland, 80-462
      • Adalbertus Hospital
• South Africa
  • Gauteng
    • Pretoria, Gauteng, South Africa, 0204
      • Sefako Makgatho Health Sciences University
• United States
  • Alabama
    • Mobile, Alabama, United States, 36604
      • University of South Alabama
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Children's Hospital Foundation Building
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Louisiana State University Health Sciences Center in New Orleans
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Detroit Medical Center (DMC)
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati Medical Center
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Case Medical Center-Case Western Reserve University (CWRU)
  • Tennessee
    • Chattanooga, Tennessee, United States, 37403
      • Regional Obstetrical Consultants
  • Texas
    • Galveston, Texas, United States, 77555
      • The University of Texas Medical Branch (UTMB)
    • Houston, Texas, United States, 77030
      • Texas Children's Hospital/Baylor College of Medicine
    • Houston, Texas, United States, 77303
      • The University of Texas Health Science Center at Houston (UTHSC-H)
    • Temple, Texas, United States, 76508
      • Baylor Scott & White Health
  • Virginia
    • Charlottesville, Virginia, United States, 29208
      • University of Virginia School of Medicine
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College Of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Fetal gestational age 23 0/7 to 31 6/7 weeks
• Treated with expectant management
• Meets modified ACOG criteria for severe preeclampsia
• Willing and able to provide written, informed consent

Exclusion Criteria:

• Decision to deliver within 24 hours has been made
• Weight > 150 kg
• Eclampsia
• Significant antecedent obstetrical problems
• Clinically significant fetal anomaly or chromosomal abnormalities
• Chronic renal disease
• Active hepatic disease, antiphospholipid antibody syndrome, or lupus
• Unstable medical or psychiatric disorder
• Need for use of digitalis like products
• History of anaphylactic allergic reactions
• Prior use of antibodies/fab fragments from sheep
• Serum creatinine ≥ 2.0 mg/dL
• Platelet count < 50,000
• Pulmonary edema
• Estimated fetal weight < 5th percentile

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: AMAG-423 (digoxin immune fab); AMAG-423 (digoxin immune fab) 3.2 mg/kg, 30 minute IV infusion, every 6 hours x 4 days	Biological: AMAG-423 (digoxin immune fab); AMAG-423 (digoxin immune fab) 3.2 mg/kg, 30 minute IV infusion, every 6 hours x 4 days; Other Names: DigiFab
Placebo Comparator: Placebo; Normal saline, 30 minute IV infusion, every 6 hours x 4 days	Other: Placebo; Normal saline, 30 minute IV infusion, every 6 hours x 4 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of infants who have severe IVH, NEC, or death by 36 weeks corrected gestational age	Proportion of infants who have severe IVH, NEC, or death by 36 weeks corrected gestational age	36 weeks corrected gestational age

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in serum creatinine	Maternal change from baseline in serum creatinine to 24 hours post first dose	From treatment initiation to 24 hours post first dose
Incidence of pulmonary edema	Maternal incidence of pulmonary edema during the treatment period	From treatment initiation until completion of treatment phase (up to 4 days)
Proportion of mothers with modified early obstetric warning score >= 3 at 24 hours post first dose	Proportion of mothers with modified early obstetric warning score >= 3 at 24 hours post final dose	24 hours post first dose
Delivery latency	Time from start of treatment until delivery	From treatment initiation until delivery
Anti-hypertensive use during treatment	Use of or change in anti-hypertensive use during the treatment period	From treatment initiation until completion of treatment phase (up to 4 days)

Collaborators and Investigators

• Sponsor: AMAG Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): April 12, 2017
• Primary Completion (Actual): August 13, 2020
• Study Completion (Actual): August 13, 2020

Study Registration Dates

• First Submitted: December 20, 2016
• First Submitted That Met QC Criteria: December 29, 2016
• First Posted (Estimate): January 2, 2017

Study Record Updates

• Last Update Posted (Actual): April 4, 2022
• Last Update Submitted That Met QC Criteria: March 31, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pregnancy Complications; Hypertension, Pregnancy-Induced; Pre-Eclampsia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Enzyme Inhibitors; Protective Agents; Cardiotonic Agents; Digoxin
• Other Study ID Numbers: AMAG-423-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No