<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03008616</url>
  </required_header>
  <id_info>
    <org_study_id>AMAG-423-201</org_study_id>
    <nct_id>NCT03008616</nct_id>
  </id_info>
  <brief_title>Study of the Efficacy and Safety of AMAG-423 (Digoxin Immune Fab) in Antepartum Subjects With Severe Preeclampsia</brief_title>
  <official_title>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</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>AMAG Pharmaceuticals, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>AMAG Pharmaceuticals, Inc.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study evaluates the use of AMAG-423 (Digoxin Immune Fab) in addition to expectant&#xD;
      management in the treatment of severe preeclampsia as compared to placebo.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Following a recommendation from the Data and Safety Monitoring Board (DSMB), the study was&#xD;
    stopped early for futility. There were no safety concerns raised.&#xD;
  </why_stopped>
  <start_date type="Actual">April 12, 2017</start_date>
  <completion_date type="Actual">August 13, 2020</completion_date>
  <primary_completion_date type="Actual">August 13, 2020</primary_completion_date>
  <phase>Phase 2/Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Proportion of infants who have severe IVH, NEC, or death by 36 weeks corrected gestational age</measure>
    <time_frame>36 weeks corrected gestational age</time_frame>
    <description>Proportion of infants who have severe IVH, NEC, or death by 36 weeks corrected gestational age</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in serum creatinine</measure>
    <time_frame>From treatment initiation to 24 hours post first dose</time_frame>
    <description>Maternal change from baseline in serum creatinine to 24 hours post first dose</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of pulmonary edema</measure>
    <time_frame>From treatment initiation until completion of treatment phase (up to 4 days)</time_frame>
    <description>Maternal incidence of pulmonary edema during the treatment period</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of mothers with modified early obstetric warning score &gt;= 3 at 24 hours post first dose</measure>
    <time_frame>24 hours post first dose</time_frame>
    <description>Proportion of mothers with modified early obstetric warning score &gt;= 3 at 24 hours post final dose</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Delivery latency</measure>
    <time_frame>From treatment initiation until delivery</time_frame>
    <description>Time from start of treatment until delivery</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Anti-hypertensive use during treatment</measure>
    <time_frame>From treatment initiation until completion of treatment phase (up to 4 days)</time_frame>
    <description>Use of or change in anti-hypertensive use during the treatment period</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">59</enrollment>
  <condition>Severe Preeclampsia</condition>
  <arm_group>
    <arm_group_label>AMAG-423 (digoxin immune fab)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>AMAG-423 (digoxin immune fab) 3.2 mg/kg, 30 minute IV infusion, every 6 hours x 4 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Normal saline, 30 minute IV infusion, every 6 hours x 4 days</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>AMAG-423 (digoxin immune fab)</intervention_name>
    <description>AMAG-423 (digoxin immune fab) 3.2 mg/kg, 30 minute IV infusion, every 6 hours x 4 days</description>
    <arm_group_label>AMAG-423 (digoxin immune fab)</arm_group_label>
    <other_name>DigiFab</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Normal saline, 30 minute IV infusion, every 6 hours x 4 days</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Fetal gestational age 23 0/7 to 31 6/7 weeks&#xD;
&#xD;
          -  Treated with expectant management&#xD;
&#xD;
          -  Meets modified ACOG criteria for severe preeclampsia&#xD;
&#xD;
          -  Willing and able to provide written, informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Decision to deliver within 24 hours has been made&#xD;
&#xD;
          -  Weight &gt; 150 kg&#xD;
&#xD;
          -  Eclampsia&#xD;
&#xD;
          -  Significant antecedent obstetrical problems&#xD;
&#xD;
          -  Clinically significant fetal anomaly or chromosomal abnormalities&#xD;
&#xD;
          -  Chronic renal disease&#xD;
&#xD;
          -  Active hepatic disease, antiphospholipid antibody syndrome, or lupus&#xD;
&#xD;
          -  Unstable medical or psychiatric disorder&#xD;
&#xD;
          -  Need for use of digitalis like products&#xD;
&#xD;
          -  History of anaphylactic allergic reactions&#xD;
&#xD;
          -  Prior use of antibodies/fab fragments from sheep&#xD;
&#xD;
          -  Serum creatinine ≥ 2.0 mg/dL&#xD;
&#xD;
          -  Platelet count &lt; 50,000&#xD;
&#xD;
          -  Pulmonary edema&#xD;
&#xD;
          -  Estimated fetal weight &lt; 5th percentile&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>University of South Alabama</name>
      <address>
        <city>Mobile</city>
        <state>Alabama</state>
        <zip>36604</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Kansas Medical Center</name>
      <address>
        <city>Kansas City</city>
        <state>Kansas</state>
        <zip>66160</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Hospital Foundation Building</name>
      <address>
        <city>Louisville</city>
        <state>Kentucky</state>
        <zip>40202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Louisiana State University Health Sciences Center in New Orleans</name>
      <address>
        <city>New Orleans</city>
        <state>Louisiana</state>
        <zip>70112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Maryland</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Detroit Medical Center (DMC)</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Of Mississippi Medical Center</name>
      <address>
        <city>Jackson</city>
        <state>Mississippi</state>
        <zip>39216</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Cincinnati Medical Center</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45219</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospitals Case Medical Center-Case Western Reserve University (CWRU)</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Regional Obstetrical Consultants</name>
      <address>
        <city>Chattanooga</city>
        <state>Tennessee</state>
        <zip>37403</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The University of Texas Medical Branch (UTMB)</name>
      <address>
        <city>Galveston</city>
        <state>Texas</state>
        <zip>77555</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Children's Hospital/Baylor College of Medicine</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The University of Texas Health Science Center at Houston (UTHSC-H)</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77303</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baylor Scott &amp; White Health</name>
      <address>
        <city>Temple</city>
        <state>Texas</state>
        <zip>76508</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Virginia School Of Medicine</name>
      <address>
        <city>Charlottesville</city>
        <state>Virginia</state>
        <zip>29208</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical College of Wisconsin</name>
      <address>
        <city>Milwaukee</city>
        <state>Wisconsin</state>
        <zip>53226</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Adalbertus Hospital</name>
      <address>
        <city>Gdansk</city>
        <state>Pomorskie</state>
        <zip>80-462</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sefako Makgatho Health Sciences University</name>
      <address>
        <city>Pretoria</city>
        <state>Gauteng</state>
        <zip>0204</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Poland</country>
    <country>South Africa</country>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2022</verification_date>
  <study_first_submitted>December 20, 2016</study_first_submitted>
  <study_first_submitted_qc>December 29, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 2, 2017</study_first_posted>
  <last_update_submitted>March 31, 2022</last_update_submitted>
  <last_update_submitted_qc>March 31, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">April 4, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pre-Eclampsia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Digoxin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03008616
org study id: AMAG-423-201
nct id: NCT03008616
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Proportion of infants who have severe IVH, NEC, or death by 36 weeks corrected gestational age
time frame: 36 weeks corrected gestational age
description: Proportion of infants who have severe IVH, NEC, or death by 36 weeks corrected gestational age
measure: Change from baseline in serum creatinine
time frame: From treatment initiation to 24 hours post first dose
description: Maternal change from baseline in serum creatinine to 24 hours post first dose
measure: Incidence of pulmonary edema
time frame: From treatment initiation until completion of treatment phase (up to 4 days)
description: Maternal incidence of pulmonary edema during the treatment period
measure: Proportion of mothers with modified early obstetric warning score >= 3 at 24 hours post first dose
time frame: 24 hours post first dose
description: Proportion of mothers with modified early obstetric warning score >= 3 at 24 hours post final dose
measure: Delivery latency
time frame: From treatment initiation until delivery
description: Time from start of treatment until delivery
measure: Anti-hypertensive use during treatment
time frame: From treatment initiation until completion of treatment phase (up to 4 days)
description: Use of or change in anti-hypertensive use during the treatment period
arm group label: AMAG-423 (digoxin immune fab)
arm group type: Active Comparator
description: AMAG-423 (digoxin immune fab) 3.2 mg/kg, 30 minute IV infusion, every 6 hours x 4 days
arm group label: Placebo
arm group type: Placebo Comparator
description: Normal saline, 30 minute IV infusion, every 6 hours x 4 days
intervention type: Biological
intervention name: AMAG-423 (digoxin immune fab)
description: AMAG-423 (digoxin immune fab) 3.2 mg/kg, 30 minute IV infusion, every 6 hours x 4 days
arm group label: AMAG-423 (digoxin immune fab)
other name: DigiFab
intervention type: Other
intervention name: Placebo
description: Normal saline, 30 minute IV infusion, every 6 hours x 4 days
arm group label: Placebo
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
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country: Poland
country: South Africa
country: United States
responsible party type: Sponsor
mesh term: Pre-Eclampsia
mesh term: Digoxin
sharing ipd: No