<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/NCT03288454</url>
  </required_header>
  <id_info>
    <org_study_id>PER977-02-011</org_study_id>
    <nct_id>NCT03288454</nct_id>
  </id_info>
  <brief_title>Phase 2 Study of Apixaban Reversal by Ciraparantag as Measured by WBCT</brief_title>
  <official_title>Phase 2 Placebo-Controlled, Single-Site, Single-Blind Study of Apixaban Reversal by Ciraparantag as Measured by WBCT</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Perosphere Pharmaceuticals Inc, a wholly owned subsidiary of AMAG Pharmaceuticals, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>AMAG Pharmaceuticals, Inc.</source>
  <oversight_info>
    <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 is a randomized, single-blind, placebo-controlled study to assess the efficacy and&#xD;
      safety of ciraparantag administered to healthy volunteers anticoagulated with apixaban&#xD;
      measuring clotting times using Whole Blood Clotting Time (WBCT).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a randomized, single-blind, placebo-controlled assessment of the efficacy and safety&#xD;
      of ciraparantag administered to healthy volunteers measuring clotting times using WBCT as&#xD;
      determined by the manual testing method. All subjects will undergo screening up to 36 days&#xD;
      prior to enrollment.&#xD;
&#xD;
      All enrolled subjects are to receive 10 mg apixaban orally for 3.5 days (every 12 hours on&#xD;
      Days 1-3 and once on the morning of Day 4). On Day 4, subjects who achieve sufficient&#xD;
      anticoagulation (WBCT ≥20% above baseline) are randomized and will receive a single dose of&#xD;
      study drug (ciraparantag or placebo) intravenously (IV) approximately 3 hours after the&#xD;
      apixaban dose, followed by serial testing of manual WBCT.&#xD;
&#xD;
      Subjects are enrolled sequentially into 3 ciraparantag dose cohorts. There will be a safety&#xD;
      review after completion of treatment in one cohort and prior to initiation of treatment in&#xD;
      the subsequent cohort.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 30, 2017</start_date>
  <completion_date type="Actual">August 5, 2019</completion_date>
  <primary_completion_date type="Actual">August 5, 2019</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>efficacy of ciraparantag in the reversal of anticoagulation induced by apixaban measured by WBCT</measure>
    <time_frame>4 days</time_frame>
    <description>efficacy of ciraparantag in the reversal of anticoagulation induced by apixaban at steady state measured by WBCT.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment</measure>
    <time_frame>10 days</time_frame>
    <description>Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">60</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>Cohort 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>ciraparantag (60 mg)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>ciraparantag (120 mg)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>ciraparantag (30 mg)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>placebo (saline for injection)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ciraparantag</intervention_name>
    <description>Ciraparantag (administered over 10 minutes)</description>
    <arm_group_label>Cohort 1</arm_group_label>
    <arm_group_label>Cohort 2</arm_group_label>
    <arm_group_label>Cohort 3</arm_group_label>
    <other_name>PER977</other_name>
    <other_name>AMAG 977</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Saline for injection</description>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>PBO</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Apixaban</intervention_name>
    <description>Apixaban 10mg given twice daily (q12h)</description>
    <arm_group_label>Cohort 1</arm_group_label>
    <arm_group_label>Cohort 2</arm_group_label>
    <arm_group_label>Cohort 3</arm_group_label>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Adults age 50 to 75 years, inclusive&#xD;
&#xD;
          2. Laboratory tests (chemistry, hematology and coagulation assessments) and urinalysis&#xD;
             performed during screening up to 36 days prior to administration of study treatment&#xD;
             deemed not clinically significant by the principal investigator.&#xD;
&#xD;
          3. No clinically significant findings on 12-lead electrocardiogram (ECG) performed during&#xD;
             screening&#xD;
&#xD;
          4. Body mass index (BMI) 18 to ≤ 32 kg/m2, inclusive&#xD;
&#xD;
          5. Male subjects agree to use appropriate contraception (i.e., latex condom with&#xD;
             spermicide) in addition to their partner using an acceptable form of contraception&#xD;
             (e.g., diaphragm, cervical cap, intrauterine device, hormonal contraceptives, surgical&#xD;
             sterilization or post-menopausal), when engaging in sexual activity during the course&#xD;
             of the study. Moreover, male subjects should not donate sperm or attempt to impregnate&#xD;
             a partner during the course of the study and for a period of 12 weeks following&#xD;
             discharge from the study.&#xD;
&#xD;
          6. Female subjects must have negative pregnancy tests at screening and check-in AND: be&#xD;
             surgically sterile at least 6 months prior to the first dose (with documentation of&#xD;
             hysterectomy, bilateral oophorectomy, bilateral salpingectomy, bilateral tubal&#xD;
             ligation/tubal occlusion); OR post-menopausal (no menstruation for a minimum of 12&#xD;
             months and confirmed by follicle stimulating hormone [FSH] of ≥ 40 mIU/ml and serum&#xD;
             estradiol &lt; 30 pg/ml at screening and check-in); OR if of childbearing potential, must&#xD;
             be using an acceptable method of contraception such as an intrauterine device (IUD),&#xD;
             implant or contraceptive injection, or two forms of the following (e.g., diaphragm,&#xD;
             cervical cap, patch or vaginal hormonal contraceptive, condom, spermicide, or sponge)&#xD;
             for the last three months. All females must agree to continue to use their method of&#xD;
             birth control for the duration of the study and for a minimum of one complete&#xD;
             menstrual cycle from the study&#xD;
&#xD;
          7. Subjects who have participated in a prior study of ciraparantag must have been&#xD;
             discharged from the study a minimum of 1 month prior to the planned treatment.&#xD;
&#xD;
          8. Subjects must understand and agree to comply with the requirements of the study and&#xD;
             they must be willing to sign the informed consent form indicating voluntary consent to&#xD;
             participate in the study prior to initiation of screening or study-related activities&#xD;
             -&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. History or current evidence of clinically significant cardiac, hepatic, renal,&#xD;
             pulmonary, endocrine, neurologic, infectious, gastrointestinal (including gallbladder&#xD;
             disease or surgery), hematologic, or oncologic disease as determined by screening&#xD;
             history, physical examination, laboratory test results or 12-lead ECG assessment.&#xD;
             History or current evidence of liver function tests greater than 50% of the upper&#xD;
             limit of normal (ULN) or renal function tests (serum creatinine) greater than 1.5&#xD;
             mg/dl and based on PI discretion. History or current evidence of QTc (QTcF) greater&#xD;
             than normal (450 msec for males or 470 msec for females).&#xD;
&#xD;
          2. History of unexplained syncope&#xD;
&#xD;
          3. History of major bleeding, trauma, or surgical procedure of any type based on PI&#xD;
             discretion&#xD;
&#xD;
          4. Vaginal delivery within six months prior to screening&#xD;
&#xD;
          5. History of peptic ulcer, gastrointestinal bleeding (including hematemesis, melena,&#xD;
             rectal bleeding) within one year prior to screening&#xD;
&#xD;
          6. Long standing history of bleeding episodes such as epistaxis, bruising or gingival&#xD;
             bleeding or if not long standing, within 1 month prior to screening&#xD;
&#xD;
          7. Personal or family history of clotting disorder or abnormality, excessive bleeding,&#xD;
             joint hematoma, thrombovascular disease or any hematologic disorder involving&#xD;
             platelets or clotting abnormalities or any condition requiring treatment with&#xD;
             transfusions, or history of thrombocytopenia&#xD;
&#xD;
          8. Females with a history of dysfunctional uterine bleeding who have not undergone&#xD;
             hysterectomy, including history of menorrhagia (heavy menstrual bleeding),&#xD;
             menometrorrhagia or polymenorrhea&#xD;
&#xD;
          9. Smokers or use of tobacco and/or nicotine containing products within 3 months prior to&#xD;
             dosing as determined by the subject's verbal history&#xD;
&#xD;
         10. Pregnant or breast-feeding&#xD;
&#xD;
         11. Males with a history of hormone therapy within 3 months prior to screening&#xD;
&#xD;
         12. Taking any type of chronic medication (including vitamin, nutritional and herbal&#xD;
             supplements) for more than 14 consecutive days within the 4 weeks prior to study entry&#xD;
             (use of hormonal contraceptives is acceptable except for oral contraceptives)&#xD;
&#xD;
         13. Positive serologic test for human immunodeficiency virus (HIV), Hepatitis C virus&#xD;
             antibody (HCV-Ab), or Hepatitis B surface antigen (HBsAg)&#xD;
&#xD;
         14. Donation of blood or blood products within 56 days prior to screening&#xD;
&#xD;
         15. Participation in any study with an investigational compound or device within 30 days&#xD;
             prior to signing informed consent&#xD;
&#xD;
         16. Active drug or alcohol dependence within the prior 12 months or any condition that, in&#xD;
             the opinion of the Investigator, would interfere with adherence to study protocol&#xD;
&#xD;
         17. Allergic to apixaban&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Frontage Clinical Services Inc.</name>
      <address>
        <city>Secaucus</city>
        <state>New Jersey</state>
        <zip>07094</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2020</verification_date>
  <study_first_submitted>September 14, 2017</study_first_submitted>
  <study_first_submitted_qc>September 18, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 20, 2017</study_first_posted>
  <disposition_first_submitted>August 21, 2020</disposition_first_submitted>
  <disposition_first_submitted_qc>September 1, 2020</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">September 2, 2020</disposition_first_posted>
  <last_update_submitted>September 1, 2020</last_update_submitted>
  <last_update_submitted_qc>September 1, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">September 2, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Ciraparantag</keyword>
  <keyword>PER977</keyword>
  <keyword>Apixaban</keyword>
  <keyword>Whole Blood Clotting Time (WBCT)</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Apixaban</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted, but a results disposition has been submitted           -->
</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/NCT03288454
org study id: PER977-02-011
nct id: NCT03288454
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
This study is a randomized, single-blind, placebo-controlled study to assess the efficacy and
      safety of ciraparantag administered to healthy volunteers anticoagulated with apixaban
      measuring clotting times using Whole Blood Clotting Time (WBCT).
This is a randomized, single-blind, placebo-controlled assessment of the efficacy and safety
      of ciraparantag administered to healthy volunteers measuring clotting times using WBCT as
      determined by the manual testing method. All subjects will undergo screening up to 36 days
      prior to enrollment.

      All enrolled subjects are to receive 10 mg apixaban orally for 3.5 days (every 12 hours on
      Days 1-3 and once on the morning of Day 4). On Day 4, subjects who achieve sufficient
      anticoagulation (WBCT ≥20% above baseline) are randomized and will receive a single dose of
      study drug (ciraparantag or placebo) intravenously (IV) approximately 3 hours after the
      apixaban dose, followed by serial testing of manual WBCT.

      Subjects are enrolled sequentially into 3 ciraparantag dose cohorts. There will be a safety
      review after completion of treatment in one cohort and prior to initiation of treatment in
      the subsequent cohort.
allocation: Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: Single (Participant)
measure: efficacy of ciraparantag in the reversal of anticoagulation induced by apixaban measured by WBCT
time frame: 4 days
description: efficacy of ciraparantag in the reversal of anticoagulation induced by apixaban at steady state measured by WBCT.
measure: Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment
time frame: 10 days
description: Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment
arm group label: Cohort 1
arm group type: Experimental
description: ciraparantag (60 mg)
arm group label: Cohort 2
arm group type: Experimental
description: ciraparantag (120 mg)
arm group label: Cohort 3
arm group type: Experimental
description: ciraparantag (30 mg)
arm group label: Placebo
arm group type: Placebo Comparator
description: placebo (saline for injection)
intervention type: Drug
intervention name: Ciraparantag
description: Ciraparantag (administered over 10 minutes)
arm group label: Cohort 1
arm group label: Cohort 2
arm group label: Cohort 3
other name: PER977
other name: AMAG 977
intervention type: Drug
intervention name: Placebo
description: Saline for injection
arm group label: Placebo
other name: PBO
intervention type: Drug
intervention name: Apixaban
description: Apixaban 10mg given twice daily (q12h)
arm group label: Cohort 1
arm group label: Cohort 2
arm group label: Cohort 3
arm group label: Placebo
criteria: 
gender: All
minimum age: 50 Years
maximum age: 75 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: United States
responsible party type: Sponsor
mesh term: Apixaban