<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/NCT02184741</url>
  </required_header>
  <id_info>
    <org_study_id>B211-11</org_study_id>
    <nct_id>NCT02184741</nct_id>
  </id_info>
  <brief_title>A Study of the Efficacy and Safety of GB-0998 in Patients With Unexplained Recurrent Miscarriage</brief_title>
  <official_title>A Double-Blind, Randomized, Placebo-Controlled Study of GB-0998 in Patients With Unexplained Recurrent Miscarriage.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Japan Blood Products Organization</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Japan Blood Products Organization</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The present survey was conducted to evaluate the efficacy and safety of&#xD;
      GB-0998(immunoglobulin) in the treatment of unexplained recurrent miscarriage in comparison&#xD;
      to placebo using a multicenter, double-blind, intergroup comparison method.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Among the patients whose risk factors for recurrent miscarriage are unknown who repeatedly&#xD;
      miscarry or patients who repeatedly miscarry despite treatment for risk factors, those who&#xD;
      have never given birth and have had four or more miscarriages. Patients were assigned into&#xD;
      two groups, GB-0998 or placebo, and received 8 ml/kg body weight of GB-0998 (400 mg/kg body&#xD;
      weight) or placebo once a day for 5 days. The primary efficacy endpoint was ongoing pregnancy&#xD;
      rate at 22 weeks of gestation (excluding miscarriages associated with fetal chromosomal&#xD;
      abnormalities) and one of the secondary endpoint was live birth rate.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 3, 2014</start_date>
  <completion_date type="Actual">September 2020</completion_date>
  <primary_completion_date type="Actual">May 2020</primary_completion_date>
  <phase>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>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Ongoing pregnancy rate (excluding miscarriages associated with fetal chromosomal abnormalities)</measure>
    <time_frame>At 22 weeks of gestation</time_frame>
    <description>To evaluate the effectiveness of the drug in preventing miscarriages, we examined the ongoing pregnancy rate at 22 weeks and 0 days of gestation in cases excluding cases of fetal chromosome aberration miscarriages.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Ongoing pregnancy rate(all patients)</measure>
    <time_frame>At 22 weeks of gestation</time_frame>
    <description>To evaluate the effectiveness of the drug in preventing miscarriages, we examined the ongoing pregnancy rate at 22 weeks and 0 days of gestation in all patients.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Live birth rate (excluding miscarriages associated with fetal chromosomal abnormalities)</measure>
    <time_frame>At the time of birth</time_frame>
    <description>To evaluate the effectiveness of the drug in total outcome of pregnancy, we examined the live birth rate in cases excluding cases of fetal chromosome aberration miscarriages.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Live birth rate(all patients)</measure>
    <time_frame>At the time of birth</time_frame>
    <description>To evaluate the effectiveness of the drug in total outcome of pregnancy, we examined the live birth rate in all patients.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">99</enrollment>
  <condition>Recurrent Miscarriage</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Infusion of normal saline</description>
  </arm_group>
  <arm_group>
    <arm_group_label>GB-0998</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Infusion of GB-0998 (Immunoglobulin)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>GB-0998</intervention_name>
    <description>Subjects received GB-0998 at 400 mg/kg body weight once daily for 5 days until 6 weeks and 6 days of gestation after confirmation of the gestational sac by ultrasonography.</description>
    <arm_group_label>GB-0998</arm_group_label>
    <other_name>Intravenous Immunoglobulin （Venoglobulin®IH，2.5g/50ml）</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Subjects received the same dose of saline as GB-0998 for 5 days after confirmation of the gestational sac by ultrasonography, up to 6 weeks and 6 days of gestation.</description>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>normal saline</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria&#xD;
&#xD;
          1. Patients with primary recurrent miscarriage&#xD;
&#xD;
          2. Patients with a history of at least 4 miscarriages (not including biochemical&#xD;
             pregnancy in the count of prior miscarriages)&#xD;
&#xD;
          3. Patients with any of the following risk factors for recurrent miscarriage&#xD;
&#xD;
        【Patients with unknown risk factors】 Patients with normal test results for each of the&#xD;
        following risk factors who have experienced miscarriage of a fetus with normal chromosome&#xD;
        karyotype&#xD;
&#xD;
          1. Abnormal uterine morphology&#xD;
&#xD;
          2. Thyroid dysfunction&#xD;
&#xD;
          3. Chromosome abnormality in the couple&#xD;
&#xD;
          4. Positive antiphospholipid antibody&#xD;
&#xD;
          5. Factor XII deficiency&#xD;
&#xD;
          6. Protein S deficiency&#xD;
&#xD;
          7. Protein C deficiency&#xD;
&#xD;
        【Patients determined to have risk factors】 Patients with the following risk factors who&#xD;
        have experienced miscarriage of a fetus with normal chromosome karyotype despite receiving&#xD;
        treatment for these factors&#xD;
&#xD;
          1. Abnormal uterine morphology (septate uterus): Patients who have undergone surgery&#xD;
&#xD;
          2. Thyroid dysfunction: Patients receiving medical treatment&#xD;
&#xD;
          3. Incidentally positive antiphospholipid antibody, factor XII deficiency, protein S&#xD;
             deficiency, protein C deficiency:Patients receiving combination therapy with aspirin&#xD;
             and heparin 4．Regardless of whether or not risk factors are present, patients should&#xD;
             have experienced at least 1 a miscarriage of a fetus with normal chromosome karyotype&#xD;
             5．Patients below the age of 42 years at the time of obtaining informed consent&#xD;
             6．Patients who can be admitted for at least the period from the start date of&#xD;
             administration of the study drug to the date of examination and assessment 1 week&#xD;
             after the start of administration of the study drug 7．Patients who have given written&#xD;
             informed consent to participate in this study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients with chromosome abnormalities in themselves or their partners that are risk&#xD;
             factors for recurrent miscarriage, patients with antiphospholipid syndrome, and&#xD;
             patients with incidentally positive antiphospholipid antibody (when the latest test&#xD;
             result is positive)&#xD;
&#xD;
          2. Patients in whom complications of diabetes mellitus or impaired glucose tolerance has&#xD;
             been identified, but who have not received appropriate treatment for this condition&#xD;
&#xD;
          3. Patients who have received intravenous immunoglobulin therapy as treatment for&#xD;
             recurrent miscarriage in the past&#xD;
&#xD;
          4. Patients with a history of stillbirth at 22 weeks of gestation or later&#xD;
&#xD;
          5. Patients receiving treatment for malignant tumor&#xD;
&#xD;
          6. Patients with a history of thromboembolism&#xD;
&#xD;
          7. Patients with a history of shock or hypersensitivity in response to the ingredients of&#xD;
             this drug or patients with hereditary fructose intolerance&#xD;
&#xD;
          8. Patients who have been diagnosed with IgA deficiency in the past or patients who have&#xD;
             a serum IgA level of &lt;5 mg/dL at laboratory tests at registration&#xD;
&#xD;
          9. Patients who have received another study drug within the period of 12 weeks prior to&#xD;
             informed consent or who are currently participating in another clinical trial&#xD;
&#xD;
         10. Patients who are unsuitable for this study for any other reason, in the opinion of a&#xD;
             principal investigator or sub-investigators&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>41 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Hideto Yamada, Director</last_name>
    <role>Principal Investigator</role>
    <affiliation>Center for Recurrent Pregnancy Loss, Teine Keijinkai Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Shigeru Saito, Professor</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Toyama</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Japan Blood Products Organization</name>
      <address>
        <city>Tokyo</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Japan</country>
  </location_countries>
  <verification_date>October 2021</verification_date>
  <study_first_submitted>July 3, 2014</study_first_submitted>
  <study_first_submitted_qc>July 8, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 9, 2014</study_first_posted>
  <last_update_submitted>January 26, 2022</last_update_submitted>
  <last_update_submitted_qc>January 26, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">January 28, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>IVIG</keyword>
  <keyword>Unexplained Recurrent miscarriage</keyword>
  <keyword>Primary Recurrent miscarriage</keyword>
  <keyword>Intravenous immunoglobulin</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Abortion, Spontaneous</mesh_term>
    <mesh_term>Abortion, Habitual</mesh_term>
    <mesh_term>Recurrence</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Immunoglobulins</mesh_term>
    <mesh_term>Immunoglobulins, Intravenous</mesh_term>
    <mesh_term>gamma-Globulins</mesh_term>
    <mesh_term>Rho(D) Immune Globulin</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/NCT02184741
org study id: B211-11
nct id: NCT02184741
lead sponsor: 
has dmc: No
The present survey was conducted to evaluate the efficacy and safety of
      GB-0998(immunoglobulin) in the treatment of unexplained recurrent miscarriage in comparison
      to placebo using a multicenter, double-blind, intergroup comparison method.
Among the patients whose risk factors for recurrent miscarriage are unknown who repeatedly
      miscarry or patients who repeatedly miscarry despite treatment for risk factors, those who
      have never given birth and have had four or more miscarriages. Patients were assigned into
      two groups, GB-0998 or placebo, and received 8 ml/kg body weight of GB-0998 (400 mg/kg body
      weight) or placebo once a day for 5 days. The primary efficacy endpoint was ongoing pregnancy
      rate at 22 weeks of gestation (excluding miscarriages associated with fetal chromosomal
      abnormalities) and one of the secondary endpoint was live birth rate.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Ongoing pregnancy rate (excluding miscarriages associated with fetal chromosomal abnormalities)
time frame: At 22 weeks of gestation
description: To evaluate the effectiveness of the drug in preventing miscarriages, we examined the ongoing pregnancy rate at 22 weeks and 0 days of gestation in cases excluding cases of fetal chromosome aberration miscarriages.
measure: Ongoing pregnancy rate(all patients)
time frame: At 22 weeks of gestation
description: To evaluate the effectiveness of the drug in preventing miscarriages, we examined the ongoing pregnancy rate at 22 weeks and 0 days of gestation in all patients.
measure: Live birth rate (excluding miscarriages associated with fetal chromosomal abnormalities)
time frame: At the time of birth
description: To evaluate the effectiveness of the drug in total outcome of pregnancy, we examined the live birth rate in cases excluding cases of fetal chromosome aberration miscarriages.
measure: Live birth rate(all patients)
time frame: At the time of birth
description: To evaluate the effectiveness of the drug in total outcome of pregnancy, we examined the live birth rate in all patients.
arm group label: Placebo
arm group type: Placebo Comparator
description: Infusion of normal saline
arm group label: GB-0998
arm group type: Experimental
description: Infusion of GB-0998 (Immunoglobulin)
intervention type: Drug
intervention name: GB-0998
description: Subjects received GB-0998 at 400 mg/kg body weight once daily for 5 days until 6 weeks and 6 days of gestation after confirmation of the gestational sac by ultrasonography.
arm group label: GB-0998
other name: Intravenous Immunoglobulin （Venoglobulin®IH，2.5g/50ml）
intervention type: Drug
intervention name: Placebo
description: Subjects received the same dose of saline as GB-0998 for 5 days after confirmation of the gestational sac by ultrasonography, up to 6 weeks and 6 days of gestation.
arm group label: Placebo
other name: normal saline
criteria: 
gender: Female
minimum age: N/A
maximum age: 41 Years
healthy volunteers: No
last name: Hideto Yamada, Director
role: Principal Investigator
affiliation: Center for Recurrent Pregnancy Loss, Teine Keijinkai Hospital
last name: Shigeru Saito, Professor
role: Principal Investigator
affiliation: University of Toyama
facility: 
country: Japan
responsible party type: Sponsor
mesh term: Abortion, Spontaneous
mesh term: Abortion, Habitual
mesh term: Recurrence
mesh term: Immunoglobulins
mesh term: Immunoglobulins, Intravenous
mesh term: gamma-Globulins
mesh term: Rho(D) Immune Globulin
sharing ipd: No