<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/NCT03767218</url>
  </required_header>
  <id_info>
    <org_study_id>D2.D12.Bemfola</org_study_id>
    <nct_id>NCT03767218</nct_id>
  </id_info>
  <brief_title>Initiation of Ovarian Stimulation With Recombinant-human FSH (Bemfola®) in the Late Follicular Phase</brief_title>
  <official_title>Initiation of Ovarian Stimulation With Recombinant-human FSH (Bemfola®) in the Late Follicular Phase, a Randomised Controlled Pilot Study.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Universitair Ziekenhuis Brussel</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Universitair Ziekenhuis Brussel</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      A randomised controlled open-label clinical trial to compare the outcome parameters after&#xD;
      ovarian stimulation using recombinant-human FSH (follicle stimulating hormone), starting on&#xD;
      day 2 of the cycle versus start in the late follicular phase of the cycle.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Objective: To determine whether late follicular stimulation using recombinant-human FSH has&#xD;
      comparable outcomes to treatment using recombinant-human FSH in early follicular phase in a&#xD;
      flexible GnRH (Gonadotropin-releasing hormone) antagonist protocol, in oocyte donor patients.&#xD;
&#xD;
      Design: Open label, phase 3 randomized trial using a two-arm design with 1:1 allocation ratio&#xD;
&#xD;
      Patients: Oocyte donors (aged 18-36 years)&#xD;
&#xD;
      Intervention(s): Reference group: Start of ovarian stimulation with recombinant-human FSH&#xD;
      (Bemfola 225 IU daily) from day 2 of follicular phase onwards. Initiation of GnRH antagonist&#xD;
      (ganirelix, 0.25mg/day) on stimulation day 6 till day of trigger.&#xD;
&#xD;
      Investigational group: Start of ovarian stimulation with recombinant-human FSH (Bemfola 225&#xD;
      IU daily) from the late follicular phase of the menstrual cycle (evaluation trough ultrasound&#xD;
      and hormonal assessment) onwards. Start of GnRH antagonist (ganirelix 0.25mg/day) when serum&#xD;
      LH (Luteinizing Hormone) &gt; 10 IU/L, till day of trigger.&#xD;
&#xD;
      Oocyte maturation trigger with GnRH agonist (0.2mg Gonapeptyl) in both groups.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 1, 2018</start_date>
  <completion_date type="Actual">November 25, 2022</completion_date>
  <primary_completion_date type="Actual">May 27, 2022</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>
    <intervention_model_description>Open label, phase 3 pilot randomized trial using a two-arm design with 1:1 allocation ratio</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>total amount of COC (cumulus-oocyte-complex)</measure>
    <time_frame>at oocyte aspiration</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Endocrine profile</measure>
    <time_frame>on menstrual cycle day 2 9, (extra days as per site protocol) and day of oocyte maturation trigger in reference group. On menstrual cycle day 2 and 12, (extra days as per site protocol) and day of oocyte maturation trigger in investigational group</time_frame>
    <description>LH (Luteinising hormone) level</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Endocrine profile</measure>
    <time_frame>on menstrual cycle day 2 and 9, (extra days as per site protocol) and day of oocyte maturation trigger in reference group. On menstrual cycle day 2 and 12, (extra days as per site protocol) and day of oocyte maturation trigger in investigational group</time_frame>
    <description>FSH level</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Endocrine profile</measure>
    <time_frame>on menstrual cycle day 2 and 9, (extra days as per site protocol) and day of oocyte maturation trigger in reference group. On menstrual cycle day 2 and 12, (extra days as per site protocol) and day of oocyte maturation trigger in investigational group</time_frame>
    <description>Progesterone level</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Endocrine profile</measure>
    <time_frame>on menstrual cycle day 2 and 9, (extra days as per site protocol) and day of oocyte maturation trigger in reference group. On menstrual cycle day 2 and 12, (extra days as per site protocol) and day of oocyte maturation trigger in investigational group</time_frame>
    <description>Estradiol level</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Consumption of gonadotrophins</measure>
    <time_frame>during the ovarian stimulation</time_frame>
    <description>totaal amount of IU (international units) used</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of days needed for ovarian stimulation</measure>
    <time_frame>during the ovarian stimulation</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Days of GnRH antagonist use</measure>
    <time_frame>during the ovarian stimulation</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total number of mature oocytes</measure>
    <time_frame>at day of oocyte aspiration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total medication cost</measure>
    <time_frame>during the ovarian stimulation</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">71</enrollment>
  <condition>Infertility, Female</condition>
  <arm_group>
    <arm_group_label>Late follicular phase stimulation with recombinant-human FSH</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Start of ovarian stimulation with recombinant-human FSH (Bemfola 225 IU daily) from the late follicular phase of the menstrual cycle onwards. Start of GnRH antagonist (ganirelix 0.25mg/day) when serum LH &gt; 10 IU/L, till day of trigger.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Early follicular phase stimulation with recombinant-human FSH</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Start of ovarian stimulation with recombinant-human FSH (Bemfola 225 IU daily) from day 2 of follicular phase onwards. Initiation of GnRH antagonist (ganirelix, 0.25mg/day) on stimulation day 6 till day of trigger.</description>
  </arm_group>
  <intervention>
    <intervention_type>Combination Product</intervention_type>
    <intervention_name>Late follicular phase stimulation with recombinant-human FSH</intervention_name>
    <description>Start of ovarian stimulation with recombinant-human FSH (Bemfola 225 IU daily) from the late follicular phase of the menstrual cycle onwards. Start of GnRH antagonist (ganirelix 0.25mg/day) when serum LH &gt; 10 IU/L, till day of trigger.</description>
    <arm_group_label>Late follicular phase stimulation with recombinant-human FSH</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Combination Product</intervention_type>
    <intervention_name>Early follicular phase stimulation with recombinant-human FSH</intervention_name>
    <description>Start of ovarian stimulation with recombinant-human FSH (Bemfola 225 IU daily) from day 2 of follicular phase onwards. Initiation of GnRH antagonist (ganirelix, 0.25mg/day) on stimulation day 6 till day of trigger.</description>
    <arm_group_label>Early follicular phase stimulation with recombinant-human FSH</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  oocyte donor patients&#xD;
&#xD;
          -  Age from 18 to 36 years&#xD;
&#xD;
          -  BMI 19 to 35&#xD;
&#xD;
          -  Regular menstrual cycle length i.e. 24-35 days&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with AMH &lt;1.1 ng/ml and/or AFC&lt;7&#xD;
&#xD;
          -  Patients with FNPO (Follicle Number Per Ovary) ≥ 19 and/ord AMH &gt;5ng/ml&#xD;
&#xD;
          -  Endometriosis grade 3-4&#xD;
&#xD;
          -  Oligo-amenorrhea&#xD;
&#xD;
          -  Any untreated endocrine abnormality&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>36 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Universitair Ziekenhuis Brussel</name>
      <address>
        <city>Brussel</city>
        <zip>1090</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
  </location_countries>
  <verification_date>April 2022</verification_date>
  <study_first_submitted>May 17, 2018</study_first_submitted>
  <study_first_submitted_qc>December 5, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 6, 2018</study_first_posted>
  <last_update_submitted>May 12, 2023</last_update_submitted>
  <last_update_submitted_qc>May 12, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 16, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Oocyte donor</keyword>
  <keyword>Ovarian stimulation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infertility</mesh_term>
    <mesh_term>Infertility, Female</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Follicle Stimulating Hormone</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
  </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/NCT03767218
org study id: D2.D12.Bemfola
nct id: NCT03767218
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
A randomised controlled open-label clinical trial to compare the outcome parameters after
      ovarian stimulation using recombinant-human FSH (follicle stimulating hormone), starting on
      day 2 of the cycle versus start in the late follicular phase of the cycle.
Objective: To determine whether late follicular stimulation using recombinant-human FSH has
      comparable outcomes to treatment using recombinant-human FSH in early follicular phase in a
      flexible GnRH (Gonadotropin-releasing hormone) antagonist protocol, in oocyte donor patients.

      Design: Open label, phase 3 randomized trial using a two-arm design with 1:1 allocation ratio

      Patients: Oocyte donors (aged 18-36 years)

      Intervention(s): Reference group: Start of ovarian stimulation with recombinant-human FSH
      (Bemfola 225 IU daily) from day 2 of follicular phase onwards. Initiation of GnRH antagonist
      (ganirelix, 0.25mg/day) on stimulation day 6 till day of trigger.

      Investigational group: Start of ovarian stimulation with recombinant-human FSH (Bemfola 225
      IU daily) from the late follicular phase of the menstrual cycle (evaluation trough ultrasound
      and hormonal assessment) onwards. Start of GnRH antagonist (ganirelix 0.25mg/day) when serum
      LH (Luteinizing Hormone) > 10 IU/L, till day of trigger.

      Oocyte maturation trigger with GnRH agonist (0.2mg Gonapeptyl) in both groups.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Open label, phase 3 pilot randomized trial using a two-arm design with 1:1 allocation ratio
primary purpose: Treatment
masking: None (Open Label)
measure: total amount of COC (cumulus-oocyte-complex)
time frame: at oocyte aspiration
measure: Endocrine profile
time frame: on menstrual cycle day 2 9, (extra days as per site protocol) and day of oocyte maturation trigger in reference group. On menstrual cycle day 2 and 12, (extra days as per site protocol) and day of oocyte maturation trigger in investigational group
description: LH (Luteinising hormone) level
measure: Endocrine profile
time frame: on menstrual cycle day 2 and 9, (extra days as per site protocol) and day of oocyte maturation trigger in reference group. On menstrual cycle day 2 and 12, (extra days as per site protocol) and day of oocyte maturation trigger in investigational group
description: FSH level
measure: Endocrine profile
time frame: on menstrual cycle day 2 and 9, (extra days as per site protocol) and day of oocyte maturation trigger in reference group. On menstrual cycle day 2 and 12, (extra days as per site protocol) and day of oocyte maturation trigger in investigational group
description: Progesterone level
measure: Endocrine profile
time frame: on menstrual cycle day 2 and 9, (extra days as per site protocol) and day of oocyte maturation trigger in reference group. On menstrual cycle day 2 and 12, (extra days as per site protocol) and day of oocyte maturation trigger in investigational group
description: Estradiol level
measure: Consumption of gonadotrophins
time frame: during the ovarian stimulation
description: totaal amount of IU (international units) used
measure: Number of days needed for ovarian stimulation
time frame: during the ovarian stimulation
measure: Days of GnRH antagonist use
time frame: during the ovarian stimulation
measure: Total number of mature oocytes
time frame: at day of oocyte aspiration
measure: Total medication cost
time frame: during the ovarian stimulation
arm group label: Late follicular phase stimulation with recombinant-human FSH
arm group type: Experimental
description: Start of ovarian stimulation with recombinant-human FSH (Bemfola 225 IU daily) from the late follicular phase of the menstrual cycle onwards. Start of GnRH antagonist (ganirelix 0.25mg/day) when serum LH > 10 IU/L, till day of trigger.
arm group label: Early follicular phase stimulation with recombinant-human FSH
arm group type: Active Comparator
description: Start of ovarian stimulation with recombinant-human FSH (Bemfola 225 IU daily) from day 2 of follicular phase onwards. Initiation of GnRH antagonist (ganirelix, 0.25mg/day) on stimulation day 6 till day of trigger.
intervention type: Combination Product
intervention name: Late follicular phase stimulation with recombinant-human FSH
description: Start of ovarian stimulation with recombinant-human FSH (Bemfola 225 IU daily) from the late follicular phase of the menstrual cycle onwards. Start of GnRH antagonist (ganirelix 0.25mg/day) when serum LH > 10 IU/L, till day of trigger.
arm group label: Late follicular phase stimulation with recombinant-human FSH
intervention type: Combination Product
intervention name: Early follicular phase stimulation with recombinant-human FSH
description: Start of ovarian stimulation with recombinant-human FSH (Bemfola 225 IU daily) from day 2 of follicular phase onwards. Initiation of GnRH antagonist (ganirelix, 0.25mg/day) on stimulation day 6 till day of trigger.
arm group label: Early follicular phase stimulation with recombinant-human FSH
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 36 Years
healthy volunteers: No
facility: 
country: Belgium
responsible party type: Sponsor
mesh term: Infertility
mesh term: Infertility, Female
mesh term: Follicle Stimulating Hormone
sharing ipd: Yes
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)