<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/NCT03809429</url>
  </required_header>
  <id_info>
    <org_study_id>000304</org_study_id>
    <secondary_id>2017-002783-40</secondary_id>
    <nct_id>NCT03809429</nct_id>
  </id_info>
  <brief_title>Follitropin Delta in Long GnRH Agonist and GnRH Antagonist Protocols (BEYOND)</brief_title>
  <acronym>BEYOND</acronym>
  <official_title>A Randomised, Controlled, Open Label, Parallel Group, Multicentre Trial Comparing the Efficacy and Safety of Individualised FE 999049 (Follitropin Delta) Dosing, Using a Long GnRH Agonist Protocol and a GnRH Antagonist Protocol in Women Undergoing Controlled Ovarian Stimulation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ferring Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Ferring Pharmaceuticals</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>
      To compare the efficacy and safety of FE 999049 (follitropin delta) and its personalized&#xD;
      dosing algorithm in controlled ovarian stimulation for in vitro fertilization&#xD;
      (IVF)/intracytoplasmic sperm injection (ICSI) using a long gonadotropin-releasing hormone&#xD;
      (GnRH) agonist protocol versus a short GnRH antagonist protocol.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 29, 2019</start_date>
  <completion_date type="Actual">February 16, 2022</completion_date>
  <primary_completion_date type="Actual">February 16, 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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of oocytes retrieved</measure>
    <time_frame>On day of oocyte retrieval (up to 22 days after start of stimulation)</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Proportion of subjects with cycle cancellation due to poor ovarian response or excessive ovarian response</measure>
    <time_frame>At end-of-stimulation (up to 20 days)</time_frame>
    <description>For each subject, the reason for cycle cancellation will be recorded</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of subjects with blastocyst transfer cancellation after oocyte retrieval due to (risk of) ovarian hyperstimulation syndrome (OHSS)</measure>
    <time_frame>At end of transfer (up to 4 weeks)</time_frame>
    <description>For each subject, the reason for blastocyst transfer cancellation will be recorded</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of follicles</measure>
    <time_frame>On stimulation day 6 and at end-of-stimulation (up to 20 days)</time_frame>
    <description>The total number of follicles and the number of follicles per size category will be reported</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of subjects with &lt;4, 4-7, 8-14, 15-19 and ≥20 oocytes retrieved</measure>
    <time_frame>On day of oocyte retrieval (up to 22 days after start of stimulation)</time_frame>
    <description>Grouped according to number of oocytes</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of metaphase II oocytes</measure>
    <time_frame>On day of oocyte retrieval (up to 22 days after start of stimulation)</time_frame>
    <description>Only applicable for those inseminated using ICSI</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fertilization rate</measure>
    <time_frame>On day 1 after oocyte retrieval (up to 23 days after start of stimulation)</time_frame>
    <description>Measured by the number of pronuclei. Fertilized oocytes with 2 pronuclei will be regarded as correctly fertilized</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of embryos</measure>
    <time_frame>On day 3 after oocyte retrieval (up to 25 days after start of stimulation)</time_frame>
    <description>The number of embryos (total and good-quality) will be reported. Embryo quality is determined by combined assesment of cleavage stage (number of blastomeres/compaction status) and embryo morphology parameters</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of blastocysts</measure>
    <time_frame>On day 5 after oocyte retrieval (up to 27 days after start of stimulation)</time_frame>
    <description>The number of blastocysts (total and good-quality) will be reported. Blastocyst quality is assessed by blastocyst expansion and hatching status, blastocyst inner cell mass grading, and trophectoderm grading. The scoring is based on the classification system by Gardner and Schoolcraft, with additional categories for inner cell mass (degenerative or no inner cell mass) and trophectoderm (degenerative or very large cells)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Circulating concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, progesterone and inhibin B</measure>
    <time_frame>On stimulation day 6, at end-of-stimulation (up to 20 days after start of stimulation) and at oocyte retrieval (up to 22 days after start of stimulation)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total gonadotropin dose</measure>
    <time_frame>Up to 20 days</time_frame>
    <description>Calculated by start dates, end dates and daily dose of investigational medicinal product</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of stimulation days</measure>
    <time_frame>Up to 20 days</time_frame>
    <description>Calculated by start dates and end dates</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Positive beta human chorionic gonadotropin (βhCG) rate</measure>
    <time_frame>13-15 days after transfer (up to approximately 1.5 months after start of stimulation)</time_frame>
    <description>Defined as positive serum βhCG test</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Implantation rate</measure>
    <time_frame>5-6 weeks after transfer (up to approximately 2.5 months after start of stimulation)</time_frame>
    <description>Defined as the number of gestational sacs after transfer divided by number of blastocysts transferred</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical pregnancy rate</measure>
    <time_frame>5-6 weeks after transfer (up to approximately 2.5 months after start of stimulation)</time_frame>
    <description>Defined as at least one gestational sac</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Vital pregnancy rate</measure>
    <time_frame>5-6 weeks after transfer (up to approximately 2.5 months after start of stimulation)</time_frame>
    <description>Defined as at least one intrauterine gestational sac with fetal heart beat</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ongoing pregnancy rate</measure>
    <time_frame>10-11 weeks after transfer (up to approximately 4 months after start of stimulation)</time_frame>
    <description>At least one intrauterine viable fetus</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ongoing implantation rate</measure>
    <time_frame>10-11 weeks after transfer (up to approximately 4 months after start of stimulation)</time_frame>
    <description>Defined as number of intrauterine viable fetuses divided by the number of blastocysts transferred</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of subjects with early OHSS (including OHSS of moderate/severe grade)</measure>
    <time_frame>Up to 9 days after triggering of final follicular maturation</time_frame>
    <description>Measured as mild, moderate or severe</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of subjects with late OHSS (including OHSS of moderate/severe grade)</measure>
    <time_frame>&gt;9 days after triggering of final follicular maturation</time_frame>
    <description>Measured as mild, moderate or severe</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Frequency of adverse events</measure>
    <time_frame>From time of signing informed consent until the end-of-trial (approximately 7 months)</time_frame>
    <description>Any untoward medical occurrence</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Intensity of adverse events</measure>
    <time_frame>From time of signing informed consent until the end-of-trial (approximately 7 months)</time_frame>
    <description>Categorized as mild, moderate or severe</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Technical malfunctions of the pre-filled injection pen</measure>
    <time_frame>Up to 20 days</time_frame>
    <description>Incidences of technical malfunctions of the pre-filled injection pen will be recorded</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">437</enrollment>
  <condition>Infertility, Female</condition>
  <arm_group>
    <arm_group_label>FE 999049 + GnRH agonist (GONAPEPTYL)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>FE 999049 + GnRH antagonist (CETROTIDE)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>FE 999049 + GnRH agonist (GONAPEPTYL)</intervention_name>
    <description>Pre-filled injection pen</description>
    <arm_group_label>FE 999049 + GnRH agonist (GONAPEPTYL)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>FE 999049 + GnRH antagonist (CETROTIDE)</intervention_name>
    <description>Powder and solvent for solution for injection</description>
    <arm_group_label>FE 999049 + GnRH antagonist (CETROTIDE)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Infertile women aged 18-40 undergoing their first IVF/ICSI cycle that are in good&#xD;
             physical and mental health and that have been diagnosed with problems in the fallopian&#xD;
             tubes, mild endometriosis or have partners with decreased sperm quality.&#xD;
&#xD;
          -  The participants must have a regular menstrual cycle, a normal uterus and 2 normal&#xD;
             ovaries.&#xD;
&#xD;
          -  The allowed body mass index is 17.5-32 Kg/m^2.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Women with very high ovarian reserve, strong preference for either treatment, severe&#xD;
             endometriosis, history of repeated miscarriage, couples with known problems in the&#xD;
             chromosomes, history or high risk of producing blood cloths, women known to have&#xD;
             chronic diseases, women recently participating in trials with non-registered drugs.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <gender_based>Yes</gender_based>
    <gender_description>Women undergoing their first IVF/ICSI cycle and aged 18-40 years will be included.</gender_description>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>40 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Global Clinical Compliance</last_name>
    <role>Study Director</role>
    <affiliation>Ferring Pharmaceuticals</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Das Kinderwunsch Institut Schenk GmbH</name>
      <address>
        <city>Dobl</city>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kepler University Hospital Linz</name>
      <address>
        <city>Linz</city>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kinderwunschzentrum Goldenes Kreuz Privatklinik</name>
      <address>
        <city>Vienna</city>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rigshospitalet</name>
      <address>
        <city>Copenhagen</city>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hillel Yafe Medical Center</name>
      <address>
        <city>Hadera</city>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Shaare Zedek Medical Center</name>
      <address>
        <city>Jerusalem</city>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Beilinson Hospital Rabin Medical Center</name>
      <address>
        <city>Petah tikva</city>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sourasky Medical Center</name>
      <address>
        <city>Tel Aviv</city>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dipartimento della Donna, del bambino e delle malattie urologiche</name>
      <address>
        <city>Bologna</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>European Hospital</name>
      <address>
        <city>Roma</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Elisabeth Ziekenhuis</name>
      <address>
        <city>Tilburg</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Isala Fertility Center</name>
      <address>
        <city>Zwolle</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oslo University Hospital</name>
      <address>
        <city>Oslo</city>
        <country>Norway</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sykehuset Telemark HF</name>
      <address>
        <city>Porsgrunn</city>
        <country>Norway</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medicus AS</name>
      <address>
        <city>Trondheim</city>
        <country>Norway</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gyn-A.R.T. AG</name>
      <address>
        <city>Zürich</city>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Austria</country>
    <country>Denmark</country>
    <country>Israel</country>
    <country>Italy</country>
    <country>Netherlands</country>
    <country>Norway</country>
    <country>Switzerland</country>
  </location_countries>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>January 7, 2019</study_first_submitted>
  <study_first_submitted_qc>January 17, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 18, 2019</study_first_posted>
  <last_update_submitted>September 28, 2022</last_update_submitted>
  <last_update_submitted_qc>September 28, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 30, 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>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>Cetrorelix</mesh_term>
    <mesh_term>Prolactin Release-Inhibiting Factors</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>February 15, 2023</submitted>
  </pending_results>
  <!-- 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/NCT03809429
org study id: 000304
secondary id: 2017-002783-40
nct id: NCT03809429
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
To compare the efficacy and safety of FE 999049 (follitropin delta) and its personalized
      dosing algorithm in controlled ovarian stimulation for in vitro fertilization
      (IVF)/intracytoplasmic sperm injection (ICSI) using a long gonadotropin-releasing hormone
      (GnRH) agonist protocol versus a short GnRH antagonist protocol.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of oocytes retrieved
time frame: On day of oocyte retrieval (up to 22 days after start of stimulation)
measure: Proportion of subjects with cycle cancellation due to poor ovarian response or excessive ovarian response
time frame: At end-of-stimulation (up to 20 days)
description: For each subject, the reason for cycle cancellation will be recorded
measure: Proportion of subjects with blastocyst transfer cancellation after oocyte retrieval due to (risk of) ovarian hyperstimulation syndrome (OHSS)
time frame: At end of transfer (up to 4 weeks)
description: For each subject, the reason for blastocyst transfer cancellation will be recorded
measure: Number of follicles
time frame: On stimulation day 6 and at end-of-stimulation (up to 20 days)
description: The total number of follicles and the number of follicles per size category will be reported
measure: Proportion of subjects with <4, 4-7, 8-14, 15-19 and ≥20 oocytes retrieved
time frame: On day of oocyte retrieval (up to 22 days after start of stimulation)
description: Grouped according to number of oocytes
measure: Number of metaphase II oocytes
time frame: On day of oocyte retrieval (up to 22 days after start of stimulation)
description: Only applicable for those inseminated using ICSI
measure: Fertilization rate
time frame: On day 1 after oocyte retrieval (up to 23 days after start of stimulation)
description: Measured by the number of pronuclei. Fertilized oocytes with 2 pronuclei will be regarded as correctly fertilized
measure: Number of embryos
time frame: On day 3 after oocyte retrieval (up to 25 days after start of stimulation)
description: The number of embryos (total and good-quality) will be reported. Embryo quality is determined by combined assesment of cleavage stage (number of blastomeres/compaction status) and embryo morphology parameters
measure: Number of blastocysts
time frame: On day 5 after oocyte retrieval (up to 27 days after start of stimulation)
description: The number of blastocysts (total and good-quality) will be reported. Blastocyst quality is assessed by blastocyst expansion and hatching status, blastocyst inner cell mass grading, and trophectoderm grading. The scoring is based on the classification system by Gardner and Schoolcraft, with additional categories for inner cell mass (degenerative or no inner cell mass) and trophectoderm (degenerative or very large cells)
measure: Circulating concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, progesterone and inhibin B
time frame: On stimulation day 6, at end-of-stimulation (up to 20 days after start of stimulation) and at oocyte retrieval (up to 22 days after start of stimulation)
measure: Total gonadotropin dose
time frame: Up to 20 days
description: Calculated by start dates, end dates and daily dose of investigational medicinal product
measure: Number of stimulation days
time frame: Up to 20 days
description: Calculated by start dates and end dates
measure: Positive beta human chorionic gonadotropin (βhCG) rate
time frame: 13-15 days after transfer (up to approximately 1.5 months after start of stimulation)
description: Defined as positive serum βhCG test
measure: Implantation rate
time frame: 5-6 weeks after transfer (up to approximately 2.5 months after start of stimulation)
description: Defined as the number of gestational sacs after transfer divided by number of blastocysts transferred
measure: Clinical pregnancy rate
time frame: 5-6 weeks after transfer (up to approximately 2.5 months after start of stimulation)
description: Defined as at least one gestational sac
measure: Vital pregnancy rate
time frame: 5-6 weeks after transfer (up to approximately 2.5 months after start of stimulation)
description: Defined as at least one intrauterine gestational sac with fetal heart beat
measure: Ongoing pregnancy rate
time frame: 10-11 weeks after transfer (up to approximately 4 months after start of stimulation)
description: At least one intrauterine viable fetus
measure: Ongoing implantation rate
time frame: 10-11 weeks after transfer (up to approximately 4 months after start of stimulation)
description: Defined as number of intrauterine viable fetuses divided by the number of blastocysts transferred
measure: Proportion of subjects with early OHSS (including OHSS of moderate/severe grade)
time frame: Up to 9 days after triggering of final follicular maturation
description: Measured as mild, moderate or severe
measure: Proportion of subjects with late OHSS (including OHSS of moderate/severe grade)
time frame: >9 days after triggering of final follicular maturation
description: Measured as mild, moderate or severe
measure: Frequency of adverse events
time frame: From time of signing informed consent until the end-of-trial (approximately 7 months)
description: Any untoward medical occurrence
measure: Intensity of adverse events
time frame: From time of signing informed consent until the end-of-trial (approximately 7 months)
description: Categorized as mild, moderate or severe
measure: Technical malfunctions of the pre-filled injection pen
time frame: Up to 20 days
description: Incidences of technical malfunctions of the pre-filled injection pen will be recorded
arm group label: FE 999049 + GnRH agonist (GONAPEPTYL)
arm group type: Experimental
arm group label: FE 999049 + GnRH antagonist (CETROTIDE)
arm group type: Experimental
intervention type: Drug
intervention name: FE 999049 + GnRH agonist (GONAPEPTYL)
description: Pre-filled injection pen
arm group label: FE 999049 + GnRH agonist (GONAPEPTYL)
intervention type: Drug
intervention name: FE 999049 + GnRH antagonist (CETROTIDE)
description: Powder and solvent for solution for injection
arm group label: FE 999049 + GnRH antagonist (CETROTIDE)
criteria: 
gender: Female
gender based: Yes
gender description: Women undergoing their first IVF/ICSI cycle and aged 18-40 years will be included.
minimum age: 18 Years
maximum age: 40 Years
healthy volunteers: No
last name: Global Clinical Compliance
role: Study Director
affiliation: Ferring Pharmaceuticals
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Austria
country: Denmark
country: Israel
country: Italy
country: Netherlands
country: Norway
country: Switzerland
responsible party type: Sponsor
mesh term: Infertility
mesh term: Infertility, Female
mesh term: Cetrorelix
mesh term: Prolactin Release-Inhibiting Factors
sharing ipd: Undecided
submitted: February 15, 2023