Follitropin Delta in Long GnRH Agonist and GnRH Antagonist Protocols (BEYOND) (BEYOND)

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

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.

Study Overview

• Status: Completed
• Conditions: Infertility, Female
• Intervention / Treatment: Drug: FE 999049 + GnRH agonist (GONAPEPTYL); Drug: FE 999049 + GnRH antagonist (CETROTIDE)

• Study Type: Interventional
• Enrollment (Actual): 437
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Dobl, Austria
    • Das Kinderwunsch Institut Schenk GmbH
  • Linz, Austria
    • Kepler University Hospital Linz
  • Vienna, Austria
    • Kinderwunschzentrum Goldenes Kreuz Privatklinik
• Denmark
  • Copenhagen, Denmark
    • Rigshospitalet
• Israel
  • Hadera, Israel
    • Hillel Yafe Medical Center
  • Jerusalem, Israel
    • Shaare Zedek Medical Center
  • Petah tikva, Israel
    • Beilinson Hospital Rabin Medical Center
  • Tel Aviv, Israel
    • Sourasky Medical Center
• Italy
  • Bologna, Italy
    • Dipartimento della Donna, del bambino e delle malattie urologiche
  • Roma, Italy
    • European Hospital
• Netherlands
  • Tilburg, Netherlands
    • St. Elisabeth Ziekenhuis
  • Zwolle, Netherlands
    • Isala Fertility Center
• Norway
  • Oslo, Norway
    • Oslo University Hospital
  • Porsgrunn, Norway
    • Sykehuset Telemark HF
  • Trondheim, Norway
    • Medicus AS
• Switzerland
  • Zürich, Switzerland
    • Gyn-A.R.T. AG

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 38 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Infertile women aged 18-40 undergoing their first IVF/ICSI cycle that are in good physical and mental health and that have been diagnosed with problems in the fallopian tubes, mild endometriosis or have partners with decreased sperm quality.
• The participants must have a regular menstrual cycle, a normal uterus and 2 normal ovaries.
• The allowed body mass index is 17.5-32 Kg/m^2.

Exclusion Criteria:

• Women with very high ovarian reserve, strong preference for either treatment, severe endometriosis, history of repeated miscarriage, couples with known problems in the chromosomes, history or high risk of producing blood cloths, women known to have chronic diseases, women recently participating in trials with non-registered drugs.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: FE 999049 + GnRH agonist (GONAPEPTYL)	Drug: FE 999049 + GnRH agonist (GONAPEPTYL); Pre-filled injection pen
Experimental: FE 999049 + GnRH antagonist (CETROTIDE)	Drug: FE 999049 + GnRH antagonist (CETROTIDE); Powder and solvent for solution for injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of oocytes retrieved	On day of oocyte retrieval (up to 22 days after start of stimulation)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of subjects with cycle cancellation due to poor ovarian response or excessive ovarian response	For each subject, the reason for cycle cancellation will be recorded	At end-of-stimulation (up to 20 days)
Proportion of subjects with blastocyst transfer cancellation after oocyte retrieval due to (risk of) ovarian hyperstimulation syndrome (OHSS)	For each subject, the reason for blastocyst transfer cancellation will be recorded	At end of transfer (up to 4 weeks)
Number of follicles	The total number of follicles and the number of follicles per size category will be reported	On stimulation day 6 and at end-of-stimulation (up to 20 days)
Proportion of subjects with <4, 4-7, 8-14, 15-19 and ≥20 oocytes retrieved	Grouped according to number of oocytes	On day of oocyte retrieval (up to 22 days after start of stimulation)
Number of metaphase II oocytes	Only applicable for those inseminated using ICSI	On day of oocyte retrieval (up to 22 days after start of stimulation)
Fertilization rate	Measured by the number of pronuclei. Fertilized oocytes with 2 pronuclei will be regarded as correctly fertilized	On day 1 after oocyte retrieval (up to 23 days after start of stimulation)
Number of embryos	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	On day 3 after oocyte retrieval (up to 25 days after start of stimulation)
Number of blastocysts	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)	On day 5 after oocyte retrieval (up to 27 days after start of stimulation)
Circulating concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, progesterone and inhibin B		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)
Total gonadotropin dose	Calculated by start dates, end dates and daily dose of investigational medicinal product	Up to 20 days
Number of stimulation days	Calculated by start dates and end dates	Up to 20 days
Positive beta human chorionic gonadotropin (βhCG) rate	Defined as positive serum βhCG test	13-15 days after transfer (up to approximately 1.5 months after start of stimulation)
Implantation rate	Defined as the number of gestational sacs after transfer divided by number of blastocysts transferred	5-6 weeks after transfer (up to approximately 2.5 months after start of stimulation)
Clinical pregnancy rate	Defined as at least one gestational sac	5-6 weeks after transfer (up to approximately 2.5 months after start of stimulation)
Vital pregnancy rate	Defined as at least one intrauterine gestational sac with fetal heart beat	5-6 weeks after transfer (up to approximately 2.5 months after start of stimulation)
Ongoing pregnancy rate	At least one intrauterine viable fetus	10-11 weeks after transfer (up to approximately 4 months after start of stimulation)
Ongoing implantation rate	Defined as number of intrauterine viable fetuses divided by the number of blastocysts transferred	10-11 weeks after transfer (up to approximately 4 months after start of stimulation)
Proportion of subjects with early OHSS (including OHSS of moderate/severe grade)	Measured as mild, moderate or severe	Up to 9 days after triggering of final follicular maturation
Proportion of subjects with late OHSS (including OHSS of moderate/severe grade)	Measured as mild, moderate or severe	>9 days after triggering of final follicular maturation
Frequency of adverse events	Any untoward medical occurrence	From time of signing informed consent until the end-of-trial (approximately 7 months)
Intensity of adverse events	Categorized as mild, moderate or severe	From time of signing informed consent until the end-of-trial (approximately 7 months)
Technical malfunctions of the pre-filled injection pen	Incidences of technical malfunctions of the pre-filled injection pen will be recorded	Up to 20 days

Collaborators and Investigators

• Sponsor: Ferring Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): April 29, 2019
• Primary Completion (Actual): February 16, 2022
• Study Completion (Actual): February 16, 2022

Study Registration Dates

• First Submitted: January 7, 2019
• First Submitted That Met QC Criteria: January 17, 2019
• First Posted (Actual): January 18, 2019

Study Record Updates

• Last Update Posted (Actual): September 30, 2022
• Last Update Submitted That Met QC Criteria: September 28, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infertility; Infertility, Female; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Reproductive Control Agents; Fertility Agents, Female; Fertility Agents; Cetrorelix; Prolactin Release-Inhibiting Factors
• Other Study ID Numbers: 000304; 2017-002783-40 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No