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

Infertility, Female Clinical Trial

— BEYOND  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03809429
• Other study ID #: 000304
• Secondary ID: 2017-002783-40
• Status: Completed
• Phase: Phase 3
• Start date: April 29, 2019
• Est. completion date: February 16, 2022

Study information

• Verified date: September 2022
• Source: Ferring Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 437
• Est. completion date: February 16, 2022
• Est. primary completion date: February 16, 2022
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 40 Years

Eligibility

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.

Related Conditions & MeSH terms

• Infertility
• Infertility, Female

Intervention

Drug:
• FE 999049 + GnRH agonist (GONAPEPTYL)
Pre-filled injection pen
• FE 999049 + GnRH antagonist (CETROTIDE)
Powder and solvent for solution for injection

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Ferring Pharmaceuticals

Countries where clinical trial is conducted

Austria,  Denmark,  Israel,  Italy,  Netherlands,  Norway,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of oocytes retrieved		On day of oocyte retrieval (up to 22 days after start of stimulation)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	Total gonadotropin dose	Calculated by start dates, end dates and daily dose of investigational medicinal product	Up to 20 days
Secondary	Number of stimulation days	Calculated by start dates and end dates	Up to 20 days
Secondary	Positive beta human chorionic gonadotropin (ßhCG) rate	Defined as positive serum ßhCG test	13-15 days after transfer (up to approximately 1.5 months after start of stimulation)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	Ongoing pregnancy rate	At least one intrauterine viable fetus	10-11 weeks after transfer (up to approximately 4 months after start of stimulation)
Secondary	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)
Secondary	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
Secondary	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
Secondary	Frequency of adverse events	Any untoward medical occurrence	From time of signing informed consent until the end-of-trial (approximately 7 months)
Secondary	Intensity of adverse events	Categorized as mild, moderate or severe	From time of signing informed consent until the end-of-trial (approximately 7 months)
Secondary	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