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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Infertility, Female

Intervention / Treatment
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* Drug: FE 999049 + GnRH agonist (GONAPEPTYL)
* Drug: FE 999049 + GnRH antagonist (CETROTIDE)


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 |