Follitropin Delta in Long GnRH Agonist and GnRH Antagonist Protocols (BEYOND)
Study Details
Study Description
Brief 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: FE 999049 + GnRH agonist (GONAPEPTYL)
|
Drug: FE 999049 + GnRH agonist (GONAPEPTYL)
FE 999049 + GnRH agonist (GONAPEPTYL)
|
| Experimental: FE 999049 + GnRH antagonist (CETROTIDE)
|
Drug: FE 999049 + GnRH antagonist (CETROTIDE)
FE 999049 + GnRH antagonist (CETROTIDE)
|
Outcome Measures
Primary Outcome Measures
- Number of oocytes retrieved [On day of oocyte retrieval (up to 22 days after start of stimulation)]
Secondary Outcome Measures
- Proportion of subjects with cycle cancellation due to poor ovarian response or excessive ovarian response [At end-of-stimulation (up to 20 days)]
For each subject, the reason for cycle cancellation will be recorded
- Proportion of subjects with blastocyst transfer cancellation after oocyte retrieval due to (risk of) ovarian hyperstimulation syndrome (OHSS) [At end of transfer (up to 4 weeks)]
For each subject, the reason for blastocyst transfer cancellation will be recorded
- Number of follicles [On stimulation day 6 and at end-of-stimulation (up to 20 days)]
The total number of follicles and the number of follicles per size category will be reported
- Proportion of subjects with <4, 4-7, 8-14, 15-19 and ≥20 oocytes retrieved [On day of oocyte retrieval (up to 22 days after start of stimulation)]
Grouped according to number of oocytes
- Number of metaphase II oocytes [On day of oocyte retrieval (up to 22 days after start of stimulation)]
Only applicable for those inseminated using ICSI
- Fertilization rate [On day 1 after oocyte retrieval (up to 23 days after start of stimulation)]
Measured by the number of pronuclei. Fertilized oocytes with 2 pronuclei will be regarded as correctly fertilized
- Number of embryos [On day 3 after oocyte retrieval (up to 25 days after start of stimulation)]
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
- Number of blastocysts [On day 5 after oocyte retrieval (up to 27 days after start of stimulation)]
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)
- 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 [Up to 20 days]
Calculated by start dates, end dates and daily dose of investigational medicinal product
- Number of stimulation days [Up to 20 days]
Calculated by start dates and end dates
- Positive beta human chorionic gonadotropin (βhCG) rate [13-15 days after transfer (up to approximately 1.5 months after start of stimulation)]
Defined as positive serum βhCG test
- Implantation rate [5-6 weeks after transfer (up to approximately 2.5 months after start of stimulation)]
Defined as the number of gestational sacs after transfer divided by number of blastocysts transferred
- Clinical pregnancy rate [5-6 weeks after transfer (up to approximately 2.5 months after start of stimulation)]
Defined as at least one gestational sac
- Vital pregnancy rate [5-6 weeks after transfer (up to approximately 2.5 months after start of stimulation)]
Defined as at least one intrauterine gestational sac with fetal heart beat
- Ongoing pregnancy rate [10-11 weeks after transfer (up to approximately 4 months after start of stimulation)]
At least one intrauterine viable fetus
- Ongoing implantation rate [10-11 weeks after transfer (up to approximately 4 months after start of stimulation)]
Defined as number of intrauterine viable fetuses divided by the number of blastocysts transferred
- Proportion of subjects with early OHSS (including OHSS of moderate/severe grade) [Up to 9 days after triggering of final follicular maturation]
Measured as mild, moderate or severe
- Proportion of subjects with late OHSS (including OHSS of moderate/severe grade) [>9 days after triggering of final follicular maturation]
Measured as mild, moderate or severe
- Frequency of adverse events [From time of signing informed consent until the end-of-trial (approximately 7 months)]
Any untoward medical occurrence
- Intensity of adverse events [From time of signing informed consent until the end-of-trial (approximately 7 months)]
Categorized as mild, moderate or severe
- Technical malfunctions of the pre-filled injection pen [Up to 20 days]
Incidences of technical malfunctions of the pre-filled injection pen will be recorded
Eligibility Criteria
Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Das Kinderwunsch Institut Schenk GmbH | Dobl | Austria | ||
| 2 | Kepler University Hospital Linz | Linz | Austria | ||
| 3 | Kinderwunschzentrum Goldenes Kreuz Privatklinik | Vienna | Austria | ||
| 4 | Rigshospitalet | Copenhagen | Denmark | ||
| 5 | Hillel Yafe Medical Center | Hadera | Israel | ||
| 6 | Shaare Zedek Medical Center | Jerusalem | Israel | ||
| 7 | Beilinson Hospital Rabin Medical Center | Petah tikva | Israel | ||
| 8 | Sourasky Medical Center | Tel Aviv | Israel | ||
| 9 | Dipartimento della Donna, del bambino e delle malattie urologiche | Bologna | Italy | ||
| 10 | European Hospital | Roma | Italy | ||
| 11 | St. Elisabeth Ziekenhuis | Tilburg | Netherlands | ||
| 12 | Isala Fertility Center | Zwolle | Netherlands | ||
| 13 | Oslo University Hospital | Oslo | Norway | ||
| 14 | Sykehuset Telemark HF | Porsgrunn | Norway | ||
| 15 | Medicus AS | Trondheim | Norway | ||
| 16 | Gyn-A.R.T. AG | Zürich | Switzerland |
Sponsors and Collaborators
- Ferring Pharmaceuticals
Investigators
- Study Director: Global Clinical Compliance, Ferring Pharmaceuticals
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 000304
- 2017-002783-40