The purpose of this phase 2 dose-ranging trial is to investigate the effects of FE 999302 on parameters influencing pregnancy rates in women undergoing Controlled Ovarian Stimulation (COS) with follitropin delta in a long gonadotropin releasing hormone (GnRH) agonist protocol. Furthermore, the study intends: * To investigate the safety of FE 999302 in women undergoing COS with follitropin delta in a long GnRH agonist protocol. * To investigate the potential immunogenicity of FE 999302 in subjects undergoing COS with follitropin delta in a long GnRH agonist protocol. * To estimate the impact of body weight on FE 999302 exposure in subjects undergoing COS with follitropin delta in a long GnRH agonist protocol.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
620
Daily dose of 1 μg of FE 999302, a recombinant human chorionic gonadotropin (rhCG) solution for subcutaneous injection; individualized follitropin delta dose.
Daily dose of 2 μg of FE 999302, a rhCG solution for subcutaneous injection; individualized follitropin delta dose.
Daily dose of 4 μg of FE 999302, a rhCG solution for subcutaneous injection; individualized follitropin delta dose.
Daily dose of 8 μg of FE 999302, a rhCG solution for subcutaneous injection; individualized follitropin delta dose.
Daily dose of 12 μg of FE 999302, a rhCG solution for subcutaneous injection; individualized follitropin delta dose.
Daily dose of placebo; individualized follitropin delta dose.
Universitair Ziekenhuis Gent (UZ Gent)
Ghent, Belgium
Universitair Ziekenhuis Brussel
Jette, Belgium
Institut fur Reproduktionsmedizin und Genetik
Karlovy Vary, Czechia
Fertimed
Olomouc, Czechia
GYNEM
Prague, Czechia
IVF CUBE
Prague, Czechia
Aalborg University Hospital
Aalborg, Denmark
Rigshospitalet
Copenhagen, Denmark
Dansk Fertilitetsklinik
Frederiksberg, Denmark
Hvidovre Hospital
Hvidovre, Denmark
...and 10 more locations
Number of good-quality blastocysts on Day 5 after oocyte retrieval
Quality of blastocysts was assessed by blastocyst expansion and hatching status, blastocyst inner cell mass grading, and trophectoderm grading. The scoring was 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 cell).
Time frame: On Day 5 after oocyte retrieval
Number of subjects with at least one good-quality blastocyst on Day 5 after oocyte retrieval
Quality of blastocysts was assessed by blastocyst expansion and hatching status, blastocyst inner cell mass grading, and trophectoderm grading. The scoring was 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 cell).
Time frame: On Day 5 after oocyte retrieval
Number of subjects with at least two good-quality blastocysts on Day 5 after oocyte retrieval
Quality of blastocysts was assessed by blastocyst expansion and hatching status, blastocyst inner cell mass grading, and trophectoderm grading. The scoring was 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 cell).
Time frame: On Day 5 after oocyte retrieval
Number and quality of embryos on Day 3 after oocyte retrieval
Embryo quality was assessed by cleavage stage and embryo morphology parameters. The total number of embryos and the number of embryos per quality category were reported.
Time frame: On Day 3 after oocyte retrieval
Number and quality of blastocysts on Day 5 after oocyte retrieval
Blastocyst quality was assessed by blastocyst expansion and hatching status, blastocyst inner cell mass grading, and trophectoderm grading. The scoring was 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). The total number of blastocysts and the number of blastocysts per quality category will be reported.
Time frame: On Day 5 after oocyte retrieval
Changes in serum hormone levels
Blood samples for analysis of hormone concentrations were drawn at stimulation Day 1, stimulation Day 6, stimulation Day 8, last day of stimulation, and at oocyte retrieval.
Time frame: Stimulation Day 1 (baseline), stimulation Day 6, stimulation Day 8, end-of-stimulation (up to 20 stimulation days), and oocyte retrieval
Number and size of follicles on stimulation Day 6
Number and size of follicles assessed using transvaginal ultrasound. The total number of follicles and the number of follicles per size category were reported.
Time frame: On stimulation Day 6
Number and size of follicles at end-of-stimulation
Number and size of follicles assessed using transvaginal ultrasound. The total number of follicles and the number of follicles per size category were reported.
Time frame: At end-of-stimulation (up to 20 stimulation days)
Positive beta human chorionic gonadotropin (βhCG) rate
Proportion of patients with positive blood βhCG confirmed by a blood test.
Time frame: 13-15 days after blastocyst transfer
Clinical pregnancy rate
Clinical pregnancy was defined as at least one gestational sac, either intrauterine or ectopic.
Time frame: 5-6 weeks after blastocyst transfer
Vital pregnancy rate
Vital pregnancy was defined as at least one intrauterine gestational sac with fetal heart beat, as assessed by transvaginal ultrasound.
Time frame: 5-6 weeks after blastocyst transfer
Ongoing pregnancy rate
Ongoing pregnancy was defined as at least one intrauterine viable fetus, assessed using transvaginal or abdominal ultrasound.
Time frame: 10-11 weeks after blastocyst transfer
Number of oocytes retrieved
Time frame: On the day of oocyte retrieval
Number of metaphase II oocytes
Time frame: On the day of oocyte retrieval
Number of fertilised 2 pronuclei (2PN) oocytes
Time frame: On day 1 after insemination
Total gonadotropin dose
The daily dose of FE 999302 or placebo, and follitropin delta were recorded.
Time frame: At end-of-stimulation (up to 20 stimulation days)
Total number of stimulation days
The start and end dates of administration of FE 999302 or placebo, and follitropin delta were recorded.
Time frame: At end-of-stimulation (up to 20 stimulation days)
Incidence of cycle cancellation
Cycle cancellation due to poor ovarian response or excessive ovarian response.
Time frame: At end-of-stimulation (up to 20 stimulation days)
Serum concentrations of FE 999302
Time frame: On stimulation Day 1 (prior to first dose of FE 999302 or placebo), stimulation Day 6, stimulation Day 8, end-of-stimulation (up to 20 stimulation days)
Incidence of ovarian hyperstimulation syndrome (OHSS) (early or late, any grade)
Early OHSS was defined as OHSS with onset less than equal to 9 days after triggering of final follicular maturation. Late OHSS was defined as OHSS with onset greater than 9 days after triggering of final follicular maturation. All OHSS cases were graded as mild, moderate or severe.
Time frame: From stimulation Day 1 to end-of-trial (estimated maximum of 4 months from start of stimulation)
Incidence and intensity of adverse events (AEs)
Time frame: From screening to end-of-trial (estimated maximum of 4 months from start of stimulation)
Changes in circulating levels of clinical chemistry and haematology parameters
Time frame: At screening, on stimulation Day 1, end-of-stimulation (up to 20 stimulation days), end-of-trial (estimated maximum of 4 months from start of stimulation)
Incidence and intensity of injection site reactions after FE 999302 administration (redness, pain, itching, swelling and bruising) assessed by the subject during the stimulation period
Time frame: Immediately after injection of FE 999302 or placebo, 30 minutes after injection, and 24 hours after injection
Incidence of treatment-induced anti-FE 999302 antibodies, overall as well as with neutralising capacity
The proportion of subjects with treatment-induced anti-FE999302 antibodies as well as the proportion of subjects with treatment-induced anti-FE999302 antibodies with neutralizing capacity were reported.
Time frame: On stimulation Day 1, end-of-stimulation (up to 20 stimulation days), 19-28 days after the last FE999302 or placebo dose
Incidence of multi-fetal gestation
Time frame: 5 to 6 weeks after transfer
Incidence of biochemical pregnancy
Biochemical pregnancy was defined as positive βhCG test but no gestational sac was observed on transvaginal ultrasound conducted later, or menstruation is was reported.
Time frame: Up to 5 to 6 weeks after transfer
Incidence of spontaneous abortion (with and without medical/surgical intervention)
Spontaneous abortion was defined as positive βhCG test but all intrauterine gestational sacs without fetal heart beat as documented by ultrasound, or there were no viable fetuses observed by ultrasound.
Time frame: Up to 10 to 11 weeks after transfer
Incidence of ectopic pregnancy (with and without medical/surgical intervention)
Ectopic pregnancy was defined as extrauterine gestational sac with or without fetal heart beat as documented by ultrasound or surgery.
Time frame: Up to 5 to 6 weeks after transfer
Incidence of vanishing twins
Vanishing twin was defined as spontaneous disappearance of an intrauterine gestational sac with or without heart beat in a pregnancy where one viable fetus remained as documented by ultrasound.
Time frame: Up to 10 to 11 weeks after transfer
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