Controlled Ovarian Simulation
Conditions
Brief summary
To demonstrate non-inferiority of FE 999049 compared with GONAL-F with respect to ongoing pregnancy rate in women undergoing controlled ovarian stimulation.
Interventions
DRUGFollitropin alfa
GONAL-F dose was fixed for the first 5 stimulation days.
REKOVELLE (FE 999049) was fixed throughout the stimulation period.
Sponsors
Ferring Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
20 Years to 40 Years
Healthy volunteers
No
Inclusion criteria
* Informed Consent Documents signed prior to screening evaluations. * In good physical and mental health in the judgement of the investigator. * Asian pre-menopausal females between the ages of 20 and 40 years. The participants must be at least 20 years (including the 20th birthday) when they sign the informed consent and no more than 40 years (up to the day before the 41st birthday) at the time of randomization. * Infertile women diagnosed with tubal infertility, unexplained infertility, endometriosis stage I/II (defined by the revised American Society for Reproductive Medicine \[ASRM\] classification, 1996) or with partners diagnosed with male factor infertility, eligible for in vitro fertilisation (IVF) and/or intracytoplasmic sperm injection (ICSI) using fresh or frozen ejaculated sperm from male partner or sperm donor. * Infertility for at least one year before randomization for participants \<35 years or for at least 6 months for participants ≥35 years (not applicable in case of tubal or severe male factor infertility). * The trial cycle will be the participant's first controlled ovarian stimulation cycle for IVF/ICSI. * Regular menstrual cycles of 24-35 days (both inclusive), presumed to be ovulatory. * Hysterosalpingography, hysteroscopy, saline infusion sonography, or transvaginal ultrasound documenting a uterus consistent with expected normal function (e.g. no evidence of clinically interfering uterine fibroids defined as submucous or intramural fibroids larger than 3 cm in diameter, no polyps and no congenital structural abnormalities which are associated with a reduced chance of pregnancy) within 1 year prior to randomization. * Transvaginal ultrasound documenting presence and adequate visualisation of both ovaries, without evidence of significant abnormality (e.g. enlarged ovaries which would contraindicate the use of gonadotropins) and normal adnexa (e.g. no hydrosalpinx) within 1 year prior to randomization. Both ovaries must be accessible for oocyte retrieval. * Early follicular phase (cycle day 2-4) serum levels of FSH between 1 and 15 IU/L (results obtained within 3 months prior to randomization). * Negative serum Hepatitis B Surface Antigen (HBsAg), Hepatitis C Virus (HCV) and Human Immunodeficiency Virus (HIV) antibody tests within 2 years prior to randomization. * Body mass index (BMI) between 17.5 and 32.0 kg/m2 (both inclusive) at screening. * Willing to accept transfer of 1-2 embryos.
Exclusion criteria
* Known endometriosis stage III-IV (defined by the revised ASRM classification, 1996). * One or more follicles ≥10 mm (including cysts) observed on the transvaginal ultrasound prior to randomization on stimulation day 1 (puncture of cysts is allowed prior to randomization). * Known history of recurrent miscarriage (defined as three consecutive losses after ultrasound confirmation of pregnancy (excl. ectopic pregnancy) and before week 24 of pregnancy). * Known abnormal karyotype of participant or of her partner / sperm donor, as applicable, depending on source of sperm used for insemination in this trial. * Any known clinically significant systemic disease (e.g. insulin-dependent diabetes). * Known inherited or acquired thrombophilia disease. * Active arterial or venous thromboembolism or severe thrombophlebitis, or a history of these events. * Known porphyria. * Any known endocrine or metabolic abnormalities (pituitary, adrenal, pancreas, liver or kidney) with the exception of controlled thyroid function disease. * Known presence of anti-FSH antibodies (based on the information available in the participant's medical records; i.e. not based on the anti-FSH antibody analyses conducted in the trial). * Known tumours of the ovary, breast, uterus, adrenal gland, pituitary or hypothalamus which would contraindicate the use of gonadotropins. * Known moderate or severe impairment of renal or hepatic function. * Any abnormal finding of clinical chemistry, haematology or vital signs at screening which is clinically significant as judged by the investigator. * Currently breast-feeding. * Undiagnosed vaginal bleeding. * Known abnormal cervical cytology of clinical significance observed within three years prior to randomization (unless the clinical significance has been resolved). * Findings at the gynaecological examination at screening which preclude gonadotropin stimulation or are associated with a reduced chance of pregnancy, e.g. congenital uterine abnormalities or retained intrauterine device. * Pregnancy (negative urinary pregnancy tests must be documented at screening and prior to randomization) or contraindication to pregnancy. * Known current active pelvic inflammatory disease. * Use of fertility modifiers during the last menstrual cycle before randomization, including dehydroepiandrosterone (DHEA), metformin or cycle programming with oral contraceptives, progestogen or estrogen preparations. * Use of hormonal preparations (except for thyroid medication) during the last menstrual cycle before randomization. * Known history of chemotherapy (except for gestational conditions) or radiotherapy. * Current or past (1 year prior to randomization) abuse of alcohol or drugs. * Current (last month) intake of more than 14 units of alcohol per week. * Current or past (3 months prior to randomization) smoking habit of more than 10 cigarettes per day. * Hypersensitivity to any active ingredient or excipients in the medicinal products used in the trial. * Previous participation in the trial. * Use of any non-registered investigational drugs during the last 3 months prior to randomization.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ongoing Pregnancy Rate | 10-11 weeks after transfer | Defined as at least one intrauterine viable fetus 10-11 weeks after transfer. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Pregnancy Rate | 5-6 weeks after transfer | Defined as at least one gestational sac 5-6 weeks after transfer. |
| Vital Pregnancy Rate | 5-6 weeks after transfer | Defined as at least one intrauterine gestational sac with fetal heart beat 5-6 weeks after transfer. |
| Implantation Rate | 5-6 weeks after transfer | Defined as number of gestational sacs 5-6 weeks after transfer divided by number of embryos transferred. |
| Ongoing Implantation Rate | 10-11 weeks after transfer | Defined as number of intrauterine viable fetuses 10-11 weeks after transfer divided by number of embryos transferred. |
| Proportion of Subjects With Extreme Ovarian Responses | Oocyte retrieval visit | Extreme ovarian response defined as \<4, ≥15 or ≥ 20 oocytes retrieved. Participants with cycle cancellation due to poor ovarian response are included as \<4 oocytes retrieved. |
| Proportion of Subjects With Early OHSS (Including OHSS of Moderate/Severe Grade) and/or Preventive Interventions for Early OHSS | Up to 9 days after triggering of final follicular maturation | Early OHSS was defined as OHSS with onset ≤9 days after triggering of final follicular maturation. Classification of grade was according to Golan's classification system, and all OHSS cases were graded as mild, moderate or severe. |
| Proportion of Subjects With Cycle Cancellation Due to Poor or Excessive Ovarian Response or Embryo Transfer Cancellation Due to Excessive Ovarian Response / OHSS Risk | End-of-stimulation visit (up to 20 days) or transfer visit | For each participant the reason for each cycle cancellation was recorded. Embryo transfer cancellation due to adverse events, such as ovarian hyperfunction, OHSS and progesterone increased in participants with embryos available for transfer, were considered as transfer cancellations due to excessive response / OHSS risk. |
| Number of Follicles on Stimulation Day 6 | On stimulation Day 6 | Counted by ultrasound for the right and left ovary for each participant. |
| Number of Follicles At End-of-stimulation (up to 20 Stimulation Days) | At end-of-stimulation (up to 20 stimulation days) | Counted by ultrasound for the right and left ovary for each participant. |
| Size of Follicles on Stimulation Day 6 | On stimulation Day 6 | Counted by ultrasound for the right and left ovary for each participant. |
| Size of Follicles At End-of-stimulation (up to 20 Stimulation Days) | At end-of-stimulation (up to 20 stimulation days) | Counted by ultrasound for the right and left ovary for each participant. |
| Number of Oocytes Retrieved | On the day of oocyte retrieval (36 h [±2h] after triggering of final follicular maturation) | The number of oocytes retrieved was recorded at the oocyte retrieval visit. |
| Proportion of Subjects With <4, 4-7, 8-14, 15-19 and ≥20 Oocytes Retrieved | On the day of oocyte retrieval | Grouped according to the number of oocytes retrieved. Participants with cycle cancellation due to poor ovarian response are included in the \<4 oocytes group. |
| Percentage of Metaphase II (MII) Oocytes | Prior to insemination | The percentage of MII oocytes to oocytes retrieved for participants where all oocytes were inseminated using intracytoplasmic sperm injection (ICSI) are presented. |
| Fertilization Rate | On Day 1 after oocyte retrieval | The fertilization rate was defined as the number of oocytes with 2 pronuclei divided by the number of oocytes retrieved. |
| Number and Quality of Embryos | On Day 3 after oocyte retrieval | Number of embryos (total and good-quality) on Day 3 are presented. A good-quality embryo was defined as an embryo with ≥6 blastomeres and ≤20% fragmentation, without signs of multinucleation. |
| Circulating Concentrations of Luteinizing Hormone (LH) | On stimulation Day 6 | Blood samples for analysis of circulating concentrations of LH were drawn. The median and inter-quartile range (IQR) of LH levels on stimulation Day 6 are presented. |
| Circulating Concentrations of LH | End-of-stimulation (up to 20 stimulation days) | Blood samples for analysis of circulating concentrations of LH were drawn. The median and IQR of LH levels at end-of-stimulation are presented. |
| Circulating Concentrations of Estradiol | On stimulation Day 6 | Blood samples for analysis of circulating concentrations of estradiol were drawn. The median and IQR of estradiol levels on stimulation Day 6 are presented. |
| Circulating Concentrations of Progesterone | On stimulation Day 6 | Blood samples for analysis of circulating concentrations of progesterone were drawn. The median and IQR of progesterone levels on stimulation Day 6 are presented. |
| Circulating Concentrations of Inhibin A | On stimulation Day 6 | Blood samples for analysis of circulating concentrations of inhibin A. The median and IQR of inhibin A levels on stimulation Day 6 are presented. |
| Circulating Concentrations of Inhibin B | On stimulation Day 6 | Blood samples for analysis of circulating concentrations of Inhibin B were drawn. The median and IQR of inhibin B levels on stimulation Day 6 are presented. |
| Circulating Concentrations of Follicle-stimulating Hormone (FSH) | On stimulation Day 6 | Blood samples for analysis of circulating concentrations of FSH were drawn. The median and IQR of FSH levels on stimulation Day 6 are presented. |
| Circulating Concentrations of FSH | End-of-stimulation (up to 20 stimulation days) | Blood samples for analysis of circulating concentrations of FSH were drawn. The median and IQR of FSH levels at end-of-stimulation are presented. |
| Total Gonadotropin Dose | Up to 20 stimulation days | Calculated by start dates, end dates and daily dose of IMP. |
| Proportion of Subjects With Investigator-requested Gonadotropin Dose Adjustments | Up to 20 stimulation days | Investigator-requested decreases and increases of the gonadotropin dose were captured during the stimulation period. |
| Number of Stimulation Days | Up to 20 stimulation days | Calculated by start dates and end dates. |
| Number of Participants With Adverse Events | From screening up to end-of-trial (up to approximately 5.5 months) | Any adverse event occurring after start of IMP and before the end-of-trial visit, or a pre-treatment adverse event or pre-existing medical condition that worsens in intensity after start of IMP and before the end-of-trial visit was considered treatment-emergent, and is presented for this endpoint. |
| Intensity of Adverse Events | From screening up to end-of-trial (up to approximately 5.5 months) | The intensity of adverse event was classified using the following 3-point scale: mild = awareness of signs or symptoms, but no disruption of usual activity; moderate = event sufficient to affect usual activity (disturbing); or severe = inability to work or perform usual activities (unacceptable). |
| Changes From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase and Gamma Glutamyl Transferase | From screening up to end-of-trial (up to approximately 5.5 months) | Blood samples were collected for the analysis of clinical chemistry parameters including: Alanine aminotransferase, Alkaline phosphatase, Aspartate aminotransferase and Gamma glutamyl transferase. |
| Change From Baseline in Clinical Chemistry Parameters: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium | From screening up to end-of-trial (approximately 5.5 months) | Blood samples were collected for the analysis of clinical chemistry parameters including: Bicarbonate, Blood urea nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium. |
| Change From Baseline in Clinical Chemistry Parameters: Albumin and Protein | From screening up to end-of-trial (approximately 5.5 months) | Blood samples were collected for the analysis of clinical chemistry parameters including: Albumin and Protein. |
| Change From Baseline in Clinical Chemistry Parameter: Lactate Dehydrogenase | From screening up to end-of-trial (approximately 5.5 months) | Blood samples were collected for the analysis of clinical chemistry parameter including: Lactate dehydrogenase. |
| Change From Baseline in Clinical Chemistry Parameter: Direct Bilirubin, Bilirubin, Creatinine, Urate | From screening up to end-of-trial (approximately 5.5 months) | Blood samples were collected for the analysis of clinical chemistry parameter including: Direct bilirubin, Bilirubin, Creatinine, Urate. |
| Proportion of Subjects With Markedly Abnormal Changes of Clinical Chemistry: Alanine Aminotransferase, Aspartate Aminotransferase, Bicarbonate, Calcium, Phosphate | End-of-stimulation visit and end-of-trial visit | The table represents the percentage of participants in each group with normal baseline values and markedly abnormal end-of-stimulation or end-of-trial values for alanine aminotransferase, aspartate aminotransferase, bicarbonate, calcium, phosphate. |
| Change From Baseline in Haematology Parameter: Erythrocytes | From screening up to end-of-trial (approximately 5.5 months) | Blood samples were collected for the analysis of haematology parameter including: Erythrocytes. |
| Change From Baseline in Haematology Parameters: Leukocytes and Platelets | From screening up to end-of-trial (approximately 5.5 months) | Blood samples were collected for the analysis of haematology parameters including: Leukocytes and Platelets. |
| Change From Baseline in Haematology Parameter: Haemoglobin | From screening up to end-of-trial (approximately 5.5 months) | Blood samples were collected for the analysis of haematology parameter including: Haemoglobin. |
| Change From Baseline in Haematology Parameter: Haematocrit | From screening up to end-of-trial (approximately 5.5 months) | Blood samples were collected for the analysis of haematology parameter including: Haematocrit. |
| Change From Baseline in Haematology Parameter: Erythrocyte Mean Corpuscular Volume | From screening up to end-of-trial (approximately 5.5 months) | Blood samples were collected for the analysis of haematology parameter including: Erythrocyte mean corpuscular volume. |
| Change From Baseline in Haematology Parameter: Erythrocyte Mean Corpuscular Haemoglobin | From screening up to end-of-trial (approximately 5.5 months) | Blood samples were collected for the analysis of haematology parameter including: Erythrocyte mean corpuscular haemoglobin. |
| Change From Baseline in Haematology Parameter: Erythrocyte Mean Corpuscular Haemoglobin Concentration | From screening up to end-of-trial (approximately 5.5 months) | Blood samples were collected for the analysis of haematology parameter including: Erythrocyte mean corpuscular haemoglobin concentration. |
| Change From Baseline in Haematology Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes and Neutrophils/Leukocytes | From screening up to end-of-trial (approximately 5.5 months) | Blood samples were collected for the analysis of haematology parameters including: Basophils/leukocytes, Eosinophils/leukocytes, Lymphocytes/leukocytes, Monocytes/leukocytes and Neutrophils/leukocytes. |
| Proportion of Subjects With Markedly Abnormal Changes of Haematology Parameters: Leukocytes, Lymphocytes/Leukocytes | End-of-stimulation visit and end-of-trial visit | The table represents the percentage of participants in each group with normal baseline values and markedly abnormal end-of-stimulation and end-of-trial values for leukocytes and lymphocytes/leukocytes. |
| Number of Immune-related Adverse Events | From screening up to end-of-trial (approximately 5.5 months) | Standardised Medical Dictionary for Regulatory Activities (MedDRA) Queries (SMQs). |
| Frequency of Injection Site Reactions | End-of-stimulation (up to 20 stimulation days) | Assessed by the participant during the stimulation period. Participants assessed the injection site reactions (redness, pain, itching, swelling and bruising) three times daily: immediately after the injection, 30 minutes after the injection and 24 hours after the injection. |
| Intensity of Injection Site Reactions | End-of-stimulation (up to 20 stimulation days) | Assessed by the participant during the stimulation period as mild, moderate or severe. Participants are tabulated according to the highest severity of their reported injection site reactions. |
| Positive Beta Unit of Human Chorionic Gonadotropin (βhCG) Rate | 13-15 days after transfer | Defined as positive βhCG test 13-15 days after transfer. |
| Intensity of Immune-related Adverse Events | From screening up to end-of-trial (approximately 5.5 months) | The intensity of immune-related adverse event was classified using the following 3-point scale: mild = awareness of signs or symptoms, but no disruption of usual activity; moderate = event sufficient to affect usual activity (disturbing); or severe = inability to work or perform usual activities (unacceptable). |
| Proportion of Subjects With Cycle Cancellations Due to an Adverse Event, Including Immune-related Adverse Events, or Due to Technical Malfunctions of the Administration Pen | Up to 20 stimulation days | For each participant the reason for cycle cancellation will be recorded. |
| Proportion of Subjects With Late OHSS | After 9 days post triggering of final follicular maturation | Late OHSS was defined as OHSS with onset \>9 days after triggering of final follicular maturation. The proportion of participants with late OHSS, and late OHSS of moderate or severe grade are presented. All OHSS cases were graded as mild, moderate, or severe. |
| Proportion of Participants With Multi-fetal Gestation | End-of-trial | Defined as pregnancy with more than one fetus. Among participants with ongoing pregnancy, percentage of participants with twin pregnancies are presented. |
| Proportion of Participants With Early Pregnancy Losses | End-of-trial | Grouped according to occurrence of biochemical pregnancy, spontaneous abortion, vanishing twin or ectopic pregnancy (with and without medical/surgical intervention). Frequency of early pregnancy losses are presented. |
| Proportion of Participants With Technical Malfunctions of the Administration Pen | End-of-stimulation (up to 20 stimulation days) | Incidences of technical malfunctions of the administration pen were recorded. |
| Proportion of Subjects With Treatment-induced Anti-FSH Antibodies, Overall as Well as With Neutralizing Capacity | Up to 28 days after end of the stimulation period | Measured by presence of anti-FSH antibodies. |
Countries
China, South Korea, Taiwan, Vietnam
Participant flow
Recruitment details
A total of 26 investigational sites randomized participants to the trial: 16 in mainland China, 4 in South Korea, 4 in Taiwan and 2 in Vietnam between Dec 2017 to Jan 2020.
Pre-assignment details
A total of 1167 participants were screened, wherein, 1011 participants met the eligibility criteria and were randomized. Of these, 1009 participants were exposed to the investigational medicinal product (IMP): 499 participants were exposed to FE 999049 and 510 participants were exposed to GONAL-F. A total of 923 participants completed the trial.
Participants by arm
| Arm | Count |
|---|---|
| FE 000049 (Follitropin Delta) FE 999049 was administered as single daily subcutaneous injections in the abdomen. Participants randomized to FE 999049 had their individual dose determined on the basis of their AMH level at screening and their body weight at randomization. The daily FE 999049 dose was fixed throughout the stimulation period and minimum and maximum allowed daily dose was 6 and 12 μg, respectively. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days. | 499 |
| GONAL-F (Follitropin Alfa) GONAL-F was administered as single daily subcutaneous injections in the abdomen. The starting dose of GONAL-F was 150 IU and fixed for the first five stimulation days, after which it could be adjusted by 75 IU based on the individual response. The maximum allowed daily dose was 450 IU. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days. | 510 |
| Total | 1,009 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 15 | 33 |
| Overall Study | Discontinuation due to liquid in uterus | 1 | 0 |
| Overall Study | Discontinuation due to risk of Human Immunodeficiency Virus | 1 | 0 |
| Overall Study | Discontinuations due to risk of ovarian hyperstimulation syndrome [OHSS] | 9 | 14 |
| Overall Study | Discontinuations due to thin endometrium or poor endometrial receptivity | 0 | 2 |
| Overall Study | Discontinuations due to withdrawal from trial | 2 | 3 |
| Overall Study | Participant withdrew consent | 3 | 1 |
| Overall Study | Protocol Deviation | 4 | 0 |
Baseline characteristics
| Characteristic | FE 000049 (Follitropin Delta) | GONAL-F (Follitropin Alfa) | Total |
|---|---|---|---|
| Age, Continuous | 31.1 years STANDARD_DEVIATION 3.7 | 31.2 years STANDARD_DEVIATION 3.8 | 31.1 years STANDARD_DEVIATION 3.7 |
| Age, Customized <35 | 394 years | 396 years | 790 years |
| Age, Customized 35-37 | 85 years | 86 years | 171 years |
| Age, Customized 38-40 | 20 years | 28 years | 48 years |
| Body Mass Index (BMI) | 21.8 kg/m^2 STANDARD_DEVIATION 2.7 | 21.8 kg/m^2 STANDARD_DEVIATION 2.8 | 21.8 kg/m^2 STANDARD_DEVIATION 2.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 499 Participants | 510 Participants | 1009 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Chinese | 379 Participants | 381 Participants | 760 Participants |
| Race/Ethnicity, Customized South Korean | 21 Participants | 25 Participants | 46 Participants |
| Race/Ethnicity, Customized Taiwanese | 50 Participants | 53 Participants | 103 Participants |
| Race/Ethnicity, Customized Vietnamese | 49 Participants | 51 Participants | 100 Participants |
| Region of Enrollment China | 378 participants | 381 participants | 759 participants |
| Region of Enrollment South Korea | 21 participants | 25 participants | 46 participants |
| Region of Enrollment Taiwan | 51 participants | 53 participants | 104 participants |
| Region of Enrollment Vietnam | 49 participants | 51 participants | 100 participants |
| Sex: Female, Male Female | 499 Participants | 510 Participants | 1009 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 499 | 0 / 510 |
| other Total, other adverse events | 97 / 499 | 94 / 510 |
| serious Total, serious adverse events | 30 / 499 | 18 / 510 |
Outcome results
Primary
Ongoing Pregnancy Rate
Defined as at least one intrauterine viable fetus 10-11 weeks after transfer.
Time frame: 10-11 weeks after transfer
Population: The FAS was defined as all randomized and exposed participants. Participants were analyzed according to randomized treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FE 000049 (Follitropin Delta) | Ongoing Pregnancy Rate | 31.3 percentage of participants |
| GONAL-F (Follitropin Alfa) | Ongoing Pregnancy Rate | 25.7 percentage of participants |
Comparison: Percentage of participants with ongoing pregnancy rate95% CI: [-0.2, 11]
Secondary
Change From Baseline in Clinical Chemistry Parameter: Direct Bilirubin, Bilirubin, Creatinine, Urate
Blood samples were collected for the analysis of clinical chemistry parameter including: Direct bilirubin, Bilirubin, Creatinine, Urate.
Time frame: From screening up to end-of-trial (approximately 5.5 months)
Population: The safety analysis set was defined as all randomized and exposed participants. Participants analyzed for this endpoint represent participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FE 000049 (Follitropin Delta) | Change From Baseline in Clinical Chemistry Parameter: Direct Bilirubin, Bilirubin, Creatinine, Urate | Direct bilirubin | -0.3 umol/L | Standard Deviation 0.8 |
| FE 000049 (Follitropin Delta) | Change From Baseline in Clinical Chemistry Parameter: Direct Bilirubin, Bilirubin, Creatinine, Urate | Bilirubin | -1.3 umol/L | Standard Deviation 3.6 |
| FE 000049 (Follitropin Delta) | Change From Baseline in Clinical Chemistry Parameter: Direct Bilirubin, Bilirubin, Creatinine, Urate | Creatinine | -3.4 umol/L | Standard Deviation 9 |
| FE 000049 (Follitropin Delta) | Change From Baseline in Clinical Chemistry Parameter: Direct Bilirubin, Bilirubin, Creatinine, Urate | Urate | -18.8 umol/L | Standard Deviation 54.1 |
| GONAL-F (Follitropin Alfa) | Change From Baseline in Clinical Chemistry Parameter: Direct Bilirubin, Bilirubin, Creatinine, Urate | Urate | -17.9 umol/L | Standard Deviation 53.5 |
| GONAL-F (Follitropin Alfa) | Change From Baseline in Clinical Chemistry Parameter: Direct Bilirubin, Bilirubin, Creatinine, Urate | Direct bilirubin | -0.2 umol/L | Standard Deviation 0.8 |
| GONAL-F (Follitropin Alfa) | Change From Baseline in Clinical Chemistry Parameter: Direct Bilirubin, Bilirubin, Creatinine, Urate | Creatinine | -3.5 umol/L | Standard Deviation 8.5 |
| GONAL-F (Follitropin Alfa) | Change From Baseline in Clinical Chemistry Parameter: Direct Bilirubin, Bilirubin, Creatinine, Urate | Bilirubin | -1.0 umol/L | Standard Deviation 3.5 |
Secondary
Change From Baseline in Clinical Chemistry Parameter: Lactate Dehydrogenase
Blood samples were collected for the analysis of clinical chemistry parameter including: Lactate dehydrogenase.
Time frame: From screening up to end-of-trial (approximately 5.5 months)
Population: The safety analysis set was defined as all randomized and exposed participants. Participants analyzed for this endpoint represent participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FE 000049 (Follitropin Delta) | Change From Baseline in Clinical Chemistry Parameter: Lactate Dehydrogenase | -3.0 U/L | Standard Deviation 17 |
| GONAL-F (Follitropin Alfa) | Change From Baseline in Clinical Chemistry Parameter: Lactate Dehydrogenase | -0.9 U/L | Standard Deviation 18.9 |
Secondary
Change From Baseline in Clinical Chemistry Parameters: Albumin and Protein
Blood samples were collected for the analysis of clinical chemistry parameters including: Albumin and Protein.
Time frame: From screening up to end-of-trial (approximately 5.5 months)
Population: The safety analysis set was defined as all randomized and exposed participants. Participants analyzed for this endpoint represent participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FE 000049 (Follitropin Delta) | Change From Baseline in Clinical Chemistry Parameters: Albumin and Protein | Albumin | -2.0 g/L | Standard Deviation 3.1 |
| FE 000049 (Follitropin Delta) | Change From Baseline in Clinical Chemistry Parameters: Albumin and Protein | Protein | -2.3 g/L | Standard Deviation 4.6 |
| GONAL-F (Follitropin Alfa) | Change From Baseline in Clinical Chemistry Parameters: Albumin and Protein | Albumin | -1.6 g/L | Standard Deviation 3 |
| GONAL-F (Follitropin Alfa) | Change From Baseline in Clinical Chemistry Parameters: Albumin and Protein | Protein | -1.5 g/L | Standard Deviation 4.5 |
Secondary
Change From Baseline in Clinical Chemistry Parameters: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium
Blood samples were collected for the analysis of clinical chemistry parameters including: Bicarbonate, Blood urea nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium.
Time frame: From screening up to end-of-trial (approximately 5.5 months)
Population: The safety analysis set was defined as all randomized and exposed participants. Participants analyzed for this endpoint represent participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FE 000049 (Follitropin Delta) | Change From Baseline in Clinical Chemistry Parameters: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium | Blood urea nitrogen | -0.27 mmol/L | Standard Deviation 1.12 |
| FE 000049 (Follitropin Delta) | Change From Baseline in Clinical Chemistry Parameters: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium | Glucose | -0.01 mmol/L | Standard Deviation 0.94 |
| FE 000049 (Follitropin Delta) | Change From Baseline in Clinical Chemistry Parameters: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium | Chloride | -0.3 mmol/L | Standard Deviation 2.3 |
| FE 000049 (Follitropin Delta) | Change From Baseline in Clinical Chemistry Parameters: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium | Phosphate | 0.037 mmol/L | Standard Deviation 0.166 |
| FE 000049 (Follitropin Delta) | Change From Baseline in Clinical Chemistry Parameters: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium | Calcium | -0.010 mmol/L | Standard Deviation 0.089 |
| FE 000049 (Follitropin Delta) | Change From Baseline in Clinical Chemistry Parameters: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium | Potassium | 0.03 mmol/L | Standard Deviation 0.34 |
| FE 000049 (Follitropin Delta) | Change From Baseline in Clinical Chemistry Parameters: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium | Cholesterol | 0.218 mmol/L | Standard Deviation 0.537 |
| FE 000049 (Follitropin Delta) | Change From Baseline in Clinical Chemistry Parameters: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium | Sodium | -1.8 mmol/L | Standard Deviation 2.6 |
| FE 000049 (Follitropin Delta) | Change From Baseline in Clinical Chemistry Parameters: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium | Bicarbonate | -0.83 mmol/L | Standard Deviation 2.52 |
| GONAL-F (Follitropin Alfa) | Change From Baseline in Clinical Chemistry Parameters: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium | Sodium | -1.7 mmol/L | Standard Deviation 2.5 |
| GONAL-F (Follitropin Alfa) | Change From Baseline in Clinical Chemistry Parameters: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium | Bicarbonate | -0.72 mmol/L | Standard Deviation 2.51 |
| GONAL-F (Follitropin Alfa) | Change From Baseline in Clinical Chemistry Parameters: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium | Blood urea nitrogen | -0.23 mmol/L | Standard Deviation 1.11 |
| GONAL-F (Follitropin Alfa) | Change From Baseline in Clinical Chemistry Parameters: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium | Calcium | 0.000 mmol/L | Standard Deviation 0.081 |
| GONAL-F (Follitropin Alfa) | Change From Baseline in Clinical Chemistry Parameters: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium | Chloride | -0.3 mmol/L | Standard Deviation 2.4 |
| GONAL-F (Follitropin Alfa) | Change From Baseline in Clinical Chemistry Parameters: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium | Cholesterol | 0.260 mmol/L | Standard Deviation 0.549 |
| GONAL-F (Follitropin Alfa) | Change From Baseline in Clinical Chemistry Parameters: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium | Glucose | -0.01 mmol/L | Standard Deviation 0.91 |
| GONAL-F (Follitropin Alfa) | Change From Baseline in Clinical Chemistry Parameters: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium | Phosphate | 0.023 mmol/L | Standard Deviation 0.169 |
| GONAL-F (Follitropin Alfa) | Change From Baseline in Clinical Chemistry Parameters: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium | Potassium | 0.04 mmol/L | Standard Deviation 0.33 |
Secondary
Change From Baseline in Haematology Parameter: Erythrocyte Mean Corpuscular Haemoglobin
Blood samples were collected for the analysis of haematology parameter including: Erythrocyte mean corpuscular haemoglobin.
Time frame: From screening up to end-of-trial (approximately 5.5 months)
Population: The safety analysis set was defined as all randomized and exposed participants. Participants analyzed for this endpoint represent participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FE 000049 (Follitropin Delta) | Change From Baseline in Haematology Parameter: Erythrocyte Mean Corpuscular Haemoglobin | 0.3 picogram | Standard Deviation 0.9 |
| GONAL-F (Follitropin Alfa) | Change From Baseline in Haematology Parameter: Erythrocyte Mean Corpuscular Haemoglobin | 0.2 picogram | Standard Deviation 0.8 |
Secondary
Change From Baseline in Haematology Parameter: Erythrocyte Mean Corpuscular Haemoglobin Concentration
Blood samples were collected for the analysis of haematology parameter including: Erythrocyte mean corpuscular haemoglobin concentration.
Time frame: From screening up to end-of-trial (approximately 5.5 months)
Population: The safety analysis set was defined as all randomized and exposed participants. Participants analyzed for this endpoint represent participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FE 000049 (Follitropin Delta) | Change From Baseline in Haematology Parameter: Erythrocyte Mean Corpuscular Haemoglobin Concentration | 0.2 mmol/L | Standard Deviation 0.8 |
| GONAL-F (Follitropin Alfa) | Change From Baseline in Haematology Parameter: Erythrocyte Mean Corpuscular Haemoglobin Concentration | 0.1 mmol/L | Standard Deviation 0.8 |
Secondary
Change From Baseline in Haematology Parameter: Erythrocyte Mean Corpuscular Volume
Blood samples were collected for the analysis of haematology parameter including: Erythrocyte mean corpuscular volume.
Time frame: From screening up to end-of-trial (approximately 5.5 months)
Population: The safety analysis set was defined as all randomized and exposed participants. Participants analyzed for this endpoint represent participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FE 000049 (Follitropin Delta) | Change From Baseline in Haematology Parameter: Erythrocyte Mean Corpuscular Volume | 0.0 Femtoliters | Standard Deviation 3.3 |
| GONAL-F (Follitropin Alfa) | Change From Baseline in Haematology Parameter: Erythrocyte Mean Corpuscular Volume | 0.1 Femtoliters | Standard Deviation 3.2 |
Secondary
Change From Baseline in Haematology Parameter: Erythrocytes
Blood samples were collected for the analysis of haematology parameter including: Erythrocytes.
Time frame: From screening up to end-of-trial (approximately 5.5 months)
Population: The safety analysis set was defined as all randomized and exposed participants. Participants analyzed for this endpoint represent participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FE 000049 (Follitropin Delta) | Change From Baseline in Haematology Parameter: Erythrocytes | -0.13 10^12 cells/L | Standard Deviation 0.31 |
| GONAL-F (Follitropin Alfa) | Change From Baseline in Haematology Parameter: Erythrocytes | -0.09 10^12 cells/L | Standard Deviation 0.27 |
Secondary
Change From Baseline in Haematology Parameter: Haematocrit
Blood samples were collected for the analysis of haematology parameter including: Haematocrit.
Time frame: From screening up to end-of-trial (approximately 5.5 months)
Population: The safety analysis set was defined as all randomized and exposed participants. Participants analyzed for this endpoint represent participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FE 000049 (Follitropin Delta) | Change From Baseline in Haematology Parameter: Haematocrit | -0.012 Ratio | Standard Deviation 0.033 |
| GONAL-F (Follitropin Alfa) | Change From Baseline in Haematology Parameter: Haematocrit | -0.008 Ratio | Standard Deviation 0.03 |
Secondary
Change From Baseline in Haematology Parameter: Haemoglobin
Blood samples were collected for the analysis of haematology parameter including: Haemoglobin.
Time frame: From screening up to end-of-trial (approximately 5.5 months)
Population: The safety analysis set was defined as all randomized and exposed participants. Participants analyzed for this endpoint represent participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FE 000049 (Follitropin Delta) | Change From Baseline in Haematology Parameter: Haemoglobin | -2.9 g/L | Standard Deviation 8.9 |
| GONAL-F (Follitropin Alfa) | Change From Baseline in Haematology Parameter: Haemoglobin | -1.7 g/L | Standard Deviation 7.9 |
Secondary
Change From Baseline in Haematology Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes and Neutrophils/Leukocytes
Blood samples were collected for the analysis of haematology parameters including: Basophils/leukocytes, Eosinophils/leukocytes, Lymphocytes/leukocytes, Monocytes/leukocytes and Neutrophils/leukocytes.
Time frame: From screening up to end-of-trial (approximately 5.5 months)
Population: The safety analysis set was defined as all randomized and exposed participants. Participants analyzed for this endpoint represent participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FE 000049 (Follitropin Delta) | Change From Baseline in Haematology Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes and Neutrophils/Leukocytes | Eosinophils/leukocytes | -0.01 percentage | Standard Deviation 1.08 |
| FE 000049 (Follitropin Delta) | Change From Baseline in Haematology Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes and Neutrophils/Leukocytes | Monocytes/leukocytes | -0.16 percentage | Standard Deviation 1.52 |
| FE 000049 (Follitropin Delta) | Change From Baseline in Haematology Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes and Neutrophils/Leukocytes | Lymphocytes/leukocytes | -2.05 percentage | Standard Deviation 9.18 |
| FE 000049 (Follitropin Delta) | Change From Baseline in Haematology Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes and Neutrophils/Leukocytes | Neutrophils/leukocytes | 2.20 percentage | Standard Deviation 10.03 |
| FE 000049 (Follitropin Delta) | Change From Baseline in Haematology Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes and Neutrophils/Leukocytes | Basophils/leukocytes | -0.01 percentage | Standard Deviation 0.37 |
| GONAL-F (Follitropin Alfa) | Change From Baseline in Haematology Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes and Neutrophils/Leukocytes | Neutrophils/leukocytes | 1.50 percentage | Standard Deviation 9.89 |
| GONAL-F (Follitropin Alfa) | Change From Baseline in Haematology Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes and Neutrophils/Leukocytes | Basophils/leukocytes | 0.02 percentage | Standard Deviation 0.36 |
| GONAL-F (Follitropin Alfa) | Change From Baseline in Haematology Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes and Neutrophils/Leukocytes | Eosinophils/leukocytes | -0.07 percentage | Standard Deviation 1.04 |
| GONAL-F (Follitropin Alfa) | Change From Baseline in Haematology Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes and Neutrophils/Leukocytes | Lymphocytes/leukocytes | -1.39 percentage | Standard Deviation 9.16 |
| GONAL-F (Follitropin Alfa) | Change From Baseline in Haematology Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes and Neutrophils/Leukocytes | Monocytes/leukocytes | -0.04 percentage | Standard Deviation 1.66 |
Secondary
Change From Baseline in Haematology Parameters: Leukocytes and Platelets
Blood samples were collected for the analysis of haematology parameters including: Leukocytes and Platelets.
Time frame: From screening up to end-of-trial (approximately 5.5 months)
Population: The safety analysis set was defined as all randomized and exposed participants. Participants analyzed for this endpoint represent participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FE 000049 (Follitropin Delta) | Change From Baseline in Haematology Parameters: Leukocytes and Platelets | Leukocytes | 1.161 10^9 cells/L | Standard Deviation 2.232 |
| FE 000049 (Follitropin Delta) | Change From Baseline in Haematology Parameters: Leukocytes and Platelets | Platelets | 19.9 10^9 cells/L | Standard Deviation 41.7 |
| GONAL-F (Follitropin Alfa) | Change From Baseline in Haematology Parameters: Leukocytes and Platelets | Leukocytes | 0.996 10^9 cells/L | Standard Deviation 2.099 |
| GONAL-F (Follitropin Alfa) | Change From Baseline in Haematology Parameters: Leukocytes and Platelets | Platelets | 23.8 10^9 cells/L | Standard Deviation 40.6 |
Secondary
Changes From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase and Gamma Glutamyl Transferase
Blood samples were collected for the analysis of clinical chemistry parameters including: Alanine aminotransferase, Alkaline phosphatase, Aspartate aminotransferase and Gamma glutamyl transferase.
Time frame: From screening up to end-of-trial (up to approximately 5.5 months)
Population: The safety analysis set was defined as all randomized and exposed participants. Participants analyzed for this endpoint represent participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FE 000049 (Follitropin Delta) | Changes From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase and Gamma Glutamyl Transferase | Alanine aminotransferase | 3.9 IU/L | Standard Deviation 13.8 |
| FE 000049 (Follitropin Delta) | Changes From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase and Gamma Glutamyl Transferase | Aspartate aminotransferase | 0.7 IU/L | Standard Deviation 7.1 |
| FE 000049 (Follitropin Delta) | Changes From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase and Gamma Glutamyl Transferase | Gamma glutamyl transferase | 1.1 IU/L | Standard Deviation 6.6 |
| FE 000049 (Follitropin Delta) | Changes From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase and Gamma Glutamyl Transferase | Alkaline phosphatase | -2.9 IU/L | Standard Deviation 8.2 |
| GONAL-F (Follitropin Alfa) | Changes From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase and Gamma Glutamyl Transferase | Alkaline phosphatase | -2.7 IU/L | Standard Deviation 8 |
| GONAL-F (Follitropin Alfa) | Changes From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase and Gamma Glutamyl Transferase | Alanine aminotransferase | 4.6 IU/L | Standard Deviation 16.7 |
| GONAL-F (Follitropin Alfa) | Changes From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase and Gamma Glutamyl Transferase | Gamma glutamyl transferase | 1.1 IU/L | Standard Deviation 10.2 |
| GONAL-F (Follitropin Alfa) | Changes From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase and Gamma Glutamyl Transferase | Aspartate aminotransferase | 1.2 IU/L | Standard Deviation 13 |
Secondary
Circulating Concentrations of Estradiol
Blood samples for analysis of circulating concentrations of estradiol were drawn. The median and IQR of estradiol levels on stimulation Day 6 are presented.
Time frame: On stimulation Day 6
Population: The FAS was defined as all randomized and exposed participants. Participants were analyzed according to randomized treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| FE 000049 (Follitropin Delta) | Circulating Concentrations of Estradiol | 2240.7 pmol/L |
| GONAL-F (Follitropin Alfa) | Circulating Concentrations of Estradiol | 2885.9 pmol/L |
Comparison: Circulating concentrations of Estradiol on stimulation Day 6p-value: <0.00195% CI: [0.7, 0.84]ANCOVA
Secondary
Circulating Concentrations of Estradiol
Blood samples for analysis of circulating concentrations of estradiol were drawn. The median and IQR of estradiol levels at end-of-stimulation are presented.
Time frame: End-of-stimulation (up to 20 stimulation days)
Population: The FAS was defined as all randomized and exposed participants. Participants were analyzed according to randomized treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| FE 000049 (Follitropin Delta) | Circulating Concentrations of Estradiol | 7429.3 pmol/L |
| GONAL-F (Follitropin Alfa) | Circulating Concentrations of Estradiol | 9055.8 pmol/L |
Comparison: Circulating concentrations of Estradiol at end-of-stimulationp-value: <0.00195% CI: [0.68, 0.81]ANCOVA
Secondary
Circulating Concentrations of Follicle-stimulating Hormone (FSH)
Blood samples for analysis of circulating concentrations of FSH were drawn. The median and IQR of FSH levels on stimulation Day 6 are presented.
Time frame: On stimulation Day 6
Population: The FAS was defined as all randomized and exposed participants. Participants were analyzed according to randomized treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| FE 000049 (Follitropin Delta) | Circulating Concentrations of Follicle-stimulating Hormone (FSH) | 11.6 IU/L |
| GONAL-F (Follitropin Alfa) | Circulating Concentrations of Follicle-stimulating Hormone (FSH) | 11.2 IU/L |
Comparison: Circulating concentrations of FSH on stimulation Day 6p-value: <0.00195% CI: [1.04, 1.12]ANCOVA
Secondary
Circulating Concentrations of FSH
Blood samples for analysis of circulating concentrations of FSH were drawn. The median and IQR of FSH levels at oocyte retrieval are presented.
Time frame: At oocyte retrieval
Population: The FAS was defined as all randomized and exposed participants. Participants were analyzed according to randomized treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| FE 000049 (Follitropin Delta) | Circulating Concentrations of FSH | 5.6 IU/L |
| GONAL-F (Follitropin Alfa) | Circulating Concentrations of FSH | 5.5 IU/L |
Comparison: Circulating concentrations of FSH at oocyte retrieval visitp-value: 0.18495% CI: [0.99, 1.07]ANCOVA
Secondary
Circulating Concentrations of FSH
Blood samples for analysis of circulating concentrations of FSH were drawn. The median and IQR of FSH levels at end-of-stimulation are presented.
Time frame: End-of-stimulation (up to 20 stimulation days)
Population: The FAS was defined as all randomized and exposed participants. Participants were analyzed according to randomized treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| FE 000049 (Follitropin Delta) | Circulating Concentrations of FSH | 11.3 IU/L |
| GONAL-F (Follitropin Alfa) | Circulating Concentrations of FSH | 12.2 IU/L |
Comparison: Circulating concentrations of FSH at end-of-stimulationp-value: <0.00195% CI: [0.89, 0.95]ANCOVA
Secondary
Circulating Concentrations of Inhibin A
Blood samples for analysis of circulating concentrations of inhibin A. The median and IQR of inhibin A levels on stimulation Day 6 are presented.
Time frame: On stimulation Day 6
Population: The FAS was defined as all randomized and exposed participants. Participants were analyzed according to randomized treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| FE 000049 (Follitropin Delta) | Circulating Concentrations of Inhibin A | 107.9 ng/L |
| GONAL-F (Follitropin Alfa) | Circulating Concentrations of Inhibin A | 129.1 ng/L |
Comparison: Circulating concentrations of Inhibin A on stimulation Day 6p-value: <0.00195% CI: [0.7, 0.83]ANCOVA
Secondary
Circulating Concentrations of Inhibin A
Blood samples for analysis of circulating concentrations of inhibin A were drawn. The median and IQR of inhibin A levels at end-of-stimulation are presented.
Time frame: End-of-stimulation (up to 20 stimulation days)
Population: The FAS was defined as all randomized and exposed participants. Participants were analyzed according to randomized treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| FE 000049 (Follitropin Delta) | Circulating Concentrations of Inhibin A | 361.7 ng/L |
| GONAL-F (Follitropin Alfa) | Circulating Concentrations of Inhibin A | 447.4 ng/L |
Comparison: Circulating concentrations of Inhibin A at end-of-stimulationp-value: <0.00195% CI: [0.71, 0.83]ANCOVA
Secondary
Circulating Concentrations of Inhibin B
Blood samples for analysis of circulating concentrations of Inhibin B were drawn. The median and IQR of inhibin B levels at end-of-stimulation are presented.
Time frame: End-of-stimulation (up to 20 stimulation days)
Population: The FAS was defined as all randomized and exposed participants. Participants were analyzed according to randomized treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| FE 000049 (Follitropin Delta) | Circulating Concentrations of Inhibin B | 1020.0 ng/L |
| GONAL-F (Follitropin Alfa) | Circulating Concentrations of Inhibin B | 1101.0 ng/L |
Comparison: Circulating concentrations of Inhibin B at end-of-stimulationp-value: 0.00195% CI: [0.8, 0.95]ANCOVA
Secondary
Circulating Concentrations of Inhibin B
Blood samples for analysis of circulating concentrations of Inhibin B were drawn. The median and IQR of inhibin B levels on stimulation Day 6 are presented.
Time frame: On stimulation Day 6
Population: The FAS was defined as all randomized and exposed participants. Participants were analyzed according to randomized treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| FE 000049 (Follitropin Delta) | Circulating Concentrations of Inhibin B | 740.0 ng/L |
| GONAL-F (Follitropin Alfa) | Circulating Concentrations of Inhibin B | 901.0 ng/L |
Comparison: Circulating concentrations of Inhibin B on stimulation Day 6p-value: <0.00195% CI: [0.77, 0.89]ANCOVA
Secondary
Circulating Concentrations of LH
Blood samples for analysis of circulating concentrations of LH were drawn. The median and IQR of LH levels at end-of-stimulation are presented.
Time frame: End-of-stimulation (up to 20 stimulation days)
Population: The FAS was defined as all randomized and exposed participants. Participants were analyzed according to randomized treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| FE 000049 (Follitropin Delta) | Circulating Concentrations of LH | 1.8 IU/L |
| GONAL-F (Follitropin Alfa) | Circulating Concentrations of LH | 2.0 IU/L |
Comparison: Circulating concentrations of LH at end-of-stimulationp-value: 0.01895% CI: [0.82, 0.98]ANCOVA
Secondary
Circulating Concentrations of Luteinizing Hormone (LH)
Blood samples for analysis of circulating concentrations of LH were drawn. The median and inter-quartile range (IQR) of LH levels on stimulation Day 6 are presented.
Time frame: On stimulation Day 6
Population: The FAS was defined as all randomized and exposed participants. Participants were analyzed according to randomized treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| FE 000049 (Follitropin Delta) | Circulating Concentrations of Luteinizing Hormone (LH) | 2.6 IU/L |
| GONAL-F (Follitropin Alfa) | Circulating Concentrations of Luteinizing Hormone (LH) | 3.1 IU/L |
Comparison: Circulating concentrations of LH on stimulation Day 6p-value: <0.00195% CI: [0.74, 0.88]ANCOVA
Secondary
Circulating Concentrations of Progesterone
Blood samples for analysis of circulating concentrations of progesterone were drawn. The median and IQR of progesterone levels at end-of-stimulation are presented.
Time frame: End-of-stimulation (up to 20 stimulation days)
Population: The FAS was defined as all randomized and exposed participants. Participants were analyzed according to randomized treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| FE 000049 (Follitropin Delta) | Circulating Concentrations of Progesterone | 2.4 nmol/L |
| GONAL-F (Follitropin Alfa) | Circulating Concentrations of Progesterone | 3.2 nmol/L |
Comparison: Circulating concentrations of Progesterone at end-of-stimulationp-value: <0.00195% CI: [0.68, 0.79]ANCOVA
Secondary
Circulating Concentrations of Progesterone
Blood samples for analysis of circulating concentrations of progesterone were drawn. The median and IQR of progesterone levels on stimulation Day 6 are presented.
Time frame: On stimulation Day 6
Population: The FAS was defined as all randomized and exposed participants. Participants were analyzed according to randomized treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| FE 000049 (Follitropin Delta) | Circulating Concentrations of Progesterone | 1.7 nmol/L |
| GONAL-F (Follitropin Alfa) | Circulating Concentrations of Progesterone | 1.9 nmol/L |
Comparison: Circulating concentrations of Progesterone on stimulation Day 6p-value: 0.00395% CI: [0.82, 0.96]ANCOVA
Secondary
Clinical Pregnancy Rate
Defined as at least one gestational sac 5-6 weeks after transfer.
Time frame: 5-6 weeks after transfer
Population: The FAS was defined as all randomized and exposed participants. Participants were analyzed according to randomized treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FE 000049 (Follitropin Delta) | Clinical Pregnancy Rate | 36.1 percentage of participants |
| GONAL-F (Follitropin Alfa) | Clinical Pregnancy Rate | 31.2 percentage of participants |
Comparison: Percentage of participants with at least one gestational sac 5-6 weeks after transfer95% CI: [-0.9, 10.7]
Secondary
Fertilization Rate
The fertilization rate was defined as the number of oocytes with 2 pronuclei divided by the number of oocytes retrieved.
Time frame: On Day 1 after oocyte retrieval
Population: Participants with oocytes retrieved.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FE 000049 (Follitropin Delta) | Fertilization Rate | 63.5 percentage of fertilized oocytes | Standard Deviation 22.9 |
| GONAL-F (Follitropin Alfa) | Fertilization Rate | 63.9 percentage of fertilized oocytes | Standard Deviation 21 |
Comparison: Fertilization rate relative to oocytes retrievedp-value: 0.79van Elteren test
Secondary
Frequency of Injection Site Reactions
Assessed by the participant during the stimulation period. Participants assessed the injection site reactions (redness, pain, itching, swelling and bruising) three times daily: immediately after the injection, 30 minutes after the injection and 24 hours after the injection.
Time frame: End-of-stimulation (up to 20 stimulation days)
Population: The safety analysis set was defined as all randomized and exposed participants. Participants were analyzed according to actual treatment received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FE 000049 (Follitropin Delta) | Frequency of Injection Site Reactions | 23.2 percentage of participants |
| GONAL-F (Follitropin Alfa) | Frequency of Injection Site Reactions | 21.6 percentage of participants |
Secondary
Implantation Rate
Defined as number of gestational sacs 5-6 weeks after transfer divided by number of embryos transferred.
Time frame: 5-6 weeks after transfer
Population: Participants with embryo transfer (a total of 548 and 546 embryos were transferred in the FE 999049 and GONAL-F groups, respectively). The experimental unit was transferred embryo.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FE 000049 (Follitropin Delta) | Implantation Rate | 35.6 percentage of sacs/embryos transferred |
| GONAL-F (Follitropin Alfa) | Implantation Rate | 31.3 percentage of sacs/embryos transferred |
Comparison: Percentage of implanted embryos 5-6 weeks after transfer95% CI: [-1.6, 9.5]
Secondary
Intensity of Adverse Events
The intensity of adverse event was classified using the following 3-point scale: mild = awareness of signs or symptoms, but no disruption of usual activity; moderate = event sufficient to affect usual activity (disturbing); or severe = inability to work or perform usual activities (unacceptable).
Time frame: From screening up to end-of-trial (up to approximately 5.5 months)
Population: The safety analysis set was defined as all randomized and exposed participants. Participants were analyzed according to actual treatment received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FE 000049 (Follitropin Delta) | Intensity of Adverse Events | Mild adverse events | 40.1 percentage of participants |
| FE 000049 (Follitropin Delta) | Intensity of Adverse Events | Moderate adverse events | 7.4 percentage of participants |
| FE 000049 (Follitropin Delta) | Intensity of Adverse Events | Severe adverse events | 3.6 percentage of participants |
| GONAL-F (Follitropin Alfa) | Intensity of Adverse Events | Mild adverse events | 37.8 percentage of participants |
| GONAL-F (Follitropin Alfa) | Intensity of Adverse Events | Moderate adverse events | 5.9 percentage of participants |
| GONAL-F (Follitropin Alfa) | Intensity of Adverse Events | Severe adverse events | 1.8 percentage of participants |
Secondary
Intensity of Immune-related Adverse Events
The intensity of immune-related adverse event was classified using the following 3-point scale: mild = awareness of signs or symptoms, but no disruption of usual activity; moderate = event sufficient to affect usual activity (disturbing); or severe = inability to work or perform usual activities (unacceptable).
Time frame: From screening up to end-of-trial (approximately 5.5 months)
Population: The safety analysis set was defined as all randomized and exposed participants. Participants were analyzed according to actual treatment received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FE 000049 (Follitropin Delta) | Intensity of Immune-related Adverse Events | Mild | 0 events |
| FE 000049 (Follitropin Delta) | Intensity of Immune-related Adverse Events | Moderate | 0 events |
| FE 000049 (Follitropin Delta) | Intensity of Immune-related Adverse Events | Severe | 0 events |
| GONAL-F (Follitropin Alfa) | Intensity of Immune-related Adverse Events | Mild | 0 events |
| GONAL-F (Follitropin Alfa) | Intensity of Immune-related Adverse Events | Moderate | 0 events |
| GONAL-F (Follitropin Alfa) | Intensity of Immune-related Adverse Events | Severe | 0 events |
Secondary
Intensity of Injection Site Reactions
Assessed by the participant during the stimulation period as mild, moderate or severe. Participants are tabulated according to the highest severity of their reported injection site reactions.
Time frame: End-of-stimulation (up to 20 stimulation days)
Population: The safety analysis set was defined as all randomized and exposed participants. Participants were analyzed according to actual treatment received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FE 000049 (Follitropin Delta) | Intensity of Injection Site Reactions | Severe injection site reaction | 0 percentage of participants |
| FE 000049 (Follitropin Delta) | Intensity of Injection Site Reactions | Mild injection site reaction | 21.6 percentage of participants |
| FE 000049 (Follitropin Delta) | Intensity of Injection Site Reactions | Moderate injection site reaction | 1.6 percentage of participants |
| GONAL-F (Follitropin Alfa) | Intensity of Injection Site Reactions | Moderate injection site reaction | 0.4 percentage of participants |
| GONAL-F (Follitropin Alfa) | Intensity of Injection Site Reactions | Mild injection site reaction | 21.2 percentage of participants |
| GONAL-F (Follitropin Alfa) | Intensity of Injection Site Reactions | Severe injection site reaction | 0 percentage of participants |
Secondary
Number and Quality of Embryos
Number of embryos (total and good-quality) on Day 3 are presented. A good-quality embryo was defined as an embryo with ≥6 blastomeres and ≤20% fragmentation, without signs of multinucleation.
Time frame: On Day 3 after oocyte retrieval
Population: The FAS was defined as all randomized and exposed participants. Participants were analyzed according to randomized treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FE 000049 (Follitropin Delta) | Number and Quality of Embryos | Number of embryos | 7.0 embryos | Standard Deviation 4.6 |
| FE 000049 (Follitropin Delta) | Number and Quality of Embryos | Number of good-quality embryos | 4.1 embryos | Standard Deviation 3.6 |
| GONAL-F (Follitropin Alfa) | Number and Quality of Embryos | Number of embryos | 8.7 embryos | Standard Deviation 5.5 |
| GONAL-F (Follitropin Alfa) | Number and Quality of Embryos | Number of good-quality embryos | 5.2 embryos | Standard Deviation 4.3 |
Comparison: Number of embryos on day 3p-value: <0.001van Elteren test
Comparison: Number of good-quality embryos on Day 3p-value: <0.001van Elteren test
Secondary
Number of Follicles At End-of-stimulation (up to 20 Stimulation Days)
Counted by ultrasound for the right and left ovary for each participant.
Time frame: At end-of-stimulation (up to 20 stimulation days)
Population: The FAS was defined as all randomized and exposed participants. Participants analyzed for this endpoint represent participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FE 000049 (Follitropin Delta) | Number of Follicles At End-of-stimulation (up to 20 Stimulation Days) | Follicles >= 10 mm | 12.4 number of follicles | Standard Deviation 5.6 |
| FE 000049 (Follitropin Delta) | Number of Follicles At End-of-stimulation (up to 20 Stimulation Days) | Follicles >= 12 mm | 10.3 number of follicles | Standard Deviation 4.9 |
| FE 000049 (Follitropin Delta) | Number of Follicles At End-of-stimulation (up to 20 Stimulation Days) | Follicles >= 15 mm | 6.5 number of follicles | Standard Deviation 3.2 |
| FE 000049 (Follitropin Delta) | Number of Follicles At End-of-stimulation (up to 20 Stimulation Days) | Follicles >= 17 mm | 4.1 number of follicles | Standard Deviation 1.8 |
| GONAL-F (Follitropin Alfa) | Number of Follicles At End-of-stimulation (up to 20 Stimulation Days) | Follicles >= 17 mm | 4.5 number of follicles | Standard Deviation 2 |
| GONAL-F (Follitropin Alfa) | Number of Follicles At End-of-stimulation (up to 20 Stimulation Days) | Follicles >= 10 mm | 14.2 number of follicles | Standard Deviation 6.6 |
| GONAL-F (Follitropin Alfa) | Number of Follicles At End-of-stimulation (up to 20 Stimulation Days) | Follicles >= 15 mm | 7.5 number of follicles | Standard Deviation 3.5 |
| GONAL-F (Follitropin Alfa) | Number of Follicles At End-of-stimulation (up to 20 Stimulation Days) | Follicles >= 12 mm | 11.9 number of follicles | Standard Deviation 5.7 |
Comparison: Number of follicles \>= 10 mmp-value: <0.001van Elteren test
Comparison: Number of follicles \>= 12 mmp-value: <0.001van Elteren test
Comparison: Number of follicles \>= 15 mmp-value: <0.001van Elteren test
Comparison: Number of follicles \>= 17 mmp-value: 0.011van Elteren test
Secondary
Number of Follicles on Stimulation Day 6
Counted by ultrasound for the right and left ovary for each participant.
Time frame: On stimulation Day 6
Population: The FAS was defined as all randomized and exposed participants. Participants analyzed for this endpoint represent participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FE 000049 (Follitropin Delta) | Number of Follicles on Stimulation Day 6 | Follicles >= 10 mm | 5.4 number of follicles | Standard Deviation 3.5 |
| FE 000049 (Follitropin Delta) | Number of Follicles on Stimulation Day 6 | Follicles >= 12 mm | 2.3 number of follicles | Standard Deviation 2.2 |
| FE 000049 (Follitropin Delta) | Number of Follicles on Stimulation Day 6 | Follicles >= 15 mm | 0.3 number of follicles | Standard Deviation 0.7 |
| FE 000049 (Follitropin Delta) | Number of Follicles on Stimulation Day 6 | Follicles >= 17 mm | 0.1 number of follicles | Standard Deviation 0.3 |
| GONAL-F (Follitropin Alfa) | Number of Follicles on Stimulation Day 6 | Follicles >= 17 mm | 0.0 number of follicles | Standard Deviation 0.2 |
| GONAL-F (Follitropin Alfa) | Number of Follicles on Stimulation Day 6 | Follicles >= 10 mm | 6.4 number of follicles | Standard Deviation 4 |
| GONAL-F (Follitropin Alfa) | Number of Follicles on Stimulation Day 6 | Follicles >= 15 mm | 0.3 number of follicles | Standard Deviation 0.8 |
| GONAL-F (Follitropin Alfa) | Number of Follicles on Stimulation Day 6 | Follicles >= 12 mm | 2.9 number of follicles | Standard Deviation 2.5 |
Comparison: Number of follicles \>= 10 mmp-value: <0.001van Elteren test
Comparison: Number of follicles \>= 12 mmp-value: <0.001van Elteren test
Comparison: Number of follicles \>= 15 mmp-value: 0.568van Elteren test
Comparison: Number of follicles \>= 17 mmp-value: 0.839van Elteren test
Secondary
Number of Immune-related Adverse Events
Standardised Medical Dictionary for Regulatory Activities (MedDRA) Queries (SMQs).
Time frame: From screening up to end-of-trial (approximately 5.5 months)
Population: The safety analysis set was defined as all randomized and exposed participants. Participants were analyzed according to actual treatment received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FE 000049 (Follitropin Delta) | Number of Immune-related Adverse Events | 0 events |
| GONAL-F (Follitropin Alfa) | Number of Immune-related Adverse Events | 0 events |
Secondary
Number of Oocytes Retrieved
The number of oocytes retrieved was recorded at the oocyte retrieval visit.
Time frame: On the day of oocyte retrieval (36 h [±2h] after triggering of final follicular maturation)
Population: The FAS was defined as all randomized and exposed participants. Participants were analyzed according to randomized treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FE 000049 (Follitropin Delta) | Number of Oocytes Retrieved | 10.0 oocytes retrieved | Standard Deviation 6.1 |
| GONAL-F (Follitropin Alfa) | Number of Oocytes Retrieved | 12.4 oocytes retrieved | Standard Deviation 7.3 |
Comparison: Mean number of oocytes retrievedp-value: <0.001van Elteren test
Secondary
Number of Participants With Adverse Events
Any adverse event occurring after start of IMP and before the end-of-trial visit, or a pre-treatment adverse event or pre-existing medical condition that worsens in intensity after start of IMP and before the end-of-trial visit was considered treatment-emergent, and is presented for this endpoint.
Time frame: From screening up to end-of-trial (up to approximately 5.5 months)
Population: The safety analysis set was defined as all randomized and exposed participants. Participants were analyzed according to actual treatment received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FE 000049 (Follitropin Delta) | Number of Participants With Adverse Events | 46.3 percentage of participants |
| GONAL-F (Follitropin Alfa) | Number of Participants With Adverse Events | 43.1 percentage of participants |
Secondary
Number of Stimulation Days
Calculated by start dates and end dates.
Time frame: Up to 20 stimulation days
Population: The FAS was defined as all randomized and exposed participants. Participants were analyzed according to randomized treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FE 000049 (Follitropin Delta) | Number of Stimulation Days | 9.2 days | Standard Deviation 1.9 |
| GONAL-F (Follitropin Alfa) | Number of Stimulation Days | 8.7 days | Standard Deviation 1.6 |
Comparison: Number of stimulation daysp-value: 0.001van Elteren
Secondary
Ongoing Implantation Rate
Defined as number of intrauterine viable fetuses 10-11 weeks after transfer divided by number of embryos transferred.
Time frame: 10-11 weeks after transfer
Population: Participants with embryo transfer (a total of 548 and 546 embryos were transferred in the FE 999049 and GONAL-F groups, respectively). The experimental unit was transferred embryos.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FE 000049 (Follitropin Delta) | Ongoing Implantation Rate | 30.7 % of viable fetus/embryos transferred |
| GONAL-F (Follitropin Alfa) | Ongoing Implantation Rate | 25.8 % of viable fetus/embryos transferred |
Comparison: Percentage of participants with ongoing implantation rate95% CI: [-0.9, 9.7]
Secondary
Percentage of Metaphase II (MII) Oocytes
The percentage of MII oocytes to oocytes retrieved for participants where all oocytes were inseminated using intracytoplasmic sperm injection (ICSI) are presented.
Time frame: Prior to insemination
Population: The FAS was defined as all randomized and exposed participants. Participants analyzed for this endpoint represent participants with all oocytes inseminated using ICSI.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FE 000049 (Follitropin Delta) | Percentage of Metaphase II (MII) Oocytes | 79.5 percentage of oocytes | Standard Deviation 17.6 |
| GONAL-F (Follitropin Alfa) | Percentage of Metaphase II (MII) Oocytes | 77.8 percentage of oocytes | Standard Deviation 17.7 |
Comparison: Percentage of MII oocytes / oocytes retrievedp-value: 0.197van Elteren test
Secondary
Positive Beta Unit of Human Chorionic Gonadotropin (βhCG) Rate
Defined as positive βhCG test 13-15 days after transfer.
Time frame: 13-15 days after transfer
Population: The FAS was defined as all randomized and exposed participants. Participants were analyzed according to randomized treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FE 000049 (Follitropin Delta) | Positive Beta Unit of Human Chorionic Gonadotropin (βhCG) Rate | 41.7 percentage of participants |
| GONAL-F (Follitropin Alfa) | Positive Beta Unit of Human Chorionic Gonadotropin (βhCG) Rate | 35.3 percentage of participants |
Comparison: Percentage of participants with positive beta-hCG95% CI: [0.3, 12.3]
Secondary
Proportion of Participants With Early Pregnancy Losses
Grouped according to occurrence of biochemical pregnancy, spontaneous abortion, vanishing twin or ectopic pregnancy (with and without medical/surgical intervention). Frequency of early pregnancy losses are presented.
Time frame: End-of-trial
Population: The safety analysis set was defined as all randomized and exposed participants. Participants analyzed for this endpoint represent participants who were evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FE 000049 (Follitropin Delta) | Proportion of Participants With Early Pregnancy Losses | 25.0 percentage of participants |
| GONAL-F (Follitropin Alfa) | Proportion of Participants With Early Pregnancy Losses | 27.2 percentage of participants |
Secondary
Proportion of Participants With Multi-fetal Gestation
Defined as pregnancy with more than one fetus. Among participants with ongoing pregnancy, percentage of participants with twin pregnancies are presented.
Time frame: End-of-trial
Population: The FAS was defined as all randomized and exposed participants. Participants analyzed for this endpoint represent participants who were evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FE 000049 (Follitropin Delta) | Proportion of Participants With Multi-fetal Gestation | 7.7 percentage of participants |
| GONAL-F (Follitropin Alfa) | Proportion of Participants With Multi-fetal Gestation | 9.9 percentage of participants |
Secondary
Proportion of Participants With Technical Malfunctions of the Administration Pen
Incidences of technical malfunctions of the administration pen were recorded.
Time frame: End-of-stimulation (up to 20 stimulation days)
Population: The safety analysis set was defined as all randomized and exposed participants. Participants were analyzed according to actual treatment received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FE 000049 (Follitropin Delta) | Proportion of Participants With Technical Malfunctions of the Administration Pen | 0.4 percentage of participants |
| GONAL-F (Follitropin Alfa) | Proportion of Participants With Technical Malfunctions of the Administration Pen | 0 percentage of participants |
Secondary
Proportion of Subjects With <4, 4-7, 8-14, 15-19 and ≥20 Oocytes Retrieved
Grouped according to the number of oocytes retrieved. Participants with cycle cancellation due to poor ovarian response are included in the \<4 oocytes group.
Time frame: On the day of oocyte retrieval
Population: The FAS was defined as all randomized and exposed participants. Participants analyzed for this endpoint represent participants with oocytes retrieved and participants with cycle cancellation due to poor ovarian response.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FE 000049 (Follitropin Delta) | Proportion of Subjects With <4, 4-7, 8-14, 15-19 and ≥20 Oocytes Retrieved | 4 -7 (moderate response) | 23.0 percentage of participants |
| FE 000049 (Follitropin Delta) | Proportion of Subjects With <4, 4-7, 8-14, 15-19 and ≥20 Oocytes Retrieved | 15-19(hyperresponse) | 12.9 percentage of participants |
| FE 000049 (Follitropin Delta) | Proportion of Subjects With <4, 4-7, 8-14, 15-19 and ≥20 Oocytes Retrieved | 8-14 (targeted response) | 46.7 percentage of participants |
| FE 000049 (Follitropin Delta) | Proportion of Subjects With <4, 4-7, 8-14, 15-19 and ≥20 Oocytes Retrieved | >=20 (severe hyperresponse) | 6.1 percentage of participants |
| FE 000049 (Follitropin Delta) | Proportion of Subjects With <4, 4-7, 8-14, 15-19 and ≥20 Oocytes Retrieved | <4 (low response) | 11.3 percentage of participants |
| GONAL-F (Follitropin Alfa) | Proportion of Subjects With <4, 4-7, 8-14, 15-19 and ≥20 Oocytes Retrieved | >=20 (severe hyperresponse) | 14.2 percentage of participants |
| GONAL-F (Follitropin Alfa) | Proportion of Subjects With <4, 4-7, 8-14, 15-19 and ≥20 Oocytes Retrieved | <4 (low response) | 4.7 percentage of participants |
| GONAL-F (Follitropin Alfa) | Proportion of Subjects With <4, 4-7, 8-14, 15-19 and ≥20 Oocytes Retrieved | 4 -7 (moderate response) | 22.3 percentage of participants |
| GONAL-F (Follitropin Alfa) | Proportion of Subjects With <4, 4-7, 8-14, 15-19 and ≥20 Oocytes Retrieved | 8-14 (targeted response) | 42.6 percentage of participants |
| GONAL-F (Follitropin Alfa) | Proportion of Subjects With <4, 4-7, 8-14, 15-19 and ≥20 Oocytes Retrieved | 15-19(hyperresponse) | 16.2 percentage of participants |
Secondary
Proportion of Subjects With Cycle Cancellation Due to Poor or Excessive Ovarian Response or Embryo Transfer Cancellation Due to Excessive Ovarian Response / OHSS Risk
For each participant the reason for each cycle cancellation was recorded. Embryo transfer cancellation due to adverse events, such as ovarian hyperfunction, OHSS and progesterone increased in participants with embryos available for transfer, were considered as transfer cancellations due to excessive response / OHSS risk.
Time frame: End-of-stimulation visit (up to 20 days) or transfer visit
Population: The FAS was defined as all randomized and exposed participants. Participants were analyzed according to randomized treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FE 000049 (Follitropin Delta) | Proportion of Subjects With Cycle Cancellation Due to Poor or Excessive Ovarian Response or Embryo Transfer Cancellation Due to Excessive Ovarian Response / OHSS Risk | Cycle cancellation due to excessive response | 0 percentage of participants |
| FE 000049 (Follitropin Delta) | Proportion of Subjects With Cycle Cancellation Due to Poor or Excessive Ovarian Response or Embryo Transfer Cancellation Due to Excessive Ovarian Response / OHSS Risk | Cycle cancellation due to poor response | 3.4 percentage of participants |
| FE 000049 (Follitropin Delta) | Proportion of Subjects With Cycle Cancellation Due to Poor or Excessive Ovarian Response or Embryo Transfer Cancellation Due to Excessive Ovarian Response / OHSS Risk | Transfer cancellation due to excessive ovarian response/ OHSS risk | 5.2 percentage of participants |
| FE 000049 (Follitropin Delta) | Proportion of Subjects With Cycle Cancellation Due to Poor or Excessive Ovarian Response or Embryo Transfer Cancellation Due to Excessive Ovarian Response / OHSS Risk | Cycle cancellation: poor/excessive response, or transfer cancellation excessive response/OHSS risk | 8.6 percentage of participants |
| GONAL-F (Follitropin Alfa) | Proportion of Subjects With Cycle Cancellation Due to Poor or Excessive Ovarian Response or Embryo Transfer Cancellation Due to Excessive Ovarian Response / OHSS Risk | Cycle cancellation: poor/excessive response, or transfer cancellation excessive response/OHSS risk | 13.1 percentage of participants |
| GONAL-F (Follitropin Alfa) | Proportion of Subjects With Cycle Cancellation Due to Poor or Excessive Ovarian Response or Embryo Transfer Cancellation Due to Excessive Ovarian Response / OHSS Risk | Cycle cancellation due to excessive response | 0 percentage of participants |
| GONAL-F (Follitropin Alfa) | Proportion of Subjects With Cycle Cancellation Due to Poor or Excessive Ovarian Response or Embryo Transfer Cancellation Due to Excessive Ovarian Response / OHSS Risk | Transfer cancellation due to excessive ovarian response/ OHSS risk | 12.4 percentage of participants |
| GONAL-F (Follitropin Alfa) | Proportion of Subjects With Cycle Cancellation Due to Poor or Excessive Ovarian Response or Embryo Transfer Cancellation Due to Excessive Ovarian Response / OHSS Risk | Cycle cancellation due to poor response | 0.8 percentage of participants |
Comparison: Proportion of participants with cycle cancellation due to poor responsep-value: 0.00295% CI: [1.52, 13.74]Regression, Logistic
Comparison: Proportion of participants with transfer cancellation due to excessive ovarian response/OHSS riskp-value: <0.00195% CI: [0.24, 0.62]Regression, Logistic
Comparison: Proportion of participants with cycle cancellation due to poor or excessive response, or transfer cancellation due to excessive response/OHSS riskp-value: 0.0295% CI: [0.42, 0.93]Regression, Logistic
Secondary
Proportion of Subjects With Cycle Cancellations Due to an Adverse Event, Including Immune-related Adverse Events, or Due to Technical Malfunctions of the Administration Pen
For each participant the reason for cycle cancellation will be recorded.
Time frame: Up to 20 stimulation days
Population: The FAS was defined as all randomized and exposed participants. Participants were analyzed according to randomized treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FE 000049 (Follitropin Delta) | Proportion of Subjects With Cycle Cancellations Due to an Adverse Event, Including Immune-related Adverse Events, or Due to Technical Malfunctions of the Administration Pen | Technical malfunctions of the administration pen | 0 percentage of participants |
| FE 000049 (Follitropin Delta) | Proportion of Subjects With Cycle Cancellations Due to an Adverse Event, Including Immune-related Adverse Events, or Due to Technical Malfunctions of the Administration Pen | Adverse event (including immune-related adverse events) | 0 percentage of participants |
| GONAL-F (Follitropin Alfa) | Proportion of Subjects With Cycle Cancellations Due to an Adverse Event, Including Immune-related Adverse Events, or Due to Technical Malfunctions of the Administration Pen | Adverse event (including immune-related adverse events) | 0.2 percentage of participants |
| GONAL-F (Follitropin Alfa) | Proportion of Subjects With Cycle Cancellations Due to an Adverse Event, Including Immune-related Adverse Events, or Due to Technical Malfunctions of the Administration Pen | Technical malfunctions of the administration pen | 0 percentage of participants |
Secondary
Proportion of Subjects With Early OHSS (Including OHSS of Moderate/Severe Grade) and/or Preventive Interventions for Early OHSS
Early OHSS was defined as OHSS with onset ≤9 days after triggering of final follicular maturation. Classification of grade was according to Golan's classification system, and all OHSS cases were graded as mild, moderate or severe.
Time frame: Up to 9 days after triggering of final follicular maturation
Population: The safety analysis set was defined as all randomized and exposed participants. Participants were analyzed according to actual treatment received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FE 000049 (Follitropin Delta) | Proportion of Subjects With Early OHSS (Including OHSS of Moderate/Severe Grade) and/or Preventive Interventions for Early OHSS | Early OHSS (any grade) | 4.0 percentage of participants |
| FE 000049 (Follitropin Delta) | Proportion of Subjects With Early OHSS (Including OHSS of Moderate/Severe Grade) and/or Preventive Interventions for Early OHSS | Any preventive intervention | 1.2 percentage of participants |
| FE 000049 (Follitropin Delta) | Proportion of Subjects With Early OHSS (Including OHSS of Moderate/Severe Grade) and/or Preventive Interventions for Early OHSS | Early OHSS (moderate/severe) | 3.6 percentage of participants |
| FE 000049 (Follitropin Delta) | Proportion of Subjects With Early OHSS (Including OHSS of Moderate/Severe Grade) and/or Preventive Interventions for Early OHSS | Early OHSS (any grade) and/or preventive interventions | 5.0 percentage of participants |
| FE 000049 (Follitropin Delta) | Proportion of Subjects With Early OHSS (Including OHSS of Moderate/Severe Grade) and/or Preventive Interventions for Early OHSS | Early OHSS (moderate/severe) and/or preventive interventions | 4.6 percentage of participants |
| GONAL-F (Follitropin Alfa) | Proportion of Subjects With Early OHSS (Including OHSS of Moderate/Severe Grade) and/or Preventive Interventions for Early OHSS | Early OHSS (any grade) and/or preventive interventions | 9.6 percentage of participants |
| GONAL-F (Follitropin Alfa) | Proportion of Subjects With Early OHSS (Including OHSS of Moderate/Severe Grade) and/or Preventive Interventions for Early OHSS | Early OHSS (moderate/severe) and/or preventive interventions | 7.8 percentage of participants |
| GONAL-F (Follitropin Alfa) | Proportion of Subjects With Early OHSS (Including OHSS of Moderate/Severe Grade) and/or Preventive Interventions for Early OHSS | Early OHSS (any grade) | 6.5 percentage of participants |
| GONAL-F (Follitropin Alfa) | Proportion of Subjects With Early OHSS (Including OHSS of Moderate/Severe Grade) and/or Preventive Interventions for Early OHSS | Early OHSS (moderate/severe) | 4.7 percentage of participants |
| GONAL-F (Follitropin Alfa) | Proportion of Subjects With Early OHSS (Including OHSS of Moderate/Severe Grade) and/or Preventive Interventions for Early OHSS | Any preventive intervention | 3.5 percentage of participants |
Comparison: Proportion of participants with early OHSS (any grade)p-value: 0.07595% CI: [0.34, 1.06]Regression, Logistic
Comparison: Proportion of participants with early OHSS (moderate/severe)p-value: 0.36595% CI: [0.4, 1.4]Regression, Logistic
Comparison: Proportion of participants with any preventive interventionp-value: 0.01295% CI: [0.13, 0.83]Regression, Logistic
Comparison: Proportion of participants with early OHSS (any grade) and/or preventive interventionsp-value: 0.00495% CI: [0.3, 0.81]Regression, Logistic
Comparison: Proportion of participants with early OHSS (moderate/severe) and/or preventive interventionsp-value: 0.02995% CI: [0.33, 0.95]Regression, Logistic
Secondary
Proportion of Subjects With Extreme Ovarian Responses
Extreme ovarian response defined as \<4, ≥15 or ≥ 20 oocytes retrieved. Participants with cycle cancellation due to poor ovarian response are included as \<4 oocytes retrieved.
Time frame: Oocyte retrieval visit
Population: The FAS was defined as all randomized and exposed participants. Participants analyzed for this endpoint represent participants with oocytes retrieved and participants with cycle cancellation due to poor ovarian response.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FE 000049 (Follitropin Delta) | Proportion of Subjects With Extreme Ovarian Responses | <4 or >=15 oocytes retrieved | 30.3 percentage of participants |
| FE 000049 (Follitropin Delta) | Proportion of Subjects With Extreme Ovarian Responses | <4 or >=20 oocytes retrieved | 17.4 percentage of participants |
| GONAL-F (Follitropin Alfa) | Proportion of Subjects With Extreme Ovarian Responses | <4 or >=15 oocytes retrieved | 35.1 percentage of participants |
| GONAL-F (Follitropin Alfa) | Proportion of Subjects With Extreme Ovarian Responses | <4 or >=20 oocytes retrieved | 18.9 percentage of participants |
Comparison: Proportion of participants with \<4 or \>=15 oocytes retrievedp-value: 0.08395% CI: [0.6, 1.03]Regression, Logistic
Comparison: Proportion of participants with \<4 or \>=20 oocytes retrievedp-value: 0.48995% CI: [0.65, 1.23]Regression, Logistic
Secondary
Proportion of Subjects With Investigator-requested Gonadotropin Dose Adjustments
Investigator-requested decreases and increases of the gonadotropin dose were captured during the stimulation period.
Time frame: Up to 20 stimulation days
Population: The FAS was defined as all randomized and exposed participants. Participants were analyzed according to randomized treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FE 000049 (Follitropin Delta) | Proportion of Subjects With Investigator-requested Gonadotropin Dose Adjustments | 57.1 percentage of participants |
| GONAL-F (Follitropin Alfa) | Proportion of Subjects With Investigator-requested Gonadotropin Dose Adjustments | 55.3 percentage of participants |
Secondary
Proportion of Subjects With Late OHSS
Late OHSS was defined as OHSS with onset \>9 days after triggering of final follicular maturation. The proportion of participants with late OHSS, and late OHSS of moderate or severe grade are presented. All OHSS cases were graded as mild, moderate, or severe.
Time frame: After 9 days post triggering of final follicular maturation
Population: The safety analysis set was defined as all randomized and exposed participants. Participants were analyzed according to actual treatment received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FE 000049 (Follitropin Delta) | Proportion of Subjects With Late OHSS | Late OHSS (Any grade) | 4.0 percentage of participants |
| FE 000049 (Follitropin Delta) | Proportion of Subjects With Late OHSS | Late OHSS (Moderate/severe) | 3.6 percentage of participants |
| GONAL-F (Follitropin Alfa) | Proportion of Subjects With Late OHSS | Late OHSS (Any grade) | 2.0 percentage of participants |
| GONAL-F (Follitropin Alfa) | Proportion of Subjects With Late OHSS | Late OHSS (Moderate/severe) | 1.8 percentage of participants |
Secondary
Proportion of Subjects With Markedly Abnormal Changes of Clinical Chemistry: Alanine Aminotransferase, Aspartate Aminotransferase, Bicarbonate, Calcium, Phosphate
The table represents the percentage of participants in each group with normal baseline values and markedly abnormal end-of-stimulation or end-of-trial values for alanine aminotransferase, aspartate aminotransferase, bicarbonate, calcium, phosphate.
Time frame: End-of-stimulation visit and end-of-trial visit
Population: The safety analysis set was defined as all randomized and exposed participants. Participants analyzed for this endpoint represent participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FE 000049 (Follitropin Delta) | Proportion of Subjects With Markedly Abnormal Changes of Clinical Chemistry: Alanine Aminotransferase, Aspartate Aminotransferase, Bicarbonate, Calcium, Phosphate | Alanine aminotransferase (IU/L) (End-of-trial) | 0.4 percentage of participants |
| FE 000049 (Follitropin Delta) | Proportion of Subjects With Markedly Abnormal Changes of Clinical Chemistry: Alanine Aminotransferase, Aspartate Aminotransferase, Bicarbonate, Calcium, Phosphate | Aspartate aminotransferase (IU/L) (End-of-stimulation) | 0 percentage of participants |
| FE 000049 (Follitropin Delta) | Proportion of Subjects With Markedly Abnormal Changes of Clinical Chemistry: Alanine Aminotransferase, Aspartate Aminotransferase, Bicarbonate, Calcium, Phosphate | Bicarbonate (mmol/L) (End-of-trial) | 1.3 percentage of participants |
| FE 000049 (Follitropin Delta) | Proportion of Subjects With Markedly Abnormal Changes of Clinical Chemistry: Alanine Aminotransferase, Aspartate Aminotransferase, Bicarbonate, Calcium, Phosphate | Phosphate (mmol/L) (End-of-stimulation) | 0.2 percentage of participants |
| FE 000049 (Follitropin Delta) | Proportion of Subjects With Markedly Abnormal Changes of Clinical Chemistry: Alanine Aminotransferase, Aspartate Aminotransferase, Bicarbonate, Calcium, Phosphate | Calcium (mmol/L) (End-of-trial) | 0 percentage of participants |
| FE 000049 (Follitropin Delta) | Proportion of Subjects With Markedly Abnormal Changes of Clinical Chemistry: Alanine Aminotransferase, Aspartate Aminotransferase, Bicarbonate, Calcium, Phosphate | Alanine aminotransferase (IU/L) (End-of-stimulation) | 0.2 percentage of participants |
| GONAL-F (Follitropin Alfa) | Proportion of Subjects With Markedly Abnormal Changes of Clinical Chemistry: Alanine Aminotransferase, Aspartate Aminotransferase, Bicarbonate, Calcium, Phosphate | Calcium (mmol/L) (End-of-trial) | 0.2 percentage of participants |
| GONAL-F (Follitropin Alfa) | Proportion of Subjects With Markedly Abnormal Changes of Clinical Chemistry: Alanine Aminotransferase, Aspartate Aminotransferase, Bicarbonate, Calcium, Phosphate | Alanine aminotransferase (IU/L) (End-of-stimulation) | 0.2 percentage of participants |
| GONAL-F (Follitropin Alfa) | Proportion of Subjects With Markedly Abnormal Changes of Clinical Chemistry: Alanine Aminotransferase, Aspartate Aminotransferase, Bicarbonate, Calcium, Phosphate | Phosphate (mmol/L) (End-of-stimulation) | 0.0 percentage of participants |
| GONAL-F (Follitropin Alfa) | Proportion of Subjects With Markedly Abnormal Changes of Clinical Chemistry: Alanine Aminotransferase, Aspartate Aminotransferase, Bicarbonate, Calcium, Phosphate | Alanine aminotransferase (IU/L) (End-of-trial) | 0.6 percentage of participants |
| GONAL-F (Follitropin Alfa) | Proportion of Subjects With Markedly Abnormal Changes of Clinical Chemistry: Alanine Aminotransferase, Aspartate Aminotransferase, Bicarbonate, Calcium, Phosphate | Bicarbonate (mmol/L) (End-of-trial) | 0.8 percentage of participants |
| GONAL-F (Follitropin Alfa) | Proportion of Subjects With Markedly Abnormal Changes of Clinical Chemistry: Alanine Aminotransferase, Aspartate Aminotransferase, Bicarbonate, Calcium, Phosphate | Aspartate aminotransferase (IU/L) (End-of-stimulation) | 0.2 percentage of participants |
Secondary
Proportion of Subjects With Markedly Abnormal Changes of Haematology Parameters: Leukocytes, Lymphocytes/Leukocytes
The table represents the percentage of participants in each group with normal baseline values and markedly abnormal end-of-stimulation and end-of-trial values for leukocytes and lymphocytes/leukocytes.
Time frame: End-of-stimulation visit and end-of-trial visit
Population: The safety analysis set was defined as all randomized and exposed participants. Participants analyzed for this endpoint represent participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FE 000049 (Follitropin Delta) | Proportion of Subjects With Markedly Abnormal Changes of Haematology Parameters: Leukocytes, Lymphocytes/Leukocytes | Leukocytes (10^9 cells/L) (End-of-stimulation) | 0.7 percentage of participants |
| FE 000049 (Follitropin Delta) | Proportion of Subjects With Markedly Abnormal Changes of Haematology Parameters: Leukocytes, Lymphocytes/Leukocytes | Lymphocytes/leukocytes (%) (End-of-stimulation) | 0.4 percentage of participants |
| FE 000049 (Follitropin Delta) | Proportion of Subjects With Markedly Abnormal Changes of Haematology Parameters: Leukocytes, Lymphocytes/Leukocytes | Lymphocytes/leukocytes (%) (End-of-trial) | 0.6 percentage of participants |
| FE 000049 (Follitropin Delta) | Proportion of Subjects With Markedly Abnormal Changes of Haematology Parameters: Leukocytes, Lymphocytes/Leukocytes | Leukocytes (10^9 cells/L) (End-of-trial) | 0.7 percentage of participants |
| GONAL-F (Follitropin Alfa) | Proportion of Subjects With Markedly Abnormal Changes of Haematology Parameters: Leukocytes, Lymphocytes/Leukocytes | Lymphocytes/leukocytes (%) (End-of-trial) | 0 percentage of participants |
| GONAL-F (Follitropin Alfa) | Proportion of Subjects With Markedly Abnormal Changes of Haematology Parameters: Leukocytes, Lymphocytes/Leukocytes | Leukocytes (10^9 cells/L) (End-of-stimulation) | 0 percentage of participants |
| GONAL-F (Follitropin Alfa) | Proportion of Subjects With Markedly Abnormal Changes of Haematology Parameters: Leukocytes, Lymphocytes/Leukocytes | Lymphocytes/leukocytes (%) (End-of-stimulation) | 0.2 percentage of participants |
| GONAL-F (Follitropin Alfa) | Proportion of Subjects With Markedly Abnormal Changes of Haematology Parameters: Leukocytes, Lymphocytes/Leukocytes | Leukocytes (10^9 cells/L) (End-of-trial) | 0 percentage of participants |
Secondary
Proportion of Subjects With Treatment-induced Anti-FSH Antibodies, Overall as Well as With Neutralizing Capacity
Measured by presence of anti-FSH antibodies.
Time frame: Up to 28 days after end of the stimulation period
Population: The safety analysis set was defined as all randomized and exposed participants. Participants were analyzed according to actual treatment received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FE 000049 (Follitropin Delta) | Proportion of Subjects With Treatment-induced Anti-FSH Antibodies, Overall as Well as With Neutralizing Capacity | Treatment-induced anti-FSH antibodies (Overall) | 1.40 percentage of participants |
| FE 000049 (Follitropin Delta) | Proportion of Subjects With Treatment-induced Anti-FSH Antibodies, Overall as Well as With Neutralizing Capacity | Treatment-induced anti-FSH antibodies with neutralizing capacity | 0 percentage of participants |
| GONAL-F (Follitropin Alfa) | Proportion of Subjects With Treatment-induced Anti-FSH Antibodies, Overall as Well as With Neutralizing Capacity | Treatment-induced anti-FSH antibodies (Overall) | 0.98 percentage of participants |
| GONAL-F (Follitropin Alfa) | Proportion of Subjects With Treatment-induced Anti-FSH Antibodies, Overall as Well as With Neutralizing Capacity | Treatment-induced anti-FSH antibodies with neutralizing capacity | 0 percentage of participants |
Secondary
Size of Follicles At End-of-stimulation (up to 20 Stimulation Days)
Counted by ultrasound for the right and left ovary for each participant.
Time frame: At end-of-stimulation (up to 20 stimulation days)
Population: The FAS was defined as all randomized and exposed participants. Participants analyzed for this endpoint represent participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FE 000049 (Follitropin Delta) | Size of Follicles At End-of-stimulation (up to 20 Stimulation Days) | Largest follicle (mm) | 19.8 mm | Standard Deviation 1.9 |
| FE 000049 (Follitropin Delta) | Size of Follicles At End-of-stimulation (up to 20 Stimulation Days) | Average follicle size (mm) | 15.0 mm | Standard Deviation 1.3 |
| FE 000049 (Follitropin Delta) | Size of Follicles At End-of-stimulation (up to 20 Stimulation Days) | Average size of 3 largest follicles (mm) | 18.6 mm | Standard Deviation 1.4 |
| GONAL-F (Follitropin Alfa) | Size of Follicles At End-of-stimulation (up to 20 Stimulation Days) | Largest follicle (mm) | 19.8 mm | Standard Deviation 1.6 |
| GONAL-F (Follitropin Alfa) | Size of Follicles At End-of-stimulation (up to 20 Stimulation Days) | Average follicle size (mm) | 15.1 mm | Standard Deviation 1.1 |
| GONAL-F (Follitropin Alfa) | Size of Follicles At End-of-stimulation (up to 20 Stimulation Days) | Average size of 3 largest follicles (mm) | 18.7 mm | Standard Deviation 1.1 |
Comparison: Largest follicle (mm)p-value: 0.848van Elteren test
Comparison: Average follicle size (mm)p-value: 0.629van Elteren test
Comparison: Average size of 3 largest follicles (mm)p-value: 0.768van Elteren test
Secondary
Size of Follicles on Stimulation Day 6
Counted by ultrasound for the right and left ovary for each participant.
Time frame: On stimulation Day 6
Population: The FAS was defined as all randomized and exposed participants. Participants analyzed for this endpoint represent participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FE 000049 (Follitropin Delta) | Size of Follicles on Stimulation Day 6 | Largest follicle (mm) | 13.1 mm | Standard Deviation 2 |
| FE 000049 (Follitropin Delta) | Size of Follicles on Stimulation Day 6 | Average follicle size (mm) | 11.5 mm | Standard Deviation 1 |
| FE 000049 (Follitropin Delta) | Size of Follicles on Stimulation Day 6 | Average size of 3 largest follicles (mm) | 12.5 mm | Standard Deviation 1.6 |
| GONAL-F (Follitropin Alfa) | Size of Follicles on Stimulation Day 6 | Largest follicle (mm) | 13.2 mm | Standard Deviation 1.8 |
| GONAL-F (Follitropin Alfa) | Size of Follicles on Stimulation Day 6 | Average follicle size (mm) | 11.6 mm | Standard Deviation 1 |
| GONAL-F (Follitropin Alfa) | Size of Follicles on Stimulation Day 6 | Average size of 3 largest follicles (mm) | 12.6 mm | Standard Deviation 1.4 |
Comparison: Largest follicle (mm)p-value: 0.14van Elteren test
Comparison: Average follicle size (mm)p-value: 0.155van Elteren test
Comparison: Treatment comparison: Average size of 3 largest follicles (mm)p-value: 0.159van Elteren test
Secondary
Total Gonadotropin Dose
Calculated by start dates, end dates and daily dose of IMP.
Time frame: Up to 20 stimulation days
Population: The FAS was defined as all randomized and exposed participants. Participants were analyzed according to randomized treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FE 000049 (Follitropin Delta) | Total Gonadotropin Dose | 77.5 microgram of dose | Standard Deviation 24.4 |
| GONAL-F (Follitropin Alfa) | Total Gonadotropin Dose | 109.9 microgram of dose | Standard Deviation 32.9 |
Comparison: Total gonadotropin dosep-value: <0.001van Elteren test
Secondary
Vital Pregnancy Rate
Defined as at least one intrauterine gestational sac with fetal heart beat 5-6 weeks after transfer.
Time frame: 5-6 weeks after transfer
Population: The FAS was defined as all randomized and exposed participants. Participants were analyzed according to randomized treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FE 000049 (Follitropin Delta) | Vital Pregnancy Rate | 32.3 percentage of participants |
| GONAL-F (Follitropin Alfa) | Vital Pregnancy Rate | 28.0 percentage of participants |
Comparison: Percentage of participants with at least one intrauterine gestational sac with fetal heart beat 5-6 weeks after transfer95% CI: [-1.5, 9.8]