Infertility, Female
Conditions
Brief summary
This trial investigates the effects of FE 999049 compared to placebo.
Interventions
FE 999049 was administered as single daily subcutaneous injections in the abdomen at a starting dose of 15 μg daily that was fixed for the first four stimulation days. Based on ovarian response, the dose could be adjusted by 3 μg, with dose increases implemented not more frequently than once every 2 days and dose decreases implemented per investigator's judgement. The minimum daily dose was 6 μg, and the maximum daily dose was 24 μg. Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early ovarian hyperstimulation syndrome (OHSS) with the exception of gonadotropin-releasing hormone (GnRH) agonist for triggering of final follicular maturation, was not allowed
DRUGPlacebo
Placebo was administered as single daily subcutaneous injection dialed to the same value (dose) as FE 999049. Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early OHSS with the exception of GnRH agonist for triggering of final follicular maturation, was not allowed.
Sponsors
Ferring Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
35 Years to 42 Years
Healthy volunteers
No
Inclusion criteria
* Informed Consent Documents signed prior to any trial-related procedure. * In good physical and mental health in the judgement of the investigator. * Pre-menopausal women between the ages of 35 and 42 years. The participants must be at least 35 years (including the 35th birthday) when they sign the informed consent and no more than 42 years (up to the day before the 42nd birthday) at the time of randomization. * Body mass index (BMI) between 17.5 and 38.0 kg/m\^2 (both inclusive) at screening. * Infertile women diagnosed with tubal infertility, unexplained infertility, endometriosis stage I/II or with partners diagnosed with male factor infertility, eligible for in vitro fertilization (IVF) and/or intracytoplasmic sperm injection (ICSI) using fresh or frozen ejaculated sperm from male partner or sperm donor. * Documented history of infertility for at least 6 months before randomization (not applicable in case of tubal or severe male factor infertility, or when the use of donor sperm is indicated). * Regular menstrual cycles of 24-35 days (both inclusive). * Hysterosalpingography, hysteroscopy or saline infusion sonography, documenting a uterus consistent with expected normal function (e.g. no evidence of clinically interfering uterine fibroids defined as submucous fibroids of any size 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) at screening or within 1 year prior to screening. * Transvaginal ultrasound documenting presence and adequate visualization 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) at screening. 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 at screening or within 6 months prior to screening. * Willing to accept the blastocyst transfer policy for the fresh cycle and the cryopreserved cycles initiated within 12 months from the start of controlled ovarian stimulation using blastocysts obtained in this trial, i.e. transfer of one blastocyst (if a good-quality blastocyst is available) or transfer of one or two blastocysts (if no good-quality blastocyst is available).
Exclusion criteria
* More than one previous controlled ovarian stimulation cycle for IVF/ICSI. * Known endometriosis stage III-IV (defined by the revised ASRM classification, 2012). * Known history of anovulation. * One or more follicles greater than or equal to 10 mm (including cysts) observed on the transvaginal ultrasound prior to randomization on stimulation day 1. * Known history of recurrent miscarriage (defined as three consecutive losses after ultrasound confirmation of pregnancy \[excluding ectopic pregnancy\] 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. In case partner sperm will be used and the sperm production is severely impaired (concentration less than 1 million/mL), normal karyotype, including no Y-chromosome microdeletion, must be documented. * Any known clinically significant systemic disease (e.g. insulin-dependent diabetes). * Known inherited or acquired thrombophilia. * Active arterial or venous thromboembolism or severe thrombophlebitis, or a history of these events. * Any known endocrine or metabolic abnormalities (pituitary, adrenal, pancreas, liver or kidney) with the exception of pharmacologically controlled sub-clinical hypothyroidism. * Known tumors 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, hematology, thyroid-stimulating hormone (TSH) or prolactin, or vital signs at screening, which is judged clinically significant by the investigator. * Known abnormal cervical cytology of clinical significance observed within three years prior to randomization (unless the clinical significance has been resolved). * Findings at the gynecological 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative Ongoing Pregnancy Rate After the Fresh Cycle and Cryopreserved Cycles Initiated Within 12 Months From the Start of Controlled Ovarian Stimulation (COS) | 8-9 weeks after transfer (up to approximately 16 months after start of stimulation) | Defined as at least one intrauterine viable fetus 8-9 weeks after transfer. Data in this endpoint are presented for the fresh cycle and the cryopreserved cycles. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Ongoing Pregnancy Rate in the Fresh Cycle and in the Cryopreserved Cycles | 8-9 weeks after transfer (up to approximately 16 months after start of stimulation) | Defined as at least one intrauterine viable fetus 8-9 weeks after transfer. Data in this endpoint are presented for the fresh cycle and the cryopreserved cycles. |
| Time From Start of COS to Ongoing Pregnancy Across the Fresh and Cryopreserved Cycles, Including Duration | 8-9 weeks after transfer (up to approximately 16 months after start of stimulation) | Time from start of COS to ongoing pregnancy, including both the fresh and cryopreserved cycles. In the placebo group, no participants achieved an ongoing pregnancy either after 12 calendar months or after 12 study months. |
| Time From Start of COS to Ongoing Pregnancy Across the Fresh and Cryopreserved Cycles, Measured in Number of Cycles Before Achieving Ongoing Pregnancy | 8-9 weeks after transfer (up to approximately 16 months after start of stimulation) | Time from start of COS to ongoing pregnancy, including both the fresh and cryopreserved cycles, measured in number of cycles before achieving ongoing pregnancy. In the placebo group, no participants achieved an ongoing pregnancy either after 12 calendar months or after 12 study months. |
| Ongoing Implantation Rate in the Fresh Cycle, the Cryopreserved Cycles and Cumulatively | 8-9 weeks after transfer (up to approximately 16 months after start of stimulation) | Defined as the number of intrauterine viable fetuses 8-9 weeks after transfer divided by number of blastocysts transferred. Data in this endpoint are presented for the fresh cycle, the cryopreserved cycles, and all cycles. One participant can contribute with a range from zero to multiple blastocysts. Data is not shown for placebo arm because no subjects underwent blastocyst transfer in the fresh cycle or cryopreserved cycles. '%' in the unit of measure refers to 'percentage'. |
| Clinical Pregnancy Rate in the Fresh Cycle, the Cryopreserved Cycles and Cumulatively | 5-6 weeks after transfer (up to approximately 15 months after start of stimulation) | Defined at least one gestational sac 5-6 weeks after transfer. Data in this endpoint are presented for the fresh cycle, the cryopreserved cycles, and all cycles. |
| Vital Pregnancy Rate in the Fresh Cycle, the Cryopreserved Cycles and Cumulatively | 5-6 weeks after transfer (up to approximately 15 months after start of stimulation) | Defined at least one intrauterine gestational sac with fetal heart beat 5-6 weeks after transfer. Data in this endpoint are presented for the fresh cycle, the cryopreserved cycles, and all cycles. |
| Implantation Rate in the Fresh Cycle, the Cryopreserved Cycles and Cumulatively | 5-6 weeks after transfer (up to approximately 15 months after start of stimulation) | Defined as the number of gestational sacs 5-6 weeks after transfer divided by number of blastocysts transferred. The endpoint are presented for the fresh cycle, the cryopreserved cycles, and all cycles. One participant can contribute with a range from zero to multiple blastocysts. Data is not shown for placebo arm because no subjects underwent blastocyst transfer in the fresh cycle or cryopreserved cycles. '%' in the unit of measure refers to 'percentage'. |
| Positive Beta Human Chorionic Gonadotropin (βhCG) Rate in the Fresh Cycle, the Cryopreserved Cycles and Cumulatively | 10-14 days after transfer (up to approximately 14 months after start of stimulation) | Defined as positive serum βhCG test 10-14 days after transfer. Data in this endpoint are presented for the fresh cycle, the cryopreserved cycles, and all cycles. |
| Proportion of Subjects in the Fresh Cycle With Triggering of Final Follicular Maturation (With hCG, With GnRH Agonist, and in Total), Cycle Cancellation and Transfer Cancellation | Up to 5 days after oocyte retrieval (up to 27 days after start of stimulation) | Data in this endpoint are presented for the fresh cycle. |
| Number of Follicles on Stimulation Day 5 | On stimulation day 5 | The total number of follicles and the number of follicles per size category are reported. |
| Number of Follicles at End-of-stimulation | At end-of-stimulation (up to 20 stimulation days) | The total number of follicles and the number of follicles per size category are reported. |
| Size of Follicles on Stimulation Day 5 | On stimulation day 5 | Counted by ultrasound for the right and left ovary for each participant. |
| Size of Follicles at End-of-stimulation | 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 day of oocyte retrieval (up to 22 days after start of stimulation) | The number of oocytes retrieved was recorded at the oocyte retrieval visit. |
| Number of Metaphase II Oocytes | On day of oocyte retrieval (up to 22 days after start of stimulation) | The number of MII oocytes to oocytes retrieved for participants where all oocytes were inseminated using ICSI are presented. |
| Number of Fertilized Oocytes | On day 1 after oocyte retrieval (up to 23 days after start of stimulation) | An oocyte was defined as fertilized if it had 2 pronuclei (2PN) at 19h (±2h). |
| Fertilization Rate | On day 1 after oocyte retrieval (up to 23 days after start of stimulation) | The fertilization rate was defined as the number of 2PN oocytes divided by the number of oocytes retrieved. Fertilization rate relative to oocytes retrieved has been reported. |
| Number and Quality of Blastocysts on Day 5 After Oocyte Retrieval | On day 5 after oocyte retrieval | Number of blastocysts (total and good-quality) on Day 5 are presented. The quality evaluation of blastocysts consisted of assessment of three parameters, as per the Gardner & Schoolcraft system: blastocyst expansion and hatching status (graded: 1-6), inner cell mass (graded: A-D) and trophectoderm (graded: A-D). A good-quality blastocyst was defined as a blastocyst of grade 3BB or higher. |
| Endometrial Thickness on Stimulation Day 5 | On stimulation day 5 | Mean endometrial thickness is reported. |
| Endometrial Thickness at End-of-stimulation | At end-of-stimulation (up to 20 stimulation days) | Mean endometrial thickness is reported. |
| Echogenicity Pattern on Stimulation Day 5 | On stimulation day 5 | The distribution of participants with hypoechogenic, isoechogenic, or hyperechogenic endometrium is reported |
| Echogenicity Pattern at End-of-stimulation | At end-of-stimulation (up to 20 stimulation days) | The distribution of participants with hypoechogenic, isoechogenic, or hyperechogenic endometrium is reported. |
| Oocyte Utilization Rate | On day of oocyte retrieval up to 12 months after start of COS | Defined as the number of blastocysts transferred or cryopreserved divided by the number of oocytes retrieved. Data in this endpoint are presented for the cryopreserved cycles. |
| Oocyte Efficiency Index | 8-9 weeks after transfer | Defined as the cumulative number of ongoing pregnancies per oocyte retrieved. Data in this endpoint are presented for the cryopreserved cycles. The unit of measure for this endpoint is 'cumulative ongoing pregnancies/oocyte retrieved'. |
| Percentage of Blastocysts Surviving Cryopreservation | 0 hour (+0.5 hour) after thawing | Data in this endpoint are presented for the cryopreserved cycles. The unit is number of blastocysts with observations. One participant can contribute with a range from zero to multiple blastocysts. |
| Percentage of Blastocysts With Re-expansion After Cryopreservation | 2.5 hour (±0.5 hour) after thawing | Data in this endpoint are presented for the cryopreserved cycles. The unit is number of blastocysts with observations. One participant can contribute with a range from zero to multiple blastocysts. |
| Number of Cryopreserved Cycles Initiated Within 12 Months From the Start of COS | Up to 12 months after start of stimulation | The total number of cryopreserved cycles initiated are reported. Data in this endpoint are presented for the cryopreserved cycles. One participant can contribute with a range from zero to multiple blastocysts. |
| Number of Cryopreserved Cycles With Blastocyst Transfer | Up to 12 months after start of stimulation | The total number of cryopreserved cycles with blastocyst transfer are reported. Data in this endpoint are presented for the cryopreserved cycles. One participant can contribute with a range from zero to multiple blastocysts. |
| Circulating Concentrations of Anti-mullerian Hormone (AMH) | From screening to the day of oocyte retrieval (up to 22 days after start of stimulation) | Blood samples for analysis of circulating concentrations of AMH were drawn. The median and inter-quartile range (IQR) of AMH levels on stimulation day 1, stimulation day 5, end-of-stimulation visit and oocyte retrieval visit are presented. |
| Circulating Concentrations of Follicle-stimulating Hormone (FSH) | From screening to the day of oocyte retrieval (up to 22 days after start of stimulation) | Blood samples for analysis of circulating concentrations of FSH were drawn. The median and IQR of FSH levels on stimulation day 1, stimulation day 5, end-of-stimulation visit and oocyte retrieval visit are presented. |
| Circulating Concentrations of Luteinizing Hormone (LH) | From screening to the day of oocyte retrieval (up to 22 days after start of stimulation) | Blood samples for analysis of circulating concentrations of LH were drawn. The median and IQR of LH levels on stimulation day 1, stimulation day 5, end-of-stimulation visit and oocyte retrieval visit are presented. |
| Circulating Concentrations of Estradiol | From screening to the day of oocyte retrieval (up to 22 days after start of stimulation) | Blood samples for analysis of circulating concentrations of estradiol were drawn. The median and IQR of estradiol levels on stimulation day 1, stimulation day 5, end-of-stimulation visit and oocyte retrieval visit are presented. |
| Circulating Concentrations of Progesterone | From screening to the day of oocyte retrieval (up to 22 days after start of stimulation) | Blood samples for analysis of circulating concentrations of progesterone were drawn. The median and IQR of progesterone levels on stimulation day 1, stimulation day 5, end-of-stimulation visit and oocyte retrieval visit are presented. |
| Circulating Concentrations of Inhibin A | From screening to the day of oocyte retrieval (up to 22 days after start of stimulation) | Blood samples for analysis of circulating concentrations of inhibin A were drawn. The median and IQR of inhibin A levels on stimulation day 1, stimulation day 5, end-of-stimulation visit and oocyte retrieval visit are presented. |
| Circulating Concentrations of Inhibin B | From screening to the day of oocyte retrieval (up to 22 days after start of stimulation) | Blood samples for analysis of circulating concentrations of inhibin B were drawn. The median and IQR of inhibin B levels on stimulation day 1, stimulation day 5, end-of-stimulation visit and oocyte retrieval visit are presented. |
| Total Gonadotropin Dose | Up to 20 stimulation days | Calculated by start dates, end dates and daily dose of IMP. |
| Number of Stimulation Days | Up to 20 stimulation days | Calculated by start dates and end dates. |
| Proportion of Participants With Investigator-requested Gonadotropin Dose Adjustments | Stimulation Day 5 | Investigator-requested decreases and increases of the gonadotropin dose. |
| Percentage of Participants With Adverse Events (AEs) | From time of signing informed consent until the end-of-cycle visit in the fresh cycle (approximately 6 months) | Any AE occurring after start of IMP and before the end-of-trial visit, or a pre-treatment AE 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. Data in this endpoint are presented for the fresh cycle. |
| Intensity of AEs | From time of signing informed consent until the end-of-cycle visit in the fresh cycle (up to approximately 6 months) | The intensity of AE 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). Data in this endpoint are presented for the fresh cycle. |
| Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Albumin, Protein | From screening (baseline) to the end-of-cycle visit in the fresh cycle (approximately 6 months) | Blood samples were collected for the analysis of clinical chemistry parameters including: Albumin and protein. Data in this endpoint are presented for the fresh cycle. |
| Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase and Gamma Glutamyl Transferase | From screening (baseline) to the end-of-cycle visit in the fresh cycle (approximately 6 months) | Blood samples were collected for the analysis of clinical chemistry parameters including: Alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase and gamma glutamyl transferase. Data in this endpoint are presented for the fresh cycle. |
| Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium | From screening (baseline) to the end-of-cycle visit in the fresh cycle (approximately 6 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. Data in this endpoint are presented for the fresh cycle. |
| Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Direct Bilirubin, Total Bilirubin, Creatinine, Urate | From screening (baseline) to the end-of-cycle visit in the fresh cycle (approximately 6 months) | Blood samples were collected for the analysis of clinical chemistry parameters including: Direct bilirubin, total bilirubin, creatinine, urate. Data in this endpoint are presented for the fresh cycle. |
| Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Lactate Dehydrogenase | From screening (baseline) to the end-of-cycle visit in the fresh cycle (approximately 6 months) | Blood samples were collected for the analysis of clinical chemistry parameters including: Lactate dehydrogenase. Data in this endpoint are presented for the fresh cycle. |
| Changes in Haematology Parameters Compared to Baseline: Erythrocytes | From screening to the end-of-cycle visit in the fresh cycle (approximately 6 months) | Blood samples were collected for the analysis of haematology parameter including: Erythrocytes. Data in this endpoint are presented for the fresh cycle. |
| Changes in Haematology Parameters Compared to Baseline: Haemoglobin | From screening (baseline) to the end-of-cycle visit in the fresh cycle (approximately 6 months) | Blood samples were collected for the analysis of haematology parameters including: Haemoglobin. Data in this endpoint are presented for the fresh cycle. |
| Changes in Haematology Parameters Compared to Baseline: Haematocrit | From screening (baseline) to the end-of-cycle visit in the fresh cycle (approximately 6 months) | Blood samples were collected for the analysis of haematology parameter including: Haematocrit. Data in this endpoint are presented for the fresh cycle. |
| Changes in Haematology Parameters Compared to Baseline: Erythrocyte Mean Corpuscular Volume | From screening (baseline) to the end-of-cycle visit in the fresh cycle (approximately 6 months) | Blood samples were collected for the analysis of haematology parameter including: Erythrocyte mean corpuscular volume. Data in this endpoint are presented for the fresh cycle. |
| Changes in Haematology Parameters Compared to Baseline: Leukocytes and Platelets | From screening (baseline) to the end-of-cycle visit in the fresh cycle (approximately 6 months) | Blood samples were collected for the analysis of haematology parameters including: Leukocytes and platelets. Data in this endpoint are presented for the fresh cycle. |
| Changes in Haematology Parameters Compared to Baseline: Erythrocyte Mean Corpuscular Hemoglobin | From screening (baseline) to the end-of-cycle visit in the fresh cycle (approximately 6 months) | Blood samples were collected for the analysis of haematology parameter including: Erythrocyte mean corpuscular haemoglobin. Data in this endpoint are presented for the fresh cycle. |
| Changes in Haematology Parameters Compared to Baseline: Erythrocyte Mean Corpuscular Haemoglobin Concentration | From screening (baseline) to the end-of-cycle visit in the fresh cycle (approximately 6 months) | Blood samples were collected for the analysis of haematology parameter including: Erythrocyte mean corpuscular haemoglobin concentration. Data in this endpoint are presented for the fresh cycle. |
| Changes in Haematology Parameters Compared to Baseline: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes and Neutrophils/Leukocytes | From screening (baseline) to the end-of-cycle visit in the fresh cycle (approximately 6 months) | Blood samples were collected for the analysis of haematology parameters including: Basophils/leukocytes, eosinophils/ leukocytes, lymphocytes/leukocytes, monocytes/leukocytes and neutrophils/leukocytes. Data in this endpoint are presented for the fresh cycle. |
| Proportion of Subjects With Markedly Abnormal Changes of Clinical Chemistry Parameters: Alanine Aminotransferase, Aspartate Aminotransferase, Bicarbonate, Calcium, Potassium | From screening (baseline) to the end-of-cycle visit in the fresh cycle (approximately 6 months) | The table represents the percentage of participants in each group with normal baseline values and markedly abnormal end-of-stimulation or end-of-cycle visit values for alanine aminotransferase, aspartate aminotransferase, bicarbonate, calcium, potassium. Data in this endpoint are presented for the fresh cycle. |
| Proportion of Subjects With Markedly Abnormal Changes of Haematology Parameters: Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Neutrophils/Leukocytes | From screening (baseline) to the end-of-stimulation visit and end-of-cycle visit in the fresh cycle (approximately 6 months) | The table represents the percentage of participants in each group with normal baseline values and markedly abnormal end-of-stimulation or end-of-cycle visit values for Leukocytes, eosinophils/leukocytes, lymphocytes/leukocytes and neutrophils/leukocytes. Data in this endpoint are presented for the fresh cycle. |
| Frequency and Intensity of Injection Site Reactions (Redness, Pain, Itching, Swelling and Bruising) Assessed by the Subject During the Stimulation Period | 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 (Redness, Pain, Itching, Swelling and Bruising) Assessed by the Subject During the Stimulation Period | End-of-stimulation (up to 20 stimulation days) | Assessed by the participant during the stimulation period as mild, moderate or severe. |
| 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. 95% Clopper-Pearson confidence interval has been reported in this endpoint. |
| Frequency and Intensity of Immune-related Adverse Events | From time of signing informed consent for participation in the trial until the end-of-cycle visit in the fresh cycle (approximately 6 months) | Standardised Medical Dictionary for Regulatory Activities (MedDRA) Queries (SMQs). |
| Proportion of Subjects With <4, 4-7, 8-14, 15-19 and ≥20 Oocytes Retrieved | On day of oocyte retrieval (up to 22 days after start of stimulation) | Grouped according to the number of oocytes retrieved. Participants with cycle cancellation due to poor ovarian response are included in the \<4 oocytes group. |
| Proportion of Subjects With OHSS, Overall and by Grade, and Proportion of Subjects With Moderate/Severe OHSS | ≤9 days after triggering of final follicular maturation (early OHSS), >9 days after triggering of final follicular maturation until 21-28 days after last IMP dose or up to ongoing pregnancy 8-9 weeks after transfer in pregnant participants (late OHSS) | Classification of grade was according to Golan's classification system, and all OHSS cases were graded as mild, moderate or severe. Data in this endpoint are presented for the fresh cycle. |
| Proportion of Subjects Hospitalized Due to OHSS and Proportion of Subjects Undergoing Paracentesis Due to OHSS | ≤9 days after triggering of final follicular maturation (early OHSS), >9 days after triggering of final follicular maturation until 21-28 days after last IMP dose or up to ongoing pregnancy 8-9 weeks after transfer in pregnant participants (late OHSS) | Percentage of participants hospitalized or undergoing paracentesis due to OHSS are reported |
| Proportion of Participants With Multi-fetal Gestation in the Fresh Cycle | Up to 8-9 weeks after transfer | Defined as pregnancy with more than one fetus. Among participants with ongoing pregnancy, percentage of participants with twin pregnancies are presented. '%' in the unit of measure refers to 'percentage'. |
| Proportion of Cryopreserved Cycles With Multi-fetal Gestation | Up to 8-9 weeks after transfer | Defined as pregnancy with more than one fetus. Among cryopreserved cycles with ongoing pregnancy, percentage of cycles with twin pregnancies are presented. '%' in the unit of measure refers to 'percentage'. |
| Biochemical Pregnancy, Spontaneous Abortion, Ectopic Pregnancy (With and Without Medical/Surgical Intervention) and Vanishing Twins in the Fresh Cycle | Up to 8-9 weeks after transfer | The percentage of participants with biochemical pregnancy, spontaneous abortion, ectopic pregnancy (with and without medical/surgical intervention) and vanishing twins in the fresh cycle are presented. Data represents participants with positive βhCG. Data is not shown for placebo arm because no participants had a positive βhCG. '%' in the unit of measure refers to 'percentage'. Unit: % of participants with early pregnancy loss. |
| Biochemical Pregnancy, Spontaneous Abortion, Ectopic Pregnancy (With and Without Medical/Surgical Intervention) and Vanishing Twins in the Cryopreserved Cycles | Up to 8-9 weeks after transfer | The percentage of cryopreserved cycles with biochemical pregnancy, spontaneous abortion, ectopic pregnancy (with and without medical/surgical intervention) and vanishing twins are presented. Data is not shown for placebo arm because no participants had a positive βhCG. '%' in the unit of measure refers to 'percentage'. |
| Proportion of Participants With Technical Malfunctions of the Administration Pen | Up to 20 stimulation days | Incidences of technical malfunctions of the administration pen were recorded. |
| 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. Data in this endpoint are presented for the fresh cycle. |
Countries
United States
Participant flow
Recruitment details
The trial was performed in 24 investigational sites in 18 states of the United States between Oct 2018 to Dec 2020.
Pre-assignment details
In total, 666 participants were screened of which 588 participants were randomized. Of the randomized participants, 587 participants were exposed to the investigational medicinal product (IMP): 533 to FE 999049 (Follitropin Delta) and 54 to Placebo. One participant was randomization failure and did not receive the IMP.
Participants by arm
| Arm | Count |
|---|---|
| FE 999049 (Follitropin Delta) FE 999049 was administered as single daily subcutaneous injections in the abdomen at a starting dose of 15 μg daily that was fixed for the first four stimulation days. Based on ovarian response, the dose could be adjusted by 3 μg, with dose increases implemented not more frequently than once every 2 days and dose decreases implemented per investigator's judgement. The minimum daily dose was 6 μg, and the maximum daily dose was 24 μg.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early OHSS with the exception of GnRH agonist for triggering of final follicular maturation, was not allowed. | 533 |
| Placebo Placebo was administered as single daily subcutaneous injection dialed to the same value (dose) as FE 999049.
Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early OHSS with the exception of GnRH agonist for triggering of final follicular maturation, was not allowed. | 54 |
| Total | 587 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 0 |
| Overall Study | Lost to Follow-up | 2 | 0 |
| Overall Study | Participant did not show to visit (stimulation day 12) | 1 | 0 |
| Overall Study | Participant relocated, unable to continue in trial | 1 | 0 |
| Overall Study | Protocol deviation | 23 | 0 |
| Overall Study | Randomization failure | 1 | 0 |
Baseline characteristics
| Characteristic | FE 999049 (Follitropin Delta) | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 37.7 years STANDARD_DEVIATION 2.1 | 37.9 years STANDARD_DEVIATION 2.1 | 37.7 years STANDARD_DEVIATION 2.1 |
| Body mass index (BMI) | 27.0 kg/m^2 STANDARD_DEVIATION 5.1 | 27.9 kg/m^2 STANDARD_DEVIATION 5.1 | 27.0 kg/m^2 STANDARD_DEVIATION 5.1 |
| Duration of infertility | 42.7 months STANDARD_DEVIATION 37.6 | 45.9 months STANDARD_DEVIATION 43.2 | 43.0 months STANDARD_DEVIATION 38.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 57 Participants | 9 Participants | 66 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 476 Participants | 45 Participants | 521 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Primary infertility | 226 participants | 26 participants | 252 participants |
| Primary reason for infertility Endometriosis stage I/II | 20 Participants | 2 Participants | 22 Participants |
| Primary reason for infertility Endometriosis stage III/IV | 1 Participants | 0 Participants | 1 Participants |
| Primary reason for infertility Mild male factor | 50 Participants | 5 Participants | 55 Participants |
| Primary reason for infertility Moderate male factor | 62 Participants | 8 Participants | 70 Participants |
| Primary reason for infertility Other | 2 Participants | 0 Participants | 2 Participants |
| Primary reason for infertility Severe male factor | 27 Participants | 4 Participants | 31 Participants |
| Primary reason for infertility Tubal infertility | 120 Participants | 7 Participants | 127 Participants |
| Primary reason for infertility Unexplained infertility | 251 Participants | 28 Participants | 279 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 57 Participants | 5 Participants | 62 Participants |
| Race (NIH/OMB) Black or African American | 70 Participants | 4 Participants | 74 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 5 Participants | 0 Participants | 5 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 398 Participants | 45 Participants | 443 Participants |
| Sex: Female, Male Female | 533 Participants | 54 Participants | 587 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 / 533 | 0 / 54 |
| other Total, other adverse events | 151 / 533 | 2 / 54 |
| serious Total, serious adverse events | 2 / 533 | 0 / 54 |
Outcome results
Primary
Cumulative Ongoing Pregnancy Rate After the Fresh Cycle and Cryopreserved Cycles Initiated Within 12 Months From the Start of Controlled Ovarian Stimulation (COS)
Defined as at least one intrauterine viable fetus 8-9 weeks after transfer. Data in this endpoint are presented for the fresh cycle and the cryopreserved cycles.
Time frame: 8-9 weeks after transfer (up to approximately 16 months after start of stimulation)
Population: The mITT analysis set comprised all randomized and exposed participants. Participants were analyzed according to planned treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FE 999049 (Follitropin Delta) | Cumulative Ongoing Pregnancy Rate After the Fresh Cycle and Cryopreserved Cycles Initiated Within 12 Months From the Start of Controlled Ovarian Stimulation (COS) | 43.3 percentage of participants |
| Placebo | Cumulative Ongoing Pregnancy Rate After the Fresh Cycle and Cryopreserved Cycles Initiated Within 12 Months From the Start of Controlled Ovarian Stimulation (COS) | 0.0 percentage of participants |
p-value: <0.00195% CI: [36.5, 47.6]Fisher Exact
Secondary
Biochemical Pregnancy, Spontaneous Abortion, Ectopic Pregnancy (With and Without Medical/Surgical Intervention) and Vanishing Twins in the Cryopreserved Cycles
The percentage of cryopreserved cycles with biochemical pregnancy, spontaneous abortion, ectopic pregnancy (with and without medical/surgical intervention) and vanishing twins are presented. Data is not shown for placebo arm because no participants had a positive βhCG. '%' in the unit of measure refers to 'percentage'.
Time frame: Up to 8-9 weeks after transfer
Population: The safety analysis set comprised all randomized and exposed participants. Participants were analyzed according to actual treatment received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FE 999049 (Follitropin Delta) | Biochemical Pregnancy, Spontaneous Abortion, Ectopic Pregnancy (With and Without Medical/Surgical Intervention) and Vanishing Twins in the Cryopreserved Cycles | Biochemical pregnancy | 16.8 % of cycles with early pregnancy loss |
| FE 999049 (Follitropin Delta) | Biochemical Pregnancy, Spontaneous Abortion, Ectopic Pregnancy (With and Without Medical/Surgical Intervention) and Vanishing Twins in the Cryopreserved Cycles | Spontaneous abortion | 18.9 % of cycles with early pregnancy loss |
| FE 999049 (Follitropin Delta) | Biochemical Pregnancy, Spontaneous Abortion, Ectopic Pregnancy (With and Without Medical/Surgical Intervention) and Vanishing Twins in the Cryopreserved Cycles | Induced abortion | 0.0 % of cycles with early pregnancy loss |
| FE 999049 (Follitropin Delta) | Biochemical Pregnancy, Spontaneous Abortion, Ectopic Pregnancy (With and Without Medical/Surgical Intervention) and Vanishing Twins in the Cryopreserved Cycles | Ectopic pregnancy | 1.1 % of cycles with early pregnancy loss |
Secondary
Biochemical Pregnancy, Spontaneous Abortion, Ectopic Pregnancy (With and Without Medical/Surgical Intervention) and Vanishing Twins in the Fresh Cycle
The percentage of participants with biochemical pregnancy, spontaneous abortion, ectopic pregnancy (with and without medical/surgical intervention) and vanishing twins in the fresh cycle are presented. Data represents participants with positive βhCG. Data is not shown for placebo arm because no participants had a positive βhCG. '%' in the unit of measure refers to 'percentage'. Unit: % of participants with early pregnancy loss.
Time frame: Up to 8-9 weeks after transfer
Population: The safety analysis set comprised all randomized and exposed participants. Participants were analyzed according to actual treatment received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FE 999049 (Follitropin Delta) | Biochemical Pregnancy, Spontaneous Abortion, Ectopic Pregnancy (With and Without Medical/Surgical Intervention) and Vanishing Twins in the Fresh Cycle | Biochemical pregnancy | 15.8 % of participants |
| FE 999049 (Follitropin Delta) | Biochemical Pregnancy, Spontaneous Abortion, Ectopic Pregnancy (With and Without Medical/Surgical Intervention) and Vanishing Twins in the Fresh Cycle | Spontaneous abortion | 15.2 % of participants |
| FE 999049 (Follitropin Delta) | Biochemical Pregnancy, Spontaneous Abortion, Ectopic Pregnancy (With and Without Medical/Surgical Intervention) and Vanishing Twins in the Fresh Cycle | Induced abortion | 0.0 % of participants |
| FE 999049 (Follitropin Delta) | Biochemical Pregnancy, Spontaneous Abortion, Ectopic Pregnancy (With and Without Medical/Surgical Intervention) and Vanishing Twins in the Fresh Cycle | Ectopic pregnancy | 0.6 % of participants |
Secondary
Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: 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. Data in this endpoint are presented for the fresh cycle.
Time frame: From screening (baseline) to the end-of-cycle visit in the fresh cycle (approximately 6 months)
Population: The safety analysis set comprised all randomized and exposed participants. Participants were analyzed according to actual treatment received.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FE 999049 (Follitropin Delta) | Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase and Gamma Glutamyl Transferase | Alanine aminotransferase (End-of-stimulation visit) | 0.3 IU/L | Standard Deviation 10.4 |
| FE 999049 (Follitropin Delta) | Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase and Gamma Glutamyl Transferase | Alanine aminotransferase (End-of-cycle visit) | -0.7 IU/L | Standard Deviation 9 |
| FE 999049 (Follitropin Delta) | Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase and Gamma Glutamyl Transferase | Alkaline phosphatase (End-of-stimulation visit) | -1.3 IU/L | Standard Deviation 7.2 |
| FE 999049 (Follitropin Delta) | Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase and Gamma Glutamyl Transferase | Alkaline phosphatase (End-of-cycle visit) | -0.6 IU/L | Standard Deviation 9.6 |
| FE 999049 (Follitropin Delta) | Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase and Gamma Glutamyl Transferase | Aspartate aminotransferase (Endof-stimulation visit) | 0.2 IU/L | Standard Deviation 8.6 |
| FE 999049 (Follitropin Delta) | Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase and Gamma Glutamyl Transferase | Aspartate aminotransferase (End-of- cycle visit) | -0.9 IU/L | Standard Deviation 6.2 |
| FE 999049 (Follitropin Delta) | Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase and Gamma Glutamyl Transferase | Gamma glutamy transferase (End-of-stimulation visit) | -1.5 IU/L | Standard Deviation 8.3 |
| FE 999049 (Follitropin Delta) | Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase and Gamma Glutamyl Transferase | Gamma glutamyl transferase (End-of-cycle visit) | -1.0 IU/L | Standard Deviation 11.8 |
| Placebo | Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase and Gamma Glutamyl Transferase | Gamma glutamyl transferase (End-of-cycle visit) | -1.0 IU/L | Standard Deviation 8.2 |
| Placebo | Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase and Gamma Glutamyl Transferase | Alanine aminotransferase (End-of-stimulation visit) | 2.3 IU/L | Standard Deviation 18.9 |
| Placebo | Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase and Gamma Glutamyl Transferase | Aspartate aminotransferase (Endof-stimulation visit) | 2.0 IU/L | Standard Deviation 8.6 |
| Placebo | Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase and Gamma Glutamyl Transferase | Alanine aminotransferase (End-of-cycle visit) | -2.3 IU/L | Standard Deviation 18 |
| Placebo | Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase and Gamma Glutamyl Transferase | Gamma glutamy transferase (End-of-stimulation visit) | -0.6 IU/L | Standard Deviation 6.5 |
| Placebo | Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase and Gamma Glutamyl Transferase | Alkaline phosphatase (End-of-stimulation visit) | 1.6 IU/L | Standard Deviation 6.2 |
| Placebo | Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase and Gamma Glutamyl Transferase | Aspartate aminotransferase (End-of- cycle visit) | -0.5 IU/L | Standard Deviation 6.4 |
| Placebo | Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase and Gamma Glutamyl Transferase | Alkaline phosphatase (End-of-cycle visit) | -0.9 IU/L | Standard Deviation 6.7 |
Secondary
Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Albumin, Protein
Blood samples were collected for the analysis of clinical chemistry parameters including: Albumin and protein. Data in this endpoint are presented for the fresh cycle.
Time frame: From screening (baseline) to the end-of-cycle visit in the fresh cycle (approximately 6 months)
Population: The safety analysis set comprised all randomized and exposed participants. Participants were analyzed according to actual treatment received.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FE 999049 (Follitropin Delta) | Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Albumin, Protein | Albumin (End-of-stimulation visit) | -1.53 g/L | Standard Deviation 2.45 |
| FE 999049 (Follitropin Delta) | Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Albumin, Protein | Albumin (End-of-cycle visit) | -1.90 g/L | Standard Deviation 2.75 |
| FE 999049 (Follitropin Delta) | Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Albumin, Protein | Protein (End-of-stimulation visit) | -2.76 g/L | Standard Deviation 3.98 |
| FE 999049 (Follitropin Delta) | Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Albumin, Protein | Protein (End-of-cycle visit) | -1.92 g/L | Standard Deviation 4.12 |
| Placebo | Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Albumin, Protein | Protein (End-of-cycle visit) | -0.96 g/L | Standard Deviation 3.55 |
| Placebo | Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Albumin, Protein | Albumin (End-of-stimulation visit) | 0.18 g/L | Standard Deviation 2.12 |
| Placebo | Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Albumin, Protein | Protein (End-of-stimulation visit) | -0.17 g/L | Standard Deviation 3.45 |
| Placebo | Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Albumin, Protein | Albumin (End-of-cycle visit) | -0.65 g/L | Standard Deviation 2.29 |
Secondary
Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: 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. Data in this endpoint are presented for the fresh cycle.
Time frame: From screening (baseline) to the end-of-cycle visit in the fresh cycle (approximately 6 months)
Population: The safety analysis set comprised all randomized and exposed participants. Participants were analyzed according to actual treatment received.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FE 999049 (Follitropin Delta) | Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium | Bicarbonate (End-of-stimulation visit) | -0.05 mmol/L | Standard Deviation 2.24 |
| FE 999049 (Follitropin Delta) | Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium | Bicarbonate (End-of-cycle visit) | -0.91 mmol/L | Standard Deviation 2.42 |
| FE 999049 (Follitropin Delta) | Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium | Blood urea nitrogen (End-of-stimulation visit) | -0.2 mmol/L | Standard Deviation 1.1 |
| FE 999049 (Follitropin Delta) | Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium | Blood urea nitrogen (End-of-cycle visit) | -0.3 mmol/L | Standard Deviation 1.1 |
| FE 999049 (Follitropin Delta) | Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium | Calcium (End-of-stimulation visit) | -0.02 mmol/L | Standard Deviation 0.08 |
| FE 999049 (Follitropin Delta) | Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium | Calcium (End-of-cycle visit) | -0.02 mmol/L | Standard Deviation 0.09 |
| FE 999049 (Follitropin Delta) | Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium | Chloride (End-of-stimulation visit) | -0.6 mmol/L | Standard Deviation 2.3 |
| FE 999049 (Follitropin Delta) | Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium | Chloride (End-of-cycle visit) | 0.4 mmol/L | Standard Deviation 2.4 |
| FE 999049 (Follitropin Delta) | Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium | Cholesterol (End-of-stimulation visit) | -0.4 mmol/L | Standard Deviation 0.5 |
| FE 999049 (Follitropin Delta) | Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium | Cholesterol (End-of-cycle visit) | 0.1 mmol/L | Standard Deviation 0.6 |
| FE 999049 (Follitropin Delta) | Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium | Glucose (End-of-stimulation visit) | -0.1 mmol/L | Standard Deviation 0.9 |
| FE 999049 (Follitropin Delta) | Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium | Glucose (End-of-cycle visit) | 0.0 mmol/L | Standard Deviation 0.9 |
| FE 999049 (Follitropin Delta) | Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium | Phosphate (End-of stimulation visit) | -0.04 mmol/L | Standard Deviation 0.16 |
| FE 999049 (Follitropin Delta) | Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium | Phosphate (End-of-cycle visit) | 0.01 mmol/L | Standard Deviation 0.18 |
| FE 999049 (Follitropin Delta) | Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium | Potassium (End-of-stimulation visit) | 0.00 mmol/L | Standard Deviation 0.44 |
| FE 999049 (Follitropin Delta) | Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium | Potassium (End-of-cycle visit) | 0.09 mmol/L | Standard Deviation 0.47 |
| FE 999049 (Follitropin Delta) | Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium | Sodium (End-of-stimulation visit) | -0.6 mmol/L | Standard Deviation 2.4 |
| FE 999049 (Follitropin Delta) | Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium | Sodium (End-of-cycle visit) | -0.4 mmol/L | Standard Deviation 2.8 |
| Placebo | Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium | Phosphate (End-of-cycle visit) | 0.00 mmol/L | Standard Deviation 0.18 |
| Placebo | Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium | Bicarbonate (End-of-stimulation visit) | 0.56 mmol/L | Standard Deviation 2.22 |
| Placebo | Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium | Cholesterol (End-of-cycle visit) | -0.1 mmol/L | Standard Deviation 0.6 |
| Placebo | Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium | Bicarbonate (End-of-cycle visit) | -0.47 mmol/L | Standard Deviation 2.38 |
| Placebo | Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium | Sodium (End-of-cycle visit) | 0.5 mmol/L | Standard Deviation 2.5 |
| Placebo | Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium | Blood urea nitrogen (End-of-stimulation visit) | -0.1 mmol/L | Standard Deviation 1.1 |
| Placebo | Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium | Glucose (End-of-stimulation visit) | 0.2 mmol/L | Standard Deviation 0.9 |
| Placebo | Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium | Blood urea nitrogen (End-of-cycle visit) | 0.0 mmol/L | Standard Deviation 1.1 |
| Placebo | Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium | Potassium (End-of-stimulation visit) | 0.19 mmol/L | Standard Deviation 0.4 |
| Placebo | Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium | Calcium (End-of-stimulation visit) | 0.02 mmol/L | Standard Deviation 0.09 |
| Placebo | Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium | Glucose (End-of-cycle visit) | 0.2 mmol/L | Standard Deviation 1.1 |
| Placebo | Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium | Calcium (End-of-cycle visit) | -0.01 mmol/L | Standard Deviation 0.09 |
| Placebo | Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium | Sodium (End-of-stimulation visit) | 0.9 mmol/L | Standard Deviation 2.5 |
| Placebo | Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium | Chloride (End-of-stimulation visit) | 0.3 mmol/L | Standard Deviation 2.1 |
| Placebo | Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium | Phosphate (End-of stimulation visit) | 0.03 mmol/L | Standard Deviation 0.13 |
| Placebo | Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium | Chloride (End-of-cycle visit) | 0.9 mmol/L | Standard Deviation 2.3 |
| Placebo | Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium | Potassium (End-of-cycle visit) | 0.25 mmol/L | Standard Deviation 0.46 |
| Placebo | Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium | Cholesterol (End-of-stimulation visit) | 0.0 mmol/L | Standard Deviation 0.5 |
Secondary
Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Direct Bilirubin, Total Bilirubin, Creatinine, Urate
Blood samples were collected for the analysis of clinical chemistry parameters including: Direct bilirubin, total bilirubin, creatinine, urate. Data in this endpoint are presented for the fresh cycle.
Time frame: From screening (baseline) to the end-of-cycle visit in the fresh cycle (approximately 6 months)
Population: The safety analysis set comprised all randomized and exposed participants. Participants were analyzed according to actual treatment received.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FE 999049 (Follitropin Delta) | Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Direct Bilirubin, Total Bilirubin, Creatinine, Urate | Direct bilirubin (End-of-stimulation visit) | -0.09 umol/L | Standard Deviation 0.94 |
| FE 999049 (Follitropin Delta) | Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Direct Bilirubin, Total Bilirubin, Creatinine, Urate | Direct bilirubin (End-of-cycle visit) | -0.28 umol/L | Standard Deviation 0.96 |
| FE 999049 (Follitropin Delta) | Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Direct Bilirubin, Total Bilirubin, Creatinine, Urate | Total bilirubin (End-of-stimulation visit) | -0.58 umol/L | Standard Deviation 3.5 |
| FE 999049 (Follitropin Delta) | Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Direct Bilirubin, Total Bilirubin, Creatinine, Urate | Total bilirubin (End-of-cycle visit) | -0.99 umol/L | Standard Deviation 3.64 |
| FE 999049 (Follitropin Delta) | Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Direct Bilirubin, Total Bilirubin, Creatinine, Urate | Creatinine (End-of-stimulation visit) | -3.99 umol/L | Standard Deviation 7.48 |
| FE 999049 (Follitropin Delta) | Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Direct Bilirubin, Total Bilirubin, Creatinine, Urate | Creatinine (End-of-cycle visit) | -3.47 umol/L | Standard Deviation 9.55 |
| FE 999049 (Follitropin Delta) | Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Direct Bilirubin, Total Bilirubin, Creatinine, Urate | Urate (End-of-stimulation visit) | -1.13 umol/L | Standard Deviation 36.24 |
| FE 999049 (Follitropin Delta) | Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Direct Bilirubin, Total Bilirubin, Creatinine, Urate | Urate (End-of-cycle visit) | -10.53 umol/L | Standard Deviation 48.58 |
| Placebo | Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Direct Bilirubin, Total Bilirubin, Creatinine, Urate | Urate (End-of-cycle visit) | 6.06 umol/L | Standard Deviation 42.05 |
| Placebo | Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Direct Bilirubin, Total Bilirubin, Creatinine, Urate | Direct bilirubin (End-of-stimulation visit) | -0.26 umol/L | Standard Deviation 0.82 |
| Placebo | Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Direct Bilirubin, Total Bilirubin, Creatinine, Urate | Creatinine (End-of-stimulation visit) | -0.18 umol/L | Standard Deviation 8.65 |
| Placebo | Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Direct Bilirubin, Total Bilirubin, Creatinine, Urate | Direct bilirubin (End-of-cycle visit) | -0.08 umol/L | Standard Deviation 0.92 |
| Placebo | Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Direct Bilirubin, Total Bilirubin, Creatinine, Urate | Urate (End-of-stimulation visit) | -5.08 umol/L | Standard Deviation 36.99 |
| Placebo | Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Direct Bilirubin, Total Bilirubin, Creatinine, Urate | Total bilirubin (End-of-stimulation visit) | -0.56 umol/L | Standard Deviation 3.92 |
| Placebo | Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Direct Bilirubin, Total Bilirubin, Creatinine, Urate | Creatinine (End-of-cycle visit) | 0.85 umol/L | Standard Deviation 7.27 |
| Placebo | Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Direct Bilirubin, Total Bilirubin, Creatinine, Urate | Total bilirubin (End-of-cycle visit) | 0.23 umol/L | Standard Deviation 3.82 |
Secondary
Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Lactate Dehydrogenase
Blood samples were collected for the analysis of clinical chemistry parameters including: Lactate dehydrogenase. Data in this endpoint are presented for the fresh cycle.
Time frame: From screening (baseline) to the end-of-cycle visit in the fresh cycle (approximately 6 months)
Population: The safety analysis set comprised all randomized and exposed participants. Participants were analyzed according to actual treatment received.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FE 999049 (Follitropin Delta) | Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Lactate Dehydrogenase | End-of-stimulation visit | -12.0 U/L | Standard Deviation 18.5 |
| FE 999049 (Follitropin Delta) | Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Lactate Dehydrogenase | End-of-cycle visit | -0.4 U/L | Standard Deviation 20.7 |
| Placebo | Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Lactate Dehydrogenase | End-of-stimulation visit | -3.8 U/L | Standard Deviation 14.3 |
| Placebo | Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Lactate Dehydrogenase | End-of-cycle visit | -0.8 U/L | Standard Deviation 16.8 |
Secondary
Changes in Haematology Parameters Compared to Baseline: 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. Data in this endpoint are presented for the fresh cycle.
Time frame: From screening (baseline) to the end-of-cycle visit in the fresh cycle (approximately 6 months)
Population: The safety analysis set comprised all randomized and exposed participants. Participants were analyzed according to actual treatment received.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FE 999049 (Follitropin Delta) | Changes in Haematology Parameters Compared to Baseline: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes and Neutrophils/Leukocytes | Basophils/leukocytes (End-of-stimulation visit) | 0.11 percentage | Standard Deviation 0.52 |
| FE 999049 (Follitropin Delta) | Changes in Haematology Parameters Compared to Baseline: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes and Neutrophils/Leukocytes | Basophils/leukocytes (End-of-cycle visit) | 0.07 percentage | Standard Deviation 0.43 |
| FE 999049 (Follitropin Delta) | Changes in Haematology Parameters Compared to Baseline: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes and Neutrophils/Leukocytes | Eosinophils/leukocytes (End-of-stimulation visit) | -0.36 percentage | Standard Deviation 1.25 |
| FE 999049 (Follitropin Delta) | Changes in Haematology Parameters Compared to Baseline: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes and Neutrophils/Leukocytes | Eosinophils/leukocytes (End-of-cycle visit) | -0.16 percentage | Standard Deviation 1.35 |
| FE 999049 (Follitropin Delta) | Changes in Haematology Parameters Compared to Baseline: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes and Neutrophils/Leukocytes | Lymphocytes/leukocytes (End-of-stimulation visit) | -5.46 percentage | Standard Deviation 6.73 |
| FE 999049 (Follitropin Delta) | Changes in Haematology Parameters Compared to Baseline: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes and Neutrophils/Leukocytes | Lymphocytes/leukocytes (End-of-cycle visit) | -1.27 percentage | Standard Deviation 8.24 |
| FE 999049 (Follitropin Delta) | Changes in Haematology Parameters Compared to Baseline: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes and Neutrophils/Leukocytes | Monocytes/leukocytes (End-of-stimulation visit) | -0.44 percentage | Standard Deviation 1.73 |
| FE 999049 (Follitropin Delta) | Changes in Haematology Parameters Compared to Baseline: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes and Neutrophils/Leukocytes | Monocytes/leukocytes (End-of-cycle visit) | 0.14 percentage | Standard Deviation 1.73 |
| FE 999049 (Follitropin Delta) | Changes in Haematology Parameters Compared to Baseline: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes and Neutrophils/Leukocytes | Neutrophils/leukocytes (End-of-stimulation visit) | 6.14 percentage | Standard Deviation 7.67 |
| FE 999049 (Follitropin Delta) | Changes in Haematology Parameters Compared to Baseline: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes and Neutrophils/Leukocytes | Neutrophils/leukocytes (End-of-cycle visit) | 1.22 percentage | Standard Deviation 9.09 |
| Placebo | Changes in Haematology Parameters Compared to Baseline: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes and Neutrophils/Leukocytes | Monocytes/leukocytes (End-of-cycle visit) | 0.66 percentage | Standard Deviation 1.8 |
| Placebo | Changes in Haematology Parameters Compared to Baseline: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes and Neutrophils/Leukocytes | Basophils/leukocytes (End-of-stimulation visit) | 0.10 percentage | Standard Deviation 0.62 |
| Placebo | Changes in Haematology Parameters Compared to Baseline: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes and Neutrophils/Leukocytes | Lymphocytes/leukocytes (End-of-cycle visit) | 0.80 percentage | Standard Deviation 5.39 |
| Placebo | Changes in Haematology Parameters Compared to Baseline: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes and Neutrophils/Leukocytes | Basophils/leukocytes (End-of-cycle visit) | 0.01 percentage | Standard Deviation 0.55 |
| Placebo | Changes in Haematology Parameters Compared to Baseline: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes and Neutrophils/Leukocytes | Neutrophils/leukocytes (End-of-cycle visit) | -1.51 percentage | Standard Deviation 6.27 |
| Placebo | Changes in Haematology Parameters Compared to Baseline: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes and Neutrophils/Leukocytes | Eosinophils/leukocytes (End-of-stimulation visit) | 0.03 percentage | Standard Deviation 1.16 |
| Placebo | Changes in Haematology Parameters Compared to Baseline: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes and Neutrophils/Leukocytes | Monocytes/leukocytes (End-of-stimulation visit) | 0.00 percentage | Standard Deviation 1.74 |
| Placebo | Changes in Haematology Parameters Compared to Baseline: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes and Neutrophils/Leukocytes | Eosinophils/leukocytes (End-of-cycle visit) | 0.04 percentage | Standard Deviation 0.99 |
| Placebo | Changes in Haematology Parameters Compared to Baseline: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes and Neutrophils/Leukocytes | Neutrophils/leukocytes (End-of-stimulation visit) | -0.73 percentage | Standard Deviation 7.4 |
| Placebo | Changes in Haematology Parameters Compared to Baseline: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes and Neutrophils/Leukocytes | Lymphocytes/leukocytes (End-of-stimulation visit) | 0.59 percentage | Standard Deviation 6.34 |
Secondary
Changes in Haematology Parameters Compared to Baseline: Erythrocyte Mean Corpuscular Haemoglobin Concentration
Blood samples were collected for the analysis of haematology parameter including: Erythrocyte mean corpuscular haemoglobin concentration. Data in this endpoint are presented for the fresh cycle.
Time frame: From screening (baseline) to the end-of-cycle visit in the fresh cycle (approximately 6 months)
Population: The safety analysis set comprised all randomized and exposed participants. Participants were analyzed according to actual treatment received.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FE 999049 (Follitropin Delta) | Changes in Haematology Parameters Compared to Baseline: Erythrocyte Mean Corpuscular Haemoglobin Concentration | End-of-stimulation visit | -0.3 mmol/L | Standard Deviation 0.8 |
| FE 999049 (Follitropin Delta) | Changes in Haematology Parameters Compared to Baseline: Erythrocyte Mean Corpuscular Haemoglobin Concentration | End-of-cycle visit | -0.2 mmol/L | Standard Deviation 0.8 |
| Placebo | Changes in Haematology Parameters Compared to Baseline: Erythrocyte Mean Corpuscular Haemoglobin Concentration | End-of-stimulation visit | -0.2 mmol/L | Standard Deviation 0.8 |
| Placebo | Changes in Haematology Parameters Compared to Baseline: Erythrocyte Mean Corpuscular Haemoglobin Concentration | End-of-cycle visit | -0.3 mmol/L | Standard Deviation 0.7 |
Secondary
Changes in Haematology Parameters Compared to Baseline: Erythrocyte Mean Corpuscular Hemoglobin
Blood samples were collected for the analysis of haematology parameter including: Erythrocyte mean corpuscular haemoglobin. Data in this endpoint are presented for the fresh cycle.
Time frame: From screening (baseline) to the end-of-cycle visit in the fresh cycle (approximately 6 months)
Population: The safety analysis set comprised all randomized and exposed participants. Participants were analyzed according to actual treatment received.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FE 999049 (Follitropin Delta) | Changes in Haematology Parameters Compared to Baseline: Erythrocyte Mean Corpuscular Hemoglobin | End-of-stimulation visit | 0.1 picogram | Standard Deviation 0.8 |
| FE 999049 (Follitropin Delta) | Changes in Haematology Parameters Compared to Baseline: Erythrocyte Mean Corpuscular Hemoglobin | End-of-cycle visit | 0.1 picogram | Standard Deviation 0.9 |
| Placebo | Changes in Haematology Parameters Compared to Baseline: Erythrocyte Mean Corpuscular Hemoglobin | End-of-stimulation visit | 0.1 picogram | Standard Deviation 1 |
| Placebo | Changes in Haematology Parameters Compared to Baseline: Erythrocyte Mean Corpuscular Hemoglobin | End-of-cycle visit | 0.1 picogram | Standard Deviation 0.8 |
Secondary
Changes in Haematology Parameters Compared to Baseline: Erythrocyte Mean Corpuscular Volume
Blood samples were collected for the analysis of haematology parameter including: Erythrocyte mean corpuscular volume. Data in this endpoint are presented for the fresh cycle.
Time frame: From screening (baseline) to the end-of-cycle visit in the fresh cycle (approximately 6 months)
Population: The safety analysis set comprised all randomized and exposed participants. Participants were analyzed according to actual treatment received.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FE 999049 (Follitropin Delta) | Changes in Haematology Parameters Compared to Baseline: Erythrocyte Mean Corpuscular Volume | End-of-stimulation visit | 1.4 fL | Standard Deviation 3 |
| FE 999049 (Follitropin Delta) | Changes in Haematology Parameters Compared to Baseline: Erythrocyte Mean Corpuscular Volume | End-of-cycle visit | 1.1 fL | Standard Deviation 3.1 |
| Placebo | Changes in Haematology Parameters Compared to Baseline: Erythrocyte Mean Corpuscular Volume | End-of-stimulation visit | 1.2 fL | Standard Deviation 3.2 |
| Placebo | Changes in Haematology Parameters Compared to Baseline: Erythrocyte Mean Corpuscular Volume | End-of-cycle visit | 1.4 fL | Standard Deviation 3 |
Secondary
Changes in Haematology Parameters Compared to Baseline: Erythrocytes
Blood samples were collected for the analysis of haematology parameter including: Erythrocytes. Data in this endpoint are presented for the fresh cycle.
Time frame: From screening to the end-of-cycle visit in the fresh cycle (approximately 6 months)
Population: The safety analysis set comprised all randomized and exposed participants. Participants were analyzed according to actual treatment received.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FE 999049 (Follitropin Delta) | Changes in Haematology Parameters Compared to Baseline: Erythrocytes | End-of-stimulation visit | -0.13 10^12 cells/L | Standard Deviation 0.23 |
| FE 999049 (Follitropin Delta) | Changes in Haematology Parameters Compared to Baseline: Erythrocytes | End-of-cycle visit | -0.15 10^12 cells/L | Standard Deviation 0.26 |
| Placebo | Changes in Haematology Parameters Compared to Baseline: Erythrocytes | End-of-stimulation visit | -0.03 10^12 cells/L | Standard Deviation 0.23 |
| Placebo | Changes in Haematology Parameters Compared to Baseline: Erythrocytes | End-of-cycle visit | -0.07 10^12 cells/L | Standard Deviation 0.23 |
Secondary
Changes in Haematology Parameters Compared to Baseline: Haematocrit
Blood samples were collected for the analysis of haematology parameter including: Haematocrit. Data in this endpoint are presented for the fresh cycle.
Time frame: From screening (baseline) to the end-of-cycle visit in the fresh cycle (approximately 6 months)
Population: The safety analysis set comprised all randomized and exposed participants. Participants were analyzed according to actual treatment received.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FE 999049 (Follitropin Delta) | Changes in Haematology Parameters Compared to Baseline: Haematocrit | End-of-stimulation visit | 0.0 ratio | Standard Deviation 0 |
| FE 999049 (Follitropin Delta) | Changes in Haematology Parameters Compared to Baseline: Haematocrit | End-of-cycle visit | 0.0 ratio | Standard Deviation 0 |
| Placebo | Changes in Haematology Parameters Compared to Baseline: Haematocrit | End-of-stimulation visit | 0.0 ratio | Standard Deviation 0 |
| Placebo | Changes in Haematology Parameters Compared to Baseline: Haematocrit | End-of-cycle visit | 0.0 ratio | Standard Deviation 0 |
Secondary
Changes in Haematology Parameters Compared to Baseline: Haemoglobin
Blood samples were collected for the analysis of haematology parameters including: Haemoglobin. Data in this endpoint are presented for the fresh cycle.
Time frame: From screening (baseline) to the end-of-cycle visit in the fresh cycle (approximately 6 months)
Population: The safety analysis set comprised all randomized and exposed participants. Participants were analyzed according to actual treatment received.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FE 999049 (Follitropin Delta) | Changes in Haematology Parameters Compared to Baseline: Haemoglobin | End-of-cycle visit | -3.94 g/L | Standard Deviation 7.64 |
| FE 999049 (Follitropin Delta) | Changes in Haematology Parameters Compared to Baseline: Haemoglobin | End-of-stimulation visit | -3.75 g/L | Standard Deviation 6.6 |
| Placebo | Changes in Haematology Parameters Compared to Baseline: Haemoglobin | End-of-stimulation visit | -0.20 g/L | Standard Deviation 6.86 |
| Placebo | Changes in Haematology Parameters Compared to Baseline: Haemoglobin | End-of-cycle visit | -1.76 g/L | Standard Deviation 6.86 |
Secondary
Changes in Haematology Parameters Compared to Baseline: Leukocytes and Platelets
Blood samples were collected for the analysis of haematology parameters including: Leukocytes and platelets. Data in this endpoint are presented for the fresh cycle.
Time frame: From screening (baseline) to the end-of-cycle visit in the fresh cycle (approximately 6 months)
Population: The safety analysis set comprised all randomized and exposed participants. Participants were analyzed according to actual treatment received.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FE 999049 (Follitropin Delta) | Changes in Haematology Parameters Compared to Baseline: Leukocytes and Platelets | Leukocytes (End-of-stimulation visit) | 0.904 10^9 cells/L | Standard Deviation 1.913 |
| FE 999049 (Follitropin Delta) | Changes in Haematology Parameters Compared to Baseline: Leukocytes and Platelets | Leukocytes (End-of-cycle visit) | 0.357 10^9 cells/L | Standard Deviation 2.174 |
| FE 999049 (Follitropin Delta) | Changes in Haematology Parameters Compared to Baseline: Leukocytes and Platelets | Platelets (End-of-stimulation visit) | -3.0 10^9 cells/L | Standard Deviation 41 |
| FE 999049 (Follitropin Delta) | Changes in Haematology Parameters Compared to Baseline: Leukocytes and Platelets | Platelets (End-of-cycle visit) | 9.5 10^9 cells/L | Standard Deviation 50.2 |
| Placebo | Changes in Haematology Parameters Compared to Baseline: Leukocytes and Platelets | Platelets (End-of-cycle visit) | -16.1 10^9 cells/L | Standard Deviation 42.1 |
| Placebo | Changes in Haematology Parameters Compared to Baseline: Leukocytes and Platelets | Leukocytes (End-of-stimulation visit) | -0.822 10^9 cells/L | Standard Deviation 1.508 |
| Placebo | Changes in Haematology Parameters Compared to Baseline: Leukocytes and Platelets | Platelets (End-of-stimulation visit) | -2.0 10^9 cells/L | Standard Deviation 35.1 |
| Placebo | Changes in Haematology Parameters Compared to Baseline: Leukocytes and Platelets | Leukocytes (End-of-cycle visit) | -0.534 10^9 cells/L | Standard Deviation 1.636 |
Secondary
Circulating Concentrations of Anti-mullerian Hormone (AMH)
Blood samples for analysis of circulating concentrations of AMH were drawn. The median and inter-quartile range (IQR) of AMH levels on stimulation day 1, stimulation day 5, end-of-stimulation visit and oocyte retrieval visit are presented.
Time frame: From screening to the day of oocyte retrieval (up to 22 days after start of stimulation)
Population: The mITT analysis set comprised all randomized and exposed participants. Participants were analyzed according to planned treatment.~No circulating concentrations of AMH were assessed for the oocyte retrieval visit for the placebo arm, because no participants who received placebo became pregnant.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| FE 999049 (Follitropin Delta) | Circulating Concentrations of Anti-mullerian Hormone (AMH) | End-of-stimulation visit | 6.4 pmol/L |
| FE 999049 (Follitropin Delta) | Circulating Concentrations of Anti-mullerian Hormone (AMH) | Stimulation day 5 | 10.9 pmol/L |
| FE 999049 (Follitropin Delta) | Circulating Concentrations of Anti-mullerian Hormone (AMH) | Oocyte retrieval visit | 5.0 pmol/L |
| FE 999049 (Follitropin Delta) | Circulating Concentrations of Anti-mullerian Hormone (AMH) | Stimulation day 1 | 13.2 pmol/L |
| Placebo | Circulating Concentrations of Anti-mullerian Hormone (AMH) | Stimulation day 5 | 13.1 pmol/L |
| Placebo | Circulating Concentrations of Anti-mullerian Hormone (AMH) | Stimulation day 1 | 11.3 pmol/L |
| Placebo | Circulating Concentrations of Anti-mullerian Hormone (AMH) | End-of-stimulation visit | 14.6 pmol/L |
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 1, stimulation day 5, end-of-stimulation visit and oocyte retrieval visit are presented.
Time frame: From screening to the day of oocyte retrieval (up to 22 days after start of stimulation)
Population: The mITT analysis set comprised all randomized and exposed participants. Participants were analyzed according to planned treatment.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| FE 999049 (Follitropin Delta) | Circulating Concentrations of Estradiol | Stimulation day 1 | 41.2 pg/mL |
| FE 999049 (Follitropin Delta) | Circulating Concentrations of Estradiol | Stimulation day 5 | 383.6 pg/mL |
| FE 999049 (Follitropin Delta) | Circulating Concentrations of Estradiol | End-of-stimulation visit | 1471.0 pg/mL |
| FE 999049 (Follitropin Delta) | Circulating Concentrations of Estradiol | Oocyte retrieval visit | 745.1 pg/mL |
| Placebo | Circulating Concentrations of Estradiol | Oocyte retrieval visit | 107.4 pg/mL |
| Placebo | Circulating Concentrations of Estradiol | Stimulation day 1 | 40.2 pg/mL |
| Placebo | Circulating Concentrations of Estradiol | End-of-stimulation visit | 109.6 pg/mL |
| Placebo | Circulating Concentrations of Estradiol | Stimulation day 5 | 59.0 pg/mL |
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 1, stimulation day 5, end-of-stimulation visit and oocyte retrieval visit are presented.
Time frame: From screening to the day of oocyte retrieval (up to 22 days after start of stimulation)
Population: The mITT analysis set comprised all randomized and exposed participants. Participants were analyzed according to planned treatment.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| FE 999049 (Follitropin Delta) | Circulating Concentrations of Follicle-stimulating Hormone (FSH) | Stimulation day 1 | 8.7 IU/L |
| FE 999049 (Follitropin Delta) | Circulating Concentrations of Follicle-stimulating Hormone (FSH) | Stimulation day 5 | 20.5 IU/L |
| FE 999049 (Follitropin Delta) | Circulating Concentrations of Follicle-stimulating Hormone (FSH) | End-of-stimulation visit | 24.8 IU/L |
| FE 999049 (Follitropin Delta) | Circulating Concentrations of Follicle-stimulating Hormone (FSH) | Oocyte retrieval visit | 14.8 IU/L |
| Placebo | Circulating Concentrations of Follicle-stimulating Hormone (FSH) | Oocyte retrieval visit | 20.2 IU/L |
| Placebo | Circulating Concentrations of Follicle-stimulating Hormone (FSH) | Stimulation day 1 | 8.9 IU/L |
| Placebo | Circulating Concentrations of Follicle-stimulating Hormone (FSH) | End-of-stimulation visit | 7.1 IU/L |
| Placebo | Circulating Concentrations of Follicle-stimulating Hormone (FSH) | Stimulation day 5 | 7.8 IU/L |
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 on stimulation day 1, stimulation day 5, end-of-stimulation visit and oocyte retrieval visit are presented.
Time frame: From screening to the day of oocyte retrieval (up to 22 days after start of stimulation)
Population: The mITT analysis set comprised all randomized and exposed participants. Participants were analyzed according to planned treatment.~No circulating concentrations of Inhibin A were assessed for the oocyte retrieval visit for the placebo arm, because no participants who received placebo became pregnant.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| FE 999049 (Follitropin Delta) | Circulating Concentrations of Inhibin A | End-of-stimulation visit | 258.7 pg/mL |
| FE 999049 (Follitropin Delta) | Circulating Concentrations of Inhibin A | Stimulation day 5 | 70.3 pg/mL |
| FE 999049 (Follitropin Delta) | Circulating Concentrations of Inhibin A | Oocyte retrieval visit | 204.3 pg/mL |
| FE 999049 (Follitropin Delta) | Circulating Concentrations of Inhibin A | Stimulation day 1 | 5.3 pg/mL |
| Placebo | Circulating Concentrations of Inhibin A | Stimulation day 5 | 8.7 pg/mL |
| Placebo | Circulating Concentrations of Inhibin A | Stimulation day 1 | 5.8 pg/mL |
| Placebo | Circulating Concentrations of Inhibin A | End-of-stimulation visit | 19.8 pg/mL |
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 1, stimulation day 5, end-of-stimulation visit and oocyte retrieval visit are presented.
Time frame: From screening to the day of oocyte retrieval (up to 22 days after start of stimulation)
Population: The mITT analysis set comprised all randomized and exposed participants. Participants were analyzed according to planned treatment.~No circulating concentrations of Inhibin B were assessed for the oocyte retrieval visit for the placebo arm, because no participants who received placebo became pregnant.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| FE 999049 (Follitropin Delta) | Circulating Concentrations of Inhibin B | End-of-stimulation visit | 671.0 pg/mL |
| FE 999049 (Follitropin Delta) | Circulating Concentrations of Inhibin B | Stimulation day 5 | 517.0 pg/mL |
| FE 999049 (Follitropin Delta) | Circulating Concentrations of Inhibin B | Oocyte retrieval visit | 301.5 pg/mL |
| FE 999049 (Follitropin Delta) | Circulating Concentrations of Inhibin B | Stimulation day 1 | 75.0 pg/mL |
| Placebo | Circulating Concentrations of Inhibin B | Stimulation day 5 | 93.5 pg/mL |
| Placebo | Circulating Concentrations of Inhibin B | Stimulation day 1 | 79.0 pg/mL |
| Placebo | Circulating Concentrations of Inhibin B | End-of-stimulation visit | 64.5 pg/mL |
Secondary
Circulating Concentrations of Luteinizing Hormone (LH)
Blood samples for analysis of circulating concentrations of LH were drawn. The median and IQR of LH levels on stimulation day 1, stimulation day 5, end-of-stimulation visit and oocyte retrieval visit are presented.
Time frame: From screening to the day of oocyte retrieval (up to 22 days after start of stimulation)
Population: The mITT analysis set comprised all randomized and exposed participants. Participants were analyzed according to planned treatment.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| FE 999049 (Follitropin Delta) | Circulating Concentrations of Luteinizing Hormone (LH) | Stimulation day 1 | 4.8 IU/L |
| FE 999049 (Follitropin Delta) | Circulating Concentrations of Luteinizing Hormone (LH) | Stimulation day 5 | 2.4 IU/L |
| FE 999049 (Follitropin Delta) | Circulating Concentrations of Luteinizing Hormone (LH) | End-of-stimulation visit | 2.0 IU/L |
| FE 999049 (Follitropin Delta) | Circulating Concentrations of Luteinizing Hormone (LH) | Oocyte retrieval visit | 2.2 IU/L |
| Placebo | Circulating Concentrations of Luteinizing Hormone (LH) | Oocyte retrieval visit | 28.1 IU/L |
| Placebo | Circulating Concentrations of Luteinizing Hormone (LH) | Stimulation day 1 | 5.0 IU/L |
| Placebo | Circulating Concentrations of Luteinizing Hormone (LH) | End-of-stimulation visit | 8.8 IU/L |
| Placebo | Circulating Concentrations of Luteinizing Hormone (LH) | Stimulation day 5 | 5.7 IU/L |
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 1, stimulation day 5, end-of-stimulation visit and oocyte retrieval visit are presented.
Time frame: From screening to the day of oocyte retrieval (up to 22 days after start of stimulation)
Population: The mITT analysis set comprised all randomized and exposed participants. Participants were analyzed according to planned treatment.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| FE 999049 (Follitropin Delta) | Circulating Concentrations of Progesterone | Stimulation day 1 | 0.5 ng/mL |
| FE 999049 (Follitropin Delta) | Circulating Concentrations of Progesterone | Stimulation day 5 | 0.6 ng/mL |
| FE 999049 (Follitropin Delta) | Circulating Concentrations of Progesterone | End-of-stimulation visit | 1.1 ng/mL |
| FE 999049 (Follitropin Delta) | Circulating Concentrations of Progesterone | Oocyte retrieval visit | 6.2 ng/mL |
| Placebo | Circulating Concentrations of Progesterone | Oocyte retrieval visit | 2.0 ng/mL |
| Placebo | Circulating Concentrations of Progesterone | Stimulation day 1 | 0.5 ng/mL |
| Placebo | Circulating Concentrations of Progesterone | End-of-stimulation visit | 0.3 ng/mL |
| Placebo | Circulating Concentrations of Progesterone | Stimulation day 5 | 0.3 ng/mL |
Secondary
Clinical Pregnancy Rate in the Fresh Cycle, the Cryopreserved Cycles and Cumulatively
Defined at least one gestational sac 5-6 weeks after transfer. Data in this endpoint are presented for the fresh cycle, the cryopreserved cycles, and all cycles.
Time frame: 5-6 weeks after transfer (up to approximately 15 months after start of stimulation)
Population: The mITT analysis set comprised all randomized and exposed participants. Participants were analyzed according to planned treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FE 999049 (Follitropin Delta) | Clinical Pregnancy Rate in the Fresh Cycle, the Cryopreserved Cycles and Cumulatively | Fresh cycle | 26.8 percentage of participants |
| FE 999049 (Follitropin Delta) | Clinical Pregnancy Rate in the Fresh Cycle, the Cryopreserved Cycles and Cumulatively | Cryopreserved cycles | 58.0 percentage of participants |
| FE 999049 (Follitropin Delta) | Clinical Pregnancy Rate in the Fresh Cycle, the Cryopreserved Cycles and Cumulatively | All cycles | 52.0 percentage of participants |
| Placebo | Clinical Pregnancy Rate in the Fresh Cycle, the Cryopreserved Cycles and Cumulatively | Fresh cycle | 0.0 percentage of participants |
| Placebo | Clinical Pregnancy Rate in the Fresh Cycle, the Cryopreserved Cycles and Cumulatively | Cryopreserved cycles | 0 percentage of participants |
| Placebo | Clinical Pregnancy Rate in the Fresh Cycle, the Cryopreserved Cycles and Cumulatively | All cycles | 0.0 percentage of participants |
Comparison: Clinical pregnancy rate in the fresh cyclep-value: <0.00195% CI: [19.8, 30.8]Fisher Exact
Comparison: Clinical pregnancy rate cumulativelyp-value: <0.00195% CI: [44.9, 56.3]Fisher Exact
Secondary
Echogenicity Pattern at End-of-stimulation
The distribution of participants with hypoechogenic, isoechogenic, or hyperechogenic endometrium is reported.
Time frame: At end-of-stimulation (up to 20 stimulation days)
Population: The mITT analysis set comprised all randomized and exposed participants. Participants were analyzed according to planned treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FE 999049 (Follitropin Delta) | Echogenicity Pattern at End-of-stimulation | Hypoechogenic | 68.0 percentage of participants |
| FE 999049 (Follitropin Delta) | Echogenicity Pattern at End-of-stimulation | Isoechogenic | 3.2 percentage of participants |
| FE 999049 (Follitropin Delta) | Echogenicity Pattern at End-of-stimulation | Hyperechogenic | 28.4 percentage of participants |
| FE 999049 (Follitropin Delta) | Echogenicity Pattern at End-of-stimulation | Not possible to evaluate | 0.4 percentage of participants |
| Placebo | Echogenicity Pattern at End-of-stimulation | Not possible to evaluate | 1.9 percentage of participants |
| Placebo | Echogenicity Pattern at End-of-stimulation | Hypoechogenic | 68.5 percentage of participants |
| Placebo | Echogenicity Pattern at End-of-stimulation | Hyperechogenic | 25.9 percentage of participants |
| Placebo | Echogenicity Pattern at End-of-stimulation | Isoechogenic | 3.7 percentage of participants |
p-value: 0.396Fisher Exact
Secondary
Echogenicity Pattern on Stimulation Day 5
The distribution of participants with hypoechogenic, isoechogenic, or hyperechogenic endometrium is reported
Time frame: On stimulation day 5
Population: The mITT analysis set comprised all randomized and exposed participants. Participants were analyzed according to planned treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FE 999049 (Follitropin Delta) | Echogenicity Pattern on Stimulation Day 5 | Hypoechogenic | 64.2 percentage of participants |
| FE 999049 (Follitropin Delta) | Echogenicity Pattern on Stimulation Day 5 | Isoechogenic | 6.4 percentage of participants |
| FE 999049 (Follitropin Delta) | Echogenicity Pattern on Stimulation Day 5 | Hyperechogenic | 28.7 percentage of participants |
| FE 999049 (Follitropin Delta) | Echogenicity Pattern on Stimulation Day 5 | Not possible to evaluate | 0.8 percentage of participants |
| Placebo | Echogenicity Pattern on Stimulation Day 5 | Not possible to evaluate | 3.7 percentage of participants |
| Placebo | Echogenicity Pattern on Stimulation Day 5 | Hypoechogenic | 57.4 percentage of participants |
| Placebo | Echogenicity Pattern on Stimulation Day 5 | Hyperechogenic | 33.3 percentage of participants |
| Placebo | Echogenicity Pattern on Stimulation Day 5 | Isoechogenic | 5.6 percentage of participants |
p-value: 0.19Fisher Exact
Secondary
Endometrial Thickness at End-of-stimulation
Mean endometrial thickness is reported.
Time frame: At end-of-stimulation (up to 20 stimulation days)
Population: The mITT analysis set comprised all randomized and exposed participants. Participants were analyzed according to planned treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FE 999049 (Follitropin Delta) | Endometrial Thickness at End-of-stimulation | 10.6 mm | Standard Deviation 2.5 |
| Placebo | Endometrial Thickness at End-of-stimulation | 7.8 mm | Standard Deviation 2.3 |
p-value: <0.001Wilcoxon rank sum test
Secondary
Endometrial Thickness on Stimulation Day 5
Mean endometrial thickness is reported.
Time frame: On stimulation day 5
Population: The mITT analysis set comprised all randomized and exposed participants. Participants were analyzed according to planned treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FE 999049 (Follitropin Delta) | Endometrial Thickness on Stimulation Day 5 | 8.0 mm | Standard Deviation 2.1 |
| Placebo | Endometrial Thickness on Stimulation Day 5 | 6.2 mm | Standard Deviation 1.9 |
p-value: <0.001Wilcoxon rank sum test
Secondary
Fertilization Rate
The fertilization rate was defined as the number of 2PN oocytes divided by the number of oocytes retrieved. Fertilization rate relative to oocytes retrieved has been reported.
Time frame: On day 1 after oocyte retrieval (up to 23 days after start of stimulation)
Population: The mITT analysis set comprised all randomized and exposed participants. Participants were analyzed according to planned treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FE 999049 (Follitropin Delta) | Fertilization Rate | 56.4 percentage of fertilized oocytes | Standard Deviation 23.3 |
| Placebo | Fertilization Rate | 100.0 percentage of fertilized oocytes | Standard Deviation 0 |
Secondary
Frequency and Intensity of Immune-related Adverse Events
Standardised Medical Dictionary for Regulatory Activities (MedDRA) Queries (SMQs).
Time frame: From time of signing informed consent for participation in the trial until the end-of-cycle visit in the fresh cycle (approximately 6 months)
Population: The safety analysis set comprised all randomized and exposed participants. Participants were analyzed according to actual treatment received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FE 999049 (Follitropin Delta) | Frequency and Intensity of Immune-related Adverse Events | SMQ = Anaphylactic reaction | 7 events |
| FE 999049 (Follitropin Delta) | Frequency and Intensity of Immune-related Adverse Events | SMQ = Hypersensitivity | 13 events |
| FE 999049 (Follitropin Delta) | Frequency and Intensity of Immune-related Adverse Events | SMQ = Angioedema | 2 events |
| FE 999049 (Follitropin Delta) | Frequency and Intensity of Immune-related Adverse Events | Any general and local hypersensitivity reactions | 11 events |
| FE 999049 (Follitropin Delta) | Frequency and Intensity of Immune-related Adverse Events | SMQ = Severe cutaneous adverse reactions | 3 events |
| Placebo | Frequency and Intensity of Immune-related Adverse Events | Any general and local hypersensitivity reactions | 1 events |
| Placebo | Frequency and Intensity of Immune-related Adverse Events | SMQ = Severe cutaneous adverse reactions | 0 events |
| Placebo | Frequency and Intensity of Immune-related Adverse Events | SMQ = Anaphylactic reaction | 1 events |
| Placebo | Frequency and Intensity of Immune-related Adverse Events | SMQ = Angioedema | 0 events |
| Placebo | Frequency and Intensity of Immune-related Adverse Events | SMQ = Hypersensitivity | 1 events |
Secondary
Frequency and Intensity of Injection Site Reactions (Redness, Pain, Itching, Swelling and Bruising) Assessed by the Subject During the Stimulation Period
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 comprised all randomized and exposed participants. Participants were analyzed according to actual treatment received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FE 999049 (Follitropin Delta) | Frequency and Intensity of Injection Site Reactions (Redness, Pain, Itching, Swelling and Bruising) Assessed by the Subject During the Stimulation Period | 4.2 percentage of events |
| Placebo | Frequency and Intensity of Injection Site Reactions (Redness, Pain, Itching, Swelling and Bruising) Assessed by the Subject During the Stimulation Period | 4.0 percentage of events |
Secondary
Implantation Rate in the Fresh Cycle, the Cryopreserved Cycles and Cumulatively
Defined as the number of gestational sacs 5-6 weeks after transfer divided by number of blastocysts transferred. The endpoint are presented for the fresh cycle, the cryopreserved cycles, and all cycles. One participant can contribute with a range from zero to multiple blastocysts. Data is not shown for placebo arm because no subjects underwent blastocyst transfer in the fresh cycle or cryopreserved cycles. '%' in the unit of measure refers to 'percentage'.
Time frame: 5-6 weeks after transfer (up to approximately 15 months after start of stimulation)
Population: The mITT analysis set comprised all randomized and exposed participants. Participants were analyzed according to planned treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FE 999049 (Follitropin Delta) | Implantation Rate in the Fresh Cycle, the Cryopreserved Cycles and Cumulatively | Fresh cycle | 40.4 % gestational sacs/blastocyst transfer |
| FE 999049 (Follitropin Delta) | Implantation Rate in the Fresh Cycle, the Cryopreserved Cycles and Cumulatively | Cryopreserved cycles | 40.2 % gestational sacs/blastocyst transfer |
| FE 999049 (Follitropin Delta) | Implantation Rate in the Fresh Cycle, the Cryopreserved Cycles and Cumulatively | All cycles | 40.3 % gestational sacs/blastocyst transfer |
Secondary
Intensity of AEs
The intensity of AE 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). Data in this endpoint are presented for the fresh cycle.
Time frame: From time of signing informed consent until the end-of-cycle visit in the fresh cycle (up to approximately 6 months)
Population: The safety analysis set comprised all randomized and exposed participants. Participants were analyzed according to actual treatment received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FE 999049 (Follitropin Delta) | Intensity of AEs | Severe AEs | 0.9 percentage of participants |
| FE 999049 (Follitropin Delta) | Intensity of AEs | Mild AEs | 44.5 percentage of participants |
| FE 999049 (Follitropin Delta) | Intensity of AEs | Moderate AEs | 15.4 percentage of participants |
| Placebo | Intensity of AEs | Mild AEs | 11.1 percentage of participants |
| Placebo | Intensity of AEs | Moderate AEs | 5.6 percentage of participants |
| Placebo | Intensity of AEs | Severe AEs | 0 percentage of participants |
Secondary
Intensity of Injection Site Reactions (Redness, Pain, Itching, Swelling and Bruising) Assessed by the Subject During the Stimulation Period
Assessed by the participant during the stimulation period as mild, moderate or severe.
Time frame: End-of-stimulation (up to 20 stimulation days)
Population: The safety analysis set comprised all randomized and exposed participants. Participants were analyzed according to actual treatment received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FE 999049 (Follitropin Delta) | Intensity of Injection Site Reactions (Redness, Pain, Itching, Swelling and Bruising) Assessed by the Subject During the Stimulation Period | Mild injection site reaction | 4.0 percentage of events |
| FE 999049 (Follitropin Delta) | Intensity of Injection Site Reactions (Redness, Pain, Itching, Swelling and Bruising) Assessed by the Subject During the Stimulation Period | Moderate injection site reaction | 0.1 percentage of events |
| FE 999049 (Follitropin Delta) | Intensity of Injection Site Reactions (Redness, Pain, Itching, Swelling and Bruising) Assessed by the Subject During the Stimulation Period | Severe injection site reaction | 0.0123 percentage of events |
| Placebo | Intensity of Injection Site Reactions (Redness, Pain, Itching, Swelling and Bruising) Assessed by the Subject During the Stimulation Period | Mild injection site reaction | 3.9 percentage of events |
| Placebo | Intensity of Injection Site Reactions (Redness, Pain, Itching, Swelling and Bruising) Assessed by the Subject During the Stimulation Period | Moderate injection site reaction | 0.1 percentage of events |
| Placebo | Intensity of Injection Site Reactions (Redness, Pain, Itching, Swelling and Bruising) Assessed by the Subject During the Stimulation Period | Severe injection site reaction | 0.0147 percentage of events |
Secondary
Number and Quality of Blastocysts on Day 5 After Oocyte Retrieval
Number of blastocysts (total and good-quality) on Day 5 are presented. The quality evaluation of blastocysts consisted of assessment of three parameters, as per the Gardner & Schoolcraft system: blastocyst expansion and hatching status (graded: 1-6), inner cell mass (graded: A-D) and trophectoderm (graded: A-D). A good-quality blastocyst was defined as a blastocyst of grade 3BB or higher.
Time frame: On day 5 after oocyte retrieval
Population: The mITT analysis set comprised all randomized and exposed participants. Participants were analyzed according to planned treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FE 999049 (Follitropin Delta) | Number and Quality of Blastocysts on Day 5 After Oocyte Retrieval | Number of blastocysts on day 5 | 3.7 blastocysts | Standard Deviation 4 |
| FE 999049 (Follitropin Delta) | Number and Quality of Blastocysts on Day 5 After Oocyte Retrieval | Number of good-quality blastocysts on day 5 | 2.3 blastocysts | Standard Deviation 3 |
| Placebo | Number and Quality of Blastocysts on Day 5 After Oocyte Retrieval | Number of blastocysts on day 5 | 0.0 blastocysts | Standard Deviation 0 |
| Placebo | Number and Quality of Blastocysts on Day 5 After Oocyte Retrieval | Number of good-quality blastocysts on day 5 | 0.0 blastocysts | Standard Deviation 0 |
Secondary
Number of Cryopreserved Cycles Initiated Within 12 Months From the Start of COS
The total number of cryopreserved cycles initiated are reported. Data in this endpoint are presented for the cryopreserved cycles. One participant can contribute with a range from zero to multiple blastocysts.
Time frame: Up to 12 months after start of stimulation
Population: The mITT analysis set comprised all randomized and exposed participants. Participants were analyzed according to planned treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FE 999049 (Follitropin Delta) | Number of Cryopreserved Cycles Initiated Within 12 Months From the Start of COS | Programmed cycles initiated | 92.1 Percentages of cycles |
| FE 999049 (Follitropin Delta) | Number of Cryopreserved Cycles Initiated Within 12 Months From the Start of COS | Natural cycles initiated | 7.9 Percentages of cycles |
Secondary
Number of Cryopreserved Cycles With Blastocyst Transfer
The total number of cryopreserved cycles with blastocyst transfer are reported. Data in this endpoint are presented for the cryopreserved cycles. One participant can contribute with a range from zero to multiple blastocysts.
Time frame: Up to 12 months after start of stimulation
Population: The mITT analysis set comprised all randomized and exposed participants. Participants were analyzed according to planned treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FE 999049 (Follitropin Delta) | Number of Cryopreserved Cycles With Blastocyst Transfer | Programmed cycles with transfer | 92.8 Percentages of cycles |
| FE 999049 (Follitropin Delta) | Number of Cryopreserved Cycles With Blastocyst Transfer | Natural cycles with transfer | 7.2 Percentages of cycles |
Secondary
Number of Fertilized Oocytes
An oocyte was defined as fertilized if it had 2 pronuclei (2PN) at 19h (±2h).
Time frame: On day 1 after oocyte retrieval (up to 23 days after start of stimulation)
Population: The mITT analysis set comprised all randomized and exposed participants. Participants were analyzed according to planned treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FE 999049 (Follitropin Delta) | Number of Fertilized Oocytes | 6.4 oocytes (number of fertilized oocytes) | Standard Deviation 5.7 |
| Placebo | Number of Fertilized Oocytes | 0.0 oocytes (number of fertilized oocytes) | Standard Deviation 0.1 |
Secondary
Number of Follicles at End-of-stimulation
The total number of follicles and the number of follicles per size category are reported.
Time frame: At end-of-stimulation (up to 20 stimulation days)
Population: The mITT analysis set comprised all randomized and exposed participants. Participants were analyzed according to planned treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FE 999049 (Follitropin Delta) | Number of Follicles at End-of-stimulation | Total number of follicles | 17.4 number of follicles | Standard Deviation 10 |
| FE 999049 (Follitropin Delta) | Number of Follicles at End-of-stimulation | Follicles >= 12 mm | 10.1 number of follicles | Standard Deviation 6.3 |
| FE 999049 (Follitropin Delta) | Number of Follicles at End-of-stimulation | Follicles >= 17 mm | 3.6 number of follicles | Standard Deviation 2.3 |
| Placebo | Number of Follicles at End-of-stimulation | Total number of follicles | 13.6 number of follicles | Standard Deviation 9.5 |
| Placebo | Number of Follicles at End-of-stimulation | Follicles >= 12 mm | 0.8 number of follicles | Standard Deviation 0.7 |
| Placebo | Number of Follicles at End-of-stimulation | Follicles >= 17 mm | 0.4 number of follicles | Standard Deviation 0.5 |
Secondary
Number of Follicles on Stimulation Day 5
The total number of follicles and the number of follicles per size category are reported.
Time frame: On stimulation day 5
Population: The mITT analysis set comprised all randomized and exposed participants. Participants were analyzed according to planned treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FE 999049 (Follitropin Delta) | Number of Follicles on Stimulation Day 5 | Total number of follicles | 14.8 number of follicles | Standard Deviation 8.4 |
| FE 999049 (Follitropin Delta) | Number of Follicles on Stimulation Day 5 | Follicles >= 12 mm | 1.7 number of follicles | Standard Deviation 1.8 |
| FE 999049 (Follitropin Delta) | Number of Follicles on Stimulation Day 5 | Follicles >= 17 mm | 0.0 number of follicles | Standard Deviation 0.2 |
| Placebo | Number of Follicles on Stimulation Day 5 | Total number of follicles | 12.5 number of follicles | Standard Deviation 8 |
| Placebo | Number of Follicles on Stimulation Day 5 | Follicles >= 12 mm | 0.4 number of follicles | Standard Deviation 0.6 |
| Placebo | Number of Follicles on Stimulation Day 5 | Follicles >= 17 mm | 0.0 number of follicles | Standard Deviation 0.2 |
Secondary
Number of Metaphase II Oocytes
The number of MII oocytes to oocytes retrieved for participants where all oocytes were inseminated using ICSI are presented.
Time frame: On day of oocyte retrieval (up to 22 days after start of stimulation)
Population: The mITT analysis set comprised all randomized and exposed participants. Participants were analyzed according to planned treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FE 999049 (Follitropin Delta) | Number of Metaphase II Oocytes | 8.8 number of MII oocytes | Standard Deviation 6.7 |
| Placebo | Number of Metaphase II Oocytes | 1.0 number of MII oocytes | Standard Deviation 0 |
Secondary
Number of Oocytes Retrieved
The number of oocytes retrieved was recorded at the oocyte retrieval visit.
Time frame: On day of oocyte retrieval (up to 22 days after start of stimulation)
Population: The mITT analysis set comprised all randomized and exposed participants. Participants were analyzed according to planned treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FE 999049 (Follitropin Delta) | Number of Oocytes Retrieved | 11.3 number of oocytes retrieved | Standard Deviation 8.9 |
| Placebo | Number of Oocytes Retrieved | 0.0 number of oocytes retrieved | Standard Deviation 0.1 |
Secondary
Number of Stimulation Days
Calculated by start dates and end dates.
Time frame: Up to 20 stimulation days
Population: The mITT analysis set comprised all randomized and exposed participants. Participants were analyzed according to planned treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FE 999049 (Follitropin Delta) | Number of Stimulation Days | 8.2 days | Standard Deviation 1.4 |
| Placebo | Number of Stimulation Days | 8.5 days | Standard Deviation 0.9 |
Secondary
Ongoing Implantation Rate in the Fresh Cycle, the Cryopreserved Cycles and Cumulatively
Defined as the number of intrauterine viable fetuses 8-9 weeks after transfer divided by number of blastocysts transferred. Data in this endpoint are presented for the fresh cycle, the cryopreserved cycles, and all cycles. One participant can contribute with a range from zero to multiple blastocysts. Data is not shown for placebo arm because no subjects underwent blastocyst transfer in the fresh cycle or cryopreserved cycles. '%' in the unit of measure refers to 'percentage'.
Time frame: 8-9 weeks after transfer (up to approximately 16 months after start of stimulation)
Population: The mITT analysis set comprised all randomized and exposed participants. Participants were analyzed according to planned treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FE 999049 (Follitropin Delta) | Ongoing Implantation Rate in the Fresh Cycle, the Cryopreserved Cycles and Cumulatively | Fresh cycle | 32.7 % of viable fetus/blastocyst transfer |
| FE 999049 (Follitropin Delta) | Ongoing Implantation Rate in the Fresh Cycle, the Cryopreserved Cycles and Cumulatively | Cryopreserved cycles | 30.6 % of viable fetus/blastocyst transfer |
| FE 999049 (Follitropin Delta) | Ongoing Implantation Rate in the Fresh Cycle, the Cryopreserved Cycles and Cumulatively | All cycles | 31.6 % of viable fetus/blastocyst transfer |
Secondary
Ongoing Pregnancy Rate in the Fresh Cycle and in the Cryopreserved Cycles
Defined as at least one intrauterine viable fetus 8-9 weeks after transfer. Data in this endpoint are presented for the fresh cycle and the cryopreserved cycles.
Time frame: 8-9 weeks after transfer (up to approximately 16 months after start of stimulation)
Population: The mITT analysis set comprised all randomized and exposed participants. Participants were analyzed according to planned treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FE 999049 (Follitropin Delta) | Ongoing Pregnancy Rate in the Fresh Cycle and in the Cryopreserved Cycles | Fresh cycle | 22.0 percentage of participants |
| FE 999049 (Follitropin Delta) | Ongoing Pregnancy Rate in the Fresh Cycle and in the Cryopreserved Cycles | Cryopreserved cycles | 47.8 percentage of participants |
| Placebo | Ongoing Pregnancy Rate in the Fresh Cycle and in the Cryopreserved Cycles | Fresh cycle | 0.0 percentage of participants |
| Placebo | Ongoing Pregnancy Rate in the Fresh Cycle and in the Cryopreserved Cycles | Cryopreserved cycles | 0 percentage of participants |
Comparison: Ongoing Pregnancy Rate in the Fresh Cyclep-value: <0.00195% CI: [14.9, 25.7]Fisher Exact
Secondary
Oocyte Efficiency Index
Defined as the cumulative number of ongoing pregnancies per oocyte retrieved. Data in this endpoint are presented for the cryopreserved cycles. The unit of measure for this endpoint is 'cumulative ongoing pregnancies/oocyte retrieved'.
Time frame: 8-9 weeks after transfer
Population: The mITT analysis set comprised all randomized and exposed participants. Participants were analyzed according to planned treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FE 999049 (Follitropin Delta) | Oocyte Efficiency Index | 4.5 ongoing pregnancies/oocyte retrieved | Standard Deviation 6.4 |
| Placebo | Oocyte Efficiency Index | 0.0 ongoing pregnancies/oocyte retrieved | Standard Deviation 0 |
Secondary
Oocyte Utilization Rate
Defined as the number of blastocysts transferred or cryopreserved divided by the number of oocytes retrieved. Data in this endpoint are presented for the cryopreserved cycles.
Time frame: On day of oocyte retrieval up to 12 months after start of COS
Population: The mITT analysis set comprised all randomized and exposed participants. Participants were analyzed according to planned treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FE 999049 (Follitropin Delta) | Oocyte Utilization Rate | 30.6 blastocysts/oocyte retrieved | Standard Deviation 21.2 |
| Placebo | Oocyte Utilization Rate | 0.0 blastocysts/oocyte retrieved | Standard Deviation 0 |
Secondary
Percentage of Blastocysts Surviving Cryopreservation
Data in this endpoint are presented for the cryopreserved cycles. The unit is number of blastocysts with observations. One participant can contribute with a range from zero to multiple blastocysts.
Time frame: 0 hour (+0.5 hour) after thawing
Population: The mITT analysis set comprised all randomized and exposed participants. Participants were analyzed according to planned treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FE 999049 (Follitropin Delta) | Percentage of Blastocysts Surviving Cryopreservation | 98.5 percentage of blastocysts |
Secondary
Percentage of Blastocysts With Re-expansion After Cryopreservation
Data in this endpoint are presented for the cryopreserved cycles. The unit is number of blastocysts with observations. One participant can contribute with a range from zero to multiple blastocysts.
Time frame: 2.5 hour (±0.5 hour) after thawing
Population: The mITT analysis set comprised all randomized and exposed participants. Participants were analyzed according to planned treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FE 999049 (Follitropin Delta) | Percentage of Blastocysts With Re-expansion After Cryopreservation | 97.2 percentage of blastocysts |
Secondary
Percentage of Participants With Adverse Events (AEs)
Any AE occurring after start of IMP and before the end-of-trial visit, or a pre-treatment AE 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. Data in this endpoint are presented for the fresh cycle.
Time frame: From time of signing informed consent until the end-of-cycle visit in the fresh cycle (approximately 6 months)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FE 999049 (Follitropin Delta) | Percentage of Participants With Adverse Events (AEs) | 49.9 percentage of participants |
| Placebo | Percentage of Participants With Adverse Events (AEs) | 13.0 percentage of participants |
Secondary
Positive Beta Human Chorionic Gonadotropin (βhCG) Rate in the Fresh Cycle, the Cryopreserved Cycles and Cumulatively
Defined as positive serum βhCG test 10-14 days after transfer. Data in this endpoint are presented for the fresh cycle, the cryopreserved cycles, and all cycles.
Time frame: 10-14 days after transfer (up to approximately 14 months after start of stimulation)
Population: The mITT analysis set comprised all randomized and exposed participants. Participants were analyzed according to planned treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FE 999049 (Follitropin Delta) | Positive Beta Human Chorionic Gonadotropin (βhCG) Rate in the Fresh Cycle, the Cryopreserved Cycles and Cumulatively | Fresh cycle | 32.1 percentage of participants |
| FE 999049 (Follitropin Delta) | Positive Beta Human Chorionic Gonadotropin (βhCG) Rate in the Fresh Cycle, the Cryopreserved Cycles and Cumulatively | Cryopreserved cycles | 65.3 percentage of participants |
| FE 999049 (Follitropin Delta) | Positive Beta Human Chorionic Gonadotropin (βhCG) Rate in the Fresh Cycle, the Cryopreserved Cycles and Cumulatively | All cycles | 58.9 percentage of participants |
| Placebo | Positive Beta Human Chorionic Gonadotropin (βhCG) Rate in the Fresh Cycle, the Cryopreserved Cycles and Cumulatively | Fresh cycle | 0.0 percentage of participants |
| Placebo | Positive Beta Human Chorionic Gonadotropin (βhCG) Rate in the Fresh Cycle, the Cryopreserved Cycles and Cumulatively | Cryopreserved cycles | 0 percentage of participants |
| Placebo | Positive Beta Human Chorionic Gonadotropin (βhCG) Rate in the Fresh Cycle, the Cryopreserved Cycles and Cumulatively | All cycles | 0.0 percentage of participants |
Comparison: Positive βhCG rate in the fresh cyclep-value: <0.00195% CI: [24.9, 36.2]Fisher Exact
Comparison: Positive βhCG rate cumulativelyp-value: <0.00195% CI: [51.9, 63]Fisher Exact
Secondary
Proportion of Cryopreserved Cycles With Multi-fetal Gestation
Defined as pregnancy with more than one fetus. Among cryopreserved cycles with ongoing pregnancy, percentage of cycles with twin pregnancies are presented. '%' in the unit of measure refers to 'percentage'.
Time frame: Up to 8-9 weeks after transfer
Population: The mITT analysis set comprised all randomized and exposed participants. Participants were analyzed according to planned treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FE 999049 (Follitropin Delta) | Proportion of Cryopreserved Cycles With Multi-fetal Gestation | 3.4 % of cycles with twin pregnancy |
Secondary
Proportion of Participants With Investigator-requested Gonadotropin Dose Adjustments
Investigator-requested decreases and increases of the gonadotropin dose.
Time frame: Stimulation Day 5
Population: The mITT analysis set comprised all randomized and exposed participants. Participants were analyzed according to planned treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FE 999049 (Follitropin Delta) | Proportion of Participants With Investigator-requested Gonadotropin Dose Adjustments | Decrease | 6.2 percentage of participants |
| FE 999049 (Follitropin Delta) | Proportion of Participants With Investigator-requested Gonadotropin Dose Adjustments | No change | 50.7 percentage of participants |
| FE 999049 (Follitropin Delta) | Proportion of Participants With Investigator-requested Gonadotropin Dose Adjustments | Increase | 43.2 percentage of participants |
| Placebo | Proportion of Participants With Investigator-requested Gonadotropin Dose Adjustments | Decrease | 0 percentage of participants |
| Placebo | Proportion of Participants With Investigator-requested Gonadotropin Dose Adjustments | No change | 13.0 percentage of participants |
| Placebo | Proportion of Participants With Investigator-requested Gonadotropin Dose Adjustments | Increase | 87.0 percentage of participants |
Secondary
Proportion of Participants With Multi-fetal Gestation in the Fresh Cycle
Defined as pregnancy with more than one fetus. Among participants with ongoing pregnancy, percentage of participants with twin pregnancies are presented. '%' in the unit of measure refers to 'percentage'.
Time frame: Up to 8-9 weeks after transfer
Population: The mITT analysis set comprised all randomized and exposed participants. Participants were analyzed according to planned treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FE 999049 (Follitropin Delta) | Proportion of Participants With Multi-fetal Gestation in the Fresh Cycle | 2.6 % of participants with twin pregnancy |
Secondary
Proportion of Participants With Technical Malfunctions of the Administration Pen
Incidences of technical malfunctions of the administration pen were recorded.
Time frame: Up to 20 stimulation days
Population: The safety analysis set comprised all randomized and exposed participants. Participants were analyzed according to actual treatment received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FE 999049 (Follitropin Delta) | Proportion of Participants With Technical Malfunctions of the Administration Pen | 0 percentage of participants |
| Placebo | Proportion of Participants With Technical Malfunctions of the Administration Pen | 0 percentage of participants |
Secondary
Proportion of Subjects Hospitalized Due to OHSS and Proportion of Subjects Undergoing Paracentesis Due to OHSS
Percentage of participants hospitalized or undergoing paracentesis due to OHSS are reported
Time frame: ≤9 days after triggering of final follicular maturation (early OHSS), >9 days after triggering of final follicular maturation until 21-28 days after last IMP dose or up to ongoing pregnancy 8-9 weeks after transfer in pregnant participants (late OHSS)
Population: The safety analysis set comprised all randomized and exposed participants. Participants were analyzed according to actual treatment received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FE 999049 (Follitropin Delta) | Proportion of Subjects Hospitalized Due to OHSS and Proportion of Subjects Undergoing Paracentesis Due to OHSS | Hospitalization | 0 percentage of participants |
| FE 999049 (Follitropin Delta) | Proportion of Subjects Hospitalized Due to OHSS and Proportion of Subjects Undergoing Paracentesis Due to OHSS | Paracentesis | 0 percentage of participants |
| Placebo | Proportion of Subjects Hospitalized Due to OHSS and Proportion of Subjects Undergoing Paracentesis Due to OHSS | Paracentesis | 0 percentage of participants |
| Placebo | Proportion of Subjects Hospitalized Due to OHSS and Proportion of Subjects Undergoing Paracentesis Due to OHSS | Hospitalization | 0 percentage of participants |
Secondary
Proportion of Subjects in the Fresh Cycle With Triggering of Final Follicular Maturation (With hCG, With GnRH Agonist, and in Total), Cycle Cancellation and Transfer Cancellation
Data in this endpoint are presented for the fresh cycle.
Time frame: Up to 5 days after oocyte retrieval (up to 27 days after start of stimulation)
Population: The mITT analysis set comprised all randomized and exposed participants. Participants were analyzed according to planned treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FE 999049 (Follitropin Delta) | Proportion of Subjects in the Fresh Cycle With Triggering of Final Follicular Maturation (With hCG, With GnRH Agonist, and in Total), Cycle Cancellation and Transfer Cancellation | Triggering drug (GnRH agonist) | 15.0 percentage of participants |
| FE 999049 (Follitropin Delta) | Proportion of Subjects in the Fresh Cycle With Triggering of Final Follicular Maturation (With hCG, With GnRH Agonist, and in Total), Cycle Cancellation and Transfer Cancellation | Cycle cancellation | 5.4 percentage of participants |
| FE 999049 (Follitropin Delta) | Proportion of Subjects in the Fresh Cycle With Triggering of Final Follicular Maturation (With hCG, With GnRH Agonist, and in Total), Cycle Cancellation and Transfer Cancellation | Triggering drug (None) | 5.4 percentage of participants |
| FE 999049 (Follitropin Delta) | Proportion of Subjects in the Fresh Cycle With Triggering of Final Follicular Maturation (With hCG, With GnRH Agonist, and in Total), Cycle Cancellation and Transfer Cancellation | Transfer cancellation | 31.5 percentage of participants |
| FE 999049 (Follitropin Delta) | Proportion of Subjects in the Fresh Cycle With Triggering of Final Follicular Maturation (With hCG, With GnRH Agonist, and in Total), Cycle Cancellation and Transfer Cancellation | Triggering drug (hCG) | 79.5 percentage of participants |
| Placebo | Proportion of Subjects in the Fresh Cycle With Triggering of Final Follicular Maturation (With hCG, With GnRH Agonist, and in Total), Cycle Cancellation and Transfer Cancellation | Transfer cancellation | 1.9 percentage of participants |
| Placebo | Proportion of Subjects in the Fresh Cycle With Triggering of Final Follicular Maturation (With hCG, With GnRH Agonist, and in Total), Cycle Cancellation and Transfer Cancellation | Triggering drug (hCG) | 1.9 percentage of participants |
| Placebo | Proportion of Subjects in the Fresh Cycle With Triggering of Final Follicular Maturation (With hCG, With GnRH Agonist, and in Total), Cycle Cancellation and Transfer Cancellation | Triggering drug (GnRH agonist) | 0.0 percentage of participants |
| Placebo | Proportion of Subjects in the Fresh Cycle With Triggering of Final Follicular Maturation (With hCG, With GnRH Agonist, and in Total), Cycle Cancellation and Transfer Cancellation | Triggering drug (None) | 98.1 percentage of participants |
| Placebo | Proportion of Subjects in the Fresh Cycle With Triggering of Final Follicular Maturation (With hCG, With GnRH Agonist, and in Total), Cycle Cancellation and Transfer Cancellation | Cycle cancellation | 98.1 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 day of oocyte retrieval (up to 22 days after start of stimulation)
Population: The mITT analysis set comprised all randomized and exposed participants. Participants were analyzed according to planned treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FE 999049 (Follitropin Delta) | Proportion of Subjects With <4, 4-7, 8-14, 15-19 and ≥20 Oocytes Retrieved | 4-7 oocytes retrieved | 23.5 percentage of participants |
| FE 999049 (Follitropin Delta) | Proportion of Subjects With <4, 4-7, 8-14, 15-19 and ≥20 Oocytes Retrieved | 15-19 oocytes retrieved | 15.2 percentage of participants |
| FE 999049 (Follitropin Delta) | Proportion of Subjects With <4, 4-7, 8-14, 15-19 and ≥20 Oocytes Retrieved | 8-14 oocytes retrieved | 33.8 percentage of participants |
| FE 999049 (Follitropin Delta) | Proportion of Subjects With <4, 4-7, 8-14, 15-19 and ≥20 Oocytes Retrieved | >=20 oocytes retrieved | 12.9 percentage of participants |
| FE 999049 (Follitropin Delta) | Proportion of Subjects With <4, 4-7, 8-14, 15-19 and ≥20 Oocytes Retrieved | <4 oocytes retrieved | 14.6 percentage of participants |
| Placebo | Proportion of Subjects With <4, 4-7, 8-14, 15-19 and ≥20 Oocytes Retrieved | >=20 oocytes retrieved | 0 percentage of participants |
| Placebo | Proportion of Subjects With <4, 4-7, 8-14, 15-19 and ≥20 Oocytes Retrieved | <4 oocytes retrieved | 100 percentage of participants |
| Placebo | Proportion of Subjects With <4, 4-7, 8-14, 15-19 and ≥20 Oocytes Retrieved | 4-7 oocytes retrieved | 0 percentage of participants |
| Placebo | Proportion of Subjects With <4, 4-7, 8-14, 15-19 and ≥20 Oocytes Retrieved | 8-14 oocytes retrieved | 0 percentage of participants |
| Placebo | Proportion of Subjects With <4, 4-7, 8-14, 15-19 and ≥20 Oocytes Retrieved | 15-19 oocytes retrieved | 0 percentage of participants |
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. Data in this endpoint are presented for the fresh cycle.
Time frame: Up to 20 stimulation days
Population: The safety analysis set comprised all randomized and exposed participants. Participants were analyzed according to actual treatment received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FE 999049 (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 | AE (including immune-related AEs) | 0 percentage of participants |
| FE 999049 (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 |
| Placebo | 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 |
| Placebo | 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 | AE (including immune-related AEs) | 0 percentage of participants |
Secondary
Proportion of Subjects With Markedly Abnormal Changes of Clinical Chemistry Parameters: Alanine Aminotransferase, Aspartate Aminotransferase, Bicarbonate, Calcium, Potassium
The table represents the percentage of participants in each group with normal baseline values and markedly abnormal end-of-stimulation or end-of-cycle visit values for alanine aminotransferase, aspartate aminotransferase, bicarbonate, calcium, potassium. Data in this endpoint are presented for the fresh cycle.
Time frame: From screening (baseline) to the end-of-cycle visit in the fresh cycle (approximately 6 months)
Population: The safety analysis set comprised all randomized and exposed participants. Participants were analyzed according to actual treatment received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FE 999049 (Follitropin Delta) | Proportion of Subjects With Markedly Abnormal Changes of Clinical Chemistry Parameters: Alanine Aminotransferase, Aspartate Aminotransferase, Bicarbonate, Calcium, Potassium | Alanine aminotransferase (End-of-stimulation visit) | 0.2 percentage of participants |
| FE 999049 (Follitropin Delta) | Proportion of Subjects With Markedly Abnormal Changes of Clinical Chemistry Parameters: Alanine Aminotransferase, Aspartate Aminotransferase, Bicarbonate, Calcium, Potassium | Aspartate aminotransferase (End-of-stimulation visit) | 0.2 percentage of participants |
| FE 999049 (Follitropin Delta) | Proportion of Subjects With Markedly Abnormal Changes of Clinical Chemistry Parameters: Alanine Aminotransferase, Aspartate Aminotransferase, Bicarbonate, Calcium, Potassium | Bicarbonate (End-of-stimulation visit) | 0.2 percentage of participants |
| FE 999049 (Follitropin Delta) | Proportion of Subjects With Markedly Abnormal Changes of Clinical Chemistry Parameters: Alanine Aminotransferase, Aspartate Aminotransferase, Bicarbonate, Calcium, Potassium | Calcium (End-of-stimulation visit) | 0.0 percentage of participants |
| FE 999049 (Follitropin Delta) | Proportion of Subjects With Markedly Abnormal Changes of Clinical Chemistry Parameters: Alanine Aminotransferase, Aspartate Aminotransferase, Bicarbonate, Calcium, Potassium | Glucose (End-of-stimulation visit) | 0.3 percentage of participants |
| FE 999049 (Follitropin Delta) | Proportion of Subjects With Markedly Abnormal Changes of Clinical Chemistry Parameters: Alanine Aminotransferase, Aspartate Aminotransferase, Bicarbonate, Calcium, Potassium | Potassium (End-of-stimulation visit) | 0.2 percentage of participants |
| FE 999049 (Follitropin Delta) | Proportion of Subjects With Markedly Abnormal Changes of Clinical Chemistry Parameters: Alanine Aminotransferase, Aspartate Aminotransferase, Bicarbonate, Calcium, Potassium | Alanine aminotransferase (End-of-cycle visit) | 0.2 percentage of participants |
| FE 999049 (Follitropin Delta) | Proportion of Subjects With Markedly Abnormal Changes of Clinical Chemistry Parameters: Alanine Aminotransferase, Aspartate Aminotransferase, Bicarbonate, Calcium, Potassium | Bicarbonate (End-of-cycle visit) | 0.2 percentage of participants |
| Placebo | Proportion of Subjects With Markedly Abnormal Changes of Clinical Chemistry Parameters: Alanine Aminotransferase, Aspartate Aminotransferase, Bicarbonate, Calcium, Potassium | Bicarbonate (End-of-cycle visit) | 0.0 percentage of participants |
| Placebo | Proportion of Subjects With Markedly Abnormal Changes of Clinical Chemistry Parameters: Alanine Aminotransferase, Aspartate Aminotransferase, Bicarbonate, Calcium, Potassium | Alanine aminotransferase (End-of-stimulation visit) | 0.0 percentage of participants |
| Placebo | Proportion of Subjects With Markedly Abnormal Changes of Clinical Chemistry Parameters: Alanine Aminotransferase, Aspartate Aminotransferase, Bicarbonate, Calcium, Potassium | Glucose (End-of-stimulation visit) | 0.0 percentage of participants |
| Placebo | Proportion of Subjects With Markedly Abnormal Changes of Clinical Chemistry Parameters: Alanine Aminotransferase, Aspartate Aminotransferase, Bicarbonate, Calcium, Potassium | Aspartate aminotransferase (End-of-stimulation visit) | 0.0 percentage of participants |
| Placebo | Proportion of Subjects With Markedly Abnormal Changes of Clinical Chemistry Parameters: Alanine Aminotransferase, Aspartate Aminotransferase, Bicarbonate, Calcium, Potassium | Alanine aminotransferase (End-of-cycle visit) | 0.0 percentage of participants |
| Placebo | Proportion of Subjects With Markedly Abnormal Changes of Clinical Chemistry Parameters: Alanine Aminotransferase, Aspartate Aminotransferase, Bicarbonate, Calcium, Potassium | Bicarbonate (End-of-stimulation visit) | 0.0 percentage of participants |
| Placebo | Proportion of Subjects With Markedly Abnormal Changes of Clinical Chemistry Parameters: Alanine Aminotransferase, Aspartate Aminotransferase, Bicarbonate, Calcium, Potassium | Potassium (End-of-stimulation visit) | 0.0 percentage of participants |
| Placebo | Proportion of Subjects With Markedly Abnormal Changes of Clinical Chemistry Parameters: Alanine Aminotransferase, Aspartate Aminotransferase, Bicarbonate, Calcium, Potassium | Calcium (End-of-stimulation visit) | 2.1 percentage of participants |
Secondary
Proportion of Subjects With Markedly Abnormal Changes of Haematology Parameters: Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Neutrophils/Leukocytes
The table represents the percentage of participants in each group with normal baseline values and markedly abnormal end-of-stimulation or end-of-cycle visit values for Leukocytes, eosinophils/leukocytes, lymphocytes/leukocytes and neutrophils/leukocytes. Data in this endpoint are presented for the fresh cycle.
Time frame: From screening (baseline) to the end-of-stimulation visit and end-of-cycle visit in the fresh cycle (approximately 6 months)
Population: The safety analysis set comprised all randomized and exposed participants. Participants were analyzed according to actual treatment received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FE 999049 (Follitropin Delta) | Proportion of Subjects With Markedly Abnormal Changes of Haematology Parameters: Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Neutrophils/Leukocytes | Leukocytes (End-of-stimulation visit) | 0.2 percentage of participants |
| FE 999049 (Follitropin Delta) | Proportion of Subjects With Markedly Abnormal Changes of Haematology Parameters: Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Neutrophils/Leukocytes | Eosinophils/leukocytes (End-of-stimulation visit) | 0.2 percentage of participants |
| FE 999049 (Follitropin Delta) | Proportion of Subjects With Markedly Abnormal Changes of Haematology Parameters: Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Neutrophils/Leukocytes | Lymphocytes/leukocytes (End-of-stimulation visit) | 0.4 percentage of participants |
| FE 999049 (Follitropin Delta) | Proportion of Subjects With Markedly Abnormal Changes of Haematology Parameters: Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Neutrophils/Leukocytes | Neutrophils/leukocytes (End-of-stimulation visit) | 0.2 percentage of participants |
| FE 999049 (Follitropin Delta) | Proportion of Subjects With Markedly Abnormal Changes of Haematology Parameters: Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Neutrophils/Leukocytes | Leukocytes (End-of-cycle visit) | 0.6 percentage of participants |
| FE 999049 (Follitropin Delta) | Proportion of Subjects With Markedly Abnormal Changes of Haematology Parameters: Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Neutrophils/Leukocytes | Eosinophils/leukocytes (End-of-cycle visit) | 0.2 percentage of participants |
| Placebo | Proportion of Subjects With Markedly Abnormal Changes of Haematology Parameters: Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Neutrophils/Leukocytes | Leukocytes (End-of-cycle visit) | 0.0 percentage of participants |
| Placebo | Proportion of Subjects With Markedly Abnormal Changes of Haematology Parameters: Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Neutrophils/Leukocytes | Leukocytes (End-of-stimulation visit) | 0.0 percentage of participants |
| Placebo | Proportion of Subjects With Markedly Abnormal Changes of Haematology Parameters: Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Neutrophils/Leukocytes | Neutrophils/leukocytes (End-of-stimulation visit) | 0.0 percentage of participants |
| Placebo | Proportion of Subjects With Markedly Abnormal Changes of Haematology Parameters: Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Neutrophils/Leukocytes | Eosinophils/leukocytes (End-of-stimulation visit) | 0.0 percentage of participants |
| Placebo | Proportion of Subjects With Markedly Abnormal Changes of Haematology Parameters: Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Neutrophils/Leukocytes | Eosinophils/leukocytes (End-of-cycle visit) | 0.0 percentage of participants |
| Placebo | Proportion of Subjects With Markedly Abnormal Changes of Haematology Parameters: Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Neutrophils/Leukocytes | Lymphocytes/leukocytes (End-of-stimulation visit) | 0.0 percentage of participants |
Secondary
Proportion of Subjects With OHSS, Overall and by Grade, and Proportion of Subjects With Moderate/Severe OHSS
Classification of grade was according to Golan's classification system, and all OHSS cases were graded as mild, moderate or severe. Data in this endpoint are presented for the fresh cycle.
Time frame: ≤9 days after triggering of final follicular maturation (early OHSS), >9 days after triggering of final follicular maturation until 21-28 days after last IMP dose or up to ongoing pregnancy 8-9 weeks after transfer in pregnant participants (late OHSS)
Population: The safety analysis set comprised all randomized and exposed participants. Participants were analyzed according to actual treatment received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FE 999049 (Follitropin Delta) | Proportion of Subjects With OHSS, Overall and by Grade, and Proportion of Subjects With Moderate/Severe OHSS | OHSS (any grade) | 2.4 percentage of participants |
| FE 999049 (Follitropin Delta) | Proportion of Subjects With OHSS, Overall and by Grade, and Proportion of Subjects With Moderate/Severe OHSS | OHSS (moderate/severe) | 1.5 percentage of participants |
| Placebo | Proportion of Subjects With OHSS, Overall and by Grade, and Proportion of Subjects With Moderate/Severe OHSS | OHSS (any grade) | 0 percentage of participants |
| Placebo | Proportion of Subjects With OHSS, Overall and by Grade, and Proportion of Subjects With Moderate/Severe OHSS | OHSS (moderate/severe) | 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. 95% Clopper-Pearson confidence interval has been reported in this endpoint.
Time frame: Up to 28 days after end of the stimulation period
Population: The safety analysis set comprised all randomized and exposed participants. Participants were analyzed according to actual treatment received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FE 999049 (Follitropin Delta) | Proportion of Subjects With Treatment-induced Anti-FSH Antibodies, Overall as Well as With Neutralizing Capacity | Treatment-induced anti-FSH antibodies (Overall) | 0.75 percentage of participants |
| FE 999049 (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 |
| Placebo | Proportion of Subjects With Treatment-induced Anti-FSH Antibodies, Overall as Well as With Neutralizing Capacity | Treatment-induced anti-FSH antibodies (Overall) | 0.00 percentage of participants |
| Placebo | 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
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 mITT analysis set comprised all randomized and exposed participants. Participants were analyzed according to planned treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FE 999049 (Follitropin Delta) | Size of Follicles at End-of-stimulation | Largest follicle (mm) | 19.8 mm | Standard Deviation 2.7 |
| FE 999049 (Follitropin Delta) | Size of Follicles at End-of-stimulation | Average size of 2 largest follicles (mm) | 18.9 mm | Standard Deviation 2.6 |
| Placebo | Size of Follicles at End-of-stimulation | Largest follicle (mm) | 14.1 mm | Standard Deviation 5.1 |
| Placebo | Size of Follicles at End-of-stimulation | Average size of 2 largest follicles (mm) | 11.5 mm | Standard Deviation 3.3 |
Secondary
Size of Follicles on Stimulation Day 5
Counted by ultrasound for the right and left ovary for each participant.
Time frame: On stimulation day 5
Population: The mITT analysis set comprised all randomized and exposed participants. Participants were analyzed according to planned treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FE 999049 (Follitropin Delta) | Size of Follicles on Stimulation Day 5 | Largest follicle (mm) | 12.4 mm | Standard Deviation 2.3 |
| FE 999049 (Follitropin Delta) | Size of Follicles on Stimulation Day 5 | Average size of 2 largest follicles (mm) | 11.8 mm | Standard Deviation 2.1 |
| Placebo | Size of Follicles on Stimulation Day 5 | Largest follicle (mm) | 10.8 mm | Standard Deviation 2.5 |
| Placebo | Size of Follicles on Stimulation Day 5 | Average size of 2 largest follicles (mm) | 9.8 mm | Standard Deviation 1.9 |
Secondary
Time From Start of COS to Ongoing Pregnancy Across the Fresh and Cryopreserved Cycles, Including Duration
Time from start of COS to ongoing pregnancy, including both the fresh and cryopreserved cycles. In the placebo group, no participants achieved an ongoing pregnancy either after 12 calendar months or after 12 study months.
Time frame: 8-9 weeks after transfer (up to approximately 16 months after start of stimulation)
Population: The mITT analysis set comprised all randomized and exposed participants. Participants were analyzed according to planned treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FE 999049 (Follitropin Delta) | Time From Start of COS to Ongoing Pregnancy Across the Fresh and Cryopreserved Cycles, Including Duration | Total number of days until ongoing pregnancy 12 study months | 134.7 days | Standard Deviation 87.2 |
| FE 999049 (Follitropin Delta) | Time From Start of COS to Ongoing Pregnancy Across the Fresh and Cryopreserved Cycles, Including Duration | Total number of days until ongoing pregnancy 12 calendar months | 130.1 days | Standard Deviation 77.8 |
Secondary
Time From Start of COS to Ongoing Pregnancy Across the Fresh and Cryopreserved Cycles, Measured in Number of Cycles Before Achieving Ongoing Pregnancy
Time from start of COS to ongoing pregnancy, including both the fresh and cryopreserved cycles, measured in number of cycles before achieving ongoing pregnancy. In the placebo group, no participants achieved an ongoing pregnancy either after 12 calendar months or after 12 study months.
Time frame: 8-9 weeks after transfer (up to approximately 16 months after start of stimulation)
Population: The mITT analysis set comprised all randomized and exposed participants. Participants were analyzed according to planned treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FE 999049 (Follitropin Delta) | Time From Start of COS to Ongoing Pregnancy Across the Fresh and Cryopreserved Cycles, Measured in Number of Cycles Before Achieving Ongoing Pregnancy | Number of cycles until ongoing pregnancy 12 study months | 1.8 Cycles | Standard Deviation 1 |
| FE 999049 (Follitropin Delta) | Time From Start of COS to Ongoing Pregnancy Across the Fresh and Cryopreserved Cycles, Measured in Number of Cycles Before Achieving Ongoing Pregnancy | Number of cycles until ongoing pregnancy 12 calendar months | 1.7 Cycles | Standard Deviation 1 |
Secondary
Total Gonadotropin Dose
Calculated by start dates, end dates and daily dose of IMP.
Time frame: Up to 20 stimulation days
Population: The mITT analysis set comprised all randomized and exposed participants. Participants were analyzed according to planned treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FE 999049 (Follitropin Delta) | Total Gonadotropin Dose | 131.2 microgram of dose | Standard Deviation 30.8 |
| Placebo | Total Gonadotropin Dose | 146.5 microgram of dose | Standard Deviation 20.4 |
Secondary
Vital Pregnancy Rate in the Fresh Cycle, the Cryopreserved Cycles and Cumulatively
Defined at least one intrauterine gestational sac with fetal heart beat 5-6 weeks after transfer. Data in this endpoint are presented for the fresh cycle, the cryopreserved cycles, and all cycles.
Time frame: 5-6 weeks after transfer (up to approximately 15 months after start of stimulation)
Population: The mITT analysis set comprised all randomized and exposed participants. Participants were analyzed according to planned treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FE 999049 (Follitropin Delta) | Vital Pregnancy Rate in the Fresh Cycle, the Cryopreserved Cycles and Cumulatively | Fresh cycle | 23.5 percentage of participants |
| FE 999049 (Follitropin Delta) | Vital Pregnancy Rate in the Fresh Cycle, the Cryopreserved Cycles and Cumulatively | Cryopreserved cycles | 49.4 percentage of participants |
| FE 999049 (Follitropin Delta) | Vital Pregnancy Rate in the Fresh Cycle, the Cryopreserved Cycles and Cumulatively | All cycles | 45.6 percentage of participants |
| Placebo | Vital Pregnancy Rate in the Fresh Cycle, the Cryopreserved Cycles and Cumulatively | Fresh cycle | 0.0 percentage of participants |
| Placebo | Vital Pregnancy Rate in the Fresh Cycle, the Cryopreserved Cycles and Cumulatively | Cryopreserved cycles | 0 percentage of participants |
| Placebo | Vital Pregnancy Rate in the Fresh Cycle, the Cryopreserved Cycles and Cumulatively | All cycles | 0.0 percentage of participants |
Comparison: Vital pregnancy rate in the fresh cyclep-value: <0.00195% CI: [16.7, 27.2]Fisher Exact
Comparison: Vital pregnancy rate cumulativelyp-value: <0.00195% CI: [38.5, 49.9]Fisher Exact