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CompletedNCT03296527Updated Aug 24, 2023Results posted

Efficacy and Safety of FE 999049 in Controlled Ovarian Stimulation in Pan-Asian Women

A Phase 3 interventional study of Follitropin alfa and Follitropin delta in Controlled Ovarian Simulation, sponsored by Ferring Pharmaceuticals. Completed at 26 sites in 4 countries. Open to female participants aged 20 Years to 40 Years. Per ClinicalTrials.gov, last updated 2023-08-24.

Sponsored by Ferring Pharmaceuticals · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
1,011
Allocation
Randomized
Ages
20 Years to 40 Years
Sex
Female
01

Study summary

To demonstrate non-inferiority of FE 999049 compared with GONAL-F with respect to ongoing pregnancy rate in women undergoing controlled ovarian stimulation.

02

Conditions studied

  • Controlled Ovarian Simulation
03

Who can participate

Ages eligible
20 Years to 40 Years
Sexes eligible
Female
Accepts healthy volunteers
No

Inclusion criteria

  • Informed Consent Documents signed prior to screening evaluations.
  • In good physical and mental health in the judgement of the investigator.
  • Asian pre-menopausal females between the ages of 20 and 40 years. The participants must be at least 20 years (including the 20th birthday) when they sign the informed consent and no more than 40 years (up to the day before the 41st birthday) at the time of randomization.
  • Infertile women diagnosed with tubal infertility, unexplained infertility, endometriosis stage I/II (defined by the revised American Society for Reproductive Medicine [ASRM] classification, 1996) or with partners diagnosed with male factor infertility, eligible for in vitro fertilisation (IVF) and/or intracytoplasmic sperm injection (ICSI) using fresh or frozen ejaculated sperm from male partner or sperm donor.
  • Infertility for at least one year before randomization for participants \<35 years or for at least 6 months for participants ≥35 years (not applicable in case of tubal or severe male factor infertility).
  • The trial cycle will be the participant's first controlled ovarian stimulation cycle for IVF/ICSI.
  • Regular menstrual cycles of 24-35 days (both inclusive), presumed to be ovulatory.
  • Hysterosalpingography, hysteroscopy, saline infusion sonography, or transvaginal ultrasound documenting a uterus consistent with expected normal function (e.g. no evidence of clinically interfering uterine fibroids defined as submucous or intramural fibroids larger than 3 cm in diameter, no polyps and no congenital structural abnormalities which are associated with a reduced chance of pregnancy) within 1 year prior to randomization.
  • Transvaginal ultrasound documenting presence and adequate visualisation of both ovaries, without evidence of significant abnormality (e.g. enlarged ovaries which would contraindicate the use of gonadotropins) and normal adnexa (e.g. no hydrosalpinx) within 1 year prior to randomization. Both ovaries must be accessible for oocyte retrieval.
  • Early follicular phase (cycle day 2-4) serum levels of FSH between 1 and 15 IU/L (results obtained within 3 months prior to randomization).
  • Negative serum Hepatitis B Surface Antigen (HBsAg), Hepatitis C Virus (HCV) and Human Immunodeficiency Virus (HIV) antibody tests within 2 years prior to randomization.
  • Body mass index (BMI) between 17.5 and 32.0 kg/m2 (both inclusive) at screening.
  • Willing to accept transfer of 1-2 embryos.

Exclusion criteria

Exclusion Criteria:

  • Known endometriosis stage III-IV (defined by the revised ASRM classification, 1996).
  • One or more follicles ≥10 mm (including cysts) observed on the transvaginal ultrasound prior to randomization on stimulation day 1 (puncture of cysts is allowed prior to randomization).
  • Known history of recurrent miscarriage (defined as three consecutive losses after ultrasound confirmation of pregnancy (excl. ectopic pregnancy) and before week 24 of pregnancy).
  • Known abnormal karyotype of participant or of her partner / sperm donor, as applicable, depending on source of sperm used for insemination in this trial.
  • Any known clinically significant systemic disease (e.g. insulin-dependent diabetes).
  • Known inherited or acquired thrombophilia disease.
  • Active arterial or venous thromboembolism or severe thrombophlebitis, or a history of these events.
  • Known porphyria.
  • Any known endocrine or metabolic abnormalities (pituitary, adrenal, pancreas, liver or kidney) with the exception of controlled thyroid function disease.
  • Known presence of anti-FSH antibodies (based on the information available in the participant's medical records; i.e. not based on the anti-FSH antibody analyses conducted in the trial).
  • Known tumours of the ovary, breast, uterus, adrenal gland, pituitary or hypothalamus which would contraindicate the use of gonadotropins.
  • Known moderate or severe impairment of renal or hepatic function.
  • Any abnormal finding of clinical chemistry, haematology or vital signs at screening which is clinically significant as judged by the investigator.
  • Currently breast-feeding.
  • Undiagnosed vaginal bleeding.
  • Known abnormal cervical cytology of clinical significance observed within three years prior to randomization (unless the clinical significance has been resolved).
  • Findings at the gynaecological examination at screening which preclude gonadotropin stimulation or are associated with a reduced chance of pregnancy, e.g. congenital uterine abnormalities or retained intrauterine device.
  • Pregnancy (negative urinary pregnancy tests must be documented at screening and prior to randomization) or contraindication to pregnancy.
  • Known current active pelvic inflammatory disease.
  • Use of fertility modifiers during the last menstrual cycle before randomization, including dehydroepiandrosterone (DHEA), metformin or cycle programming with oral contraceptives, progestogen or estrogen preparations.
  • Use of hormonal preparations (except for thyroid medication) during the last menstrual cycle before randomization.
  • Known history of chemotherapy (except for gestational conditions) or radiotherapy.
  • Current or past (1 year prior to randomization) abuse of alcohol or drugs.
  • Current (last month) intake of more than 14 units of alcohol per week.
  • Current or past (3 months prior to randomization) smoking habit of more than 10 cigarettes per day.
  • Hypersensitivity to any active ingredient or excipients in the medicinal products used in the trial.
  • Previous participation in the trial.
  • Use of any non-registered investigational drugs during the last 3 months prior to randomization.
04

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Investigator, Outcomes assessor)
Enrollment
1,011 participants (actual)

Study arms

  • Experimental
    Follitropin delta

    Recombinant follicle-stimulating hormone (rFSH). Follitropin delta for subcutaneous injection

    Drug: Follitropin delta

  • Active comparator
    Gonal-F

    rFSH. Follitropin alfa for subcutaneous injection

    Drug: Follitropin alfa

Interventions

  • DrugFollitropin alfa

    GONAL-F dose was fixed for the first 5 stimulation days.

    Also known as: GONAL-F

  • DrugFollitropin delta

    REKOVELLE (FE 999049) was fixed throughout the stimulation period.

    Also known as: FE 999049, REKOVELLE

05

What researchers measure

Primary outcomes

  1. Ongoing Pregnancy Rate

    Defined as at least one intrauterine viable fetus 10-11 weeks after transfer.

    Time frame: 10-11 weeks after transfer

Secondary outcomes

  1. Positive Beta Unit of Human Chorionic Gonadotropin (βhCG) Rate

    Defined as positive βhCG test 13-15 days after transfer.

    Time frame: 13-15 days after transfer

  2. Clinical Pregnancy Rate

    Defined as at least one gestational sac 5-6 weeks after transfer.

    Time frame: 5-6 weeks after transfer

  3. Vital Pregnancy Rate

    Defined as at least one intrauterine gestational sac with fetal heart beat 5-6 weeks after transfer.

    Time frame: 5-6 weeks after transfer

  4. Implantation Rate

    Defined as number of gestational sacs 5-6 weeks after transfer divided by number of embryos transferred.

    Time frame: 5-6 weeks after transfer

  5. Ongoing Implantation Rate

    Defined as number of intrauterine viable fetuses 10-11 weeks after transfer divided by number of embryos transferred.

    Time frame: 10-11 weeks after transfer

  6. Proportion of Subjects With Extreme Ovarian Responses

    Extreme ovarian response defined as \<4, ≥15 or ≥ 20 oocytes retrieved. Participants with cycle cancellation due to poor ovarian response are included as \<4 oocytes retrieved.

    Time frame: Oocyte retrieval visit

  7. Proportion of Subjects With Early OHSS (Including OHSS of Moderate/Severe Grade) and/or Preventive Interventions for Early OHSS

    Early OHSS was defined as OHSS with onset ≤9 days after triggering of final follicular maturation. Classification of grade was according to Golan's classification system, and all OHSS cases were graded as mild, moderate or severe.

    Time frame: Up to 9 days after triggering of final follicular maturation

  8. Proportion of Subjects With Cycle Cancellation Due to Poor or Excessive Ovarian Response or Embryo Transfer Cancellation Due to Excessive Ovarian Response / OHSS Risk

    For each participant the reason for each cycle cancellation was recorded. Embryo transfer cancellation due to adverse events, such as ovarian hyperfunction, OHSS and progesterone increased in participants with embryos available for transfer, were considered as transfer cancellations due to excessive response / OHSS risk.

    Time frame: End-of-stimulation visit (up to 20 days) or transfer visit

  9. Number of Follicles on Stimulation Day 6

    Counted by ultrasound for the right and left ovary for each participant.

    Time frame: On stimulation Day 6

  10. Number of Follicles At End-of-stimulation (up to 20 Stimulation Days)

    Counted by ultrasound for the right and left ovary for each participant.

    Time frame: At end-of-stimulation (up to 20 stimulation days)

  11. Size of Follicles on Stimulation Day 6

    Counted by ultrasound for the right and left ovary for each participant.

    Time frame: On stimulation Day 6

  12. Size of Follicles At End-of-stimulation (up to 20 Stimulation Days)

    Counted by ultrasound for the right and left ovary for each participant.

    Time frame: At end-of-stimulation (up to 20 stimulation days)

  13. Number of Oocytes Retrieved

    The number of oocytes retrieved was recorded at the oocyte retrieval visit.

    Time frame: On the day of oocyte retrieval (36 h [±2h] after triggering of final follicular maturation)

  14. Proportion of Subjects With <4, 4-7, 8-14, 15-19 and ≥20 Oocytes Retrieved

    Grouped according to the number of oocytes retrieved. Participants with cycle cancellation due to poor ovarian response are included in the \<4 oocytes group.

    Time frame: On the day of oocyte retrieval

  15. Percentage of Metaphase II (MII) Oocytes

    The percentage of MII oocytes to oocytes retrieved for participants where all oocytes were inseminated using intracytoplasmic sperm injection (ICSI) are presented.

    Time frame: Prior to insemination

  16. Fertilization Rate

    The fertilization rate was defined as the number of oocytes with 2 pronuclei divided by the number of oocytes retrieved.

    Time frame: On Day 1 after oocyte retrieval

  17. Number and Quality of Embryos

    Number of embryos (total and good-quality) on Day 3 are presented. A good-quality embryo was defined as an embryo with ≥6 blastomeres and ≤20% fragmentation, without signs of multinucleation.

    Time frame: On Day 3 after oocyte retrieval

  18. Circulating Concentrations of Luteinizing Hormone (LH)

    Blood samples for analysis of circulating concentrations of LH were drawn. The median and inter-quartile range (IQR) of LH levels on stimulation Day 6 are presented.

    Time frame: On stimulation Day 6

  19. Circulating Concentrations of LH

    Blood samples for analysis of circulating concentrations of LH were drawn. The median and IQR of LH levels at end-of-stimulation are presented.

    Time frame: End-of-stimulation (up to 20 stimulation days)

  20. Circulating Concentrations of Estradiol

    Blood samples for analysis of circulating concentrations of estradiol were drawn. The median and IQR of estradiol levels on stimulation Day 6 are presented.

    Time frame: On stimulation Day 6

  21. Circulating Concentrations of Estradiol

    Blood samples for analysis of circulating concentrations of estradiol were drawn. The median and IQR of estradiol levels at end-of-stimulation are presented.

    Time frame: End-of-stimulation (up to 20 stimulation days)

  22. Circulating Concentrations of Progesterone

    Blood samples for analysis of circulating concentrations of progesterone were drawn. The median and IQR of progesterone levels on stimulation Day 6 are presented.

    Time frame: On stimulation Day 6

  23. Circulating Concentrations of Progesterone

    Blood samples for analysis of circulating concentrations of progesterone were drawn. The median and IQR of progesterone levels at end-of-stimulation are presented.

    Time frame: End-of-stimulation (up to 20 stimulation days)

  24. Circulating Concentrations of Inhibin A

    Blood samples for analysis of circulating concentrations of inhibin A. The median and IQR of inhibin A levels on stimulation Day 6 are presented.

    Time frame: On stimulation Day 6

  25. Circulating Concentrations of Inhibin A

    Blood samples for analysis of circulating concentrations of inhibin A were drawn. The median and IQR of inhibin A levels at end-of-stimulation are presented.

    Time frame: End-of-stimulation (up to 20 stimulation days)

  26. Circulating Concentrations of Inhibin B

    Blood samples for analysis of circulating concentrations of Inhibin B were drawn. The median and IQR of inhibin B levels on stimulation Day 6 are presented.

    Time frame: On stimulation Day 6

  27. Circulating Concentrations of Inhibin B

    Blood samples for analysis of circulating concentrations of Inhibin B were drawn. The median and IQR of inhibin B levels at end-of-stimulation are presented.

    Time frame: End-of-stimulation (up to 20 stimulation days)

  28. Circulating Concentrations of Follicle-stimulating Hormone (FSH)

    Blood samples for analysis of circulating concentrations of FSH were drawn. The median and IQR of FSH levels on stimulation Day 6 are presented.

    Time frame: On stimulation Day 6

  29. Circulating Concentrations of FSH

    Blood samples for analysis of circulating concentrations of FSH were drawn. The median and IQR of FSH levels at end-of-stimulation are presented.

    Time frame: End-of-stimulation (up to 20 stimulation days)

  30. Circulating Concentrations of FSH

    Blood samples for analysis of circulating concentrations of FSH were drawn. The median and IQR of FSH levels at oocyte retrieval are presented.

    Time frame: At oocyte retrieval

  31. Total Gonadotropin Dose

    Calculated by start dates, end dates and daily dose of IMP.

    Time frame: Up to 20 stimulation days

  32. Proportion of Subjects With Investigator-requested Gonadotropin Dose Adjustments

    Investigator-requested decreases and increases of the gonadotropin dose were captured during the stimulation period.

    Time frame: Up to 20 stimulation days

  33. Number of Stimulation Days

    Calculated by start dates and end dates.

    Time frame: Up to 20 stimulation days

  34. Number of Participants With Adverse Events

    Any adverse event occurring after start of IMP and before the end-of-trial visit, or a pre-treatment adverse event or pre-existing medical condition that worsens in intensity after start of IMP and before the end-of-trial visit was considered treatment-emergent, and is presented for this endpoint.

    Time frame: From screening up to end-of-trial (up to approximately 5.5 months)

  35. Intensity of Adverse Events

    The intensity of adverse event was classified using the following 3-point scale: mild = awareness of signs or symptoms, but no disruption of usual activity; moderate = event sufficient to affect usual activity (disturbing); or severe = inability to work or perform usual activities (unacceptable).

    Time frame: From screening up to end-of-trial (up to approximately 5.5 months)

  36. Changes From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase and Gamma Glutamyl Transferase

    Blood samples were collected for the analysis of clinical chemistry parameters including: Alanine aminotransferase, Alkaline phosphatase, Aspartate aminotransferase and Gamma glutamyl transferase.

    Time frame: From screening up to end-of-trial (up to approximately 5.5 months)

  37. Change From Baseline in Clinical Chemistry Parameters: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium

    Blood samples were collected for the analysis of clinical chemistry parameters including: Bicarbonate, Blood urea nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium.

    Time frame: From screening up to end-of-trial (approximately 5.5 months)

  38. Change From Baseline in Clinical Chemistry Parameters: Albumin and Protein

    Blood samples were collected for the analysis of clinical chemistry parameters including: Albumin and Protein.

    Time frame: From screening up to end-of-trial (approximately 5.5 months)

  39. Change From Baseline in Clinical Chemistry Parameter: Lactate Dehydrogenase

    Blood samples were collected for the analysis of clinical chemistry parameter including: Lactate dehydrogenase.

    Time frame: From screening up to end-of-trial (approximately 5.5 months)

  40. Change From Baseline in Clinical Chemistry Parameter: Direct Bilirubin, Bilirubin, Creatinine, Urate

    Blood samples were collected for the analysis of clinical chemistry parameter including: Direct bilirubin, Bilirubin, Creatinine, Urate.

    Time frame: From screening up to end-of-trial (approximately 5.5 months)

  41. Proportion of Subjects With Markedly Abnormal Changes of Clinical Chemistry: Alanine Aminotransferase, Aspartate Aminotransferase, Bicarbonate, Calcium, Phosphate

    The table represents the percentage of participants in each group with normal baseline values and markedly abnormal end-of-stimulation or end-of-trial values for alanine aminotransferase, aspartate aminotransferase, bicarbonate, calcium, phosphate.

    Time frame: End-of-stimulation visit and end-of-trial visit

  42. Change From Baseline in Haematology Parameter: Erythrocytes

    Blood samples were collected for the analysis of haematology parameter including: Erythrocytes.

    Time frame: From screening up to end-of-trial (approximately 5.5 months)

  43. Change From Baseline in Haematology Parameters: Leukocytes and Platelets

    Blood samples were collected for the analysis of haematology parameters including: Leukocytes and Platelets.

    Time frame: From screening up to end-of-trial (approximately 5.5 months)

  44. Change From Baseline in Haematology Parameter: Haemoglobin

    Blood samples were collected for the analysis of haematology parameter including: Haemoglobin.

    Time frame: From screening up to end-of-trial (approximately 5.5 months)

  45. Change From Baseline in Haematology Parameter: Haematocrit

    Blood samples were collected for the analysis of haematology parameter including: Haematocrit.

    Time frame: From screening up to end-of-trial (approximately 5.5 months)

  46. Change From Baseline in Haematology Parameter: Erythrocyte Mean Corpuscular Volume

    Blood samples were collected for the analysis of haematology parameter including: Erythrocyte mean corpuscular volume.

    Time frame: From screening up to end-of-trial (approximately 5.5 months)

  47. Change From Baseline in Haematology Parameter: Erythrocyte Mean Corpuscular Haemoglobin

    Blood samples were collected for the analysis of haematology parameter including: Erythrocyte mean corpuscular haemoglobin.

    Time frame: From screening up to end-of-trial (approximately 5.5 months)

  48. Change From Baseline in Haematology Parameter: Erythrocyte Mean Corpuscular Haemoglobin Concentration

    Blood samples were collected for the analysis of haematology parameter including: Erythrocyte mean corpuscular haemoglobin concentration.

    Time frame: From screening up to end-of-trial (approximately 5.5 months)

  49. Change From Baseline in Haematology Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes and Neutrophils/Leukocytes

    Blood samples were collected for the analysis of haematology parameters including: Basophils/leukocytes, Eosinophils/leukocytes, Lymphocytes/leukocytes, Monocytes/leukocytes and Neutrophils/leukocytes.

    Time frame: From screening up to end-of-trial (approximately 5.5 months)

  50. Proportion of Subjects With Markedly Abnormal Changes of Haematology Parameters: Leukocytes, Lymphocytes/Leukocytes

    The table represents the percentage of participants in each group with normal baseline values and markedly abnormal end-of-stimulation and end-of-trial values for leukocytes and lymphocytes/leukocytes.

    Time frame: End-of-stimulation visit and end-of-trial visit

  51. Number of Immune-related Adverse Events

    Standardised Medical Dictionary for Regulatory Activities (MedDRA) Queries (SMQs).

    Time frame: From screening up to end-of-trial (approximately 5.5 months)

  52. Frequency of Injection Site Reactions

    Assessed by the participant during the stimulation period. Participants assessed the injection site reactions (redness, pain, itching, swelling and bruising) three times daily: immediately after the injection, 30 minutes after the injection and 24 hours after the injection.

    Time frame: End-of-stimulation (up to 20 stimulation days)

  53. Intensity of Injection Site Reactions

    Assessed by the participant during the stimulation period as mild, moderate or severe. Participants are tabulated according to the highest severity of their reported injection site reactions.

    Time frame: End-of-stimulation (up to 20 stimulation days)

  54. Proportion of Subjects With Treatment-induced Anti-FSH Antibodies, Overall as Well as With Neutralizing Capacity

    Measured by presence of anti-FSH antibodies.

    Time frame: Up to 28 days after end of the stimulation period

  55. Intensity of Immune-related Adverse Events

    The intensity of immune-related adverse event was classified using the following 3-point scale: mild = awareness of signs or symptoms, but no disruption of usual activity; moderate = event sufficient to affect usual activity (disturbing); or severe = inability to work or perform usual activities (unacceptable).

    Time frame: From screening up to end-of-trial (approximately 5.5 months)

  56. Proportion of Subjects With Cycle Cancellations Due to an Adverse Event, Including Immune-related Adverse Events, or Due to Technical Malfunctions of the Administration Pen

    For each participant the reason for cycle cancellation will be recorded.

    Time frame: Up to 20 stimulation days

  57. Proportion of Subjects With Late OHSS

    Late OHSS was defined as OHSS with onset \>9 days after triggering of final follicular maturation. The proportion of participants with late OHSS, and late OHSS of moderate or severe grade are presented. All OHSS cases were graded as mild, moderate, or severe.

    Time frame: After 9 days post triggering of final follicular maturation

  58. Proportion of Participants With Multi-fetal Gestation

    Defined as pregnancy with more than one fetus. Among participants with ongoing pregnancy, percentage of participants with twin pregnancies are presented.

    Time frame: End-of-trial

  59. Proportion of Participants With Early Pregnancy Losses

    Grouped according to occurrence of biochemical pregnancy, spontaneous abortion, vanishing twin or ectopic pregnancy (with and without medical/surgical intervention). Frequency of early pregnancy losses are presented.

    Time frame: End-of-trial

  60. Proportion of Participants With Technical Malfunctions of the Administration Pen

    Incidences of technical malfunctions of the administration pen were recorded.

    Time frame: End-of-stimulation (up to 20 stimulation days)

06

Results

Posted Jun 1, 2021

Participant flow

A total of 26 investigational sites randomized participants to the trial: 16 in mainland China, 4 in South Korea, 4 in Taiwan and 2 in Vietnam between Dec 2017 to Jan 2020.

Participant flow — Overall Study
MilestoneFE 000049 (Follitropin Delta)GONAL-F (Follitropin Alfa)
Started500511
Full analysis set499510
Completed465458
Not completed3553
Withdrew: Adverse event1533
Withdrew: Protocol deviation40
Withdrew: Participant withdrew consent31
Withdrew: Discontinuations due to risk of ovarian hyperstimulation syndrome [ohss]914
Withdrew: Discontinuations due to withdrawal from trial23
Withdrew: Discontinuations due to thin endometrium or poor endometrial receptivity02
Withdrew: Discontinuation due to liquid in uterus10
Withdrew: Discontinuation due to risk of human immunodeficiency virus10

Outcome measures

PrimaryOngoing Pregnancy Rate

Defined as at least one intrauterine viable fetus 10-11 weeks after transfer.

Time frame:
10-11 weeks after transfer
Reported as:
Number · percentage of participants
Ongoing Pregnancy Rate
percentage of participantsFE 000049 (Follitropin Delta)GONAL-F (Follitropin Alfa)
Ongoing Pregnancy Rate31.325.7
Statistical analysis
  • FE 000049 (Follitropin Delta) vs GONAL-F (Follitropin Alfa) · Risk difference (rd): 5.4 · 95% CI -0.2 to 11.0The difference (FE 999049 - GONAL-F) in rates was estimated and a two-sided 95% Cl was constructed using the Mantel-Haenszel method to combine results across age strata.
SecondaryPositive Beta Unit of Human Chorionic Gonadotropin (βhCG) Rate

Defined as positive βhCG test 13-15 days after transfer.

Time frame:
13-15 days after transfer
Reported as:
Number · percentage of participants
Positive Beta Unit of Human Chorionic Gonadotropin (βhCG) Rate
percentage of participantsFE 000049 (Follitropin Delta)GONAL-F (Follitropin Alfa)
Positive Beta Unit of Human Chorionic Gonadotropin (βhCG) Rate41.735.3
Statistical analysis
  • FE 000049 (Follitropin Delta) vs GONAL-F (Follitropin Alfa) · Risk difference (rd): 6.3 · 95% CI 0.3 to 12.3The difference (FE 999049 - GONAL-F) in rates was estimated and a two-sided 95% Cl was constructed using the Mantel-Haenszel method to combine results across age strata.
SecondaryClinical Pregnancy Rate

Defined as at least one gestational sac 5-6 weeks after transfer.

Time frame:
5-6 weeks after transfer
Reported as:
Number · percentage of participants
Clinical Pregnancy Rate
percentage of participantsFE 000049 (Follitropin Delta)GONAL-F (Follitropin Alfa)
Clinical Pregnancy Rate36.131.2
Statistical analysis
  • FE 000049 (Follitropin Delta) vs GONAL-F (Follitropin Alfa) · Risk difference (rd): 4.9 · 95% CI -0.9 to 10.7The difference (FE 999049 - GONAL-F) in rates was estimated and a two-sided 95% Cl was constructed using the Mantel-Haenszel method to combine results across age strata.
SecondaryVital Pregnancy Rate

Defined as at least one intrauterine gestational sac with fetal heart beat 5-6 weeks after transfer.

Time frame:
5-6 weeks after transfer
Reported as:
Number · percentage of participants
Vital Pregnancy Rate
percentage of participantsFE 000049 (Follitropin Delta)GONAL-F (Follitropin Alfa)
Vital Pregnancy Rate32.328.0
Statistical analysis
  • FE 000049 (Follitropin Delta) vs GONAL-F (Follitropin Alfa) · Risk difference (rd): 4.2 · 95% CI -1.5 to 9.8The difference (FE 999049 - GONAL-F) in rates was estimated and a two-sided 95% Cl was constructed using the Mantel-Haenszel method to combine results across age strata.
SecondaryImplantation Rate

Defined as number of gestational sacs 5-6 weeks after transfer divided by number of embryos transferred.

Time frame:
5-6 weeks after transfer
Reported as:
Number · percentage of sacs/embryos transferred
Implantation Rate
percentage of sacs/embryos transferredFE 000049 (Follitropin Delta)GONAL-F (Follitropin Alfa)
Implantation Rate35.631.3
Statistical analysis
  • FE 000049 (Follitropin Delta) vs GONAL-F (Follitropin Alfa) · Risk difference (rd): 3.9 · 95% CI -1.6 to 9.5The difference (FE 999049 - GONAL-F) in rates was estimated and a two-sided 95% Cl was constructed using the Mantel-Haenszel method to combine results across age strata.
SecondaryOngoing Implantation Rate

Defined as number of intrauterine viable fetuses 10-11 weeks after transfer divided by number of embryos transferred.

Time frame:
10-11 weeks after transfer
Reported as:
Number · % of viable fetus/embryos transferred
Ongoing Implantation Rate
% of viable fetus/embryos transferredFE 000049 (Follitropin Delta)GONAL-F (Follitropin Alfa)
Ongoing Implantation Rate30.725.8
Statistical analysis
  • FE 000049 (Follitropin Delta) vs GONAL-F (Follitropin Alfa) · Risk difference (rd): 4.4 · 95% CI -0.9 to 9.7The difference (FE 999049 - GONAL-F) in rates was estimated and a two-sided 95% Cl was constructed using the Mantel-Haenszel method to combine results across age strata.
SecondaryProportion of Subjects With Extreme Ovarian Responses

Extreme ovarian response defined as \<4, ≥15 or ≥ 20 oocytes retrieved. Participants with cycle cancellation due to poor ovarian response are included as \<4 oocytes retrieved.

Time frame:
Oocyte retrieval visit
Reported as:
Number · percentage of participants
Proportion of Subjects With Extreme Ovarian Responses
percentage of participantsFE 000049 (Follitropin Delta)GONAL-F (Follitropin Alfa)
<4 or >=15 oocytes retrieved30.335.1
<4 or >=20 oocytes retrieved17.418.9
Statistical analysis
  • FE 000049 (Follitropin Delta) vs GONAL-F (Follitropin Alfa) · Regression, Logistic · p = 0.083 (The p-value is based on the likelihood ratio test.) · Odds ratio (or): 0.79 · 95% CI 0.60 to 1.03Odds ratio is equal to FE 999049/GONAL-F.
  • FE 000049 (Follitropin Delta) vs GONAL-F (Follitropin Alfa) · Regression, Logistic · p = 0.489 (The p-value is based on the likelihood ratio test.) · Odds ratio (or): 0.89 · 95% CI 0.65 to 1.23Odds ratio is equal to FE 999049/GONAL-F.
SecondaryProportion of Subjects With Early OHSS (Including OHSS of Moderate/Severe Grade) and/or Preventive Interventions for Early OHSS

Early OHSS was defined as OHSS with onset ≤9 days after triggering of final follicular maturation. Classification of grade was according to Golan's classification system, and all OHSS cases were graded as mild, moderate or severe.

Time frame:
Up to 9 days after triggering of final follicular maturation
Reported as:
Number · percentage of participants
Proportion of Subjects With Early OHSS (Including OHSS of Moderate/Severe Grade) and/or Preventive Interventions for Early OHSS
percentage of participantsFE 000049 (Follitropin Delta)GONAL-F (Follitropin Alfa)
Early OHSS (any grade)4.06.5
Early OHSS (moderate/severe)3.64.7
Any preventive intervention1.23.5
Early OHSS (any grade) and/or preventive interventions5.09.6
Early OHSS (moderate/severe) and/or preventive interventions4.67.8
Statistical analysis
  • FE 000049 (Follitropin Delta) vs GONAL-F (Follitropin Alfa) · Regression, Logistic · p = 0.075 (The p-value is based on the likelihood ratio test.) · Odds ratio (or): 0.60 · 95% CI 0.34 to 1.06Odds ratio is equal to FE 999049/GONAL-F.
  • FE 000049 (Follitropin Delta) vs GONAL-F (Follitropin Alfa) · Regression, Logistic · p = 0.365 (The p-value is based on the likelihood ratio test.) · Odds ratio (or): 0.75 · 95% CI 0.40 to 1.40Odds ratio is equal to FE 999049/GONAL-F.
  • FE 000049 (Follitropin Delta) vs GONAL-F (Follitropin Alfa) · Regression, Logistic · p = 0.012 (The p-value is based on the likelihood ratio test.) · Odds ratio (or): 0.33 · 95% CI 0.13 to 0.83Odds ratio is equal to FE 999049/GONAL-F.
  • FE 000049 (Follitropin Delta) vs GONAL-F (Follitropin Alfa) · Regression, Logistic · p = 0.004 (The p-value is based on the likelihood ratio test.) · Odds ratio (or): 0.49 · 95% CI 0.30 to 0.81Odds ratio is equal to FE 999049/GONAL-F.
  • FE 000049 (Follitropin Delta) vs GONAL-F (Follitropin Alfa) · Regression, Logistic · p = 0.029 · Odds ratio (or): 0.56 · 95% CI 0.33 to 0.95Odds ratio is equal to FE 999049/GONAL-F.
SecondaryProportion of Subjects With Cycle Cancellation Due to Poor or Excessive Ovarian Response or Embryo Transfer Cancellation Due to Excessive Ovarian Response / OHSS Risk

For each participant the reason for each cycle cancellation was recorded. Embryo transfer cancellation due to adverse events, such as ovarian hyperfunction, OHSS and progesterone increased in participants with embryos available for transfer, were considered as transfer cancellations due to excessive response / OHSS risk.

Time frame:
End-of-stimulation visit (up to 20 days) or transfer visit
Reported as:
Number · percentage of participants
Proportion of Subjects With Cycle Cancellation Due to Poor or Excessive Ovarian Response or Embryo Transfer Cancellation Due to Excessive Ovarian Response / OHSS Risk
percentage of participantsFE 000049 (Follitropin Delta)GONAL-F (Follitropin Alfa)
Cycle cancellation due to poor response3.40.8
Cycle cancellation due to excessive response00
Transfer cancellation due to excessive ovarian response/ OHSS risk5.212.4
Cycle cancellation: poor/excessive response, or transfer cancellation excessive response/OHSS risk8.613.1
Statistical analysis
  • FE 000049 (Follitropin Delta) vs GONAL-F (Follitropin Alfa) · Regression, Logistic · p = 0.002 (The p-value is based on the likelihood ratio test.) · Odds ratio (or): 4.58 · 95% CI 1.52 to 13.74Odds ratio is equal to FE 999049/GONAL-F.
  • FE 000049 (Follitropin Delta) vs GONAL-F (Follitropin Alfa) · Regression, Logistic · p = <0.001 (The p-value is based on the likelihood ratio test.) · Odds ratio (or): 0.39 · 95% CI 0.24 to 0.62Odds ratio is equal to FE 999049/GONAL-F.
  • FE 000049 (Follitropin Delta) vs GONAL-F (Follitropin Alfa) · Regression, Logistic · p = 0.020 (The p-value is based on the likelihood ratio test.) · Odds ratio (or): 0.62 · 95% CI 0.42 to 0.93Odds ratio is equal to FE 999049/GONAL-F.
SecondaryNumber of Follicles on Stimulation Day 6

Counted by ultrasound for the right and left ovary for each participant.

Time frame:
On stimulation Day 6
Reported as:
Mean · number of follicles
Number of Follicles on Stimulation Day 6
number of folliclesFE 000049 (Follitropin Delta)GONAL-F (Follitropin Alfa)
Follicles >= 10 mm5.4 ± 3.56.4 ± 4.0
Follicles >= 12 mm2.3 ± 2.22.9 ± 2.5
Follicles >= 15 mm0.3 ± 0.70.3 ± 0.8
Follicles >= 17 mm0.1 ± 0.30.0 ± 0.2
Statistical analysis
  • FE 000049 (Follitropin Delta) vs GONAL-F (Follitropin Alfa) · van Elteren test · p = <.001 (2-sided)p-value based on van Elteren test adjusted for age stratum.
  • FE 000049 (Follitropin Delta) vs GONAL-F (Follitropin Alfa) · van Elteren test · p = <.001 (2-sided)p-value based on van Elteren test adjusted for age stratum.
  • FE 000049 (Follitropin Delta) vs GONAL-F (Follitropin Alfa) · van Elteren test · p = 0.568 (2-sided)p-value based on van Elteren test adjusted for age stratum.
  • FE 000049 (Follitropin Delta) vs GONAL-F (Follitropin Alfa) · van Elteren test · p = 0.839 (2-sided)p-value based on van Elteren test adjusted for age stratum.
SecondaryNumber of Follicles At End-of-stimulation (up to 20 Stimulation Days)

Counted by ultrasound for the right and left ovary for each participant.

Time frame:
At end-of-stimulation (up to 20 stimulation days)
Reported as:
Mean · number of follicles
Number of Follicles At End-of-stimulation (up to 20 Stimulation Days)
number of folliclesFE 000049 (Follitropin Delta)GONAL-F (Follitropin Alfa)
Follicles >= 10 mm12.4 ± 5.614.2 ± 6.6
Follicles >= 12 mm10.3 ± 4.911.9 ± 5.7
Follicles >= 15 mm6.5 ± 3.27.5 ± 3.5
Follicles >= 17 mm4.1 ± 1.84.5 ± 2.0
Statistical analysis
  • FE 000049 (Follitropin Delta) vs GONAL-F (Follitropin Alfa) · van Elteren test · p = <.001p-value based on van Elteren test adjusted for age stratum.
  • FE 000049 (Follitropin Delta) vs GONAL-F (Follitropin Alfa) · van Elteren test · p = <.001p-value based on van Elteren test adjusted for age stratum.
  • FE 000049 (Follitropin Delta) vs GONAL-F (Follitropin Alfa) · van Elteren test · p = <.001p-value based on van Elteren test adjusted for age stratum.
  • FE 000049 (Follitropin Delta) vs GONAL-F (Follitropin Alfa) · van Elteren test · p = 0.011p-value based on van Elteren test adjusted for age stratum.
SecondarySize of Follicles on Stimulation Day 6

Counted by ultrasound for the right and left ovary for each participant.

Time frame:
On stimulation Day 6
Reported as:
Mean · mm
Size of Follicles on Stimulation Day 6
mmFE 000049 (Follitropin Delta)GONAL-F (Follitropin Alfa)
Largest follicle (mm)13.1 ± 2.013.2 ± 1.8
Average follicle size (mm)11.5 ± 1.011.6 ± 1.0
Average size of 3 largest follicles (mm)12.5 ± 1.612.6 ± 1.4
Statistical analysis
  • FE 000049 (Follitropin Delta) vs GONAL-F (Follitropin Alfa) · van Elteren test · p = 0.140p-value based on van Elteren test adjusted for age stratum.
  • FE 000049 (Follitropin Delta) vs GONAL-F (Follitropin Alfa) · van Elteren test · p = 0.155p-value based on van Elteren test adjusted for age stratum.
  • FE 000049 (Follitropin Delta) vs GONAL-F (Follitropin Alfa) · van Elteren test · p = 0.159p-value based on van Elteren test adjusted for age stratum.
SecondarySize of Follicles At End-of-stimulation (up to 20 Stimulation Days)

Counted by ultrasound for the right and left ovary for each participant.

Time frame:
At end-of-stimulation (up to 20 stimulation days)
Reported as:
Mean · mm
Size of Follicles At End-of-stimulation (up to 20 Stimulation Days)
mmFE 000049 (Follitropin Delta)GONAL-F (Follitropin Alfa)
Largest follicle (mm)19.8 ± 1.919.8 ± 1.6
Average follicle size (mm)15.0 ± 1.315.1 ± 1.1
Average size of 3 largest follicles (mm)18.6 ± 1.418.7 ± 1.1
Statistical analysis
  • FE 000049 (Follitropin Delta) vs GONAL-F (Follitropin Alfa) · van Elteren test · p = 0.848p-value based on van Elteren test adjusted for age stratum.
  • FE 000049 (Follitropin Delta) vs GONAL-F (Follitropin Alfa) · van Elteren test · p = 0.629p-value based on van Elteren test adjusted for age stratum.
  • FE 000049 (Follitropin Delta) vs GONAL-F (Follitropin Alfa) · van Elteren test · p = 0.768p-value based on van Elteren test adjusted for age stratum.
SecondaryNumber of Oocytes Retrieved

The number of oocytes retrieved was recorded at the oocyte retrieval visit.

Time frame:
On the day of oocyte retrieval (36 h [±2h] after triggering of final follicular maturation)
Reported as:
Mean · oocytes retrieved
Number of Oocytes Retrieved
oocytes retrievedFE 000049 (Follitropin Delta)GONAL-F (Follitropin Alfa)
Number of Oocytes Retrieved10.0 ± 6.112.4 ± 7.3
Statistical analysis
  • FE 000049 (Follitropin Delta) vs GONAL-F (Follitropin Alfa) · van Elteren test · p = <.001p-value based on van Elteren test adjusted for age stratum.
SecondaryProportion of Subjects With <4, 4-7, 8-14, 15-19 and ≥20 Oocytes Retrieved

Grouped according to the number of oocytes retrieved. Participants with cycle cancellation due to poor ovarian response are included in the \<4 oocytes group.

Time frame:
On the day of oocyte retrieval
Reported as:
Number · percentage of participants
Proportion of Subjects With <4, 4-7, 8-14, 15-19 and ≥20 Oocytes Retrieved
percentage of participantsFE 000049 (Follitropin Delta)GONAL-F (Follitropin Alfa)
<4 (low response)11.34.7
4 -7 (moderate response)23.022.3
8-14 (targeted response)46.742.6
15-19(hyperresponse)12.916.2
>=20 (severe hyperresponse)6.114.2
SecondaryPercentage of Metaphase II (MII) Oocytes

The percentage of MII oocytes to oocytes retrieved for participants where all oocytes were inseminated using intracytoplasmic sperm injection (ICSI) are presented.

Time frame:
Prior to insemination
Reported as:
Mean · percentage of oocytes
Percentage of Metaphase II (MII) Oocytes
percentage of oocytesFE 000049 (Follitropin Delta)GONAL-F (Follitropin Alfa)
Percentage of Metaphase II (MII) Oocytes79.5 ± 17.677.8 ± 17.7
Statistical analysis
  • FE 000049 (Follitropin Delta) vs GONAL-F (Follitropin Alfa) · van Elteren test · p = 0.197p-value based on van Elteren test adjusted for age stratum.
SecondaryFertilization Rate

The fertilization rate was defined as the number of oocytes with 2 pronuclei divided by the number of oocytes retrieved.

Time frame:
On Day 1 after oocyte retrieval
Reported as:
Mean · percentage of fertilized oocytes
Fertilization Rate
percentage of fertilized oocytesFE 000049 (Follitropin Delta)GONAL-F (Follitropin Alfa)
Fertilization Rate63.5 ± 22.963.9 ± 21.0
Statistical analysis
  • FE 000049 (Follitropin Delta) vs GONAL-F (Follitropin Alfa) · van Elteren test · p = 0.790p-value based on van Elteren test adjusted for age stratum.
SecondaryNumber and Quality of Embryos

Number of embryos (total and good-quality) on Day 3 are presented. A good-quality embryo was defined as an embryo with ≥6 blastomeres and ≤20% fragmentation, without signs of multinucleation.

Time frame:
On Day 3 after oocyte retrieval
Reported as:
Mean · embryos
Number and Quality of Embryos
embryosFE 000049 (Follitropin Delta)GONAL-F (Follitropin Alfa)
Number of embryos7.0 ± 4.68.7 ± 5.5
Number of good-quality embryos4.1 ± 3.65.2 ± 4.3
Statistical analysis
  • FE 000049 (Follitropin Delta) vs GONAL-F (Follitropin Alfa) · van Elteren test · p = <.001p-value based on van Elteren test adjusted for age stratum.
  • FE 000049 (Follitropin Delta) vs GONAL-F (Follitropin Alfa) · van Elteren test · p = <.001p-value based on van Elteren test adjusted for age stratum.
SecondaryCirculating Concentrations of Luteinizing Hormone (LH)

Blood samples for analysis of circulating concentrations of LH were drawn. The median and inter-quartile range (IQR) of LH levels on stimulation Day 6 are presented.

Time frame:
On stimulation Day 6
Reported as:
Median · IU/L
Circulating Concentrations of Luteinizing Hormone (LH)
IU/LFE 000049 (Follitropin Delta)GONAL-F (Follitropin Alfa)
Circulating Concentrations of Luteinizing Hormone (LH)2.6 (1.7 to 4.7)3.1 (1.9 to 6.8)
Statistical analysis
  • FE 000049 (Follitropin Delta) vs GONAL-F (Follitropin Alfa) · ANCOVA · p = <0.001 (The p-value corresponds to F-test of treatment effect.) · Mean ratio: 0.81 · 95% CI 0.74 to 0.88Mean ratio is equal to FE 999049/GONAL-F.
SecondaryCirculating Concentrations of LH

Blood samples for analysis of circulating concentrations of LH were drawn. The median and IQR of LH levels at end-of-stimulation are presented.

Time frame:
End-of-stimulation (up to 20 stimulation days)
Reported as:
Median · IU/L
Circulating Concentrations of LH
IU/LFE 000049 (Follitropin Delta)GONAL-F (Follitropin Alfa)
Circulating Concentrations of LH1.8 (1.1 to 2.9)2.0 (1.2 to 3.1)
Statistical analysis
  • FE 000049 (Follitropin Delta) vs GONAL-F (Follitropin Alfa) · ANCOVA · p = 0.018 (The p-value corresponds to F-test of treatment effect.) · Mean ratio: 0.90 · 95% CI 0.82 to 0.98The multiplicative ANCOVA model included treatment and age stratum as fixed factors.
SecondaryCirculating Concentrations of Estradiol

Blood samples for analysis of circulating concentrations of estradiol were drawn. The median and IQR of estradiol levels on stimulation Day 6 are presented.

Time frame:
On stimulation Day 6
Reported as:
Median · pmol/L
Circulating Concentrations of Estradiol
pmol/LFE 000049 (Follitropin Delta)GONAL-F (Follitropin Alfa)
Circulating Concentrations of Estradiol2240.7 (1325.8 to 3641.1)2885.9 (1729.4 to 4492.1)
Statistical analysis
  • FE 000049 (Follitropin Delta) vs GONAL-F (Follitropin Alfa) · ANCOVA · p = <0.001 (The p-value corresponds to F-test of treatment effect.) · Mean ratio: 0.77 · 95% CI 0.70 to 0.84Mean ratio is equal to FE 999049/GONAL-F.
SecondaryCirculating Concentrations of Estradiol

Blood samples for analysis of circulating concentrations of estradiol were drawn. The median and IQR of estradiol levels at end-of-stimulation are presented.

Time frame:
End-of-stimulation (up to 20 stimulation days)
Reported as:
Median · pmol/L
Circulating Concentrations of Estradiol
pmol/LFE 000049 (Follitropin Delta)GONAL-F (Follitropin Alfa)
Circulating Concentrations of Estradiol7429.3 (4786.2 to 10439.8)9055.8 (6214.2 to 12964.3)
Statistical analysis
  • FE 000049 (Follitropin Delta) vs GONAL-F (Follitropin Alfa) · ANCOVA · p = <0.001 (The p-value corresponds to F-test of treatment effect.) · Mean ratio: 0.74 · 95% CI 0.68 to 0.81Mean ratio is equal to FE 999049/GONAL-F.
SecondaryCirculating Concentrations of Progesterone

Blood samples for analysis of circulating concentrations of progesterone were drawn. The median and IQR of progesterone levels on stimulation Day 6 are presented.

Time frame:
On stimulation Day 6
Reported as:
Median · nmol/L
Circulating Concentrations of Progesterone
nmol/LFE 000049 (Follitropin Delta)GONAL-F (Follitropin Alfa)
Circulating Concentrations of Progesterone1.7 (0.8 to 2.6)1.9 (0.8 to 2.9)
Statistical analysis
  • FE 000049 (Follitropin Delta) vs GONAL-F (Follitropin Alfa) · ANCOVA · p = 0.003 (The p-value corresponds to the two-sided F-test of treatment effect.) · Mean ratio: 0.89 · 95% CI 0.82 to 0.96Mean ratio is equal to FE 999049/GONAL-F.
SecondaryCirculating Concentrations of Progesterone

Blood samples for analysis of circulating concentrations of progesterone were drawn. The median and IQR of progesterone levels at end-of-stimulation are presented.

Time frame:
End-of-stimulation (up to 20 stimulation days)
Reported as:
Median · nmol/L
Circulating Concentrations of Progesterone
nmol/LFE 000049 (Follitropin Delta)GONAL-F (Follitropin Alfa)
Circulating Concentrations of Progesterone2.4 (1.7 to 3.5)3.2 (2.2 to 4.4)
Statistical analysis
  • FE 000049 (Follitropin Delta) vs GONAL-F (Follitropin Alfa) · ANCOVA · p = <0.001 (The p-value corresponds to F-test of treatment effect.) · Mean ratio: 0.74 · 95% CI 0.68 to 0.79Mean ratio is equal to FE 999049/GONAL-F.
SecondaryCirculating Concentrations of Inhibin A

Blood samples for analysis of circulating concentrations of inhibin A. The median and IQR of inhibin A levels on stimulation Day 6 are presented.

Time frame:
On stimulation Day 6
Reported as:
Median · ng/L
Circulating Concentrations of Inhibin A
ng/LFE 000049 (Follitropin Delta)GONAL-F (Follitropin Alfa)
Circulating Concentrations of Inhibin A107.9 (61.6 to 163.5)129.1 (84.6 to 203.6)
Statistical analysis
  • FE 000049 (Follitropin Delta) vs GONAL-F (Follitropin Alfa) · ANCOVA · p = <0.001 (The p-value corresponds to F-test of treatment effect.) · Mean ratio: 0.76 · 95% CI 0.70 to 0.83The multiplicative ANCOVA model included treatment and age stratum as fixed factors.
SecondaryCirculating Concentrations of Inhibin A

Blood samples for analysis of circulating concentrations of inhibin A were drawn. The median and IQR of inhibin A levels at end-of-stimulation are presented.

Time frame:
End-of-stimulation (up to 20 stimulation days)
Reported as:
Median · ng/L
Circulating Concentrations of Inhibin A
ng/LFE 000049 (Follitropin Delta)GONAL-F (Follitropin Alfa)
Circulating Concentrations of Inhibin A361.7 (252.8 to 525.6)447.4 (307.5 to 630.9)
Statistical analysis
  • FE 000049 (Follitropin Delta) vs GONAL-F (Follitropin Alfa) · ANCOVA · p = <0.001 (The p-value corresponds to F-test of treatment effect.) · Mean ratio: 0.77 · 95% CI 0.71 to 0.83Mean ratio is equal to FE 999049/GONAL-F.
SecondaryCirculating Concentrations of Inhibin B

Blood samples for analysis of circulating concentrations of Inhibin B were drawn. The median and IQR of inhibin B levels on stimulation Day 6 are presented.

Time frame:
On stimulation Day 6
Reported as:
Median · ng/L
Circulating Concentrations of Inhibin B
ng/LFE 000049 (Follitropin Delta)GONAL-F (Follitropin Alfa)
Circulating Concentrations of Inhibin B740.0 (481.0 to 1069.0)901.0 (588.0 to 1317.5)
Statistical analysis
  • FE 000049 (Follitropin Delta) vs GONAL-F (Follitropin Alfa) · ANCOVA · p = <0.001 (The p-value corresponds to F-test of treatment effect.) · Mean ratio: 0.83 · 95% CI 0.77 to 0.89Mean ratio is equal to FE 999049/GONAL-F.
SecondaryCirculating Concentrations of Inhibin B

Blood samples for analysis of circulating concentrations of Inhibin B were drawn. The median and IQR of inhibin B levels at end-of-stimulation are presented.

Time frame:
End-of-stimulation (up to 20 stimulation days)
Reported as:
Median · ng/L
Circulating Concentrations of Inhibin B
ng/LFE 000049 (Follitropin Delta)GONAL-F (Follitropin Alfa)
Circulating Concentrations of Inhibin B1020.0 (689.0 to 1488.0)1101.0 (738.0 to 1665.0)
Statistical analysis
  • FE 000049 (Follitropin Delta) vs GONAL-F (Follitropin Alfa) · ANCOVA · p = 0.001 (The p-value corresponds to F-test of treatment effect.) · Mean ratio: 0.87 · 95% CI 0.80 to 0.95Mean ratio is equal to FE 999049/GONAL-F.
SecondaryCirculating Concentrations of Follicle-stimulating Hormone (FSH)

Blood samples for analysis of circulating concentrations of FSH were drawn. The median and IQR of FSH levels on stimulation Day 6 are presented.

Time frame:
On stimulation Day 6
Reported as:
Median · IU/L
Circulating Concentrations of Follicle-stimulating Hormone (FSH)
IU/LFE 000049 (Follitropin Delta)GONAL-F (Follitropin Alfa)
Circulating Concentrations of Follicle-stimulating Hormone (FSH)11.6 (9.5 to 14.8)11.2 (9.5 to 13.3)
Statistical analysis
  • FE 000049 (Follitropin Delta) vs GONAL-F (Follitropin Alfa) · ANCOVA · p = <0.001 (The p-value corresponds to F-test of treatment effect.) · Mean ratio: 1.08 · 95% CI 1.04 to 1.12Mean ratio is equal to FE 999049/GONAL-F.
SecondaryCirculating Concentrations of FSH

Blood samples for analysis of circulating concentrations of FSH were drawn. The median and IQR of FSH levels at end-of-stimulation are presented.

Time frame:
End-of-stimulation (up to 20 stimulation days)
Reported as:
Median · IU/L
Circulating Concentrations of FSH
IU/LFE 000049 (Follitropin Delta)GONAL-F (Follitropin Alfa)
Circulating Concentrations of FSH11.3 (9.2 to 14.4)12.2 (10.4 to 15.2)
Statistical analysis
  • FE 000049 (Follitropin Delta) vs GONAL-F (Follitropin Alfa) · ANCOVA · p = <0.001 (The p-value corresponds to F-test of treatment effect.) · Mean ratio: 0.92 · 95% CI 0.89 to 0.95Mean ratio is equal to FE 999049/GONAL-F.
SecondaryCirculating Concentrations of FSH

Blood samples for analysis of circulating concentrations of FSH were drawn. The median and IQR of FSH levels at oocyte retrieval are presented.

Time frame:
At oocyte retrieval
Reported as:
Median · IU/L
Circulating Concentrations of FSH
IU/LFE 000049 (Follitropin Delta)GONAL-F (Follitropin Alfa)
Circulating Concentrations of FSH5.6 (4.5 to 7.1)5.5 (4.4 to 6.9)
Statistical analysis
  • FE 000049 (Follitropin Delta) vs GONAL-F (Follitropin Alfa) · ANCOVA · p = 0.184 (The p-value corresponds to the two-sided F-test of treatment effect.) · Mean ratio: 1.03 · 95% CI 0.99 to 1.07Mean ratio is equal to FE 999049/GONAL-F.
SecondaryTotal Gonadotropin Dose

Calculated by start dates, end dates and daily dose of IMP.

Time frame:
Up to 20 stimulation days
Reported as:
Mean · microgram of dose
Total Gonadotropin Dose
microgram of doseFE 000049 (Follitropin Delta)GONAL-F (Follitropin Alfa)
Total Gonadotropin Dose77.5 ± 24.4109.9 ± 32.9
Statistical analysis
  • FE 000049 (Follitropin Delta) vs GONAL-F (Follitropin Alfa) · van Elteren test · p = <.001p-value is based on van Elteren test adjusted for AMH group.
SecondaryProportion of Subjects With Investigator-requested Gonadotropin Dose Adjustments

Investigator-requested decreases and increases of the gonadotropin dose were captured during the stimulation period.

Time frame:
Up to 20 stimulation days
Reported as:
Number · percentage of participants
Proportion of Subjects With Investigator-requested Gonadotropin Dose Adjustments
percentage of participantsFE 000049 (Follitropin Delta)GONAL-F (Follitropin Alfa)
Proportion of Subjects With Investigator-requested Gonadotropin Dose Adjustments57.155.3
SecondaryNumber of Stimulation Days

Calculated by start dates and end dates.

Time frame:
Up to 20 stimulation days
Reported as:
Mean · days
Number of Stimulation Days
daysFE 000049 (Follitropin Delta)GONAL-F (Follitropin Alfa)
Number of Stimulation Days9.2 ± 1.98.7 ± 1.6
Statistical analysis
  • FE 000049 (Follitropin Delta) vs GONAL-F (Follitropin Alfa) · van Elteren · p = 0.001p-value is based on van Elteren test adjusted for AMH group.
SecondaryNumber of Participants With Adverse Events

Any adverse event occurring after start of IMP and before the end-of-trial visit, or a pre-treatment adverse event or pre-existing medical condition that worsens in intensity after start of IMP and before the end-of-trial visit was considered treatment-emergent, and is presented for this endpoint.

Time frame:
From screening up to end-of-trial (up to approximately 5.5 months)
Reported as:
Number · percentage of participants
Number of Participants With Adverse Events
percentage of participantsFE 000049 (Follitropin Delta)GONAL-F (Follitropin Alfa)
Number of Participants With Adverse Events46.343.1
SecondaryIntensity of Adverse Events

The intensity of adverse event was classified using the following 3-point scale: mild = awareness of signs or symptoms, but no disruption of usual activity; moderate = event sufficient to affect usual activity (disturbing); or severe = inability to work or perform usual activities (unacceptable).

Time frame:
From screening up to end-of-trial (up to approximately 5.5 months)
Reported as:
Number · percentage of participants
Intensity of Adverse Events
percentage of participantsFE 000049 (Follitropin Delta)GONAL-F (Follitropin Alfa)
Mild adverse events40.137.8
Moderate adverse events7.45.9
Severe adverse events3.61.8
SecondaryChanges From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase and Gamma Glutamyl Transferase

Blood samples were collected for the analysis of clinical chemistry parameters including: Alanine aminotransferase, Alkaline phosphatase, Aspartate aminotransferase and Gamma glutamyl transferase.

Time frame:
From screening up to end-of-trial (up to approximately 5.5 months)
Reported as:
Mean · IU/L
Changes From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase and Gamma Glutamyl Transferase
IU/LFE 000049 (Follitropin Delta)GONAL-F (Follitropin Alfa)
Alanine aminotransferase3.9 ± 13.84.6 ± 16.7
Alkaline phosphatase-2.9 ± 8.2-2.7 ± 8.0
Aspartate aminotransferase0.7 ± 7.11.2 ± 13.0
Gamma glutamyl transferase1.1 ± 6.61.1 ± 10.2
SecondaryChange From Baseline in Clinical Chemistry Parameters: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium

Blood samples were collected for the analysis of clinical chemistry parameters including: Bicarbonate, Blood urea nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium.

Time frame:
From screening up to end-of-trial (approximately 5.5 months)
Reported as:
Mean · mmol/L
Change From Baseline in Clinical Chemistry Parameters: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium
mmol/LFE 000049 (Follitropin Delta)GONAL-F (Follitropin Alfa)
Bicarbonate-0.83 ± 2.52-0.72 ± 2.51
Blood urea nitrogen-0.27 ± 1.12-0.23 ± 1.11
Calcium-0.010 ± 0.0890.000 ± 0.081
Chloride-0.3 ± 2.3-0.3 ± 2.4
Cholesterol0.218 ± 0.5370.260 ± 0.549
Glucose-0.01 ± 0.94-0.01 ± 0.91
Phosphate0.037 ± 0.1660.023 ± 0.169
Potassium0.03 ± 0.340.04 ± 0.33
Sodium-1.8 ± 2.6-1.7 ± 2.5
SecondaryChange From Baseline in Clinical Chemistry Parameters: Albumin and Protein

Blood samples were collected for the analysis of clinical chemistry parameters including: Albumin and Protein.

Time frame:
From screening up to end-of-trial (approximately 5.5 months)
Reported as:
Mean · g/L
Change From Baseline in Clinical Chemistry Parameters: Albumin and Protein
g/LFE 000049 (Follitropin Delta)GONAL-F (Follitropin Alfa)
Albumin-2.0 ± 3.1-1.6 ± 3.0
Protein-2.3 ± 4.6-1.5 ± 4.5
SecondaryChange From Baseline in Clinical Chemistry Parameter: Lactate Dehydrogenase

Blood samples were collected for the analysis of clinical chemistry parameter including: Lactate dehydrogenase.

Time frame:
From screening up to end-of-trial (approximately 5.5 months)
Reported as:
Mean · U/L
Change From Baseline in Clinical Chemistry Parameter: Lactate Dehydrogenase
U/LFE 000049 (Follitropin Delta)GONAL-F (Follitropin Alfa)
Change From Baseline in Clinical Chemistry Parameter: Lactate Dehydrogenase-3.0 ± 17.0-0.9 ± 18.9
SecondaryChange From Baseline in Clinical Chemistry Parameter: Direct Bilirubin, Bilirubin, Creatinine, Urate

Blood samples were collected for the analysis of clinical chemistry parameter including: Direct bilirubin, Bilirubin, Creatinine, Urate.

Time frame:
From screening up to end-of-trial (approximately 5.5 months)
Reported as:
Mean · umol/L
Change From Baseline in Clinical Chemistry Parameter: Direct Bilirubin, Bilirubin, Creatinine, Urate
umol/LFE 000049 (Follitropin Delta)GONAL-F (Follitropin Alfa)
Direct bilirubin-0.3 ± 0.8-0.2 ± 0.8
Bilirubin-1.3 ± 3.6-1.0 ± 3.5
Creatinine-3.4 ± 9.0-3.5 ± 8.5
Urate-18.8 ± 54.1-17.9 ± 53.5
SecondaryProportion of Subjects With Markedly Abnormal Changes of Clinical Chemistry: Alanine Aminotransferase, Aspartate Aminotransferase, Bicarbonate, Calcium, Phosphate

The table represents the percentage of participants in each group with normal baseline values and markedly abnormal end-of-stimulation or end-of-trial values for alanine aminotransferase, aspartate aminotransferase, bicarbonate, calcium, phosphate.

Time frame:
End-of-stimulation visit and end-of-trial visit
Reported as:
Number · percentage of participants
Proportion of Subjects With Markedly Abnormal Changes of Clinical Chemistry: Alanine Aminotransferase, Aspartate Aminotransferase, Bicarbonate, Calcium, Phosphate
percentage of participantsFE 000049 (Follitropin Delta)GONAL-F (Follitropin Alfa)
Alanine aminotransferase (IU/L) (End-of-stimulation)0.20.2
Aspartate aminotransferase (IU/L) (End-of-stimulation)00.2
Phosphate (mmol/L) (End-of-stimulation)0.20.0
Alanine aminotransferase (IU/L) (End-of-trial)0.40.6
Bicarbonate (mmol/L) (End-of-trial)1.30.8
Calcium (mmol/L) (End-of-trial)00.2
SecondaryChange From Baseline in Haematology Parameter: Erythrocytes

Blood samples were collected for the analysis of haematology parameter including: Erythrocytes.

Time frame:
From screening up to end-of-trial (approximately 5.5 months)
Reported as:
Mean · 10^12 cells/L
Change From Baseline in Haematology Parameter: Erythrocytes
10^12 cells/LFE 000049 (Follitropin Delta)GONAL-F (Follitropin Alfa)
Change From Baseline in Haematology Parameter: Erythrocytes-0.13 ± 0.31-0.09 ± 0.27
SecondaryChange From Baseline in Haematology Parameters: Leukocytes and Platelets

Blood samples were collected for the analysis of haematology parameters including: Leukocytes and Platelets.

Time frame:
From screening up to end-of-trial (approximately 5.5 months)
Reported as:
Mean · 10^9 cells/L
Change From Baseline in Haematology Parameters: Leukocytes and Platelets
10^9 cells/LFE 000049 (Follitropin Delta)GONAL-F (Follitropin Alfa)
Leukocytes1.161 ± 2.2320.996 ± 2.099
Platelets19.9 ± 41.723.8 ± 40.6
SecondaryChange From Baseline in Haematology Parameter: Haemoglobin

Blood samples were collected for the analysis of haematology parameter including: Haemoglobin.

Time frame:
From screening up to end-of-trial (approximately 5.5 months)
Reported as:
Mean · g/L
Change From Baseline in Haematology Parameter: Haemoglobin
g/LFE 000049 (Follitropin Delta)GONAL-F (Follitropin Alfa)
Change From Baseline in Haematology Parameter: Haemoglobin-2.9 ± 8.9-1.7 ± 7.9
SecondaryChange From Baseline in Haematology Parameter: Haematocrit

Blood samples were collected for the analysis of haematology parameter including: Haematocrit.

Time frame:
From screening up to end-of-trial (approximately 5.5 months)
Reported as:
Mean · Ratio
Change From Baseline in Haematology Parameter: Haematocrit
RatioFE 000049 (Follitropin Delta)GONAL-F (Follitropin Alfa)
Change From Baseline in Haematology Parameter: Haematocrit-0.012 ± 0.033-0.008 ± 0.030
SecondaryChange From Baseline in Haematology Parameter: Erythrocyte Mean Corpuscular Volume

Blood samples were collected for the analysis of haematology parameter including: Erythrocyte mean corpuscular volume.

Time frame:
From screening up to end-of-trial (approximately 5.5 months)
Reported as:
Mean · Femtoliters
Change From Baseline in Haematology Parameter: Erythrocyte Mean Corpuscular Volume
FemtolitersFE 000049 (Follitropin Delta)GONAL-F (Follitropin Alfa)
Change From Baseline in Haematology Parameter: Erythrocyte Mean Corpuscular Volume0.0 ± 3.30.1 ± 3.2
SecondaryChange From Baseline in Haematology Parameter: Erythrocyte Mean Corpuscular Haemoglobin

Blood samples were collected for the analysis of haematology parameter including: Erythrocyte mean corpuscular haemoglobin.

Time frame:
From screening up to end-of-trial (approximately 5.5 months)
Reported as:
Mean · picogram
Change From Baseline in Haematology Parameter: Erythrocyte Mean Corpuscular Haemoglobin
picogramFE 000049 (Follitropin Delta)GONAL-F (Follitropin Alfa)
Change From Baseline in Haematology Parameter: Erythrocyte Mean Corpuscular Haemoglobin0.3 ± 0.90.2 ± 0.8
SecondaryChange From Baseline in Haematology Parameter: Erythrocyte Mean Corpuscular Haemoglobin Concentration

Blood samples were collected for the analysis of haematology parameter including: Erythrocyte mean corpuscular haemoglobin concentration.

Time frame:
From screening up to end-of-trial (approximately 5.5 months)
Reported as:
Mean · mmol/L
Change From Baseline in Haematology Parameter: Erythrocyte Mean Corpuscular Haemoglobin Concentration
mmol/LFE 000049 (Follitropin Delta)GONAL-F (Follitropin Alfa)
Change From Baseline in Haematology Parameter: Erythrocyte Mean Corpuscular Haemoglobin Concentration0.2 ± 0.80.1 ± 0.8
SecondaryChange From Baseline in Haematology Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes and Neutrophils/Leukocytes

Blood samples were collected for the analysis of haematology parameters including: Basophils/leukocytes, Eosinophils/leukocytes, Lymphocytes/leukocytes, Monocytes/leukocytes and Neutrophils/leukocytes.

Time frame:
From screening up to end-of-trial (approximately 5.5 months)
Reported as:
Mean · percentage
Change From Baseline in Haematology Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes and Neutrophils/Leukocytes
percentageFE 000049 (Follitropin Delta)GONAL-F (Follitropin Alfa)
Basophils/leukocytes-0.01 ± 0.370.02 ± 0.36
Eosinophils/leukocytes-0.01 ± 1.08-0.07 ± 1.04
Lymphocytes/leukocytes-2.05 ± 9.18-1.39 ± 9.16
Monocytes/leukocytes-0.16 ± 1.52-0.04 ± 1.66
Neutrophils/leukocytes2.20 ± 10.031.50 ± 9.89
SecondaryProportion of Subjects With Markedly Abnormal Changes of Haematology Parameters: Leukocytes, Lymphocytes/Leukocytes

The table represents the percentage of participants in each group with normal baseline values and markedly abnormal end-of-stimulation and end-of-trial values for leukocytes and lymphocytes/leukocytes.

Time frame:
End-of-stimulation visit and end-of-trial visit
Reported as:
Number · percentage of participants
Proportion of Subjects With Markedly Abnormal Changes of Haematology Parameters: Leukocytes, Lymphocytes/Leukocytes
percentage of participantsFE 000049 (Follitropin Delta)GONAL-F (Follitropin Alfa)
Leukocytes (10^9 cells/L) (End-of-stimulation)0.70
Lymphocytes/leukocytes (%) (End-of-stimulation)0.40.2
Leukocytes (10^9 cells/L) (End-of-trial)0.70
Lymphocytes/leukocytes (%) (End-of-trial)0.60
SecondaryNumber of Immune-related Adverse Events

Standardised Medical Dictionary for Regulatory Activities (MedDRA) Queries (SMQs).

Time frame:
From screening up to end-of-trial (approximately 5.5 months)
Reported as:
Number · events
Number of Immune-related Adverse Events
eventsFE 000049 (Follitropin Delta)GONAL-F (Follitropin Alfa)
Number of Immune-related Adverse Events00
SecondaryFrequency of Injection Site Reactions

Assessed by the participant during the stimulation period. Participants assessed the injection site reactions (redness, pain, itching, swelling and bruising) three times daily: immediately after the injection, 30 minutes after the injection and 24 hours after the injection.

Time frame:
End-of-stimulation (up to 20 stimulation days)
Reported as:
Number · percentage of participants
Frequency of Injection Site Reactions
percentage of participantsFE 000049 (Follitropin Delta)GONAL-F (Follitropin Alfa)
Frequency of Injection Site Reactions23.221.6
SecondaryIntensity of Injection Site Reactions

Assessed by the participant during the stimulation period as mild, moderate or severe. Participants are tabulated according to the highest severity of their reported injection site reactions.

Time frame:
End-of-stimulation (up to 20 stimulation days)
Reported as:
Number · percentage of participants
Intensity of Injection Site Reactions
percentage of participantsFE 000049 (Follitropin Delta)GONAL-F (Follitropin Alfa)
Mild injection site reaction21.621.2
Moderate injection site reaction1.60.4
Severe injection site reaction00
SecondaryProportion of Subjects With Treatment-induced Anti-FSH Antibodies, Overall as Well as With Neutralizing Capacity

Measured by presence of anti-FSH antibodies.

Time frame:
Up to 28 days after end of the stimulation period
Reported as:
Number · percentage of participants
Proportion of Subjects With Treatment-induced Anti-FSH Antibodies, Overall as Well as With Neutralizing Capacity
percentage of participantsFE 000049 (Follitropin Delta)GONAL-F (Follitropin Alfa)
Treatment-induced anti-FSH antibodies (Overall)1.40 (0.57 to 2.87)0.98 (0.32 to 2.27)
Treatment-induced anti-FSH antibodies with neutralizing capacity0 (NA to NA)0 (NA to NA)
SecondaryIntensity of Immune-related Adverse Events

The intensity of immune-related adverse event was classified using the following 3-point scale: mild = awareness of signs or symptoms, but no disruption of usual activity; moderate = event sufficient to affect usual activity (disturbing); or severe = inability to work or perform usual activities (unacceptable).

Time frame:
From screening up to end-of-trial (approximately 5.5 months)
Reported as:
Number · events
Intensity of Immune-related Adverse Events
eventsFE 000049 (Follitropin Delta)GONAL-F (Follitropin Alfa)
Mild00
Moderate00
Severe00
SecondaryProportion of Subjects With Cycle Cancellations Due to an Adverse Event, Including Immune-related Adverse Events, or Due to Technical Malfunctions of the Administration Pen

For each participant the reason for cycle cancellation will be recorded.

Time frame:
Up to 20 stimulation days
Reported as:
Number · percentage of participants
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
percentage of participantsFE 000049 (Follitropin Delta)GONAL-F (Follitropin Alfa)
Adverse event (including immune-related adverse events)00.2
Technical malfunctions of the administration pen00
SecondaryProportion of Subjects With Late OHSS

Late OHSS was defined as OHSS with onset \>9 days after triggering of final follicular maturation. The proportion of participants with late OHSS, and late OHSS of moderate or severe grade are presented. All OHSS cases were graded as mild, moderate, or severe.

Time frame:
After 9 days post triggering of final follicular maturation
Reported as:
Number · percentage of participants
Proportion of Subjects With Late OHSS
percentage of participantsFE 000049 (Follitropin Delta)GONAL-F (Follitropin Alfa)
Late OHSS (Any grade)4.02.0
Late OHSS (Moderate/severe)3.61.8
SecondaryProportion of Participants With Multi-fetal Gestation

Defined as pregnancy with more than one fetus. Among participants with ongoing pregnancy, percentage of participants with twin pregnancies are presented.

Time frame:
End-of-trial
Reported as:
Number · percentage of participants
Proportion of Participants With Multi-fetal Gestation
percentage of participantsFE 000049 (Follitropin Delta)GONAL-F (Follitropin Alfa)
Proportion of Participants With Multi-fetal Gestation7.79.9
SecondaryProportion of Participants With Early Pregnancy Losses

Grouped according to occurrence of biochemical pregnancy, spontaneous abortion, vanishing twin or ectopic pregnancy (with and without medical/surgical intervention). Frequency of early pregnancy losses are presented.

Time frame:
End-of-trial
Reported as:
Number · percentage of participants
Proportion of Participants With Early Pregnancy Losses
percentage of participantsFE 000049 (Follitropin Delta)GONAL-F (Follitropin Alfa)
Proportion of Participants With Early Pregnancy Losses25.027.2
SecondaryProportion of Participants With Technical Malfunctions of the Administration Pen

Incidences of technical malfunctions of the administration pen were recorded.

Time frame:
End-of-stimulation (up to 20 stimulation days)
Reported as:
Number · percentage of participants
Proportion of Participants With Technical Malfunctions of the Administration Pen
percentage of participantsFE 000049 (Follitropin Delta)GONAL-F (Follitropin Alfa)
Proportion of Participants With Technical Malfunctions of the Administration Pen0.40

Adverse events

Collected over Adverse events were recorded from screening up to end-of-trial (up to approximately 5.5 months).. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
FE 000049 (Follitropin Delta)0/499 (0%)30/499 (6%)97/499 (19.4%)
GONAL-F (Follitropin Alfa)0/510 (0%)18/510 (3.5%)94/510 (18.4%)
Most frequent serious events
Showing 10 of 13
Most frequent serious events
EventFE 000049 (Follitropin Delta)GONAL-F (Follitropin Alfa)
Ovarian hyperstimulation syndromeReproductive system and breast disorders11/4998/510
Ectopic pregnancyPregnancy, puerperium and perinatal conditions8/4991/510
Abortion threatenedPregnancy, puerperium and perinatal conditions4/4992/510
Abortion spontaneousPregnancy, puerperium and perinatal conditions3/4994/510
EnteritisGastrointestinal disorders1/4990/510
BronchitisInfections and infestations1/4990/510
Biochemical pregnancyPregnancy, puerperium and perinatal conditions1/4990/510
Hyperemesis gravidarumPregnancy, puerperium and perinatal conditions1/4990/510
Adnexal torsionReproductive system and breast disorders1/4991/510
Bartholin's abscessInfections and infestations0/4991/510
Most frequent other events
Most frequent other events
EventFE 000049 (Follitropin Delta)GONAL-F (Follitropin Alfa)
Ovarian hyperstimulation syndromeReproductive system and breast disorders29/49935/510
Pelvic discomfortReproductive system and breast disorders25/49928/510
Biochemical pregnancyPregnancy, puerperium and perinatal conditions25/49921/510
Haemorrhage in pregnancyPregnancy, puerperium and perinatal conditions25/49918/510

Baseline characteristics

The full analysis set (FAS) was defined as all randomized and exposed participants. Participants were analyzed according to randomized treatment.

Age, Continuous
Age, Continuous(years)FE 000049 (Follitropin Delta)GONAL-F (Follitropin Alfa)Total
Mean31.1 ± 3.731.2 ± 3.831.1 ± 3.7
Age, Customized
Age, Customized(years)FE 000049 (Follitropin Delta)GONAL-F (Follitropin Alfa)Total
<35394396790
35-378586171
38-40202848
Sex: Female, Male
Sex: Female, Male(Participants)FE 000049 (Follitropin Delta)GONAL-F (Follitropin Alfa)Total
Female4995101009
Male000
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)FE 000049 (Follitropin Delta)GONAL-F (Follitropin Alfa)Total
Hispanic or Latino000
Not Hispanic or Latino4995101009
Unknown or Not Reported000
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)FE 000049 (Follitropin Delta)GONAL-F (Follitropin Alfa)Total
Chinese379381760
South Korean212546
Vietnamese4951100
Taiwanese5053103
Region of Enrollment
Region of Enrollment(participants)FE 000049 (Follitropin Delta)GONAL-F (Follitropin Alfa)Total
China378381759
South Korea212546
Vietnam4951100
Taiwan5153104
Body Mass Index (BMI)
Body Mass Index (BMI)(kg/m^2)FE 000049 (Follitropin Delta)GONAL-F (Follitropin Alfa)Total
Mean21.8 ± 2.721.8 ± 2.821.8 ± 2.7
07

Study locations

26 sites
  • Beijing Obstetrics and Gynecology Hospital,Capital Medical University
    Beijing, China
  • Medical Center for Human Reproduction, Peking University Third Hospital
    Beijing, China
  • Peking University First Hospital
    Beijing, China
  • West China Second University Hospital of Sichuan University
    Chengdu, China
  • Sun Yat-sen Memorial Hospital, Sun Yat-sen University
    Guangzhou, China
  • The Sixth Affiliated Hospital of Sun Yat-sen University
    Guangzhou, China
  • The Third Affiliated Hospital of Guangzhou Medical University
    Guangzhou, China
  • The First Affiliated Hospital of An'hui Medical University
    Hefei, China
  • Jiangsu Province Hospital
    Nanjing, China
  • ShengJing Hospital of China Medical University
    Shenyang, China
  • Peking University Shenzhen Hospital
    Shenzhen, China
  • Tianjin Central Hospital of Gynaecology and Obstetrics
    Tianjin, China
  • Tianjin Medical University General Hospital
    Tianjin, China
  • Renmin Hospital of Wuhan University
    Wuhan, China
  • Tongji Hospital,Tongji Medical College, Huazhong University of Science & Technology
    Wuhan, China
  • The First Affiliated Hospital of Zhengzhou University
    Zhengzhou, China
  • Seoul National University Bundang Hospital
    Seongnam-si, Korea, Republic of
  • Asan Medical Center
    Seoul, Korea, Republic of
  • Samsung Medical Center
    Seoul, Korea, Republic of
  • Seoul National University Hospital
    Seoul, Korea, Republic of
  • Taichung Veterans General Hospital
    Taichung, Taiwan
  • National Taiwan University Hospital
    Taipei, Taiwan
  • Taipei Medical University Hospital
    Taipei, Taiwan
  • Chang Gung Memorial Hospital
    Taoyuan, Taiwan
  • National Center for Assisted Reproductive Technology
    Hanoi, Vietnam
  • My Duc Hospital
    Ho Chi Minh City, Vietnam
08

References and documents

Publications

  • Qiao J, Zhang Y, Liang X, Ho T, Huang HY, Kim SH, Goethberg M, Mannaerts B, Arce JC. A randomised controlled trial to clinically validate follitropin delta in its individualised dosing regimen for ovarian stimulation in Asian IVF/ICSI patients. Hum Reprod. 2021 Aug 18;36(9):2452-2462. doi: 10.1093/humrep/deab155. PubMed 34179971 ↗
  • Yang R, Zhang Y, Liang X, Song X, Wei Z, Liu J, Yang Y, Tan J, Zhang Q, Sun Y, Wang W, Qian W, Jin L, Wang S, Xu Y, Yang J, Goethberg M, Mannaerts B, Wu W, Zheng Z, Qiao J. Comparative clinical outcome following individualized follitropin delta dosing in Chinese women undergoing ovarian stimulation for in vitro fertilization /intracytoplasmic sperm injection. Reprod Biol Endocrinol. 2022 Oct 4;20(1):147. doi: 10.1186/s12958-022-01016-y. PubMed 36195924 ↗
  • Fernandez-Sanchez M, Fatemi H, Garcia-Velasco JA, Heiser PW, Daftary GS, Mannaerts B. Incidence and severity of ovarian hyperstimulation syndrome (OHSS) in high responders after gonadotropin-releasing hormone (GnRH) agonist trigger in "freeze-all" approach. Gynecol Endocrinol. 2023 Dec;39(1):2205952. doi: 10.1080/09513590.2023.2205952. PubMed 37156263 ↗

Study documents

  • Study protocol · Sep 27, 2018
  • Study protocol · Sep 27, 2018
  • Statistical analysis plan · Dec 8, 2017

Documents are hosted by the registry — open the source record to download them.

09

Registry details

Key details

Study ID
NCT03296527
Lead sponsor
Ferring Pharmaceuticals
Responsible party
Sponsor
First posted
Sep 28, 2017
Start date
Dec 1, 2017
Primary completion
Jan 3, 2020
Completion
Jul 26, 2020
Results posted
Jun 1, 2021
Last update
Aug 24, 2023

Study contacts

Global Clinical Compliance
study director · Ferring Pharmaceuticals

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
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