Skip to main content
OpenTrials
Completed

NCT Number: NCT03296527

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

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

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Controlled Ovarian Simulation

Age range

20 year–40 year

Sex eligibility

Female

Study type

Interventional

Phase

Phase 3

Primary location

Beijing Obstetrics and Gynecology Hospital,Capital Medical University, Beijing, China

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

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

Exclusion criteria

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

Treatment and study plan

Follitropin alfa

Drug

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

Other names: GONAL-F

Follitropin delta

Drug

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

Other names: FE 999049, REKOVELLE

Primary outcomes

  1. Ongoing Pregnancy Rate

    Time frame: 10-11 weeks after transfer

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

Secondary outcomes

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

    Time frame: 13-15 days after transfer

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

  2. Clinical Pregnancy Rate

    Time frame: 5-6 weeks after transfer

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

  3. Vital Pregnancy Rate

    Time frame: 5-6 weeks after transfer

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

  4. Implantation Rate

    Time frame: 5-6 weeks after transfer

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

  5. Ongoing Implantation Rate

    Time frame: 10-11 weeks after transfer

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

  6. Proportion of Subjects With Extreme Ovarian Responses

    Time frame: Oocyte retrieval visit

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

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

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

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

  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

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

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

  9. Number of Follicles on Stimulation Day 6

    Time frame: On stimulation Day 6

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

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

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

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

  11. Size of Follicles on Stimulation Day 6

    Time frame: On stimulation Day 6

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

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

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

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

  13. Number of Oocytes Retrieved

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

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

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

    Time frame: On the day of oocyte retrieval

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

  15. Percentage of Metaphase II (MII) Oocytes

    Time frame: Prior to insemination

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

  16. Fertilization Rate

    Time frame: On Day 1 after oocyte retrieval

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

  17. Number and Quality of Embryos

    Time frame: On Day 3 after oocyte retrieval

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

  18. Circulating Concentrations of Luteinizing Hormone (LH)

    Time frame: On stimulation Day 6

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

  19. Circulating Concentrations of LH

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

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

  20. Circulating Concentrations of Estradiol

    Time frame: On stimulation Day 6

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

  21. Circulating Concentrations of Estradiol

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

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

  22. Circulating Concentrations of Progesterone

    Time frame: On stimulation Day 6

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

  23. Circulating Concentrations of Progesterone

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

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

  24. Circulating Concentrations of Inhibin A

    Time frame: On stimulation Day 6

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

  25. Circulating Concentrations of Inhibin A

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

    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.

  26. Circulating Concentrations of Inhibin B

    Time frame: On stimulation Day 6

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

  27. Circulating Concentrations of Inhibin B

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

    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.

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

    Time frame: On stimulation Day 6

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

  29. Circulating Concentrations of FSH

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

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

  30. Circulating Concentrations of FSH

    Time frame: At oocyte retrieval

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

  31. Total Gonadotropin Dose

    Time frame: Up to 20 stimulation days

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

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

    Time frame: Up to 20 stimulation days

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

  33. Number of Stimulation Days

    Time frame: Up to 20 stimulation days

    Calculated by start dates and end dates.

  34. Number of Participants With Adverse Events

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

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

  35. Intensity of Adverse Events

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

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

  36. Changes From Baseline in Clinical Chemistry Parameters: 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)

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

  37. Change From Baseline in Clinical Chemistry Parameters: 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)

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

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

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

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

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

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

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

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

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

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

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

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

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

  42. Change From Baseline in Haematology Parameter: Erythrocytes

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

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

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

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

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

  44. Change From Baseline in Haematology Parameter: Haemoglobin

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

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

  45. Change From Baseline in Haematology Parameter: Haematocrit

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

  51. Number of Immune-related Adverse Events

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

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

  52. Frequency of Injection Site Reactions

    Time frame: 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.

  53. Intensity of Injection Site Reactions

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

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

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

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

    Measured by presence of anti-FSH antibodies.

  55. Intensity of Immune-related Adverse Events

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

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

  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

    Time frame: Up to 20 stimulation days

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

  57. Proportion of Subjects With Late OHSS

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

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

  58. Proportion of Participants With Multi-fetal Gestation

    Time frame: End-of-trial

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

  59. Proportion of Participants With Early Pregnancy Losses

    Time frame: End-of-trial

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

    Frequency of early pregnancy losses are presented.

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

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

    Incidences of technical malfunctions of the administration pen were recorded.

Sponsors and collaborators

Lead sponsor

Ferring Pharmaceuticals

Industry

Registry information

Official study title

A Randomised, Controlled, Assessor-blind, Parallel Groups, Multicentre, Pan-Asian Trial Comparing the Efficacy and Safety of FE 999049 With Follitropin Alfa (GONAL-F) in Controlled Ovarian Stimulation in Women Undergoing Assisted Reproductive Technology Programme

Important dates

Study start
2017
Primary completion
2020
Study completion
2020
First posted
Sep 28, 2017
Registry last updated
Aug 24, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.