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Completed

NCT Number: NCT03738618

Recombinant FSH Investigation in the Treatment of Infertility With Assisted Reproductive Technology (ART) (RITA-2)

This trial investigates the effects of FE 999049 compared to placebo.

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Key information

Conditions

Infertility, Female Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Genital Diseases Genital Diseases, Female Infertility Urogenital Diseases

Age range

35 year–42 year

Sex eligibility

Female

Study type

Interventional

Phase

Phase 3

Primary location

Fertility Treatment Center, Tempe, Arizona, United States

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 any trial-related procedure.
  • In good physical and mental health in the judgement of the investigator.
  • Pre-menopausal women between the ages of 35 and 42 years. The participants must be at least 35 years (including the 35th birthday) when they sign the informed consent and no more than 42 years (up to the day before the 42nd birthday) at the time of randomization.
  • Body mass index (BMI) between 17.5 and 38.0 kg/m^2 (both inclusive) at screening.
  • Infertile women diagnosed with tubal infertility, unexplained infertility, endometriosis stage I/II or with partners diagnosed with male factor infertility, eligible for in vitro fertilization (IVF) and/or intracytoplasmic sperm injection (ICSI) using fresh or frozen ejaculated sperm from male partner or sperm donor.
  • Documented history of infertility for at least 6 months before randomization (not applicable in case of tubal or severe male factor infertility, or when the use of donor sperm is indicated).
  • Regular menstrual cycles of 24-35 days (both inclusive).
  • Hysterosalpingography, hysteroscopy or saline infusion sonography, documenting a uterus consistent with expected normal function (e.g. no evidence of clinically interfering uterine fibroids defined as submucous fibroids of any size or intramural fibroids larger than 3 cm in diameter, no polyps and no congenital structural abnormalities which are associated with a reduced chance of pregnancy) at screening or within 1 year prior to screening.
  • Transvaginal ultrasound documenting presence and adequate visualization of both ovaries, without evidence of significant abnormality (e.g. enlarged ovaries which would contraindicate the use of gonadotropins) and normal adnexa (e.g. no hydrosalpinx) at screening. Both ovaries must be accessible for oocyte retrieval.
  • Early follicular phase (cycle day 2-4) serum levels of FSH between 1 and 15 IU/L (results obtained within 3 months prior to randomization).
  • Negative serum Hepatitis B Surface Antigen (HBsAg), Hepatitis C Virus (HCV) and Human Immunodeficiency Virus (HIV) antibody tests at screening or within 6 months prior to screening.
  • Willing to accept the blastocyst transfer policy for the fresh cycle and the cryopreserved cycles initiated within 12 months from the start of controlled ovarian stimulation using blastocysts obtained in this trial, i.e. transfer of one blastocyst (if a good-quality blastocyst is available) or transfer of one or two blastocysts (if no good-quality blastocyst is available).

Exclusion criteria

  • More than one previous controlled ovarian stimulation cycle for IVF/ICSI.
  • Known endometriosis stage III-IV (defined by the revised ASRM classification, 2012).
  • Known history of anovulation.
  • One or more follicles greater than or equal to 10 mm (including cysts) observed on the transvaginal ultrasound prior to randomization on stimulation day 1.
  • Known history of recurrent miscarriage (defined as three consecutive losses after ultrasound confirmation of pregnancy [excluding ectopic pregnancy] and before week 24 of pregnancy).
  • Known abnormal karyotype of participant or of her partner / sperm donor, as applicable, depending on source of sperm used for insemination in this trial. In case partner sperm will be used and the sperm production is severely impaired (concentration less than 1 million/mL), normal karyotype, including no Y-chromosome microdeletion, must be documented.
  • Any known clinically significant systemic disease (e.g. insulin-dependent diabetes).
  • Known inherited or acquired thrombophilia.
  • Active arterial or venous thromboembolism or severe thrombophlebitis, or a history of these events.
  • Any known endocrine or metabolic abnormalities (pituitary, adrenal, pancreas, liver or kidney) with the exception of pharmacologically controlled sub-clinical hypothyroidism.
  • Known tumors of the ovary, breast, uterus, adrenal gland, pituitary or hypothalamus which would contraindicate the use of gonadotropins.
  • Known moderate or severe impairment of renal or hepatic function.
  • Any abnormal finding of clinical chemistry, hematology, thyroid-stimulating hormone (TSH) or prolactin, or vital signs at screening, which is judged clinically significant by the investigator.
  • Known abnormal cervical cytology of clinical significance observed within three years prior to randomization (unless the clinical significance has been resolved).
  • Findings at the gynecological examination at screening which preclude gonadotropin stimulation or are associated with a reduced chance of pregnancy, e.g. congenital uterine abnormalities or retained intrauterine device.
  • Pregnancy (negative urinary pregnancy tests must be documented at screening and prior to randomization) or contraindication to pregnancy.
  • Known current active pelvic inflammatory disease.
  • Use of fertility modifiers during the last menstrual cycle before randomization, including dehydroepiandrosterone (DHEA), metformin or cycle programming with oral contraceptives, progestogen or estrogen preparations.

Treatment and study plan

Follitropin delta

Drug

FE 999049 was administered as single daily subcutaneous injections in the abdomen at a starting dose of 15 μg daily that was fixed for the first four stimulation days. Based on ovarian response, the dose could be adjusted by 3 μg, with dose increases implemented not more frequently than once every 2 days and dose decreases implemented per investigator's judgement. The minimum daily dose was 6 μg, and the maximum daily dose was 24 μg.

Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early ovarian hyperstimulation syndrome (OHSS) with the exception of gonadotropin-releasing hormone (GnRH) agonist for triggering of final follicular maturation, was not allowed

Other names: FE 999049, REKOVELLE

Placebo

Drug

Placebo was administered as single daily subcutaneous injection dialed to the same value (dose) as FE 999049.

Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early OHSS with the exception of GnRH agonist for triggering of final follicular maturation, was not allowed.

Primary outcomes

  1. Cumulative Ongoing Pregnancy Rate After the Fresh Cycle and Cryopreserved Cycles Initiated Within 12 Months From the Start of Controlled Ovarian Stimulation (COS)

    Time frame: 8-9 weeks after transfer (up to approximately 16 months after start of stimulation)

    Defined as at least one intrauterine viable fetus 8-9 weeks after transfer. Data in this endpoint are presented for the fresh cycle and the cryopreserved cycles.

Secondary outcomes

  1. Ongoing Pregnancy Rate in the Fresh Cycle and in the Cryopreserved Cycles

    Time frame: 8-9 weeks after transfer (up to approximately 16 months after start of stimulation)

    Defined as at least one intrauterine viable fetus 8-9 weeks after transfer. Data in this endpoint are presented for the fresh cycle and the cryopreserved cycles.

  2. Time From Start of COS to Ongoing Pregnancy Across the Fresh and Cryopreserved Cycles, Including Duration

    Time frame: 8-9 weeks after transfer (up to approximately 16 months after start of stimulation)

    Time from start of COS to ongoing pregnancy, including both the fresh and cryopreserved cycles.

    In the placebo group, no participants achieved an ongoing pregnancy either after 12 calendar months or after 12 study months.

  3. Time From Start of COS to Ongoing Pregnancy Across the Fresh and Cryopreserved Cycles, Measured in Number of Cycles Before Achieving Ongoing Pregnancy

    Time frame: 8-9 weeks after transfer (up to approximately 16 months after start of stimulation)

    Time from start of COS to ongoing pregnancy, including both the fresh and cryopreserved cycles, measured in number of cycles before achieving ongoing pregnancy.

    In the placebo group, no participants achieved an ongoing pregnancy either after 12 calendar months or after 12 study months.

  4. Ongoing Implantation Rate in the Fresh Cycle, the Cryopreserved Cycles and Cumulatively

    Time frame: 8-9 weeks after transfer (up to approximately 16 months after start of stimulation)

    Defined as the number of intrauterine viable fetuses 8-9 weeks after transfer divided by number of blastocysts transferred. Data in this endpoint are presented for the fresh cycle, the cryopreserved cycles, and all cycles.

    One participant can contribute with a range from zero to multiple blastocysts.

    Data is not shown for placebo arm because no subjects underwent blastocyst transfer in the fresh cycle or cryopreserved cycles.

    '%' in the unit of measure refers to 'percentage'.

  5. Clinical Pregnancy Rate in the Fresh Cycle, the Cryopreserved Cycles and Cumulatively

    Time frame: 5-6 weeks after transfer (up to approximately 15 months after start of stimulation)

    Defined at least one gestational sac 5-6 weeks after transfer. Data in this endpoint are presented for the fresh cycle, the cryopreserved cycles, and all cycles.

  6. Vital Pregnancy Rate in the Fresh Cycle, the Cryopreserved Cycles and Cumulatively

    Time frame: 5-6 weeks after transfer (up to approximately 15 months after start of stimulation)

    Defined at least one intrauterine gestational sac with fetal heart beat 5-6 weeks after transfer. Data in this endpoint are presented for the fresh cycle, the cryopreserved cycles, and all cycles.

  7. Implantation Rate in the Fresh Cycle, the Cryopreserved Cycles and Cumulatively

    Time frame: 5-6 weeks after transfer (up to approximately 15 months after start of stimulation)

    Defined as the number of gestational sacs 5-6 weeks after transfer divided by number of blastocysts transferred. The endpoint are presented for the fresh cycle, the cryopreserved cycles, and all cycles.

    One participant can contribute with a range from zero to multiple blastocysts.

    Data is not shown for placebo arm because no subjects underwent blastocyst transfer in the fresh cycle or cryopreserved cycles.

    '%' in the unit of measure refers to 'percentage'.

  8. Positive Beta Human Chorionic Gonadotropin (βhCG) Rate in the Fresh Cycle, the Cryopreserved Cycles and Cumulatively

    Time frame: 10-14 days after transfer (up to approximately 14 months after start of stimulation)

    Defined as positive serum βhCG test 10-14 days after transfer. Data in this endpoint are presented for the fresh cycle, the cryopreserved cycles, and all cycles.

  9. Proportion of Subjects in the Fresh Cycle With Triggering of Final Follicular Maturation (With hCG, With GnRH Agonist, and in Total), Cycle Cancellation and Transfer Cancellation

    Time frame: Up to 5 days after oocyte retrieval (up to 27 days after start of stimulation)

    Data in this endpoint are presented for the fresh cycle.

  10. Number of Follicles on Stimulation Day 5

    Time frame: On stimulation day 5

    The total number of follicles and the number of follicles per size category are reported.

  11. Number of Follicles at End-of-stimulation

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

    The total number of follicles and the number of follicles per size category are reported.

  12. Size of Follicles on Stimulation Day 5

    Time frame: On stimulation day 5

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

  13. Size of Follicles at End-of-stimulation

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

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

  14. Number of Oocytes Retrieved

    Time frame: On day of oocyte retrieval (up to 22 days after start of stimulation)

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

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

    Time frame: On day of oocyte retrieval (up to 22 days after start of stimulation)

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

  16. Number of Metaphase II Oocytes

    Time frame: On day of oocyte retrieval (up to 22 days after start of stimulation)

    The number of MII oocytes to oocytes retrieved for participants where all oocytes were inseminated using ICSI are presented.

  17. Number of Fertilized Oocytes

    Time frame: On day 1 after oocyte retrieval (up to 23 days after start of stimulation)

    An oocyte was defined as fertilized if it had 2 pronuclei (2PN) at 19h (±2h).

  18. Fertilization Rate

    Time frame: On day 1 after oocyte retrieval (up to 23 days after start of stimulation)

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

    Fertilization rate relative to oocytes retrieved has been reported.

  19. Number and Quality of Blastocysts on Day 5 After Oocyte Retrieval

    Time frame: On day 5 after oocyte retrieval

    Number of blastocysts (total and good-quality) on Day 5 are presented. The quality evaluation of blastocysts consisted of assessment of three parameters, as per the Gardner & Schoolcraft system: blastocyst expansion and hatching status (graded: 1-6), inner cell mass (graded: A-D) and trophectoderm (graded: A-D). A good-quality blastocyst was defined as a blastocyst of grade 3BB or higher.

  20. Endometrial Thickness on Stimulation Day 5

    Time frame: On stimulation day 5

    Mean endometrial thickness is reported.

  21. Endometrial Thickness at End-of-stimulation

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

    Mean endometrial thickness is reported.

  22. Echogenicity Pattern on Stimulation Day 5

    Time frame: On stimulation day 5

    The distribution of participants with hypoechogenic, isoechogenic, or hyperechogenic endometrium is reported

  23. Echogenicity Pattern at End-of-stimulation

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

    The distribution of participants with hypoechogenic, isoechogenic, or hyperechogenic endometrium is reported.

  24. Oocyte Utilization Rate

    Time frame: On day of oocyte retrieval up to 12 months after start of COS

    Defined as the number of blastocysts transferred or cryopreserved divided by the number of oocytes retrieved.

    Data in this endpoint are presented for the cryopreserved cycles.

  25. Oocyte Efficiency Index

    Time frame: 8-9 weeks after transfer

    Defined as the cumulative number of ongoing pregnancies per oocyte retrieved.

    Data in this endpoint are presented for the cryopreserved cycles.

    The unit of measure for this endpoint is 'cumulative ongoing pregnancies/oocyte retrieved'.

  26. Percentage of Blastocysts Surviving Cryopreservation

    Time frame: 0 hour (+0.5 hour) after thawing

    Data in this endpoint are presented for the cryopreserved cycles.

    The unit is number of blastocysts with observations. One participant can contribute with a range from zero to multiple blastocysts.

  27. Percentage of Blastocysts With Re-expansion After Cryopreservation

    Time frame: 2.5 hour (±0.5 hour) after thawing

    Data in this endpoint are presented for the cryopreserved cycles.

    The unit is number of blastocysts with observations. One participant can contribute with a range from zero to multiple blastocysts.

  28. Number of Cryopreserved Cycles Initiated Within 12 Months From the Start of COS

    Time frame: Up to 12 months after start of stimulation

    The total number of cryopreserved cycles initiated are reported. Data in this endpoint are presented for the cryopreserved cycles.

    One participant can contribute with a range from zero to multiple blastocysts.

  29. Number of Cryopreserved Cycles With Blastocyst Transfer

    Time frame: Up to 12 months after start of stimulation

    The total number of cryopreserved cycles with blastocyst transfer are reported. Data in this endpoint are presented for the cryopreserved cycles.

    One participant can contribute with a range from zero to multiple blastocysts.

  30. Circulating Concentrations of Anti-mullerian Hormone (AMH)

    Time frame: From screening to the day of oocyte retrieval (up to 22 days after start of stimulation)

    Blood samples for analysis of circulating concentrations of AMH were drawn. The median and inter-quartile range (IQR) of AMH levels on stimulation day 1, stimulation day 5, end-of-stimulation visit and oocyte retrieval visit are presented.

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

    Time frame: From screening to the day of oocyte retrieval (up to 22 days after start of stimulation)

    Blood samples for analysis of circulating concentrations of FSH were drawn. The median and IQR of FSH levels on stimulation day 1, stimulation day 5, end-of-stimulation visit and oocyte retrieval visit are presented.

  32. Circulating Concentrations of Luteinizing Hormone (LH)

    Time frame: From screening to the day of oocyte retrieval (up to 22 days after start of stimulation)

    Blood samples for analysis of circulating concentrations of LH were drawn. The median and IQR of LH levels on stimulation day 1, stimulation day 5, end-of-stimulation visit and oocyte retrieval visit are presented.

  33. Circulating Concentrations of Estradiol

    Time frame: From screening to the day of oocyte retrieval (up to 22 days after start of stimulation)

    Blood samples for analysis of circulating concentrations of estradiol were drawn. The median and IQR of estradiol levels on stimulation day 1, stimulation day 5, end-of-stimulation visit and oocyte retrieval visit are presented.

  34. Circulating Concentrations of Progesterone

    Time frame: From screening to the day of oocyte retrieval (up to 22 days after start of stimulation)

    Blood samples for analysis of circulating concentrations of progesterone were drawn. The median and IQR of progesterone levels on stimulation day 1, stimulation day 5, end-of-stimulation visit and oocyte retrieval visit are presented.

  35. Circulating Concentrations of Inhibin A

    Time frame: From screening to the day of oocyte retrieval (up to 22 days after start of stimulation)

    Blood samples for analysis of circulating concentrations of inhibin A were drawn. The median and IQR of inhibin A levels on stimulation day 1, stimulation day 5, end-of-stimulation visit and oocyte retrieval visit are presented.

  36. Circulating Concentrations of Inhibin B

    Time frame: From screening to the day of oocyte retrieval (up to 22 days after start of stimulation)

    Blood samples for analysis of circulating concentrations of inhibin B were drawn. The median and IQR of inhibin B levels on stimulation day 1, stimulation day 5, end-of-stimulation visit and oocyte retrieval visit are presented.

  37. Total Gonadotropin Dose

    Time frame: Up to 20 stimulation days

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

  38. Number of Stimulation Days

    Time frame: Up to 20 stimulation days

    Calculated by start dates and end dates.

  39. Proportion of Participants With Investigator-requested Gonadotropin Dose Adjustments

    Time frame: Stimulation Day 5

    Investigator-requested decreases and increases of the gonadotropin dose.

  40. Percentage of Participants With Adverse Events (AEs)

    Time frame: From time of signing informed consent until the end-of-cycle visit in the fresh cycle (approximately 6 months)

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

    Data in this endpoint are presented for the fresh cycle.

  41. Intensity of AEs

    Time frame: From time of signing informed consent until the end-of-cycle visit in the fresh cycle (up to approximately 6 months)

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

    Data in this endpoint are presented for the fresh cycle.

  42. Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Albumin, Protein

    Time frame: From screening (baseline) to the end-of-cycle visit in the fresh cycle (approximately 6 months)

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

    Data in this endpoint are presented for the fresh cycle.

  43. Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase and Gamma Glutamyl Transferase

    Time frame: From screening (baseline) to the end-of-cycle visit in the fresh cycle (approximately 6 months)

    Blood samples were collected for the analysis of clinical chemistry parameters including: Alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase and gamma glutamyl transferase.

    Data in this endpoint are presented for the fresh cycle.

  44. Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium

    Time frame: From screening (baseline) to the end-of-cycle visit in the fresh cycle (approximately 6 months)

    Blood samples were collected for the analysis of clinical chemistry parameters including: Bicarbonate, blood urea nitrogen, calcium, chloride, cholesterol, glucose, Phosphate, Potassium and Sodium.

    Data in this endpoint are presented for the fresh cycle.

  45. Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Direct Bilirubin, Total Bilirubin, Creatinine, Urate

    Time frame: From screening (baseline) to the end-of-cycle visit in the fresh cycle (approximately 6 months)

    Blood samples were collected for the analysis of clinical chemistry parameters including: Direct bilirubin, total bilirubin, creatinine, urate.

    Data in this endpoint are presented for the fresh cycle.

  46. Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Lactate Dehydrogenase

    Time frame: From screening (baseline) to the end-of-cycle visit in the fresh cycle (approximately 6 months)

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

    Data in this endpoint are presented for the fresh cycle.

  47. Changes in Haematology Parameters Compared to Baseline: Erythrocytes

    Time frame: From screening to the end-of-cycle visit in the fresh cycle (approximately 6 months)

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

    Data in this endpoint are presented for the fresh cycle.

  48. Changes in Haematology Parameters Compared to Baseline: Haemoglobin

    Time frame: From screening (baseline) to the end-of-cycle visit in the fresh cycle (approximately 6 months)

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

    Data in this endpoint are presented for the fresh cycle.

  49. Changes in Haematology Parameters Compared to Baseline: Haematocrit

    Time frame: From screening (baseline) to the end-of-cycle visit in the fresh cycle (approximately 6 months)

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

    Data in this endpoint are presented for the fresh cycle.

  50. Changes in Haematology Parameters Compared to Baseline: Erythrocyte Mean Corpuscular Volume

    Time frame: From screening (baseline) to the end-of-cycle visit in the fresh cycle (approximately 6 months)

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

    Data in this endpoint are presented for the fresh cycle.

  51. Changes in Haematology Parameters Compared to Baseline: Leukocytes and Platelets

    Time frame: From screening (baseline) to the end-of-cycle visit in the fresh cycle (approximately 6 months)

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

    Data in this endpoint are presented for the fresh cycle.

  52. Changes in Haematology Parameters Compared to Baseline: Erythrocyte Mean Corpuscular Hemoglobin

    Time frame: From screening (baseline) to the end-of-cycle visit in the fresh cycle (approximately 6 months)

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

    Data in this endpoint are presented for the fresh cycle.

  53. Changes in Haematology Parameters Compared to Baseline: Erythrocyte Mean Corpuscular Haemoglobin Concentration

    Time frame: From screening (baseline) to the end-of-cycle visit in the fresh cycle (approximately 6 months)

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

    Data in this endpoint are presented for the fresh cycle.

  54. Changes in Haematology Parameters Compared to Baseline: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes and Neutrophils/Leukocytes

    Time frame: From screening (baseline) to the end-of-cycle visit in the fresh cycle (approximately 6 months)

    Blood samples were collected for the analysis of haematology parameters including: Basophils/leukocytes, eosinophils/ leukocytes, lymphocytes/leukocytes, monocytes/leukocytes and neutrophils/leukocytes.

    Data in this endpoint are presented for the fresh cycle.

  55. Proportion of Subjects With Markedly Abnormal Changes of Clinical Chemistry Parameters: Alanine Aminotransferase, Aspartate Aminotransferase, Bicarbonate, Calcium, Potassium

    Time frame: From screening (baseline) to the end-of-cycle visit in the fresh cycle (approximately 6 months)

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

    Data in this endpoint are presented for the fresh cycle.

  56. Proportion of Subjects With Markedly Abnormal Changes of Haematology Parameters: Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Neutrophils/Leukocytes

    Time frame: From screening (baseline) to the end-of-stimulation visit and end-of-cycle visit in the fresh cycle (approximately 6 months)

    The table represents the percentage of participants in each group with normal baseline values and markedly abnormal end-of-stimulation or end-of-cycle visit values for Leukocytes, eosinophils/leukocytes, lymphocytes/leukocytes and neutrophils/leukocytes.

    Data in this endpoint are presented for the fresh cycle.

  57. Frequency and Intensity of Injection Site Reactions (Redness, Pain, Itching, Swelling and Bruising) Assessed by the Subject During the Stimulation Period

    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.

  58. Intensity of Injection Site Reactions (Redness, Pain, Itching, Swelling and Bruising) Assessed by the Subject During the Stimulation Period

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

    Assessed by the participant during the stimulation period as mild, moderate or severe.

  59. 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.

    95% Clopper-Pearson confidence interval has been reported in this endpoint.

  60. Frequency and Intensity of Immune-related Adverse Events

    Time frame: From time of signing informed consent for participation in the trial until the end-of-cycle visit in the fresh cycle (approximately 6 months)

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

  61. 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.

    Data in this endpoint are presented for the fresh cycle.

  62. Proportion of Subjects With OHSS, Overall and by Grade, and Proportion of Subjects With Moderate/Severe OHSS

    Time frame: ≤9 days after triggering of final follicular maturation (early OHSS), >9 days after triggering of final follicular maturation until 21-28 days after last IMP dose or up to ongoing pregnancy 8-9 weeks after transfer in pregnant participants (late OHSS)

    Classification of grade was according to Golan's classification system, and all OHSS cases were graded as mild, moderate or severe.

    Data in this endpoint are presented for the fresh cycle.

  63. Proportion of Subjects Hospitalized Due to OHSS and Proportion of Subjects Undergoing Paracentesis Due to OHSS

    Time frame: ≤9 days after triggering of final follicular maturation (early OHSS), >9 days after triggering of final follicular maturation until 21-28 days after last IMP dose or up to ongoing pregnancy 8-9 weeks after transfer in pregnant participants (late OHSS)

    Percentage of participants hospitalized or undergoing paracentesis due to OHSS are reported

  64. Proportion of Participants With Multi-fetal Gestation in the Fresh Cycle

    Time frame: Up to 8-9 weeks after transfer

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

    '%' in the unit of measure refers to 'percentage'.

  65. Proportion of Cryopreserved Cycles With Multi-fetal Gestation

    Time frame: Up to 8-9 weeks after transfer

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

    '%' in the unit of measure refers to 'percentage'.

  66. Biochemical Pregnancy, Spontaneous Abortion, Ectopic Pregnancy (With and Without Medical/Surgical Intervention) and Vanishing Twins in the Fresh Cycle

    Time frame: Up to 8-9 weeks after transfer

    The percentage of participants with biochemical pregnancy, spontaneous abortion, ectopic pregnancy (with and without medical/surgical intervention) and vanishing twins in the fresh cycle are presented.

    Data represents participants with positive βhCG.

    Data is not shown for placebo arm because no participants had a positive βhCG.

    '%' in the unit of measure refers to 'percentage'.

    Unit: % of participants with early pregnancy loss.

  67. Biochemical Pregnancy, Spontaneous Abortion, Ectopic Pregnancy (With and Without Medical/Surgical Intervention) and Vanishing Twins in the Cryopreserved Cycles

    Time frame: Up to 8-9 weeks after transfer

    The percentage of cryopreserved cycles with biochemical pregnancy, spontaneous abortion, ectopic pregnancy (with and without medical/surgical intervention) and vanishing twins are presented.

    Data is not shown for placebo arm because no participants had a positive βhCG.

    '%' in the unit of measure refers to 'percentage'.

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

    Time frame: 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 Randomized, Double-blind, Placebo-controlled, Parallel Groups, Multicenter Trial Investigating the Efficacy and Safety of FE 999049 in Controlled Ovarian Stimulation in Women Aged 35-42 Years Undergoing Assisted Reproductive Technology

Acronym: RITA-2

Important dates

Study start
2018
Primary completion
2020
Study completion
2020
First posted
Nov 13, 2018
Registry last updated
Jan 18, 2024

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.

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