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

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

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

Study Overview

• Status: Completed
• Conditions: Infertility, Female
• Intervention / Treatment: Drug: Follitropin delta; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 588
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tempe, Arizona, United States, 85284
      • Fertility Treatment Center
  • California
    • Encino, California, United States, 91436
      • HRC Fertility
  • Connecticut
    • Farmington, Connecticut, United States, 06032
      • Center for Advanced Reproductive Services PC
  • Delaware
    • Newark, Delaware, United States, 19713
      • Reproductive Associates of Delaware
  • Florida
    • Clearwater, Florida, United States, 33759
      • Women's Medical Research Group, LLC
    • Winter Park, Florida, United States, 32789
      • Center for Reproductive Medicine
  • Hawaii
    • Honolulu, Hawaii, United States, 96814
      • Fertility Institute of Hawaii, INC
  • Illinois
    • Chicago, Illinois, United States, 60610
      • Fertility Centers of Illinois (RH)
    • Hoffman Estates, Illinois, United States, 60169
      • InVia Fertility
  • Massachusetts
    • Waltham, Massachusetts, United States, 02451
      • Boston IVF
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • New York
    • New York, New York, United States, 10019
      • Columbia University Fertility Center
  • North Carolina
    • Charlotte, North Carolina, United States, 28207
      • Reproductive Endocrinology Associates of Charlotte (REACH) S. Corporation
    • Raleigh, North Carolina, United States, 27607
      • Carolina Conceptions
  • Ohio
    • Cincinnati, Ohio, United States, 45209
      • Institute for Reproductive Health
  • Pennsylvania
    • Abington, Pennsylvania, United States, 19046
      • Abington Reproductive Medicine
    • Bryn Mawr, Pennsylvania, United States, 19010
      • Main Line Fertility Center
  • Tennessee
    • Memphis, Tennessee, United States, 38120
      • Fertility Associates of Memphis, PLLC
  • Texas
    • Bedford, Texas, United States, 76022
      • Center for Assisted Reproduction
    • Houston, Texas, United States, 77063
      • Houston Fertility Institute
    • Webster, Texas, United States, 77598
      • Center of Reproductive Medicine
  • Utah
    • Pleasant Grove, Utah, United States, 84062
      • Utah Fertility Center
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • Eastern Virginia Medical School | EVMS Obstetrics & Gynecology
  • Washington
    • Seattle, Washington, United States, 98109
      • Seattle Reproductive Medicine WA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 42 years (Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Placebo was administered as single daily subcutaneous injection dialed to the same value (dose) as FE 999049. Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early OHSS with the exception of GnRH agonist for triggering of final follicular maturation, was not allowed.
Experimental: FE 999049 (Follitropin Delta)	Drug: Follitropin delta; FE 999049 was administered as single daily subcutaneous injections in the abdomen at a starting dose of 15 μg daily that was fixed for the first four stimulation days. Based on ovarian response, the dose could be adjusted by 3 μg, with dose increases implemented not more frequently than once every 2 days and dose decreases implemented per investigator's judgement. The minimum daily dose was 6 μg, and the maximum daily dose was 24 μg. Participants could be treated for a maximum of 20 days. Coasting, use of dopamine agonist or any other drug to prevent early 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative Ongoing Pregnancy Rate After the Fresh Cycle and Cryopreserved Cycles Initiated Within 12 Months From the Start of Controlled Ovarian Stimulation (COS)	Defined as at least one intrauterine viable fetus 8-9 weeks after transfer. Data in this endpoint are presented for the fresh cycle and the cryopreserved cycles.	8-9 weeks after transfer (up to approximately 16 months after start of stimulation)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Gonadotropin Dose	Calculated by start dates, end dates and daily dose of IMP.	Up to 20 stimulation days
Number of Stimulation Days	Calculated by start dates and end dates.	Up to 20 stimulation days
Number of Oocytes Retrieved	The number of oocytes retrieved was recorded at the oocyte retrieval visit.	On day of oocyte retrieval (up to 22 days after start of stimulation)
Ongoing Pregnancy Rate in the Fresh Cycle and in the Cryopreserved Cycles	Defined as at least one intrauterine viable fetus 8-9 weeks after transfer. Data in this endpoint are presented for the fresh cycle and the cryopreserved cycles.	8-9 weeks after transfer (up to approximately 16 months after start of stimulation)
Time From Start of COS to Ongoing Pregnancy Across the Fresh and Cryopreserved Cycles, Measured in Number of Cycles Before Achieving Ongoing Pregnancy	Time from start of COS to ongoing pregnancy, including both the fresh and cryopreserved cycles, measured in number of cycles before achieving ongoing pregnancy. In the placebo group, no participants achieved an ongoing pregnancy either after 12 calendar months or after 12 study months.	8-9 weeks after transfer (up to approximately 16 months after start of stimulation)
Clinical Pregnancy Rate in the Fresh Cycle, the Cryopreserved Cycles and Cumulatively	Defined at least one gestational sac 5-6 weeks after transfer. Data in this endpoint are presented for the fresh cycle, the cryopreserved cycles, and all cycles.	5-6 weeks after transfer (up to approximately 15 months after start of stimulation)
Vital Pregnancy Rate in the Fresh Cycle, the Cryopreserved Cycles and Cumulatively	Defined at least one intrauterine gestational sac with fetal heart beat 5-6 weeks after transfer. Data in this endpoint are presented for the fresh cycle, the cryopreserved cycles, and all cycles.	5-6 weeks after transfer (up to approximately 15 months after start of stimulation)
Positive Beta Human Chorionic Gonadotropin (βhCG) Rate in the Fresh Cycle, the Cryopreserved Cycles and Cumulatively	Defined as positive serum βhCG test 10-14 days after transfer. Data in this endpoint are presented for the fresh cycle, the cryopreserved cycles, and all cycles.	10-14 days after transfer (up to approximately 14 months after start of stimulation)
Size of Follicles on Stimulation Day 5	Counted by ultrasound for the right and left ovary for each participant.	On stimulation day 5
Size of Follicles at End-of-stimulation	Counted by ultrasound for the right and left ovary for each participant.	At end-of-stimulation (up to 20 stimulation days)
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.	On day of oocyte retrieval (up to 22 days after start of stimulation)
Number of Metaphase II Oocytes	The number of MII oocytes to oocytes retrieved for participants where all oocytes were inseminated using ICSI are presented.	On day of oocyte retrieval (up to 22 days after start of stimulation)
Number of Fertilized Oocytes	An oocyte was defined as fertilized if it had 2 pronuclei (2PN) at 19h (±2h).	On day 1 after oocyte retrieval (up to 23 days after start of stimulation)
Number and Quality of Blastocysts on Day 5 After Oocyte Retrieval	Number of blastocysts (total and good-quality) on Day 5 are presented. The quality evaluation of blastocysts consisted of assessment of three parameters, as per the Gardner & Schoolcraft system: blastocyst expansion and hatching status (graded: 1-6), inner cell mass (graded: A-D) and trophectoderm (graded: A-D). A good-quality blastocyst was defined as a blastocyst of grade 3BB or higher.	On day 5 after oocyte retrieval
Endometrial Thickness on Stimulation Day 5	Mean endometrial thickness is reported.	On stimulation day 5
Endometrial Thickness at End-of-stimulation	Mean endometrial thickness is reported.	At end-of-stimulation (up to 20 stimulation days)
Echogenicity Pattern at End-of-stimulation	The distribution of participants with hypoechogenic, isoechogenic, or hyperechogenic endometrium is reported.	At end-of-stimulation (up to 20 stimulation days)
Oocyte Utilization Rate	Defined as the number of blastocysts transferred or cryopreserved divided by the number of oocytes retrieved. Data in this endpoint are presented for the cryopreserved cycles.	On day of oocyte retrieval up to 12 months after start of COS
Oocyte Efficiency Index	Defined as the cumulative number of ongoing pregnancies per oocyte retrieved. Data in this endpoint are presented for the cryopreserved cycles. The unit of measure for this endpoint is 'cumulative ongoing pregnancies/oocyte retrieved'.	8-9 weeks after transfer
Percentage of Blastocysts Surviving Cryopreservation	Data in this endpoint are presented for the cryopreserved cycles. The unit is number of blastocysts with observations. One participant can contribute with a range from zero to multiple blastocysts.	0 hour (+0.5 hour) after thawing
Percentage of Blastocysts With Re-expansion After Cryopreservation	Data in this endpoint are presented for the cryopreserved cycles. The unit is number of blastocysts with observations. One participant can contribute with a range from zero to multiple blastocysts.	2.5 hour (±0.5 hour) after thawing
Circulating Concentrations of Anti-mullerian Hormone (AMH)	Blood samples for analysis of circulating concentrations of AMH were drawn. The median and inter-quartile range (IQR) of AMH levels on stimulation day 1, stimulation day 5, end-of-stimulation visit and oocyte retrieval visit are presented.	From screening to the day of oocyte retrieval (up to 22 days after start of stimulation)
Circulating Concentrations of Follicle-stimulating Hormone (FSH)	Blood samples for analysis of circulating concentrations of FSH were drawn. The median and IQR of FSH levels on stimulation day 1, stimulation day 5, end-of-stimulation visit and oocyte retrieval visit are presented.	From screening to the day of oocyte retrieval (up to 22 days after start of stimulation)
Circulating Concentrations of Luteinizing Hormone (LH)	Blood samples for analysis of circulating concentrations of LH were drawn. The median and IQR of LH levels on stimulation day 1, stimulation day 5, end-of-stimulation visit and oocyte retrieval visit are presented.	From screening to the day of oocyte retrieval (up to 22 days after start of stimulation)
Circulating Concentrations of Estradiol	Blood samples for analysis of circulating concentrations of estradiol were drawn. The median and IQR of estradiol levels on stimulation day 1, stimulation day 5, end-of-stimulation visit and oocyte retrieval visit are presented.	From screening to the day of oocyte retrieval (up to 22 days after start of stimulation)
Circulating Concentrations of Progesterone	Blood samples for analysis of circulating concentrations of progesterone were drawn. The median and IQR of progesterone levels on stimulation day 1, stimulation day 5, end-of-stimulation visit and oocyte retrieval visit are presented.	From screening to the day of oocyte retrieval (up to 22 days after start of stimulation)
Circulating Concentrations of Inhibin A	Blood samples for analysis of circulating concentrations of inhibin A were drawn. The median and IQR of inhibin A levels on stimulation day 1, stimulation day 5, end-of-stimulation visit and oocyte retrieval visit are presented.	From screening to the day of oocyte retrieval (up to 22 days after start of stimulation)
Circulating Concentrations of Inhibin B	Blood samples for analysis of circulating concentrations of inhibin B were drawn. The median and IQR of inhibin B levels on stimulation day 1, stimulation day 5, end-of-stimulation visit and oocyte retrieval visit are presented.	From screening to the day of oocyte retrieval (up to 22 days after start of stimulation)
Proportion of Participants With Investigator-requested Gonadotropin Dose Adjustments	Investigator-requested decreases and increases of the gonadotropin dose.	Stimulation Day 5
Intensity of AEs	The intensity of AE was classified using the following 3-point scale: mild = awareness of signs or symptoms, but no disruption of usual activity; moderate = event sufficient to affect usual activity (disturbing); or severe = inability to work or perform usual activities (unacceptable). Data in this endpoint are presented for the fresh cycle.	From time of signing informed consent until the end-of-cycle visit in the fresh cycle (up to approximately 6 months)
Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Albumin, Protein	Blood samples were collected for the analysis of clinical chemistry parameters including: Albumin and protein. Data in this endpoint are presented for the fresh cycle.	From screening (baseline) to the end-of-cycle visit in the fresh cycle (approximately 6 months)
Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase and Gamma Glutamyl Transferase	Blood samples were collected for the analysis of clinical chemistry parameters including: Alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase and gamma glutamyl transferase. Data in this endpoint are presented for the fresh cycle.	From screening (baseline) to the end-of-cycle visit in the fresh cycle (approximately 6 months)
Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Direct Bilirubin, Total Bilirubin, Creatinine, Urate	Blood samples were collected for the analysis of clinical chemistry parameters including: Direct bilirubin, total bilirubin, creatinine, urate. Data in this endpoint are presented for the fresh cycle.	From screening (baseline) to the end-of-cycle visit in the fresh cycle (approximately 6 months)
Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Lactate Dehydrogenase	Blood samples were collected for the analysis of clinical chemistry parameters including: Lactate dehydrogenase. Data in this endpoint are presented for the fresh cycle.	From screening (baseline) to the end-of-cycle visit in the fresh cycle (approximately 6 months)
Changes in Haematology Parameters Compared to Baseline: Erythrocytes	Blood samples were collected for the analysis of haematology parameter including: Erythrocytes. Data in this endpoint are presented for the fresh cycle.	From screening to the end-of-cycle visit in the fresh cycle (approximately 6 months)
Changes in Haematology Parameters Compared to Baseline: Leukocytes and Platelets	Blood samples were collected for the analysis of haematology parameters including: Leukocytes and platelets. Data in this endpoint are presented for the fresh cycle.	From screening (baseline) to the end-of-cycle visit in the fresh cycle (approximately 6 months)
Changes in Haematology Parameters Compared to Baseline: Haemoglobin	Blood samples were collected for the analysis of haematology parameters including: Haemoglobin. Data in this endpoint are presented for the fresh cycle.	From screening (baseline) to the end-of-cycle visit in the fresh cycle (approximately 6 months)
Changes in Haematology Parameters Compared to Baseline: Haematocrit	Blood samples were collected for the analysis of haematology parameter including: Haematocrit. Data in this endpoint are presented for the fresh cycle.	From screening (baseline) to the end-of-cycle visit in the fresh cycle (approximately 6 months)
Changes in Haematology Parameters Compared to Baseline: Erythrocyte Mean Corpuscular Volume	Blood samples were collected for the analysis of haematology parameter including: Erythrocyte mean corpuscular volume. Data in this endpoint are presented for the fresh cycle.	From screening (baseline) to the end-of-cycle visit in the fresh cycle (approximately 6 months)
Changes in Haematology Parameters Compared to Baseline: Erythrocyte Mean Corpuscular Haemoglobin Concentration	Blood samples were collected for the analysis of haematology parameter including: Erythrocyte mean corpuscular haemoglobin concentration. Data in this endpoint are presented for the fresh cycle.	From screening (baseline) to the end-of-cycle visit in the fresh cycle (approximately 6 months)
Intensity of Injection Site Reactions (Redness, Pain, Itching, Swelling and Bruising) Assessed by the Subject During the Stimulation Period	Assessed by the participant during the stimulation period as mild, moderate or severe.	End-of-stimulation (up to 20 stimulation days)
Proportion of Subjects With Treatment-induced Anti-FSH Antibodies, Overall as Well as With Neutralizing Capacity	Measured by presence of anti-FSH antibodies. 95% Clopper-Pearson confidence interval has been reported in this endpoint.	Up to 28 days after end of the stimulation period
Proportion of Subjects With OHSS, Overall and by Grade, and Proportion of Subjects With Moderate/Severe OHSS	Classification of grade was according to Golan's classification system, and all OHSS cases were graded as mild, moderate or severe. Data in this endpoint are presented for the fresh cycle.	≤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)
Proportion of Participants With Multi-fetal Gestation in the Fresh Cycle	Defined as pregnancy with more than one fetus. Among participants with ongoing pregnancy, percentage of participants with twin pregnancies are presented. '%' in the unit of measure refers to 'percentage'.	Up to 8-9 weeks after transfer
Proportion of Cryopreserved Cycles With Multi-fetal Gestation	Defined as pregnancy with more than one fetus. Among cryopreserved cycles with ongoing pregnancy, percentage of cycles with twin pregnancies are presented. '%' in the unit of measure refers to 'percentage'.	Up to 8-9 weeks after transfer
Proportion of Participants With Technical Malfunctions of the Administration Pen	Incidences of technical malfunctions of the administration pen were recorded.	Up to 20 stimulation days
Time From Start of COS to Ongoing Pregnancy Across the Fresh and Cryopreserved Cycles, Including Duration	Time from start of COS to ongoing pregnancy, including both the fresh and cryopreserved cycles. In the placebo group, no participants achieved an ongoing pregnancy either after 12 calendar months or after 12 study months.	8-9 weeks after transfer (up to approximately 16 months after start of stimulation)
Ongoing Implantation Rate in the Fresh Cycle, the Cryopreserved Cycles and Cumulatively	Defined as the number of intrauterine viable fetuses 8-9 weeks after transfer divided by number of blastocysts transferred. Data in this endpoint are presented for the fresh cycle, the cryopreserved cycles, and all cycles. One participant can contribute with a range from zero to multiple blastocysts. Data is not shown for placebo arm because no subjects underwent blastocyst transfer in the fresh cycle or cryopreserved cycles. '%' in the unit of measure refers to 'percentage'.	8-9 weeks after transfer (up to approximately 16 months after start of stimulation)
Implantation Rate in the Fresh Cycle, the Cryopreserved Cycles and Cumulatively	Defined as the number of gestational sacs 5-6 weeks after transfer divided by number of blastocysts transferred. The endpoint are presented for the fresh cycle, the cryopreserved cycles, and all cycles. One participant can contribute with a range from zero to multiple blastocysts. Data is not shown for placebo arm because no subjects underwent blastocyst transfer in the fresh cycle or cryopreserved cycles. '%' in the unit of measure refers to 'percentage'.	5-6 weeks after transfer (up to approximately 15 months after start of stimulation)
Proportion of Subjects in the Fresh Cycle With Triggering of Final Follicular Maturation (With hCG, With GnRH Agonist, and in Total), Cycle Cancellation and Transfer Cancellation	Data in this endpoint are presented for the fresh cycle.	Up to 5 days after oocyte retrieval (up to 27 days after start of stimulation)
Number of Follicles on Stimulation Day 5	The total number of follicles and the number of follicles per size category are reported.	On stimulation day 5
Number of Follicles at End-of-stimulation	The total number of follicles and the number of follicles per size category are reported.	At end-of-stimulation (up to 20 stimulation days)
Fertilization Rate	The fertilization rate was defined as the number of 2PN oocytes divided by the number of oocytes retrieved. Fertilization rate relative to oocytes retrieved has been reported.	On day 1 after oocyte retrieval (up to 23 days after start of stimulation)
Echogenicity Pattern on Stimulation Day 5	The distribution of participants with hypoechogenic, isoechogenic, or hyperechogenic endometrium is reported	On stimulation day 5
Number of Cryopreserved Cycles Initiated Within 12 Months From the Start of COS	The total number of cryopreserved cycles initiated are reported. Data in this endpoint are presented for the cryopreserved cycles. One participant can contribute with a range from zero to multiple blastocysts.	Up to 12 months after start of stimulation
Number of Cryopreserved Cycles With Blastocyst Transfer	The total number of cryopreserved cycles with blastocyst transfer are reported. Data in this endpoint are presented for the cryopreserved cycles. One participant can contribute with a range from zero to multiple blastocysts.	Up to 12 months after start of stimulation
Percentage of Participants With Adverse Events (AEs)	Any AE occurring after start of IMP and before the end-of-trial visit, or a pre-treatment AE or pre-existing medical condition that worsens in intensity after start of IMP and before the end-of-trial visit was considered treatment-emergent, and is presented for this endpoint. Data in this endpoint are presented for the fresh cycle.	From time of signing informed consent until the end-of-cycle visit in the fresh cycle (approximately 6 months)
Changes in Circulating Levels of Clinical Chemistry Compared to Baseline: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium	Blood samples were collected for the analysis of clinical chemistry parameters including: Bicarbonate, blood urea nitrogen, calcium, chloride, cholesterol, glucose, Phosphate, Potassium and Sodium. Data in this endpoint are presented for the fresh cycle.	From screening (baseline) to the end-of-cycle visit in the fresh cycle (approximately 6 months)
Changes in Haematology Parameters Compared to Baseline: Erythrocyte Mean Corpuscular Hemoglobin	Blood samples were collected for the analysis of haematology parameter including: Erythrocyte mean corpuscular haemoglobin. Data in this endpoint are presented for the fresh cycle.	From screening (baseline) to the end-of-cycle visit in the fresh cycle (approximately 6 months)
Changes in Haematology Parameters Compared to Baseline: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes and Neutrophils/Leukocytes	Blood samples were collected for the analysis of haematology parameters including: Basophils/leukocytes, eosinophils/ leukocytes, lymphocytes/leukocytes, monocytes/leukocytes and neutrophils/leukocytes. Data in this endpoint are presented for the fresh cycle.	From screening (baseline) to the end-of-cycle visit in the fresh cycle (approximately 6 months)
Proportion of Subjects With Markedly Abnormal Changes of Clinical Chemistry Parameters: Alanine Aminotransferase, Aspartate Aminotransferase, Bicarbonate, Calcium, Potassium	The table represents the percentage of participants in each group with normal baseline values and markedly abnormal end-of-stimulation or end-of-cycle visit values for alanine aminotransferase, aspartate aminotransferase, bicarbonate, calcium, potassium. Data in this endpoint are presented for the fresh cycle.	From screening (baseline) to the end-of-cycle visit in the fresh cycle (approximately 6 months)
Proportion of Subjects With Markedly Abnormal Changes of Haematology Parameters: Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Neutrophils/Leukocytes	The table represents the percentage of participants in each group with normal baseline values and markedly abnormal end-of-stimulation or end-of-cycle visit values for Leukocytes, eosinophils/leukocytes, lymphocytes/leukocytes and neutrophils/leukocytes. Data in this endpoint are presented for the fresh cycle.	From screening (baseline) to the end-of-stimulation visit and end-of-cycle visit in the fresh cycle (approximately 6 months)
Frequency and Intensity of Injection Site Reactions (Redness, Pain, Itching, Swelling and Bruising) Assessed by the Subject During the Stimulation Period	Assessed by the participant during the stimulation period. Participants assessed the injection site reactions (redness, pain, itching, swelling and bruising) three times daily: immediately after the injection, 30 minutes after the injection and 24 hours after the injection.	End-of-stimulation (up to 20 stimulation days)
Frequency and Intensity of Immune-related Adverse Events	Standardised Medical Dictionary for Regulatory Activities (MedDRA) Queries (SMQs).	From time of signing informed consent for participation in the trial until the end-of-cycle visit in the fresh cycle (approximately 6 months)
Proportion of Subjects With Cycle Cancellations Due to an Adverse Event, Including Immune-related Adverse Events, or Due to Technical Malfunctions of the Administration Pen	For each participant the reason for cycle cancellation will be recorded. Data in this endpoint are presented for the fresh cycle.	Up to 20 stimulation days
Proportion of Subjects Hospitalized Due to OHSS and Proportion of Subjects Undergoing Paracentesis Due to OHSS	Percentage of participants hospitalized or undergoing paracentesis due to OHSS are reported	≤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)
Biochemical Pregnancy, Spontaneous Abortion, Ectopic Pregnancy (With and Without Medical/Surgical Intervention) and Vanishing Twins in the Fresh Cycle	The percentage of participants with biochemical pregnancy, spontaneous abortion, ectopic pregnancy (with and without medical/surgical intervention) and vanishing twins in the fresh cycle are presented. Data represents participants with positive βhCG. Data is not shown for placebo arm because no participants had a positive βhCG. '%' in the unit of measure refers to 'percentage'. Unit: % of participants with early pregnancy loss.	Up to 8-9 weeks after transfer
Biochemical Pregnancy, Spontaneous Abortion, Ectopic Pregnancy (With and Without Medical/Surgical Intervention) and Vanishing Twins in the Cryopreserved Cycles	The percentage of cryopreserved cycles with biochemical pregnancy, spontaneous abortion, ectopic pregnancy (with and without medical/surgical intervention) and vanishing twins are presented. Data is not shown for placebo arm because no participants had a positive βhCG. '%' in the unit of measure refers to 'percentage'.	Up to 8-9 weeks after transfer

Collaborators and Investigators

• Sponsor: Ferring Pharmaceuticals
• Investigators: Study Director: Global Clinical Compliance, Ferring Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): October 29, 2018
• Primary Completion (Actual): December 21, 2020
• Study Completion (Actual): December 21, 2020

Study Registration Dates

• First Submitted: October 24, 2018
• First Submitted That Met QC Criteria: November 9, 2018
• First Posted (Actual): November 13, 2018

Study Record Updates

• Last Update Posted (Actual): January 18, 2024
• Last Update Submitted That Met QC Criteria: December 21, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Infertility; Infertility, Female; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Follicle Stimulating Hormone
• Other Study ID Numbers: 000002

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No