Efficacy and Safety of FE 999049 in Controlled Ovarian Stimulation in Pan-Asian Women
Condition: Controlled Ovarian Simulation
Intervention: Follitropin alfa; Follitropin delta
Intervention description: GONAL-F dose was fixed for the first 5 stimulation days.; REKOVELLE (FE 999049) was fixed throughout the stimulation period.
Intervention MeSH terms: Follicle Stimulating Hormone
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Investigator, Outcomes Assessor)
Enrollment: 1011.0
Sex: Female
Minimum age: 20 Years
Maximum age: 40 Years
Healthy volunteers: No

Summary:

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

Eligibility criteria:

        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.