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

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

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

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.