Clinical trial: Efficacy and Safety of FE 999049 in Controlled Ovarian Stimulation in India Women (NCT04773353)

Eligibility criteria:
Inclusion Criteria:

          -  Informed Consent Forms signed prior to screening evaluations.

          -  In good physical and mental health as judged by the investigator.

          -  Indian (i.e., possessing an Indian identification card and having native Indian
             parents) pre-menopausal females between the ages of 21 and 40 years. The subjects must
             be at least 21 years (including the 21st 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 fertilization (IVF) and/or ICSI using fresh or
             frozen ejaculated sperm from male partner or sperm donor.

          -  Infertility for at least one year before randomization for subjects <35 years or for
             at least 6 months for subjects ≥35 years (not applicable in case of tubal or severe
             male factor infertility).

          -  The trial cycle will be the subject'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 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) 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 1 year prior to randomization.

          -  Body mass index (BMI) between 17.5 and 32.0 kg/m^2 (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 [excluding ectopic pregnancy] and before Week 24
             of pregnancy).

          -  Known abnormal karyotype of subject 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
             subject's medical records).

          -  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, 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 3 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.

          -  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.
Female
No healthy subjects accepted to join the trial.
Subject must be at least 21 Years old.
Subject must be at most 40 Years

Patient description (medical language): A 32-year-old woman comes to the hospital with vaginal spotting.  Her last menstrual period was 10 weeks ago. She has regular menses lasting for 6 days and repeating every 29 days. Medical history is significant for appendectomy and several complicated UTIs. She has multiple male partners, and she is inconsistent with using barrier contraceptives. Vital signs are normal.  Serum β-hCG level is 1800 mIU/mL, and a repeat level after 2 days shows an abnormal rise to 2100 mIU/mL.  Pelvic ultrasound reveals a thin endometrium with no gestational sac in the uterus.

Patient description (patient's own words): I just turned 32 and last morning I woke up with strange blood stains on my underwear. My last periods were more than 2 months ago, which is unusual for me because I used to have regular periods lasting for 6 days every 29 days, more or less. I had several UTIs in the past. I also had appendicitis. I'm currently seeing several men and, to be honest, some of them do struggle to wear a condom. I went to the hospital to check myself up and they told me that my vitals were normal. I also had a blood test on Monday, and my β-hCG level was 1800 mIU/mL, and then on Wednesday, it went up to 2100 mIU/mL. The gynecologist also did an ultrasound and she told me that, hopefully, there was no ovule.

Does the patient match the trial criteria? 0