Recombinant FSH Investigation in the Treatment of Infertility With Assisted Reproductive Technology (ART) (RITA-2)
Condition: Infertility, Female
MeSH terms: Infertility; Infertility, Female
Intervention: Follitropin delta; Placebo
Intervention description: 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; 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.
Intervention MeSH terms: Follicle Stimulating Hormone
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 588.0
Sex: Female
Minimum age: 35 Years
Maximum age: 42 Years
Healthy volunteers: No

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

Eligibility criteria:

        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.