Trial to Assess the Clinical Efficacy and Safety of MSJ-0011 in Inducing Ovulation in Anovulatory or Oligo-ovulatory Japanese Women
Condition: Anovulation; Oligo-ovulation; Hypothalamic-pituitary Dysfunction; Polycystic Ovarian Syndrome
MeSH terms: Polycystic Ovary Syndrome; Pituitary Diseases; Anovulation; Syndrome
Intervention: MSJ-0011; urinary hCG (u-hCG); Follitropin alpha
Intervention description: Subjects who underwent ovarian stimulation with follitropin alfa according to a low-dose step-up protocol for maximum of 28 days will receive a single dose of 250 microgram (mcg) MSJ-0011 (choriogonadotropin alfa [recombinant human Chorionic Gonadotropin, r-hCG]) subcutaneously (SC) within 32 hours after the last dose of follitropin alfa administration unless dominant follicle reached a mean diameter of greater than or equal to (>=) 18 millimeter (mm); not more than 3 follicles each with a mean diameter of >=16 mm and serum Estradiol (E2) level within an acceptable range for the number of follicle present, and not more than 2,000 picogram per milliliter (pg/mL).; Subjects who underwent ovarian stimulation with follitropin alfa according to a low-dose step-up protocol for maximum of 28 days will receive a single dose of 5,000 IU u-hCG intramuscularly dose within 32 hours after the last dose of follitropin alfa administration unless dominant follicle reached a mean diameter of >=18 mm; not more than 3 follicles each with a mean diameter of >=16 mm and serum E2 level within an acceptable range for the number of follicle present, and not more than 2,000 pg/mL.; Low-dose step-up protocol involves starting dose of follitropin alfa as 75 International Units (IU) subcutaneously per day ,increments by 37.5 IU every 7 days (Day 8, 15, 28) will be done if no ovarian response will be observed for maximum of 28 days.
Intervention MeSH terms: Chorionic Gonadotropin; Follicle Stimulating Hormone
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 81.0
Sex: Female
Minimum age: 20 Years
Maximum age: 39 Years
Healthy volunteers: No
Keywords: Japanese

Summary:

      This is an open-label, parallel-group, randomized, multicenter Phase III trial to compare the
      efficacy and safety of a single 250 microgram (mcg) subcutaneous dose of MSJ-0011 to a single
      5,000 international units (IU) intramuscular dose of urinary human chorionic gonadotropin
      (hCG) in inducing ovulation in Japanese women diagnosed with anovulation or oligo-ovulation.
      Ovulation induction therapy will be undertaken with follitropin alfa. The primary objective
      is to show that MSJ-0011 is non-inferior to urinary hCG, as assessed by the ovulation rate.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Premenopausal women aged between 20 to 39 years inclusive and wishing to conceive

          -  Body Mass Index (BMI) of 17.0 to 29.0 kilogram per square meter (kg/m^2) inclusive
             (value up to first decimal place)

          -  No clinically significant abnormalities in serum thyroid stimulating hormone (TSH),
             dehydroepiandrosterone sulfate (DHEA-S), 17-hydroxyProgesterone (17-OHP), prolactin
             (PRL) and follicle-stimulating hormone (FSH) levels in the early follicular phase

          -  Anovulation or oligo-ovulation

          -  Any one of the following: spontaneous menstruation (at least twice per year) or a
             positive response to progestin as evidenced by menstruation.

          -  Eligible for ovarian stimulation with gonadotropins (e.g. documented failure to
             ovulate or achieve pregnancy with anti-estrogenic therapy such as clomiphene citrate)

          -  Male partner with normal semen analysis, as defined by World Health Organization (WHO)
             standards, within 12 months prior to date of informed consent

          -  Normal cervical smear results (Papanicolaou [PAP] score less than or equal to [<=] II)
             taken within 12 months prior to date of informed consent; if not available a cervical
             smear will be performed as part of screening

          -  Full comprehension of the trial and voluntary consent obtained in writing prior to
             participation in this trial

        Exclusion Criteria:

          -  Infertility involving gynecological factors other than anovulation or oligo-ovulation
             secondary to hypothalamic-pituitary dysfunction (Grade 1 Amenorrhea, Oligomenorrhea or
             Anovulatory Cycles) or polycystic ovarian syndrome (PCOS) and for whom ovulation
             induction (OI) therapy is contraindicated

          -  Subjects with known surgical/histological diagnosis of endometriosis greater than
             Stage II (American Fertility Society classification), or endometriosis requiring
             treatment

          -  Infertility secondary to amenorrhea of uterine cause

          -  Infertility secondary to primary or premature ovarian failure

          -  Infertility secondary to known adrenal or thyroid dysfunction, or hyperprolactinemia

          -  Failure of ovulation in 2 or more consecutive previous cycles with any gonadotropins

          -  Subjects in whom pregnancy is contraindicated, e.g. malformations of sexual organs or
             fibroid tumors of the uterus incompatible with pregnancy

          -  Extrauterine pregnancy in the previous 3 months

          -  History or presence of intracranial tumor (e.g. hypothalamic or pituitary tumor)

          -  Presence of or suspected gonadotropin- or estrogen-dependent malignancy (e.g. ovarian,
             uterine or mammary carcinoma)

          -  Untreated endometrial hyperplasia

          -  Abnormal hemorrhage of the reproductive tract of unknown origin

          -  History of severe ovarian hyper stimulation syndrome (OHSS) (Classification of OHSS
             Severity, Japan Reproductive/Endocrine Working Group)

          -  Clinically significant systemic disease (e.g. insulin-dependent diabetes, epilepsy,
             severe migraine, intermittent porphyria, hepatic, renal or cardiovascular disease,
             severe corticosteroid-dependent asthma)

          -  Participation in another clinical trial within 3 months prior to date of informed
             consent or simultaneous participation in another clinical trial

          -  Gonadotropin treatment within 2 months prior to date of informed consent

          -  Legal incapacity or limited legal capacity