Clinical trial NCT01653743: Trial to Assess the Clinical Efficacy and Safety of MSJ-0011 in Inducing Ovulation in Anovulatory or Oligo-ovulatory Japanese Women
Official title: Open-Label, Parallel-Group, Randomized, Multicenter Phase III Trial to Compare the Efficacy and Safety of a 250 mcg SC Dose of MSJ-0011 to a 5,000 IU IM Dose of Urinary Human Chorionic Gonadotropin in Inducing Ovulation in Japanese Women Diagnosed With Anovulation or Oligo-Ovulation Secondary to Hypothalamic-Pituitary Dysfunction or Polycystic Ovarian Syndrome, and Who Are Undergoing Ovulation Induction With Follitropin Alfa
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Anovulation
Oligo-ovulation
Hypothalamic-pituitary Dysfunction
Polycystic Ovarian Syndrome
Keywords: Japanese
Lead sponsor: Merck KGaA, Darmstadt, Germany
Sponsor class: INDUSTRY
Collaborators: name: Merck Serono Co., Ltd., Japan
First posted: 2012-07-31
Enrollment: 81
Sex: FEMALE
Minimum age (years): 20
Maximum age (years): 39
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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

Primary outcomes:
measure: Percentage of Subjects With Ovulation Mid-luteal Serum Progesterone (P4) Level of Greater Than or Equal (>=) 5 Nanogram Per Milliliter (ng/mL) or Clinical Pregnancy
timeFrame: Mid-luteal phase progesterone assessed (Day 5 to 10) or clinical pregnancy (Day 35 to 42) post hCG treatment
Secondary outcomes:
measure: Percentage of Subjects With Ovulation Mid-Luteal Serum Progesterone (P4) Level of Greater Than or Equal (>=) 9.4 Nanogram Per Milliliter (ng/mL) or Clinical Pregnancy
timeFrame: Mid-luteal phase progesterone assessed (Day 5 to 10) or clinical pregnancy (Day 35 to 42) post hCG treatment
measure: Mid-luteal Endometrial Thickness
timeFrame: Day 5 to 7 post hCG treatment
measure: Percentage of Participants With Biochemical Pregnancy
timeFrame: Day 35 to 42 post hCG treatment
measure: Percentage of Participants With Clinical Pregnancy
timeFrame: Day 35 to 42 post hCG treatment
Other outcomes:
Locations:
city: Hyogo
country: Japan
facility: Hanabusa Women's Central Fertility Clinic
city: Kanagawa
country: Japan
facility: Bashamichi Ladies Clinic
city: Kanagawa
country: Japan
facility: Sophia Ladies Clinic
city: Osaka
country: Japan
facility: Ivf Namba Clinic
city: Osaka
country: Japan
facility: Ivf Osaka Clinic
city: Saitama
country: Japan
facility: Department of Obstetrics and Gynecology, Saitama Medical University Hospital
Study officials:
affiliation: Merck Serono Co., Ltd., Japan
name: Medical Responsible
role: STUDY_DIRECTOR
References: