Trial to Assess the Clinical Efficacy and Safety of MSJ-0011 in Inducing Ovulation in Anovulatory or Oligo-ovulatory Japanese Women

Phase 3

Completed

• Conditions: Oligo-ovulation; Anovulation; Polycystic Ovarian Syndrome; Hypothalamic-pituitary Dysfunction
• Interventions: Drug: MSJ-0011; Drug: urinary hCG (u-hCG); Drug: Follitropin alpha

• Registration Number: NCT01653743
• Lead Sponsor: Merck KGaA, Darmstadt, Germany

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2012-07-20
• Study First Submitted QC: 2012-07-30
• Study First Posted: 2012-07-31
• Study Start: 2012-09
• Primary Completion: 2014-11
• Study Completion: 2014-12
• Status Verified: 2015-12
• Results First Submitted: 2015-12-01
• Results First Submitted QC: 2015-12-01
• Last Update Submitted: 2015-12-01
• Results First Posted: 2016-01-07
• Last Update Posted: 2016-01-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 81

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
MSJ-0011	MSJ-0011	-
urinary hCG	urinary hCG (u-hCG)	-
MSJ-0011	Follitropin alpha	-
urinary hCG	Follitropin alpha	-

Primary Outcome Measures

Name	Time	Method
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	Mid-luteal phase progesterone assessed (Day 5 to 10) or clinical pregnancy (Day 35 to 42) post hCG treatment	Ovulation was defined as mid-luteal serum progesterone level of \>= 5 ng/mL or clinical pregnancy. Clinical pregnancy was defined as the presence of at least a fetal sac on transvaginal ultrasound (TVUS).

Secondary Outcome Measures

Name	Time	Method
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	Mid-luteal phase progesterone assessed (Day 5 to 10) or clinical pregnancy (Day 35 to 42) post hCG treatment	Ovulation was defined as mid-luteal serum progesterone level of \>= 9.4 ng/mL or clinical pregnancy. Clinical pregnancy was defined as the presence of at least a fetal sac on TVUS.
Mid-luteal Endometrial Thickness	Day 5 to 7 post hCG treatment	Endometrial thickness was measured using TVUS.
Percentage of Participants With Biochemical Pregnancy	Day 35 to 42 post hCG treatment	Percentage of subjects with biochemical pregnancy was assessed. Biochemical pregnancy was defined as any miscarriage without any evidence of a fetal sac on TVUS on the Day 35 to 42 post hCG treatment, but with a positive serum β-hCG pregnancy test on Day 15 to 20 post hCG treatment (Beta-hCG level greater than \[\>\] 10 IU/Liter)
Percentage of Participants With Clinical Pregnancy	Day 35 to 42 post hCG treatment	Percentage of subjects with clinical pregnancy was assessed. Clinical pregnancy was defined as the presence of at least a fetal sac on TVUS.

Trial Locations

Locations (6)

Bashamichi Ladies Clinic; 🇯🇵 Kanagawa, Japan

Hanabusa Women's Central Fertility Clinic; 🇯🇵 Hyogo, Japan

Sophia Ladies Clinic; 🇯🇵 Kanagawa, Japan

Ivf Namba Clinic; 🇯🇵 Osaka, Japan

Ivf Osaka Clinic; 🇯🇵 Osaka, Japan

Department of Obstetrics and Gynecology, Saitama Medical University Hospital; 🇯🇵 Saitama, Japan