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

Polycystic Ovarian Syndrome Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01653743
• Other study ID #: EMR701173_002
• Status: Completed
• Phase: Phase 3
• First received: July 20, 2012
• Last updated: December 1, 2015
• Start date: September 2012
• Est. completion date: December 2014

Study information

• Verified date: December 2015
• Source: Merck KGaA
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Pharmaceuticals and Medical Devices Agency
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 81
• Est. completion date: December 2014
• Est. primary completion date: November 2014
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 20 Years to 39 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Anovulation
• Hypothalamic-pituitary Dysfunction
• Oligo-ovulation
• Pituitary Diseases
• Polycystic Ovarian Syndrome
• Polycystic Ovary Syndrome

Intervention

Drug:
• MSJ-0011
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).
• urinary hCG (u-hCG)
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.
• Follitropin alpha
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.

Locations

Country	Name	City	State
Japan	Hanabusa Women's Central Fertility Clinic	Hyogo
Japan	Bashamichi Ladies Clinic	Kanagawa
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

Sponsors (2)

Lead Sponsor	Collaborator
Merck KGaA	Merck Serono Co., Ltd., Japan

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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).	Mid-luteal phase progesterone assessed (Day 5 to 10) or clinical pregnancy (Day 35 to 42) post hCG treatment	No
Secondary	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	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 phase progesterone assessed (Day 5 to 10) or clinical pregnancy (Day 35 to 42) post hCG treatment	No
Secondary	Mid-luteal Endometrial Thickness	Endometrial thickness was measured using TVUS.	Day 5 to 7 post hCG treatment	No
Secondary	Percentage of Participants With Biochemical Pregnancy	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 ß-hCG pregnancy test on Day 15 to 20 post hCG treatment (Beta-hCG level greater than [>] 10 IU/Liter)	Day 35 to 42 post hCG treatment	No
Secondary	Percentage of Participants With Clinical Pregnancy	Percentage of subjects with clinical pregnancy was assessed. Clinical pregnancy was defined as the presence of at least a fetal sac on TVUS.	Day 35 to 42 post hCG treatment	No