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

NCT01653743 | Completed Phase 3 Results

• 1 other identifier: EMR701173_002
• Study Type: interventional
• Target: 81
• Locations: 1 country
• Sites: 6

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.

Conditions

Anovulation; Oligo-ovulation; Hypothalamic-pituitary Dysfunction; Polycystic Ovarian Syndrome

Keywords

Japanese

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (4)

• 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

• Mid-luteal Endometrial Thickness

  Day 5 to 7 post hCG treatment

• Percentage of Participants With Biochemical Pregnancy

  Day 35 to 42 post hCG treatment

• Percentage of Participants With Clinical Pregnancy

  Day 35 to 42 post hCG treatment

Study Arms (2)

MSJ-0011

EXPERIMENTAL

Drug: MSJ-0011; Drug: Follitropin alpha

urinary hCG

ACTIVE COMPARATOR

Drug: urinary hCG (u-hCG); Drug: Follitropin alpha

Interventions

MSJ-0011 DRUG

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).

MSJ-0011

urinary hCG (u-hCG) DRUG

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.

urinary hCG

Follitropin alpha DRUG

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.

MSJ-0011; urinary hCG

Eligibility Criteria

• Age: 20 Years - 39 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck KGaA, Darmstadt, Germany: lead
• Merck Serono Co., Ltd., Japan: collaborator

Study Sites (6)

Hanabusa Women's Central Fertility Clinic

Hyōgo, Japan

Location

Bashamichi Ladies Clinic

Kanagawa, Japan

Location

Sophia Ladies Clinic

Kanagawa, Japan

Location

Ivf Namba Clinic

Osaka, Japan

Location

Ivf Osaka Clinic

Osaka, Japan

Location

Department of Obstetrics and Gynecology, Saitama Medical University Hospital

Saitama, Japan

Location

MeSH Terms

Conditions

Anovulation; Polycystic Ovary Syndrome

Interventions

Chorionic Gonadotropin; Glycoprotein Hormones, alpha Subunit

Condition Hierarchy (Ancestors)

Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Gonadal Disorders; Endocrine System Diseases; Ovarian Cysts; Cysts; Neoplasms

Intervention Hierarchy (Ancestors)

Gonadotropins; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Placental Hormones; Peptides; Amino Acids, Peptides, and Proteins; Pregnancy Proteins; Proteins; Follicle Stimulating Hormone; Gonadotropins, Pituitary; Luteinizing Hormone; Pituitary Hormones, Anterior; Pituitary Hormones; Thyrotropin

Results Point of Contact

• Title: Merck KGaA Communication Center
• Organization: Merck KGaA

service@merckgroup.com

+49-6151-72-5200

Study Officials

• Medical Responsible

  Merck Serono Co., Ltd., Japan

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 20, 2012
• First Posted: July 31, 2012
• Study Start: September 1, 2012
• Primary Completion: November 1, 2014
• Study Completion: December 1, 2014
• Last Updated: January 7, 2016
• Results First Posted: January 7, 2016

Record last verified: 2015-12

Locations

JP (6)