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

This study has been completed.
Sponsor:
Collaborator:
Merck Serono Co., Ltd., Japan
Information provided by (Responsible Party):
Merck KGaA
ClinicalTrials.gov Identifier:
NCT01653743
First received: July 20, 2012
Last updated: December 1, 2015
Last verified: December 2015
  Purpose
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.

Condition Intervention Phase
Anovulation
Oligo-ovulation
Hypothalamic-pituitary Dysfunction
Polycystic Ovarian Syndrome
Drug: MSJ-0011
Drug: urinary hCG (u-hCG)
Drug: Follitropin alpha
Phase 3

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

Resource links provided by NLM:


Further study details as provided by Merck KGaA:

Primary Outcome Measures:
  • 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 [ Time Frame: Mid-luteal phase progesterone assessed (Day 5 to 10) or clinical pregnancy (Day 35 to 42) post hCG treatment ] [ Designated as safety issue: No ]
    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:
  • 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 [ Time Frame: Mid-luteal phase progesterone assessed (Day 5 to 10) or clinical pregnancy (Day 35 to 42) post hCG treatment ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 5 to 7 post hCG treatment ] [ Designated as safety issue: No ]
    Endometrial thickness was measured using TVUS.

  • Percentage of Participants With Biochemical Pregnancy [ Time Frame: Day 35 to 42 post hCG treatment ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 35 to 42 post hCG treatment ] [ Designated as safety issue: No ]
    Percentage of subjects with clinical pregnancy was assessed. Clinical pregnancy was defined as the presence of at least a fetal sac on TVUS.


Enrollment: 81
Study Start Date: September 2012
Study Completion Date: December 2014
Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MSJ-0011 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).
Drug: 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.
Active Comparator: urinary hCG Drug: 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.
Drug: 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.

  Eligibility

Ages Eligible for Study:   20 Years to 39 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01653743

Locations
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, Japan
Sponsors and Collaborators
Merck KGaA
Merck Serono Co., Ltd., Japan
Investigators
Study Director: Medical Responsible Merck Serono Co., Ltd., Japan
  More Information

Responsible Party: Merck KGaA
ClinicalTrials.gov Identifier: NCT01653743     History of Changes
Other Study ID Numbers: EMR701173_002 
Study First Received: July 20, 2012
Results First Received: December 1, 2015
Last Updated: December 1, 2015
Health Authority: Japan: Pharmaceuticals and Medical Devices Agency

Keywords provided by Merck KGaA:
Japanese

Additional relevant MeSH terms:
Anovulation
Pituitary Diseases
Polycystic Ovary Syndrome
Adnexal Diseases
Brain Diseases
Central Nervous System Diseases
Cysts
Endocrine System Diseases
Genital Diseases, Female
Gonadal Disorders
Hypothalamic Diseases
Neoplasms
Nervous System Diseases
Ovarian Cysts
Ovarian Diseases
Chorionic Gonadotropin
Follicle Stimulating Hormone
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Reproductive Control Agents

ClinicalTrials.gov processed this record on May 24, 2016