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

Primary Purpose

Anovulation, Oligo-ovulation, Hypothalamic-pituitary Dysfunction

Status
Completed
Phase
Phase 3
Locations
Japan
Study Type
Interventional
Intervention
MSJ-0011
urinary hCG (u-hCG)
Follitropin alpha
Sponsored by
Merck KGaA, Darmstadt, Germany
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Anovulation focused on measuring Japanese

Eligibility Criteria

20 Years - 39 Years (Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

  • Hanabusa Women's Central Fertility Clinic
  • Bashamichi Ladies Clinic
  • Sophia Ladies Clinic
  • Ivf Namba Clinic
  • Ivf Osaka Clinic
  • Department of Obstetrics and Gynecology, Saitama Medical University Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

MSJ-0011

urinary hCG

Arm Description

Outcomes

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
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
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
Endometrial thickness was measured using TVUS.
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 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
Percentage of subjects with clinical pregnancy was assessed. Clinical pregnancy was defined as the presence of at least a fetal sac on TVUS.

Full Information

First Posted
July 20, 2012
Last Updated
December 1, 2015
Sponsor
Merck KGaA, Darmstadt, Germany
Collaborators
Merck Serono Co., Ltd., Japan
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1. Study Identification

Unique Protocol Identification Number
NCT01653743
Brief Title
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

2. Study Status

Record Verification Date
December 2015
Overall Recruitment Status
Completed
Study Start Date
September 2012 (undefined)
Primary Completion Date
November 2014 (Actual)
Study Completion Date
December 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck KGaA, Darmstadt, Germany
Collaborators
Merck Serono Co., Ltd., Japan

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Anovulation, Oligo-ovulation, Hypothalamic-pituitary Dysfunction, Polycystic Ovarian Syndrome
Keywords
Japanese

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
81 (Actual)

8. Arms, Groups, and Interventions

Arm Title
MSJ-0011
Arm Type
Experimental
Arm Title
urinary hCG
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
MSJ-0011
Intervention Description
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).
Intervention Type
Drug
Intervention Name(s)
urinary hCG (u-hCG)
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Follitropin alpha
Intervention Description
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.
Primary Outcome Measure Information:
Title
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
Description
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).
Time Frame
Mid-luteal phase progesterone assessed (Day 5 to 10) or clinical pregnancy (Day 35 to 42) post hCG treatment
Secondary Outcome Measure Information:
Title
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
Description
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.
Time Frame
Mid-luteal phase progesterone assessed (Day 5 to 10) or clinical pregnancy (Day 35 to 42) post hCG treatment
Title
Mid-luteal Endometrial Thickness
Description
Endometrial thickness was measured using TVUS.
Time Frame
Day 5 to 7 post hCG treatment
Title
Percentage of Participants With Biochemical Pregnancy
Description
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)
Time Frame
Day 35 to 42 post hCG treatment
Title
Percentage of Participants With Clinical Pregnancy
Description
Percentage of subjects with clinical pregnancy was assessed. Clinical pregnancy was defined as the presence of at least a fetal sac on TVUS.
Time Frame
Day 35 to 42 post hCG treatment

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
39 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Responsible
Organizational Affiliation
Merck Serono Co., Ltd., Japan
Official's Role
Study Director
Facility Information:
Facility Name
Hanabusa Women's Central Fertility Clinic
City
Hyogo
Country
Japan
Facility Name
Bashamichi Ladies Clinic
City
Kanagawa
Country
Japan
Facility Name
Sophia Ladies Clinic
City
Kanagawa
Country
Japan
Facility Name
Ivf Namba Clinic
City
Osaka
Country
Japan
Facility Name
Ivf Osaka Clinic
City
Osaka
Country
Japan
Facility Name
Department of Obstetrics and Gynecology, Saitama Medical University Hospital
City
Saitama
Country
Japan

12. IPD Sharing Statement

Learn more about this trial

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

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