AnovulationPhase 3NCT01653743
Trial to Assess the Clinical Efficacy and Safety of MSJ-0011 in Inducing Ovulation in Anovulatory or Oligo-ovulatory Japanese Women
A Phase 3 study testing MSJ-0011, urinary hCG (u-hCG) and Follitropin alpha in people with Anovulation and Oligo-ovulation, run by Merck KGaA, Darmstadt, Germany at 6 sites in Japan.
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… Read more about this study
- Who is it for?
- Ages 20 to 39 years, women only
- Conditions the study is for
- Anovulation, Oligo-ovulation, Hypothalamic-pituitary Dysfunction
- What is being tested?
- MSJ-0011, urinary hCG (u-hCG) and Follitropin alpha
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 81 participants
- Where
- 6 sitesJapan
- Study dates
- Sep 2012to Dec 2014
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 39 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- 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)
Show all 9Show fewer
- 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
Who cannot join
- 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
Show all 17Show fewer
- 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
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
Japan6 sites
Hanabusa Women's Central Fertility Clinic
Hyōgo
Bashamichi Ladies Clinic
Kanagawa
Sophia Ladies Clinic
Kanagawa
Ivf Namba Clinic
Osaka
Ivf Osaka Clinic
Osaka
Department of Obstetrics and Gynecology, Saitama Medical University Hospital
Saitama
About this study
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
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
- Being tested
- MSJ-0011, urinary hCG (u-hCG), Follitropin alpha
- Keywords
- Japanese
- Medical subject headings
- Anovulation, Polycystic Ovary Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MSJ-0011Drug
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)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.
Follitropin alphaDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| MSJ-0011 | Experimental | Not described Receives: Drug: MSJ-0011; Drug: Follitropin alpha |
| urinary hCG | Active comparator | Not described Receives: Drug: urinary hCG (u-hCG); Drug: Follitropin alpha |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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
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.
Measured: Mid-luteal phase progesterone assessed (Day 5 to 10) or clinical pregnancy (Day 35 to 42) post hCG treatment
Mid-luteal Endometrial Thickness
Endometrial thickness was measured using TVUS.
Measured: Day 5 to 7 post hCG treatment
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)
Measured: Day 35 to 42 post hCG treatment
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.
Measured: Day 35 to 42 post hCG treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jul 2012 (estimated)
- Study startSep 2012
- Primary completionNov 2014
- Study completionDec 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for AnovulationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 81 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck KGaA, Darmstadt, Germany
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Merck Serono Co., Ltd., Japan
- Responsible party
- Sponsor
- Investigators
- Medical Responsible, Study director, Merck Serono Co., Ltd., Japan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01653743
- Sponsor's protocol ID
- EMR701173_002
- Status last verified
- Dec 2015
- First submitted
- 20 Jul 2012
- Last updated
- 7 Jan 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Jan 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01653743
- Acronym / sponsor ID
- EMR701173_002
- Conditions
- Anovulation, Oligo-ovulation, Hypothalamic-pituitary Dysfunction, Polycystic Ovarian Syndrome
- Keywords
- Japanese
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 81 participants (actual)
- Lead sponsor
- Merck KGaA, Darmstadt, GermanyIndustry (pharma, biotech, devices)
- Collaborators
- Merck Serono Co., Ltd., Japan
- Study start
- Sep 2012
- Primary completion
- Nov 2014 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 31 Jul 2012 (estimated)
- Results
- Posted 7 Jan 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| MSJ-0011 | Experimental | Drug: MSJ-0011, Drug: Follitropin alpha |
| urinary hCG | Active comparator | Drug: urinary hCG (u-hCG), Drug: Follitropin alpha |
Who may qualify
- Ages
- 20 to 39 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- 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.
Key exclusion criteria (17 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MSJ-0011Subjects 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 | MSJ-0011 |
| 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 | urinary hCG |
| Follitropin alphaLow-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. | Drug | MSJ-0011, urinary hCG |
Primary outcome
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
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).
4 secondary outcomes
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
Mid-luteal Endometrial Thickness
Time frame: Day 5 to 7 post hCG treatment
Percentage of Participants With Biochemical Pregnancy
Time frame: Day 35 to 42 post hCG treatment
Percentage of Participants With Clinical Pregnancy
Time frame: Day 35 to 42 post hCG treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jan 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Anovulation
RecruitingPhase 1
Efficacy of Injectable Vitamin D Supplementation in Females With Polycystic Ovary Syndrome
Anovulatory Infertility
RecruitingPhase 2
A Study to Investigate Mibavademab in Adult Women With Functional Hypothalamic Amenorrhea
Functional Hypothalamic Amenorrhea, FHA
Not yet recruitingObservational study
Half-dose vs Conventional-dose Cetrorelix in ICSI Cycles
Infertility, Infertility, Female
Recruiting
Sperm Preparation Prior to Intrauterine Insemination Study
Infertility, Infertility Secondary
Not yet recruiting
Ovarian Stromal Stiffness and Ovarian Reserve Parameters Via Transvaginal Shear Wave Elastography
Ovarian Reserve Markers, Ovarian Function
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Responsible study director
Merck Serono Co., Ltd., Japan
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing MSJ-0011, urinary hCG (u-hCG) and Follitropin alpha in people with Anovulation and Oligo-ovulation, run by Merck KGaA, Darmstadt, Germany at 6 sites in Japan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Jan 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 Jan 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jan 2016.