InfertilityPhase 4LoGoNCT01871532
Low-dose Gonal-f® in Ovulation Induction
A Phase 4 study testing Gonal-f® in people with Infertility and Monofollicular Development, run by Merck KGaA, Darmstadt, Germany at 10 sites in 2 countries.
Trial summary
This is a prospective, multicenter, open-label, comparative and parallel-group study of ovulation induction evaluating tailoring of Recombinant follicle stimulating hormone (FSH) treatment using the Gonal-f® prefilled pen in World Health Organization (WHO) Type 2 anovulatory subjects who have previously failed to… Read more about this study
- Who is it for?
- Ages 18 to 37 years, women only
- Conditions the study is for
- Infertility, Monofollicular Development
- What is being tested?
- Gonal-f®
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 10 sitesin 2 countries
- Study dates
- Jul 2013to Nov 2014
- Phase
- Phase 4
- 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 18 to 37 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Subjects eligible for ovulation induction treatment, where monofollicular development is the desired treatment outcome and the dose schedule outlined in the protocol is deemed appropriate
- Premenopausal female subjects, aged between 18 and 37 years inclusive
- Subjects desirous of pregnancy/willing to conceive
- Subjects who are infertile due to chronic anovulation demonstrated by cycle duration of greater than 35 days.
- Subjects who have been treated with clomifene citrate therapy, according to standard site practice, and have failed to ovulate and/or conceive
- Subjects with follicle stimulating hormone (FSH) and prolactin (PRL) serum values within the normal range in the early follicular phase
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- Subjects with an overall total antral follicle count greater than 10 (of follicle size greater than or equal to 2 millimeter [mm] and less than 11 mm) (that is, total between both ovaries)
- Subjects with at least one patent tube, as documented by recent (within 2 years before treatment assignment) hysterosalpingography (HSG) or hysterosalpingo contrast sonography (HyCoSy)
- Subjects with normal uterine cavity, as documented by recent (within 2 years before treatment assignment) hysteroscopy, HSG or ultrasound scan
- Subjects with body mass index (BMI) greater than 20 and less than or equal to 32 kilogram per square meter (kg/m^2) (BMI is equal to body weight [kilogram {kg}] divided by Height * Height [square meter {m^2}])
- Subjects with negative cervical Papanicolaou (PAP) test conducted according to national guidelines and/or standard site practice
- Male partners of female subjects with sperm compatible with non-assisted fertilization or availability of donor sperm, as confirmed by the Investigator
- Subjects who are willing and able to comply with protocol requirements and have provided written, informed consent
Who cannot join
- Subjects with history of hypersensitivity to the investigational medicinal product (IMP) (active substance follitropin alpha, FSH, or to any of the excipients of Gonal-f®) or any other drug used in the trial (that is, Ovitrelle)
- Subjects with ovarian enlargement or ovarian cyst unrelated to Polycystic Ovary Syndrome (PCOS), and of unknown origin on ultrasound
- Subjects with evidence of diminished ovarian reserve (cycle length less than 26 days; FSH above the upper limit of local serum FSH values, total antral follicle count [AFC] in both ovaries less than 10)
- Subjects with uterine pathology/abnormalities, which in the opinion of the Investigator could impair pregnancy evolution
- Subjects who have undergone three or more previous miscarriages
- Subjects with any previous extrauterine pregnancy
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- Pregnant or lactating female subjects
- Subjects with abnormal gynecological bleeding of unknown etiology.
- Subjects with previous history of severe ovarian hyper stimulation syndrome (OHSS) (after clomifene treatment)
- Subjects who have evidence of current or previous pelvic inflammatory disease before treatment assignment
- Subjects with tumors of the hypothalamus and pituitary gland
- Subjects with ovarian, uterine or mammary carcinoma
- Subjects treated with clomifene citrate or gonadotropins within 1 month of the screening evaluation
- Subjects with any medical condition which, in the opinion of the Investigator, would prevent an effective response, such as primary ovarian failure, or malformations of the reproductive organs incompatible with pregnancy
- Subjects with any medical condition which, in the opinion of the Investigator, may interfere with the absorption, distribution, metabolism or excretion of the drug
- Subjects with any clinically significant systemic disease (for example, insulin-dependent diabetes) or any contraindication to being pregnant and/or carrying a pregnancy to term
- An active substance abuser
- Known infection with human immunodeficiency virus (HIV), Hepatitis B or C virus in the trial subject or her male partner
- Subjects who are currently participating in another clinical trial
- Subjects who are unable to give written informed consent
Trial locations and contacts
10 sites in 2 countries.
10 sites in 2 countries
United Kingdom7 sites
Research Site
Cambridge
Research site
Cheshunt
Research Site
Derby
Research Site
Edinburgh
Research Site
Glasgow
Research site
London
Research Site
Nottingham
About this study
Official title: A Multi-Centre, Two-Arm, Interventional, Phase IV Study to Evaluate Tailoring of Recombinant FSH Treatment in Subjects With Chronic Anovulation Using the Gonal-f® Prefilled Pen in Women Undergoing Ovulation Induction
This is a prospective, multicenter, open-label, comparative and parallel-group study of ovulation induction evaluating tailoring of Recombinant follicle stimulating hormone (FSH) treatment using the Gonal-f® prefilled pen in World Health Organization (WHO) Type 2 anovulatory subjects who have previously failed to conceive with clomifene treatment.
Read the detailed description
Subjects will enter a screening period of up to one month before being randomized at the Baseline Visit, which will occur on Day 1 of the subject's menstrual cycle. Each subject will then receive up to 4 weeks treatment with Gonal-f®. If adequate follicular development (assessed by transvaginal ultrasound) is achieved, the subject will proceed to administration of human chorionic gonadotropin (hCG) within 24-48hrs of last Gonal-f® injection (or according to standard site practice).
Following administration of hCG, subjects will attempt to become pregnant via intercourse or intrauterine insemination. The method of conception will be determined by the subject's requirements and standard practice at the clinic site.
All subjects will be followed up appropriately until confirmation of biochemical pregnancy (hCG + minimum 14 days) and clinical pregnancy (hCG + minimum 42 days, for subjects with positive biochemical pregnancy test).
- Conditions
- Infertility, Monofollicular Development
- Being tested
- Gonal-f®
- Keywords
- Monofollicular Development, Gonal-f®, Recombinant Follicle Stimulating Hormone, Ovarian hyperstimulation syndrome (OHSS)
- Medical subject headings
- Infertility, Ovarian Hyperstimulation Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Gonal-f®Drug
Also called Recombinant follicle stimulating hormone (r-FSH)
| Study group | Role | What they receive |
|---|---|---|
| Low Dose Gonal-f® Protocol | Experimental | Gonal-f was administered subcutaneously daily at a starting dose of 50 International unit (IU) for Week 1, then dose was gradually increased by 12.5 IU for two weeks, with a final increase of 25 IU, up to maximum dose of 100 IU, until Week 4 for subjects with minimal response. After adequate follicular development was achieved, the subject was administration human chorionic gonadotropin (hCG) within 24-48 hours of last Gonal-f injection as per investigator discretion. Receives: Drug: Gonal-f® |
| Standard Low Dose Gonal-f® Protocol | Active comparator | Gonal-f was administered subcutaneously daily at a starting dose of 50 International Units (IU) for Week 1, then dose was gradually increased by 12.5 IU for two weeks, up to maximum dose of 125 IU, until Week 4 for subjects with minimal response. After adequate follicular development was achieved, the subject was administration human chorionic gonadotropin (hCG) within 24-48 hours of last Gonal-f injection as per investigator discretion. Receives: Drug: Gonal-f® |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Cycles With Monofollicular Development
The monofollicular development was defined as the number of cycles with monofollicular development only one Follicle Greater Than or Equal (>= to 17 millimeter (mm) and no other follicles Greater than or equal to 14 mm following up to 4 weeks Gonal-f treatment.
Measured: Baseline up to 4 weeks
Secondary outcomes (14)
Percentage of Cycles With Bifollicular Development
The bifollicular development was defined as the number of cycles with bifollicular development of only two follicles greater than or equal to 17 millimeter.
Measured: Baseline up to 4 weeks
Percentage of Cycles With Multifollicular Development
The multifollicular development was defined as the number of cycles with multifollicular development of three or more follicles greater than or equal to 14 millimeter
Measured: Baseline up to 4 weeks
Percentage of Ovulatory Cycles
Ovulation was defined as a serum progesterone (P4 ) level greater than or equal to 10 nanogram per milliliter (ng/mL) or Clinical Pregnancy. Clinical pregnancy was defined as pregnancy diagnosed by ultrasonographic visualization of one or more gestational sacs or definitive clinical signs of pregnancy. It excludes ectopic pregnancy.
Measured: Baseline up to 42 days post human chorionic gonadotrophin (hCG) administration
Percentage of Cycles Wherein Human Chorionic Gonadotropin (hCG) Was Not Administered
Measured: Baseline up to 4 weeks
Percentage of Cycles Resulting in Clinical Pregnancy
Clinical pregnancy was defined as pregnancy diagnosed by ultrasonographic visualization of one or more gestational sacs or definitive clinical signs of pregnancy. It excludes ectopic pregnancy.
Measured: 35-42 days post hCG administration
Number of Multiple Pregnancy
Multiple pregnancy is a pregnancy where more than one fetus develops simultaneously in the womb. There are two types of twinning-identical and fraternal. Identical twins represent the splitting of a single fertilized zygote (union of two gametes or male/female sex cells that produce a developing fetus) into two separate individuals.
Measured: 35-42 days post hCG administration
Number of Fetuses
Measured: 35-42 days post hCG administration
Number of Miscarriages After Confirmation of Clinical Pregnancy
Miscarriages were calculated per clinical pregnancy, and clinical pregnancy was defined as pregnancy diagnosed by ultrasonographic visualization of one or more gestational sacs or confirmed by clinical signs of pregnancy. It excludes ectopic pregnancy.
Measured: 35-42 days post hCG administration
Number of Subjects With Ovarian Hyper Stimulation Syndrome (OHSS)
OHSS was defined as an exaggerated systemic response to ovarian stimulation characterized by a wide spectrum of clinical and laboratory manifestations, classified as mild, moderate or severe according to the degree of abdominal distention, ovarian enlargement and respiratory, hemodynamic and metabolic complications.
Measured: up to 42 days post hCG administration
Duration of Recombinant Follicle Stimulating Hormone (rFSH) Stimulation
Measured: Baseline up to 4 weeks
Total Dose of Recombinant Follicle Stimulating Hormone (r-FSH) Administered Per Cycle
Measured: Baseline up to 4 weeks
Change From Baseline in Anti-Mullerian Hormone (AMH) Levels at Week 4
Measured: Baseline, Week 4
Testosterone Levels
Measured: Baseline
Sex Hormone Binding Globulin (SHBG) Levels
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jun 2013 (estimated)
- Study startJul 2013
- Primary completionMar 2014
- Study completionNov 2014
Why it stopped: Study was terminated because of delays in sourcing replacement Investigational Medicinal Product for the study due to manufacturing delays.
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 InfertilityStudies 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck KGaA, Darmstadt, Germany
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Responsible, Study director, Merck Serono Limited, UK
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01871532
- Sponsor's protocol ID
- EMR700623_535
- Other IDs
- 2012-003227-38
- Acronym
- LoGo
- Status last verified
- Jun 2016
- First submitted
- 4 Jun 2013
- Last updated
- 11 Aug 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 11 Aug 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-Centre, Two-Arm, Interventional, Phase IV Study to Evaluate Tailoring of Recombinant FSH Treatment in Subjects With Chronic Anovulation Using the Gonal-f® Prefilled Pen in Women Undergoing Ovulation Induction
- ClinicalTrials.gov ID
- NCT01871532
- Acronym / sponsor ID
- LoGo / EMR700623_535
- Conditions
- Infertility, Monofollicular Development
- Keywords
- Monofollicular Development, Gonal-f®, Recombinant Follicle Stimulating Hormone, Ovarian hyperstimulation syndrome (OHSS)
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study was terminated because of delays in sourcing replacement Investigational Medicinal Product for the study due to manufacturing delays.
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Merck KGaA, Darmstadt, GermanyIndustry (pharma, biotech, devices)
- Study start
- Jul 2013
- Primary completion
- Mar 2014 (actual)
- Study completion
- Nov 2014 (actual)
- First posted
- 6 Jun 2013 (estimated)
- Results
- Posted 11 Aug 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 a prospective, multicenter, open-label, comparative and parallel-group study of ovulation induction evaluating tailoring of Recombinant follicle stimulating hormone (FSH) treatment using the Gonal-f® prefilled pen in World Health Organization (WHO) Type 2 anovulatory subjects who have previously failed to conceive with clomifene treatment.
Detailed description
Subjects will enter a screening period of up to one month before being randomized at the Baseline Visit, which will occur on Day 1 of the subject's menstrual cycle. Each subject will then receive up to 4 weeks treatment with Gonal-f®. If adequate follicular development (assessed by transvaginal ultrasound) is achieved, the subject will proceed to administration of human chorionic gonadotropin (hCG) within 24-48hrs of last Gonal-f® injection (or according to standard site practice).
Following administration of hCG, subjects will attempt to become pregnant via intercourse or intrauterine insemination. The method of conception will be determined by the subject's requirements and standard practice at the clinic site.
All subjects will be followed up appropriately until confirmation of biochemical pregnancy (hCG + minimum 14 days) and clinical pregnancy (hCG + minimum 42 days, for subjects with positive biochemical pregnancy test).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Low Dose Gonal-f® Protocol | Experimental | Drug: Gonal-f®Gonal-f was administered subcutaneously daily at a starting dose of 50 International unit (IU) for Week 1, then dose was gradually increased by 12.5 IU for two weeks, with a final increase of 25 IU, up to maximum dose of 100 IU, until Week 4 for subjects with minimal response. After adequate follicular development was achieved, the subject was administration human chorionic gonadotropin (hCG) within 24-48 hours of last Gonal-f injection as per investigator discretion. |
| Standard Low Dose Gonal-f® Protocol | Active comparator | Drug: Gonal-f®Gonal-f was administered subcutaneously daily at a starting dose of 50 International Units (IU) for Week 1, then dose was gradually increased by 12.5 IU for two weeks, up to maximum dose of 125 IU, until Week 4 for subjects with minimal response. After adequate follicular development was achieved, the subject was administration human chorionic gonadotropin (hCG) within 24-48 hours of last Gonal-f injection as per investigator discretion. |
Who may qualify
- Ages
- 18 to 37 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (13 listed)
- Subjects eligible for ovulation induction treatment, where monofollicular development is the desired treatment outcome and the dose schedule outlined in the protocol is deemed appropriate
- Premenopausal female subjects, aged between 18 and 37 years inclusive
- Subjects desirous of pregnancy/willing to conceive
- Subjects who are infertile due to chronic anovulation demonstrated by cycle duration of greater than 35 days.
- Subjects who have been treated with clomifene citrate therapy, according to standard site practice, and have failed to ovulate and/or conceive
Key exclusion criteria (20 listed)
- Subjects with history of hypersensitivity to the investigational medicinal product (IMP) (active substance follitropin alpha, FSH, or to any of the excipients of Gonal-f®) or any other drug used in the trial (that is, Ovitrelle)
- Subjects with ovarian enlargement or ovarian cyst unrelated to Polycystic Ovary Syndrome (PCOS), and of unknown origin on ultrasound
- Subjects with evidence of diminished ovarian reserve (cycle length less than 26 days; FSH above the upper limit of local serum FSH values, total antral follicle count [AFC] in both ovaries less than 10)
- Subjects with uterine pathology/abnormalities, which in the opinion of the Investigator could impair pregnancy evolution
- Subjects who have undergone three or more previous miscarriages
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 |
|---|---|---|
| Gonal-f®Also: Recombinant follicle stimulating hormone (r-FSH) | Drug | Low Dose Gonal-f® Protocol, Standard Low Dose Gonal-f® Protocol |
Primary outcome
Percentage of Cycles With Monofollicular Development
Time frame: Baseline up to 4 weeks
The monofollicular development was defined as the number of cycles with monofollicular development only one Follicle Greater Than or Equal (>= to 17 millimeter (mm) and no other follicles Greater than or equal to 14 mm following up to 4 weeks Gonal-f treatment.
14 secondary outcomes
Percentage of Cycles With Bifollicular Development
Time frame: Baseline up to 4 weeks
Percentage of Cycles With Multifollicular Development
Time frame: Baseline up to 4 weeks
Percentage of Ovulatory Cycles
Time frame: Baseline up to 42 days post human chorionic gonadotrophin (hCG) administration
Percentage of Cycles Wherein Human Chorionic Gonadotropin (hCG) Was Not Administered
Time frame: Baseline up to 4 weeks
Percentage of Cycles Resulting in Clinical Pregnancy
Time frame: 35-42 days post hCG administration
Number of Multiple Pregnancy
Time frame: 35-42 days post hCG administration
Number of Fetuses
Time frame: 35-42 days post hCG administration
Number of Miscarriages After Confirmation of Clinical Pregnancy
Time frame: 35-42 days post hCG administration
Number of Subjects With Ovarian Hyper Stimulation Syndrome (OHSS)
Time frame: up to 42 days post hCG administration
Duration of Recombinant Follicle Stimulating Hormone (rFSH) Stimulation
Time frame: Baseline up to 4 weeks
Total Dose of Recombinant Follicle Stimulating Hormone (r-FSH) Administered Per Cycle
Time frame: Baseline up to 4 weeks
Change From Baseline in Anti-Mullerian Hormone (AMH) Levels at Week 4
Time frame: Baseline, Week 4
Testosterone Levels
Time frame: Baseline
Sex Hormone Binding Globulin (SHBG) Levels
Time frame: Baseline
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Aug 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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 Limited, UK
10 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Gonal-f® in people with Infertility and Monofollicular Development, run by Merck KGaA, Darmstadt, Germany at 10 sites in 2 countries.
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 13 inclusion and 20 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: stopped early, as of the sponsor's last update on 11 Aug 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United Kingdom, Ireland. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 11 Aug 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 Cycles With Monofollicular Development (time frame: Baseline up to 4 weeks). 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 11 Aug 2016; AzTrials last refreshed its copy on 30 Oct 2026.