Clinical trial NCT01871532: Low-dose Gonal-f® in Ovulation Induction
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Infertility
Monofollicular Development
Keywords: Monofollicular Development
Gonal-f®
Recombinant Follicle Stimulating Hormone
Ovarian hyperstimulation syndrome (OHSS)
Lead sponsor: Merck KGaA, Darmstadt, Germany
Sponsor class: INDUSTRY
First posted: 2013-06-06
Enrollment: 24
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 37
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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 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).

Eligibility criteria: Inclusion Criteria:

* 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
* 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

Exclusion Criteria:

* 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
* 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

Primary outcomes:
measure: Percentage of Cycles With Monofollicular Development
timeFrame: Baseline up to 4 weeks
Secondary outcomes:
measure: Percentage of Cycles With Bifollicular Development
timeFrame: Baseline up to 4 weeks
measure: Percentage of Cycles With Multifollicular Development
timeFrame: Baseline up to 4 weeks
measure: Percentage of Ovulatory Cycles
timeFrame: Baseline up to 42 days post human chorionic gonadotrophin (hCG) administration
measure: Percentage of Cycles Wherein Human Chorionic Gonadotropin (hCG) Was Not Administered
timeFrame: Baseline up to 4 weeks
measure: Percentage of Cycles Resulting in Clinical Pregnancy
timeFrame: 35-42 days post hCG administration
measure: Number of Multiple Pregnancy
timeFrame: 35-42 days post hCG administration
measure: Number of Fetuses
timeFrame: 35-42 days post hCG administration
measure: Number of Miscarriages After Confirmation of Clinical Pregnancy
timeFrame: 35-42 days post hCG administration
measure: Number of Subjects With Ovarian Hyper Stimulation Syndrome (OHSS)
timeFrame: up to 42 days post hCG administration
measure: Duration of Recombinant Follicle Stimulating Hormone (rFSH) Stimulation
timeFrame: Baseline up to 4 weeks
measure: Total Dose of Recombinant Follicle Stimulating Hormone (r-FSH) Administered Per Cycle
timeFrame: Baseline up to 4 weeks
measure: Change From Baseline in Anti-Mullerian Hormone (AMH) Levels at Week 4
timeFrame: Baseline, Week 4
measure: Testosterone Levels
timeFrame: Baseline
measure: Sex Hormone Binding Globulin (SHBG) Levels
timeFrame: Baseline
Other outcomes:
Locations:
city: Cork
country: Ireland
facility: Research Site
city: Dublin
country: Ireland
facility: Research Site
city: Galway
country: Ireland
facility: Research Site
city: Cambridge
country: United Kingdom
facility: Research Site
city: Cheshunt
country: United Kingdom
facility: Research site
city: Derby
country: United Kingdom
facility: Research Site
city: Edinburgh
country: United Kingdom
facility: Research Site
city: Glasgow
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research site
city: Nottingham
country: United Kingdom
facility: Research Site
Study officials:
affiliation: Merck Serono Limited, UK
name: Medical Responsible
role: STUDY_DIRECTOR
References: