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
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 入组人数
- 24
- 试验地点
- 2
- 主要终点
- Percentage of Cycles With Monofollicular Development
研究概览
简要总结
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.
详细描述
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 37 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Low Dose Gonal-f® Protocol
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.
干预措施: Gonal-f® (Drug)
Standard Low Dose Gonal-f® Protocol
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.
干预措施: Gonal-f® (Drug)
结局指标
主要结局
Percentage of Cycles With Monofollicular Development
时间窗: 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.
次要结局
- Percentage of Cycles Resulting in Clinical Pregnancy(35-42 days post hCG administration)
- Number of Multiple Pregnancy(35-42 days post hCG administration)
- Number of Miscarriages After Confirmation of Clinical Pregnancy(35-42 days post hCG administration)
- Percentage of Cycles With Multifollicular Development(Baseline up to 4 weeks)
- Percentage of Cycles With Bifollicular Development(Baseline up to 4 weeks)
- Change From Baseline in Anti-Mullerian Hormone (AMH) Levels at Week 4(Baseline, Week 4)
- Percentage of Ovulatory Cycles(Baseline up to 42 days post human chorionic gonadotrophin (hCG) administration)
- Number of Fetuses(35-42 days post hCG administration)
- Percentage of Cycles Wherein Human Chorionic Gonadotropin (hCG) Was Not Administered(Baseline up to 4 weeks)
- Number of Subjects With Ovarian Hyper Stimulation Syndrome (OHSS)(up to 42 days post hCG administration)
- Total Dose of Recombinant Follicle Stimulating Hormone (r-FSH) Administered Per Cycle(Baseline up to 4 weeks)
- Testosterone Levels(Baseline)
- Duration of Recombinant Follicle Stimulating Hormone (rFSH) Stimulation(Baseline up to 4 weeks)
- Sex Hormone Binding Globulin (SHBG) Levels(Baseline)