Phase III Investigator and Assessor Blinded 1:1 Randomized, Parallel-group Multicenter Study to Compare Efficacy and Safety of Two r-hFSH Formulations (AFOLIA vs Gonal-f® RFF) in Normal Ovulatory Women 35 to 42 Years Old Undergoing in Vitro Fertilization
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 1,100
- 试验地点
- 22
- 主要终点
- Clinical Pregnancy Rate After One Cycle of Treatment - ITT Population
研究概览
简要总结
The purpose of this study is to show that AFOLIA, a recombinant manufactured human follicle stimulating hormone (r-hFSH) has a similar efficacy and safety profile compared to Gonal-f® RFF.
详细描述
Comparison of the clinical pregnancy rate in the AFOLIA group compared to the US approved Gonal-f® RFF Redi-ject group as the primary endpoint. Comparison of the number and size of follicles, the number of cycle cancellation, the hormone parameters and adverse events in the AFOLIA group compared to the Gonal-f® RFF group as secondary endpoints.
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
- Double (Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 35 Years 至 42 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •35 to 42 years of age
- •Indication for controlled ovarian stimulation and IVF or intracytoplasmic sperm injection (ICSI)
- •Regular menstrual cycles (25-35 days)
- •History of a maximum of two fresh cycle treatments in the present series of assisted reproductive technologies (ART) at the day of first screening (thawed cycles are not subject to that criteria)
- •Body mass index (BMI) ≥18 and ≤38 kg/m2
- •Basal FSH <12 IU/L (cycle day 2-5)
- •Antral follicle count (AFC) ≥ 10 to ≤20 follicles with a diameter of <11mm (sum of both ovaries) as measured on ultrasound (US) in the early follicular phase (menstrual cycle day 2-5)
- •Documented history of infertility due to any of the following factors: tubal factor, mild endometriosis (American Society for Reproductive Medicine [ASRM] stage 1-2), male factor, unexplained infertility
- •Presence of both ovaries by ultrasonography and normal uterine cavity (confirmed by hysterosalpingography, saline infusion sonography or hysteroscopy within 6 months before randomization)
- •Male partner with semen analysis that is at least adequate for ICSI within 6 months prior to patient beginning down-regulation (invasive or surgical sperm retrieval, donor and/or cryopreserved sperm may be used)
- •Willingness to participate in the study and to comply with the study protocol
- •Signed informed consent prior to screening
排除标准
- •Presence of pregnancy
- •History of or active polycystic ovary syndrome (PCOS)
- •AFC >20 follicles with a diameter of <11 mm (both ovaries combined) as measured on US in the early follicular phase (menstrual cycle day 2-5)
- •History of >2 unsuccessful fresh ART retrieval cycles
- •Presence of uncontrolled endocrine disorder
- •Previous history or presence of severe OHSS
- •Intrauterine fibroids ≥5 cm or otherwise clinically relevant pathology that could impair embryo implantation or pregnancy continuation
- •History of recurrent spontaneous abortion (3 or more, even when unexplained)
- •Presence of severe endometriosis (ASRM stage 3 or stage 4) or hydrosalpinx
- •Neoplasia, including tumors of the hypothalamus and pituitary gland
- •Abnormal bleeding of undetermined origin
- •History of extrauterine pregnancy in the previous 3 months
- •Known allergy or hypersensitivity to progesterone or to any of the excipients (including peanut oil) of the additional study medications (GnRH agonist, Ovidrel®, and Crinone 8%®)
- •History of poor response to gonadotropin treatment (defined as fewer than 5 oocytes retrieved in a previous attempt)
- •Any hormonal treatment within 1 month before the start of the FSH treatment, with the exception of levothyroxine)
- •Egg donor
- •Administration of other investigational products within the previous month
- •Clinically abnormal findings at Visit 1
- •Concomitant participation in another study protocol
研究组 & 干预措施
AFOLIA
One subcutaneous injection of 225IU AFOLIA (follitropin alfa) per day (initial dose) for the first 5 days. From day 6 dose could be adjusted up (to a max of 450IU per day) or down (to a min of 75IU per day) in multiple increments of 37.5IU.
干预措施: AFOLIA (Drug)
Gonal-f® RFF
One subcutaneous injection of 225IU Gonal-f® RFF (follitropin alfa) per day (initial dose) for the first 5 days. From day 6 dose could be adjusted up (to a max of 450IU per day) or down (to a min of 75IU per day) in multiple increments of 37.5IU.
干预措施: Gonal-f® RFF (Drug)
结局指标
主要结局
Clinical Pregnancy Rate After One Cycle of Treatment - ITT Population
时间窗: Six weeks post embryo transfer
Clinical pregnancy was defined as presence of at least one intrauterine gestational sac and fetal heart activity as demonstrated by vaginal ultrasound at six weeks (42 +/- 1 day) post ET (Visit 11). The clinical pregnancy rate is the proportion of subjects who achieve clinical pregnancy, relative to the number of patients in the ITT population of the respective treatment arm.
Clinical Pregnancy Rate After One Cycle of Treatment - PP Population
时间窗: Six weeks post embryo transfer
Clinical pregnancy was defined as presence of at least one intrauterine gestational sac and fetal heart activity as demonstrated by vaginal ultrasound at six weeks (42 +/- 1 day) post ET (Visit 11). The clinical pregnancy rate is the proportion of subjects who achieve clinical pregnancy, relative to the number of patients in the PP population of the respective treatment arm.
次要结局
- Exposure to r-hFSH Injections: Days of r-hFSH Stimulation - Cycle 1(Measured at discretionary visits between Days 9 and 15 after FSH starts)
- Exposure to r-hFSH Injections: Total Dose of r-hFSH (IU) - Cycle 1(Measured at discretionary visits between Days 9 and 15 after FSH starts.)
- Adverse Events of Special Interest: Ovarian Hyperstimulation Syndrome (OHSS) - Cycle 2(Measured either 3 days after ooctye pick up (Visit 9) or 18 +/- 1 days after oocyte pick up (Visit 10).)
- Adverse Events of Special Interest: Ovarian Hyperstimulation Syndrome (OHSS) - Cycle 3(Measured either 3 days after ooctye pick up (Visit 9) or 18 +/- 1 days after oocyte pick up (Visit 10).)
- Number of Subjects With Detectable Specific Serum Binding to FSH by Surface Plasmon Resonance - Cycle 1(Immunogenicity samples were taken at baseline, Visit 5 (8 days after start of treatment), Visit 9 (5 days after the end of FSH treatment), Visit 10 (18 +/- 1 days after oocyte retrieval), and Visit 11 (42 +/- 1 days after embryo transfer).)
- Number of Subjects With Detectable Specific Serum Binding to FSH by Surface Plasmon Resonance - Cycle 2(Immunogenicity samples were taken at baseline, Visit 5 (8 days after start of treatment), Visit 9 (5 days after the end of FSH treatment), Visit 10 (18 +/- 1 days after oocyte retrieval), and Visit 11 (42 +/- 1 days after embryo transfer).)
- Exposure to r-hFSH Injections: Daily Dose of r-hFSH (IU) - Cycle 1(Measured at discretionary visits between Days 9 and 15 after FSH starts.)
- Number of Oocytes Retrieved - Cycle 1(Visit 8, 34-36 hours after hCG administration)
- Local and Systemic Adverse Events: Dermal Response to Injection - Cycle 1(Measure recorded in the Patient Diary which is maintained through entire FSH treatment, from FSH Start through to Day 16 after start of FSH (16 days).)
- Local and Systemic Adverse Events: Dermal Response to Injection by Severity - Cycle 1(Measure recorded in the Patient Diary which is maintained through entire FSH treatment, from FSH through to Day 16 after start of FSH (16 days).)
- Overall Summary of Adverse Events (AEs) - Cycle 1(Measured from the start of FSH treatment through to either the end FSH treatment + 30 days (up to 46 days) or to the last Telephone Follow-up / Live Birth Questionnaire on pregnancy outcome (if applicable) (up to 10 months).)
- Adverse Events of Special Interest: Ovarian Hyperstimulation Syndrome (OHSS) - Cycle 1(Measured either 3 days after ooctye pick up (Visit 9) or 18 +/- 1 days after oocyte pick up (Visit 10).)
- Number of Subjects With Detectable Specific Serum Binding to FSH by Surface Plasmon Resonance - Cycle 3(Immunogenicity samples were taken at baseline, Visit 5 (8 days after start of treatment), Visit 9 (5 days after the end of FSH treatment), Visit 10 (18 +/- 1 days after oocyte retrieval), and Visit 11 (42 +/- 1 days after embryo transfer).)