An Efficacy and Safety Study of Corifollitropin Alfa Versus Daily Follitropin Beta for Controlled Ovarian Stimulation in Women 35-42 Years Old With a Body Weight ≥ 50 kg Undergoing IVF Treatment.
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 400
- 试验地点
- 2
- 主要终点
- number of oocytes
研究概览
简要总结
A prospective, randomized, controlled study to explore the efficacy and safety of using either corifollitropin alfa 150 mcg or daily recombinant follicle stimulation hormone (FSH) 300 international unit (IU) for the stimulation treatment of subjects undergoing controlled ovarian stimulation prior to IVF.
The study is designed as a non-inferiority trial. The sample size for this trial of 400 subjects, in both groups, being treated for one IVF cycle is based upon the primary endpoint of the number of oocytes retrieved.
详细描述
Stimulation regimen and assisted reproductive technology procedures
Corifollitropin Alfa Group: On day 2 or day 3 of the menstrual cycle, a single subcutaneous injection of corifollitropin alfa 150 mg/ 0.5 mL is administered (stimulation day 1).
FSH Group: Daily subcutaneous injections with recombinant FSH (Follitropin Beta) 300 international units (IU) is started on On day 2 or day 3 of the menstrual cycle (stimulation day 1) and continue up to and including stimulation day 7.
From stimulation day 8 onwards, subjects from both treatment groups will continue with a daily subcutaneous dose of FSH up to the day before human chorionic gonadotropin (hCG) administration or gonadotropin releasing hormone agonist administration day. The maximum FSH dose to continue treatment after the first 7 days is 300 IU, but the dose could be reduced when desired.
To prevent premature luteinizing hormone (LH) surges the gonadotropin releasing hormone (GnRH) antagonist (ganirelix acetate subcutaneous injection, 0.25 mg/ 0.5 mL) is administered, starting on stimulation day 5.
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
- 35 Years 至 42 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Each subject must be willing and able to provide written informed consent for the study.
- •Each subject must be female with years of age ≥35 to ≤42 at the time of recruitment..
- •Each subject must have an indication for controlled ovarian stimulation and IVF
- •Each subject must have a body weight ≥ 50.0 kg, with a body mass index (BMI) ≥18.0 to ≤32.0 kg/m
- •Each subject must have a regular spontaneous menstrual cycle with an intra-individual variation not outside the 24 to 35 days range.
- •For each subject, ejaculatory sperm must be available (use of donated and/or cryopreserved sperm is allowed; sperm obtained via surgical sperm retrieval is not allowed).
- •Each subject must have results of clinical laboratory test (complete blood count, blood chemistries, and urinalysis) within normal limits or clinically acceptable to the investigator, as measured by the local laboratory at screening. A normal cervical smear result, obtained within 12 months, otherwise it must be obtained during screening.
- •Each subject must have results of a physical examination, including blood pressure, within normal limits or clinically acceptable limits to the investigator.
- •Each subject must have normal ovarian reserve, based on anti-Mullerian hormon (AMH) of 1.38 - 3.25ng/ml or an antral follicle count (AFC) of 7-20, taken within 2 months prior to corifollitropin alfa start.
- •Each subject must be able to adhere to dose and visit schedules and willing to disclose any medical events to the investigator.
排除标准
- •The subject has a recent (ie, within 3 years) history of/ or any current endocrine abnormality (irrespective whether the patient is stabilized on treatment).
- •The subject has a history of ovarian hyper-response (ie, previous IVF cycle with more than 30 follicles ≥11 mm on ultrasound) or ovarian hyperstimulation syndrome (OHSS).
- •The subject has a history of/or current polycystic ovary syndrome (PCOS)
- •The subject has more 20 basal antral follicles <11 mm (both ovaries combined) as measured on ultrasound in the early follicle phase (menstrual cycle day 2-5).
- •The subject has less than 2 ovaries in any other ovarian abnormality (including endometrioma > 10 mm; visible on ultrasound).
- •The subject has unilateral or bilateral hydrosalpinx (visible on ultrasound, less clipped).
- •The subject has any intra-uterine fibroids >5 cm or any clinically relevant pathology, which could impair embryo implantation or pregnancy continuation.
- •The subject has more than three unsuccessful treatment cycles for IVF/ICSI.
- •The subject has a history of non- or low avarian response to FSH / Human Menopausal Gonadotropin (hMG) treatment (ie, previous COS cycle cancelled due to insufficient ovarian response or ≤3 oocytes obtained).
- •The subject has a history of current miscarriage (3 or more, even when explained).
- •The subject has FSH > 15.0 IU/L or LH > 12 .0 IU/L as measured by the local laboratory (sample taken during the early follicle phase: menstrual cycle day 2 to 5).
- •The subject has tested positive for human immunodeficiency virus (HIV) or Hepatitis B (results obtained within one year) .
- •The subject has contra-indications for the use of gonadotropins (eg, tumors, pregnancy/lactation, undiagnosed vaginal bleeding, hypersensitivity, or ovarian cysts) or GnRH antagonist (eg, hypersensitivity, pregnancy/lactation).
- •The subject has a concomitant use of either LH or hMG/urinary FSH preparations in study cycle.
- •The subject has a recent history of/or current epilepsy, thrombophilia, diabetes, cardiovascular, gastro-intestinal, hepatic, renal or pulmonary or auto-immune disease requiring regular treatment.
- •The subject or the sperm donor has known gene defects, genetic abnormalities, or abnormal karyotyping, relevant for the current indications or for the health of the offspring.
- •The subject smokes or has recently stopped smoking (ie, within the last 3 months prior to signing ICF).
- •The subject has a history or presence of alcohol or drug abuse within 12 months prior to signing informed consent.
- •The subject has an allergy/ sensitivity to investigational drugs or their excipients.
- •The subject has used any experimental drugs within 3 months prior to signing informed consent.
- •The subject is participating in any other clinical study (excluding surveys).
研究组 & 干预措施
corifollitropin alfa (long action FSH)
corifollitropin alfa 150 mcg subcutaneous injection. Seven days after, combines with recombinant FSH 300 IU daily subcutaneous injection
干预措施: corifollitropin alfa (Drug)
Follitropin Beta (recombinant FSH)
300 IU of recombinant FSH, daily subcutaneous injection
干预措施: Follitropin Beta (Drug)
结局指标
主要结局
number of oocytes
时间窗: 10 minutes after oocyte retrieval completed
in 10 minutes after oocyte retrieval, total number of oocytes retrieved is counted and recorded
次要结局
- Rate of moderate and severe ovarian hyperstimulation syndrome(8 days after oocyte retrieval)
- Live birth(at the time of delivery)
- number of MII oocytes(2 hours after oocyte retrieval completed)
- number of 2PN(18 hours after sperm injection)
- estradiol level(on the day of hCG administration)
- FSH dose(calculated on the day of hCG administration)
- implantation rate(5 to 6 weeks after embryo transfer)
- number of mature follicles >11 mm(on the day of hCG administration)
- Clinical pregnancy(at 5 to 6 six weeks after embryo transfer)
- Ectopic pregnancy(7 to 8 weeks after embryo transfer)
- Miscarriage(7 to 12 weeks of gestation)
- Multiple pregnancy(at 7 weeks of gestation)
- Ongoing pregnancy(at 10 weeks after embryo transfer)
- Cumulative ongoing pregnancy(at 12 months after randomization)
- Pregnancy-induced hypertension(measured at or after 20 weeks gestation)
- Pre-eclampsia(measured at or after 20 weeks gestation)
- HELLP syndrome(measured at or after 20 weeks gestation)
- Gestational diabetes mellitus(measured at or after 20 weeks gestation)
- Prematurity(at 24 weeks gestation, at 32 weeks gestation, at 34 weeks gestation, and at 37 weeks' gestation)
- Cumulative live birth(at 12 months after randomization)
研究者
Manh Tuong Ho
Doctor
Vietnam National University