A Randomised, Partially Double-blind, Placebo-controlled, Parallel-group Exploratory Trial to Investigate the Effect of FE999302 in Women Undergoing Controlled Ovarian Stimulation With a Fixed Dose of Follitropin Delta in a Gonadotropin-releasing Hormone Antagonist Protocol
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 310
- 试验地点
- 1
- 主要终点
- Number of good-quality blastocysts
研究概览
简要总结
This is a phase 1b clinical trial with Choriogonadotropin beta (FE999302) and Follitropin delta (Rekovelle).
The trial is multicentre, randomized, partially double-blind, placebo-controlled, parallel-group investigating the effect of FE999302 on parameters influencing pregnancy rates in women undergoing controlled ovarian stimulation with a fixed dose of follitropin.
The primary endpoint is the number of good-quality blastocysts on day 5 after oocyte retrieval.
Secondary endpoints are number of follicles by size category and serum concentration of different hormones on stimulation day 6 and end-of stimulation, the number of stimulation days and oocytes retrieved, the number of metaphase II oocytes and fertilised oocytes, number of blastocysts on day 5, number of cryopreserved blastocysts, endometrial thickness at eos, positive bhcg rate, clinical pregnancy, vital pregnancy and ongoing pregnancy.
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
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 40 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Subject informed consent form signed before any trial-related activities.
- •In good physical and mental health as judged by the investigator.
- •Serum anti-Müllerian hormone (AMH) levels of 15.0-35.0 pmol/L at screening (measured at central laboratory).
- •Pre-menopausal women between the ages of 18 and 40 years. The subjects must be at least 18 years (including the 18th birthday) and no more than 40 years (up to the day before the 41st birthday) when they sign the informed consent(s).
- •Infertile women diagnosed with tubal infertility, unexplained infertility, endometriosis stage I/II or with partners diagnosed with male factor infertility, eligible for in vitro fertilisation (IVF) and/or intracytoplasmic sperm injection (ICSI) using fresh or frozen ejaculated sperm from male partner or sperm donor.
- •Infertility for at least 1 year before screening for subjects <35 years or for at least 6 months for subjects ≥35 years (not applicable in case of tubal or severe male factor infertility).
- •No more than two controlled ovarian stimulation cycles initiated, regardless of outcome (taking exclusion criteria 2 and 3 into account) and the subject must be suitable for treatment with 10 or 15 µg/day follitropin delta (corresponding to 150 or 225 IU).
- •Regular menstrual cycles of 24-35 days (both inclusive), presumed to be ovulatory.
- •Early follicular phase (cycle day 2-5) serum levels of follicle-stimulating hormone (FSH) between 1 and 15 IU/L (measured at central laboratory).
- •Body mass index (BMI) between 18.0 and 30.0 kg/m2 (both inclusive) at screening.
排除标准
- •Known polycystic ovary syndrome (PCOS) or known endometriosis stage III-IV (American Society for Reproductive Medicine, 2012).
- •Poor response in a previous controlled ovarian stimulation cycle using a gonadotropin starting dose of 150 IU/day or higher. Poor response is defined as <4 oocytes retrieved, or cycle cancellation before oocyte retrieval due to inadequate follicular development.
- •Excessive ovarian response in a previous controlled ovarian stimulation cycle for IVF/ICSI using a daily FSH/ human menopausal gonadotropin (hMG) dose of ≤225 IU, defined as ≥25 oocytes retrieved or cycle cancellation before oocyte retrieval due to excessive ovarian response, including risk of ovarian hyperstimulation syndrome (OHSS).
- •One or more follicles ≥10 mm (including cysts) observed on the transvaginal ultrasound before randomisation on stimulation day 1 (puncture of cysts is allowed before randomisation).
- •Known history of recurrent miscarriage (defined as three consecutive losses after ultrasound confirmation of pregnancy [excluding ectopic pregnancy] and before week 24 of pregnancy).
- •Any known clinically significant systemic disease (e.g. insulin-dependent diabetes).
- •Any known endocrine or metabolic abnormalities (pituitary, adrenal, pancreas, liver, or kidney) with the exception of controlled thyroid function disease.
- •Known tumours of the ovary, breast, uterus, adrenal gland, pituitary, or hypothalamus which would contraindicate the use of gonadotropins.
- •Any abnormal finding of clinical chemistry and haematology at screening or vital signs at randomisation, which is judged clinically relevant by the investigator and/or requires intervention.
- •Currently breast-feeding.
- •Undiagnosed vaginal bleeding.
- •Findings at the gynaecological examination at screening which preclude gonadotropin stimulation or are associated with a reduced chance of pregnancy, e.g. congenital uterine abnormalities or retained intrauterine device.
- •Pregnancy (negative urinary pregnancy tests must be documented at screening and before randomisation) or contraindication to pregnancy.
- •Use of fertility modifiers during the last menstrual cycle before start of stimulation in the trial, including dehydroepiandrosterone (DHEA) and metformin or cycle programming with oral contraceptives, progestogen, or estrogen preparations
研究组 & 干预措施
Placebo
Follitropin delta and FE 999302 placebo
干预措施: Follitropin delta (Drug)
Placebo
Follitropin delta and FE 999302 placebo
干预措施: FE999302 Placebo (Drug)
FE999302 and Placebo Every 2nd Day Group
Follitropin delta and FE 999302 every 2nd day and FE 999302 placebo every 2nd day
干预措施: Follitropin delta (Drug)
FE999302 and Placebo Every 2nd Day Group
Follitropin delta and FE 999302 every 2nd day and FE 999302 placebo every 2nd day
干预措施: FE999302 (Drug)
FE999302 and Placebo Every 2nd Day Group
Follitropin delta and FE 999302 every 2nd day and FE 999302 placebo every 2nd day
干预措施: FE999302 Placebo (Drug)
FE999302 Dose Group 1
Follitropin delta and FE 999302
干预措施: Follitropin delta (Drug)
FE999302 Dose Group 1
Follitropin delta and FE 999302
干预措施: FE999302 (Drug)
FE999302 Dose Group 2
Follitropin delta and FE 999302
干预措施: Follitropin delta (Drug)
FE999302 Dose Group 2
Follitropin delta and FE 999302
干预措施: FE999302 (Drug)
Placebo Group 2
Follitropin delta and FE 999302 placebo
干预措施: Follitropin delta (Drug)
Placebo Group 2
Follitropin delta and FE 999302 placebo
干预措施: FE999302 Placebo (Drug)
FE999302 Dose Group 3
Follitropin delta and FE 999302
干预措施: Follitropin delta (Drug)
FE999302 Dose Group 3
Follitropin delta and FE 999302
干预措施: FE999302 (Drug)
结局指标
主要结局
Number of good-quality blastocysts
时间窗: Day 5 after oocyte retrieval.
The number of good-quality blastocysts
次要结局
- Number of oocytes(Up to 22 days)
- Number of fertilised oocytes(Up to 22 days)
- Number of cryopreserved blastocysts(Up to 28 days)
- Number and size of follicles(On stimulation day 6 and up to 20 days)
- Number of Stimulation days(Up to 20 days)
- Number of blastocysts(Up to 27 days)
- Vital pregnancy(5-6 weeks after fresh transfer)
- Ongoing pregnancy(10-11 weeks after fresh transfer)
- Serum hormone concentrations(Up to 22 days)
- Number of metaphase II oocytes(Up to 22 days)
- Positive βhCG(13 to 15 days after fresh transfer)
- Clinical pregnancy(5-6 weeks after fresh transfer)
- Endometrial thickness(Up to 20 days, and up to 27 days)