A Phase III, Randomized, Double-Blind, Active-Controlled, Non-Inferiority Clinical Trial to Investigate the Efficacy and Safety of a Single Injection of Org 36286 (Corifollitropin Alfa) to Induce Multifollicular Development for Controlled Ovarian Stimulation Using Daily Recombinant FSH as Reference
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 1,509
- 主要终点
- Percentage of Participants With an Ongoing Pregnancy (Ongoing Pregnancy Rate)
研究概览
简要总结
To investigate the efficacy and safety of a single injection of 150 μg Corifollitropin Alfa (Organon 36286) to induce multifollicular development for controlled ovarian stimulation using daily recombinant FSH (recFSH) as a reference. The primary hypothesis is that a single injection of Corifollitropin Alfa is non-inferior to daily treatment with recFSH in initiating multifollicular growth.
详细描述
This is a randomized, double-blind, active-controlled, non-inferiority clinical trial investigating the efficacy and safety of a new treatment regimen with Corifollitropin Alfa, a recombinant gonadotropin applied to initiate and sustain follicular stimulation in controlled ovarian stimulation for Assisted Reproductive Technology (ART). For this regimen, participants receive a single injection of Corifollitropin Alfa and one week later, treatment is continued with daily recFSH up to the day of triggering final oocyte maturation. In the reference group participants receive daily injections of recFSH up to the day of triggering final oocyte maturation. Non-inferiority in ongoing pregnancy rates (assessed at least 10 weeks after embryo transfer) will be the primary endpoint for this trial. The number of oocytes retrieved will be analyzed as co-primary endpoint.
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 (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 36 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Females of couples with an indication for Controlled Ovarian Stimulation (COS) and in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI);
- •>=18 and <=36 years of age at the time of signing informed consent;
- •Body weight > 60 and <=90 kg and body mass index (BMI) >=18 and <=32 kg/m^2;
- •Normal menstrual cycle length: 24-35 days;
- •Availability of ejaculatory sperm (use of donated and/or cryopreserved sperm is allowed);
- •Willing and able to sign informed consent.
排除标准
- •History of/or any current (treated) endocrine abnormality;
- •History of ovarian hyper-response or ovarian hyperstimulation syndrome
- •History of/or current polycystic ovary syndrome (PCOS);
- •More than 20 basal antral follicles <11 mm (both ovaries combined) as measured on ultrasound scan (USS) in the early follicular phase (menstrual cycle day 2-5);
- •Less than 2 ovaries or any other ovarian abnormality (including endometrioma > 10 mm; visible on USS);
- •Presence of unilateral or bilateral hydrosalphinx (visible on USS);
- •Presence of any clinically relevant pathology affecting the uterine cavity or fibroids >=5 cm;
- •More than three unsuccessful IVF cycles since the last established ongoing pregnancy (if applicable);
- •History of non- or low ovarian response to FSH/ human menopausal gonadotropin (hMG) treatment;
- •History of recurrent miscarriage (3 or more, even when unexplained);
- •FSH > 12 IU/L or LH > 12 IU/L as measured by the local laboratory (sample taken during the early follicular phase: menstrual cycle day 2-5);
- •Any clinically relevant abnormal laboratory value based on a sample taken during the screening phase;
- •Contraindications for the use of gonadotropins (e.g. tumors, pregnancy/lactation, undiagnosed vaginal bleeding, hypersensitivity, ovarian cysts);
- •Recent history of/or current epilepsy, human immunodeficiency virus (HIV) infection, diabetes, cardiovascular, gastro-intestinal, hepatic, renal or pulmonary disease;
- •Abnormal karyotyping of the patient or her partner (if karyotyping is performed);
- •Smoking more than 5 cigarettes per day;
- •History or presence of alcohol or drug abuse within 12 months prior to signing informed consent;
- •Previous use of Org 36286;
- •Use of hormonal preparations within 1 month prior to randomization;
- •Hypersensitivity to any of the concomitant medication prescribed as part of the treatment regimen in this protocol;
- •Administration of investigational drugs within three months prior to signing informed consent.
研究组 & 干预措施
150 µg Corifollitropin Alfa
Participants received a single subcutaneous (SC) injection of 150 µg Corifollitropin Alfa (org 36286) on day 2 or 3 of the menstrual cycle (Stimulation Day 1); 7 daily SC injections from Stimulation Days 1 to 7 with placebo-recFSH; followed by daily SC injections with 200 IU recFSH up to the day of hCG. Daily SC injections of Ganirelix were administered from Stimulation Day 5 to the day of hCG; at which time a single dose of hCG was given when 3 follicles >= 17 mm. On the day of oocyte pick up (OPU) daily doses of progesterone were started and continued for up to 6 weeks or menses.
干预措施: Corifollitropin alfa (Drug)
150 µg Corifollitropin Alfa
Participants received a single subcutaneous (SC) injection of 150 µg Corifollitropin Alfa (org 36286) on day 2 or 3 of the menstrual cycle (Stimulation Day 1); 7 daily SC injections from Stimulation Days 1 to 7 with placebo-recFSH; followed by daily SC injections with 200 IU recFSH up to the day of hCG. Daily SC injections of Ganirelix were administered from Stimulation Day 5 to the day of hCG; at which time a single dose of hCG was given when 3 follicles >= 17 mm. On the day of oocyte pick up (OPU) daily doses of progesterone were started and continued for up to 6 weeks or menses.
干预措施: Placebo RecFSH / follitropin beta (Drug)
150 µg Corifollitropin Alfa
Participants received a single subcutaneous (SC) injection of 150 µg Corifollitropin Alfa (org 36286) on day 2 or 3 of the menstrual cycle (Stimulation Day 1); 7 daily SC injections from Stimulation Days 1 to 7 with placebo-recFSH; followed by daily SC injections with 200 IU recFSH up to the day of hCG. Daily SC injections of Ganirelix were administered from Stimulation Day 5 to the day of hCG; at which time a single dose of hCG was given when 3 follicles >= 17 mm. On the day of oocyte pick up (OPU) daily doses of progesterone were started and continued for up to 6 weeks or menses.
干预措施: RecFSH / Follitropin beta (Days 8 to hCG) (Biological)
150 µg Corifollitropin Alfa
Participants received a single subcutaneous (SC) injection of 150 µg Corifollitropin Alfa (org 36286) on day 2 or 3 of the menstrual cycle (Stimulation Day 1); 7 daily SC injections from Stimulation Days 1 to 7 with placebo-recFSH; followed by daily SC injections with 200 IU recFSH up to the day of hCG. Daily SC injections of Ganirelix were administered from Stimulation Day 5 to the day of hCG; at which time a single dose of hCG was given when 3 follicles >= 17 mm. On the day of oocyte pick up (OPU) daily doses of progesterone were started and continued for up to 6 weeks or menses.
干预措施: Ganirelix (Drug)
150 µg Corifollitropin Alfa
Participants received a single subcutaneous (SC) injection of 150 µg Corifollitropin Alfa (org 36286) on day 2 or 3 of the menstrual cycle (Stimulation Day 1); 7 daily SC injections from Stimulation Days 1 to 7 with placebo-recFSH; followed by daily SC injections with 200 IU recFSH up to the day of hCG. Daily SC injections of Ganirelix were administered from Stimulation Day 5 to the day of hCG; at which time a single dose of hCG was given when 3 follicles >= 17 mm. On the day of oocyte pick up (OPU) daily doses of progesterone were started and continued for up to 6 weeks or menses.
干预措施: hCG (Biological)
150 µg Corifollitropin Alfa
Participants received a single subcutaneous (SC) injection of 150 µg Corifollitropin Alfa (org 36286) on day 2 or 3 of the menstrual cycle (Stimulation Day 1); 7 daily SC injections from Stimulation Days 1 to 7 with placebo-recFSH; followed by daily SC injections with 200 IU recFSH up to the day of hCG. Daily SC injections of Ganirelix were administered from Stimulation Day 5 to the day of hCG; at which time a single dose of hCG was given when 3 follicles >= 17 mm. On the day of oocyte pick up (OPU) daily doses of progesterone were started and continued for up to 6 weeks or menses.
干预措施: Progesterone (Biological)
200 IU recFSH
Participants received a single SC injection of placebo Corifollitropin Alfa on day 2 or 3 of the menstrual cycle (Stimulation Day 1); 7 daily SC injections with 200 IU recFSH from Stimulation Days 1 to 7; followed by daily SC injections with 200 IU recFSH up to the day of hCG. Daily SC injections of Ganirelix were given from Stimulation Day 5 to the day of hCG; at which time a single dose of hCG was administered when 3 follicles >= 17 mm. On the day of OPU daily doses of progesterone were started and continued for up to 6 weeks or menses.
干预措施: RecFSH / Follitropin beta (Days 1 to 7) (Biological)
200 IU recFSH
Participants received a single SC injection of placebo Corifollitropin Alfa on day 2 or 3 of the menstrual cycle (Stimulation Day 1); 7 daily SC injections with 200 IU recFSH from Stimulation Days 1 to 7; followed by daily SC injections with 200 IU recFSH up to the day of hCG. Daily SC injections of Ganirelix were given from Stimulation Day 5 to the day of hCG; at which time a single dose of hCG was administered when 3 follicles >= 17 mm. On the day of OPU daily doses of progesterone were started and continued for up to 6 weeks or menses.
干预措施: Placebo Corifollitropin alfa (Drug)
200 IU recFSH
Participants received a single SC injection of placebo Corifollitropin Alfa on day 2 or 3 of the menstrual cycle (Stimulation Day 1); 7 daily SC injections with 200 IU recFSH from Stimulation Days 1 to 7; followed by daily SC injections with 200 IU recFSH up to the day of hCG. Daily SC injections of Ganirelix were given from Stimulation Day 5 to the day of hCG; at which time a single dose of hCG was administered when 3 follicles >= 17 mm. On the day of OPU daily doses of progesterone were started and continued for up to 6 weeks or menses.
干预措施: RecFSH / Follitropin beta (Days 8 to hCG) (Biological)
200 IU recFSH
Participants received a single SC injection of placebo Corifollitropin Alfa on day 2 or 3 of the menstrual cycle (Stimulation Day 1); 7 daily SC injections with 200 IU recFSH from Stimulation Days 1 to 7; followed by daily SC injections with 200 IU recFSH up to the day of hCG. Daily SC injections of Ganirelix were given from Stimulation Day 5 to the day of hCG; at which time a single dose of hCG was administered when 3 follicles >= 17 mm. On the day of OPU daily doses of progesterone were started and continued for up to 6 weeks or menses.
干预措施: Ganirelix (Drug)
200 IU recFSH
Participants received a single SC injection of placebo Corifollitropin Alfa on day 2 or 3 of the menstrual cycle (Stimulation Day 1); 7 daily SC injections with 200 IU recFSH from Stimulation Days 1 to 7; followed by daily SC injections with 200 IU recFSH up to the day of hCG. Daily SC injections of Ganirelix were given from Stimulation Day 5 to the day of hCG; at which time a single dose of hCG was administered when 3 follicles >= 17 mm. On the day of OPU daily doses of progesterone were started and continued for up to 6 weeks or menses.
干预措施: hCG (Biological)
200 IU recFSH
Participants received a single SC injection of placebo Corifollitropin Alfa on day 2 or 3 of the menstrual cycle (Stimulation Day 1); 7 daily SC injections with 200 IU recFSH from Stimulation Days 1 to 7; followed by daily SC injections with 200 IU recFSH up to the day of hCG. Daily SC injections of Ganirelix were given from Stimulation Day 5 to the day of hCG; at which time a single dose of hCG was administered when 3 follicles >= 17 mm. On the day of OPU daily doses of progesterone were started and continued for up to 6 weeks or menses.
干预措施: Progesterone (Biological)
结局指标
主要结局
Percentage of Participants With an Ongoing Pregnancy (Ongoing Pregnancy Rate)
时间窗: Assessed at least 10 weeks after embryo transfer (up to 1 year)
An ongoing pregnancy is a fetus with heart activity at least 10 weeks after embryo transfer as assessed by Ultrasound Scan (USS) or Doppler or is confirmed by live birth. The ongoing pregnancy rate is 100 times the number of participants with an ongoing pregnancy after embryo transfer, divided by the total number of participants who started treatment. Calculations were made per attempt, meaning that participants who did not have embryo transfers were considered not pregnant.
Mean Number of Oocytes Retrieved
时间窗: Up to 36 hours after administration of hCG (up to 1 year)
Up to 36 hours after receiving hCG, cumulus-oocyte-complexes were retrieved. Mean numbers retrieved were calculated per attempt, meaning that if a participant did not reach this stage in In Vitro Fertilization (IVF) treatment, zero values were imputed.
次要结局
- Median Amount of Recombinant FSH Needed to Induce Multifollicular Development Starting at Day 1(From Day 1 to day of hCG treatment (up to 1 year))
- Serum Estradiol (E2) Levels During Stimulation(Up to day of hCG treatment (up to 1 year))
- Serum Progesterone (P) Levels During Stimulation(Up to day of hCG treatment (up to 1 year))
- Median Amount of Recombinant FSH Needed to Induce Multifollicular Development Starting at Day 8(From Day 8 to Day of hCG treatment (up to 1 year))
- Serum FSH Levels During Stimulation(Up to day of hCG treatment (up to 1 year))
- Percentage of Fertilized Oocytes (Fertilization Rate)(Up to 18 hours after start of fertilization (up to 1 year))
- Percentage of Gestational Sacs (Implantation Rate)(Up to 6 weeks after embryo transfer (up to 1 year))
- Serum Luteinizing Hormone (LH) Levels During Stimulation(Up to day of hCG treatment (up to 1 year))
- Percentage of Participants With a Biochemical Pregnancy (Pregnancy Rate) Per Attempt(Two weeks after embryo transfer (up to 1 year))
- Percentage of Participants With a Biochemical Pregnancy (Pregnancy Rate) Per Embryo Transfer(Two weeks after embryo transfer (up to 1 year))
- Serum Inhibin-B Levels During Stimulation(Up to day of hCG treatment (up to 1 year))
- Number of Follicles Categorized by Size on Stimulation Day 5(On Day 5 of treatment (up to 1 year))
- Number of Follicles Categorized by Size on Stimulation Day 1(On Day 1 of treatment (up to 1 year))
- Number of Follicles Categorized by Size on Stimulation Day 8(On Day 8 of treatment (up to 1 year))
- Number of Follicles Categorized by Size on the Day of hCG(Day of HCG treatment (up to 1 year))
- Number of Cumulus-oocyte-complexes(Up to 36 hours after administration of hCG (up to 1 year))
- Number of Embryos Obtained on Day 3 Categorized by Quality(Post fertilization Day 3 (up to 1 year))
- Number of Embryos Transferred on Day 3(Post fertilization Day 3 (up to 1 year))
- Number of Oocytes Assessed Prior to Intracytoplasmic Sperm Injection (ICSI)(Up to 36 hours after administration of hCG (up to 1 year))
- Percentage of Participants With a Miscarriage (Miscarriage Rate) Per Clinical Pregnancy(Up to day of miscarriage (up to 1 year))
- Percentage of Participants With a Miscarriage (Miscarriage Rate) Per Vital Pregnancy(Up to day of miscarriage (up to 1 year))