A Phase II, Randomized, Controlled, Open-label, Feasibility Trial to Evaluate if a Single or Repeated Dose of Org 36286 (Corifollitropin Alfa) Followed by a Low Daily Dose of Either hCG or Recombinant FSH Can Induce Monofollicular Growth in Women With WHO Group II Anovulatory Infertility
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 8
- 主要终点
- Percentage of Participants With Monofollicular Response (Monofollicular Rate)
研究概览
简要总结
The primary objective of this trial is to evaluate whether a corifollitropin alfa (Org 36286) regimen applying a single or repeated dose of corifollitropin alfa followed by a low daily dose of Human Chorion Gonadotropin (hCG) or recombinant Follicular Stimulating Hormone (recFSH) can induce monofollicular growth (one follicle ≥18 mm and no other follicle ≥15 mm at day of bolus injection of hCG) in women with WHO group II anovulatory infertility.
详细描述
This trial will include two separate stages (Ia+Ib and II).
Stage Ia will be open-label and uncontrolled in a small cohort of women (n=5) to explore whether the intended dosing regimen of corifollitropin alfa followed by daily low dose recFSH provide an appropriate response in eligible participants meeting all inclusion and none of the exclusion criteria.
Stage Ib will be open-label and uncontrolled in a small cohort of women (n=5) to explore whether the intended dosing regimen of corifollitropin alfa followed by daily low dose hCG provide an appropriate response in eligible participants meeting all inclusion and none of the exclusion criteria.
Stage II is open-label and randomized (n=40) to evaluate whether the intended dosing regimen of corifollitropin alfa followed by low dose FSH (n=20) or hCG (n=20) provide an appropriate response in eligible participants meeting all inclusion and none of the exclusion criteria.
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 39 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Oligomenorrhea (average cycle length ≥35 days and <6 months)
- •Amenorrhea (average cycle length ≥6 months)
- •Body Mass Index ≥18 and ≤30 kg/m^2
- •Normal serum FSH levels and normal estradiol levels at screening
- •Progestagen induced withdrawal bleeding
- •Age ≥18 years and ≤39 years at the time of signing informed consent
- •Willing and able to sign informed consent
排除标准
- •History of or current ovarian cysts or enlarged ovaries not related to polycystic ovarian syndrome (PCOS)
- •History of or current tumors of the ovary, breast, uterus, pituitary or
- •hypothalamus
- •Less than 2 ovaries
- •Undiagnosed vaginal bleeding
- •Any ovarian and/or abdominal abnormality interfering with ultrasound
- •examination
- •Malformations of the sexual organs incompatible with pregnancy
- •Pregnancy or lactation
- •Abnormal serum endocrinology levels based on screening sample
- •Any clinically relevant abnormal laboratory value based on screening sample
- •Alcohol or drug abuse within the 12 months preceding signing of informed consent
- •Hypersensitivity to any of the substances in corifollitropin alfa
- •Hypersensitivity to hCG/ Puregon® or any of its components
- •Previous use of corifollitropin alfa
- •Use of any investigational drug during 90 days before screening
研究组 & 干预措施
corifollitropin alfa + recFSH
Eligible participants will receive a subcutaneous (SC) injection of corifollitropin alfa (Stage 1a: 15mcg, Stage Ib/II: 30 mcg) the first, second, or third day after onset of a progestagen-induced withdrawal bleeding. If the follicle growth is insufficient, the participant will receive a second or third dose of corifollitropin alfa (Stage 1a: 15 mcg, Stage Ib/II: 20 mcg). As soon as the largest follicle reaches a size of ≥12 mm, the participant will start daily SC injections with FSH (Stage 1A: 50 IU, Stage II: 75 IU) the same day. A bolus injection of hCG (5000 IU) will be administered if at least one follicle is ≥18 mm and in total no more than two follicles ≥15 mm are observed.
干预措施: corifollitropin alfa (Drug)
corifollitropin alfa + recFSH
Eligible participants will receive a subcutaneous (SC) injection of corifollitropin alfa (Stage 1a: 15mcg, Stage Ib/II: 30 mcg) the first, second, or third day after onset of a progestagen-induced withdrawal bleeding. If the follicle growth is insufficient, the participant will receive a second or third dose of corifollitropin alfa (Stage 1a: 15 mcg, Stage Ib/II: 20 mcg). As soon as the largest follicle reaches a size of ≥12 mm, the participant will start daily SC injections with FSH (Stage 1A: 50 IU, Stage II: 75 IU) the same day. A bolus injection of hCG (5000 IU) will be administered if at least one follicle is ≥18 mm and in total no more than two follicles ≥15 mm are observed.
干预措施: recombinant Follicle Stimulating Hormone (recFSH) (Biological)
corifollitropin alfa + recFSH
Eligible participants will receive a subcutaneous (SC) injection of corifollitropin alfa (Stage 1a: 15mcg, Stage Ib/II: 30 mcg) the first, second, or third day after onset of a progestagen-induced withdrawal bleeding. If the follicle growth is insufficient, the participant will receive a second or third dose of corifollitropin alfa (Stage 1a: 15 mcg, Stage Ib/II: 20 mcg). As soon as the largest follicle reaches a size of ≥12 mm, the participant will start daily SC injections with FSH (Stage 1A: 50 IU, Stage II: 75 IU) the same day. A bolus injection of hCG (5000 IU) will be administered if at least one follicle is ≥18 mm and in total no more than two follicles ≥15 mm are observed.
干预措施: hCG Bolus injection (Biological)
corifollitropin alfa + hCG
Eligible participants will receive a SC injection of corifollitropin alfa (Stage Ia:15 mcg, Stage Ib/II: 30 mcg) the first, second or third day after onset of a progestagen-induced withdrawal bleeding. If the follicle growth is insufficient the participant will receive a second or third dose of corifollitropin alfa (Stage IA: 15 mcg, stage Ib/II: 20 mcg). As soon as the largest follicle reaches a size of ≥12 mm the participant will start daily SC injections with hCG (Stage Ib/II: 200 IU) the same day. A bolus injection of hCG (5000 IU) will be administered if at least one follicle is ≥18 mm and in total no more than two follicles ≥15 mm are observed.
干预措施: corifollitropin alfa (Drug)
corifollitropin alfa + hCG
Eligible participants will receive a SC injection of corifollitropin alfa (Stage Ia:15 mcg, Stage Ib/II: 30 mcg) the first, second or third day after onset of a progestagen-induced withdrawal bleeding. If the follicle growth is insufficient the participant will receive a second or third dose of corifollitropin alfa (Stage IA: 15 mcg, stage Ib/II: 20 mcg). As soon as the largest follicle reaches a size of ≥12 mm the participant will start daily SC injections with hCG (Stage Ib/II: 200 IU) the same day. A bolus injection of hCG (5000 IU) will be administered if at least one follicle is ≥18 mm and in total no more than two follicles ≥15 mm are observed.
干预措施: human Chorion Gonadotropin (hCG) (Biological)
corifollitropin alfa + hCG
Eligible participants will receive a SC injection of corifollitropin alfa (Stage Ia:15 mcg, Stage Ib/II: 30 mcg) the first, second or third day after onset of a progestagen-induced withdrawal bleeding. If the follicle growth is insufficient the participant will receive a second or third dose of corifollitropin alfa (Stage IA: 15 mcg, stage Ib/II: 20 mcg). As soon as the largest follicle reaches a size of ≥12 mm the participant will start daily SC injections with hCG (Stage Ib/II: 200 IU) the same day. A bolus injection of hCG (5000 IU) will be administered if at least one follicle is ≥18 mm and in total no more than two follicles ≥15 mm are observed.
干预措施: hCG Bolus injection (Biological)
结局指标
主要结局
Percentage of Participants With Monofollicular Response (Monofollicular Rate)
时间窗: At day of bolus injection of hCG (up to 20 days)
The monofollicular rate was defined as the number of participants with monofollicular response (one follicle ≥18 mm and no other follicle ≥15 mm on the day of the bolus injection of hCG) divided by the number of the treated participants.
次要结局
- Percentage of Participants With Ovulation (Ovulation Rate)(8 days after bolus injection of hCG (up to 28 days))
- Percentage of Participants Who Cancelled Treatment (Cancellation Rate)(Up to 3 weeks after bolus injection of hCG (up to 41 days))
- Percentage of Participants With Monofollicular Ovulation (Monofollicular Ovulation Rate)(8 days after bolus injection of hCG (up to 28 days))
- Number of Participants With Pregnancy(At least 10 weeks after bolus injection of hCG (up to 13 weeks))
- Number of Participants With AEs of Ovarian Hyperstimulation Syndrome (OHSS)(During In-Treatment Period (up to 14 weeks after first corifollitropin injection))