A Randomised Trial Comparing the Ovarian Response of a Starting Dose of Either 10 μg or 15 μg Follitropin Delta (FE 999049) to a Starting Dose of Either 150 IU or 225 IU Follitropin Alfa (GONAL-F) in Conventional Regimens in China

Study Overview
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Brief Summary
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This is a phase 3b clinical trial with follitropin delta (FE 999049) and Gonal-F. The trial is a randomised, controlled, assessor-blind, parallel groups, multicentre trial comparing the ovarian response of a starting dose of either 10mg or 15 mg follitropin delta to a starting dose of either 150 IU or 225 IU Gonal-F in a long GnRH agonist protocol in women undergoing an assisted reproductive technology programme in China.

Official Title
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A Randomised, Controlled, Assessor-blind, Parallel Groups, Multicentre Trial Comparing the Ovarian Response of a Starting Dose of Either 10 μg or 15 μg Follitropin Delta (FE 999049) to a Starting Dose of Either 150 IU or 225 IU Follitropin Alfa (GONAL-F) in Conventional Regimens in Controlled Ovarian Stimulation in Women Undergoing an Assisted Reproductive Technology Programme in China

Conditions
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Infertility, Female

Intervention / Treatment
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* Drug: FE 999049
* Drug: GONAL-F


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed and dated Informed Consent Form for participation in the trial, obtained before any trial-related procedures. In good physical and mental health in the judgement of the investigator. Chinese pre-menopausal female between the ages of 20 and 40 years; at least 20 years (including the 20th birthday) when signing the informed consent and no more than 40 years (up to the day before the 41st birthday) at the time of randomisation. Eligible for ovarian stimulation with a dose equivalent to 150 IU GONAL-F or 225 IU GONAL-F, as judged by the investigator. Body mass index (BMI) between 17.5 and 32.0 kg/m2 (both inclusive) at screening. 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) or intracytoplasmic sperm injection (ICSI) using fresh or frozen ejaculated sperm from male partner or sperm donor Infertility for at least one year before randomisation for subjects <35 years or for at least 6 months for subjects ≥35 years (criteria not applicable in case of tubal or severe male factor infertility). Regular menstrual cycles of 24-35 days (both inclusive), presumed to be ovulatory. Transvaginal ultrasound documenting presence and adequate visualisation of both ovaries, without evidence of significant abnormality. Both ovaries must be accessible for oocyte retrieval. Early follicular phase (cycle day 2-4) serum levels of follicle-stimulating hormone (FSH) between 1 and 15 IU/L (results obtained within 3 months prior to randomisation). Serum anti-Müllerian hormone (AMH) concentration of ≤35 pmol/L at screening. Exclusion Criteria: Primary ovarian failure. More than three previous controlled ovarian stimulation cycles initiated, regardless of outcome. History of previous episode of OHSS, exuberant ovarian response to gonadotropins, or polycystic ovarian syndrome. Known endocrine or metabolic abnormalities (pituitary, adrenal, pancreas, liver or kidney) which can compromise participation in the trial 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. Fibroid tumours of the uterus incompatible with pregnancy. Currently breast-feeding. Known inherited or acquired thrombophilia disease. Active arterial or venous thromboembolism or severe thrombophlebitis, or a history of these events. Known porphyria.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FE 999049<br>The participants receive either low or high starting dose as appropriate according to Investigators Judgement. 10 or 15 µg | Drug: FE 999049<br>* FE 999049 was administered as single daily subcutaneous injections at a starting dose of either 10 or 15 µg daily that was fixed for the first five stimulation days. Based on ovarian response, the dose could be increased or decreased by 5 µg, with dose adjustments implemented not more frequently than once every 2 days per investigator's judgement. The minimum daily dose was 5 µg, and the maximum daily dose was 20 µg. Participants could be treated for a maximum of 20 days.<br>* Other names: Follitropin Delta;|
| Active Comparator: GONAL-F<br>The participants receive either low or high starting dose as appropriate according to Investigators Judgement. 150 or 225 IU. | Drug: GONAL-F<br>* GONAL-F was administered as single daily subcutaneous injections at a starting dose of either 150 or 225 IU daily that was fixed for the first five stimulation days. Based on ovarian response, the dose could be increased or decreased by 75 IU, with dose adjustments implemented not more frequently than once every 2 days per investigator's judgement. The minimum daily dose was 75 IU, and the maximum daily dose was 300 IU. Participants could be treated for a maximum of 20 days. Coasting was not allowed.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of oocytes retrieved |  | On day of oocyte retrieval (up to 22 days after start of stimulation) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of follicles (total and by size category) on stimulation day 6 and end-of-stimulation |  | Stimulation day 6 and end-of-stimulation (maximum stimulation day 20) | 
| Serum concentrations of estradiol on stimulation day 6 and end-of-stimulation |  | stimulation day 6 and end-of-stimulation (maximum stimulation day 20) | 
| Serum concentrations of progesterone on stimulation day 6 and end-of-stimulation |  | stimulation day 6 and end-of-stimulation (maximum stimulation day 20) | 
| Number of fertilised oocytes |  | On day 1 after oocyte retrieval (up to 23 days after start of stimulation) | 
| Fertilisation rate |  | On day 1 after oocyte retrieval (up to 23 days after start of stimulation) | 
| Number of embryos (total and by quality) |  | Day 3 after oocyte retrieval | 
| Total gonadotropin dose |  | Up to 20 stimulation days | 
| Number of stimulation days |  | Up to 20 stimulation days | 
| Positive βhCG (positive serum βhCG test 13-15 days after transfer) rate |  | 13-15 days after transfer | 
| Clinical pregnancy (at least one gestational sac 5-6 weeks after transfer) rate |  | 5-6 weeks after transfer | 
| Vital pregnancy (at least one intrauterine gestational sac with fetal heart beat 5-6 weeks after transfer) rate |  | 5-6 weeks after transfer | 
| Implantation rate (number of gestational sacs 5-6 weeks after transfer divided by number of embryos transferred) |  | 5-6 weeks after transfer | 
| Ongoing pregnancy (at least one intrauterine viable fetus 10-11 weeks after transfer) rate |  | 10-11 weeks after transfer | 
| Ongoing implantation rate (number of intrauterine viable fetuses 10-11 weeks after transfer divided by number of embryos transferred) |  | 10-11 weeks after transfer | 
| Early ovarian hyperstimulation syndrome (OHSS), late OHSS, and total OHSS (all overall and by grade) |  | ≤9 days after triggering of final follicular maturation (early OHSS), >9 days after triggering of final follicular maturation until 21-28 days after last IMP dose or up to ongoing pregnancy 8-9 weeks after transfer in pregnant participants (late OHSS) |