A Trial to Compare the Ovarian Response of REKOVELLE and GONAL-F in Conventional Dosing in Women Undergoing Controlled Ovarian Stimulation

Study Overview
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Brief Summary
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Hormone preparations like REKOVELLE and GONAL-F are used to make the body produce multiple egg sacs, allowing more eggs to be collected from women undergoing infertility treatment. The main purpose of this trial is to see how many eggs are produced with a starting dose of 15 µg REKOVELLE compared to a starting dose of 225 IU GONAL-F. This research is intended to provide more knowledge about REKOVELLE, including the doses given in the trial.

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

Conditions
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Infertility

Intervention / Treatment
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* Drug: REKOVELLE (Follitropin Delta)
* Other: GONAL-F (Follitropin Alfa)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Infertile women aged 18-40 years Diagnosed with tubal infertility, unexplained infertility, mild endometriosis (stage I/II) or partners with decreased sperm quality Medically prepared for in vitro fertilization (IVF) and/or intracytoplasmic sperm injection (ICSI) Infertility for at least one year for participants below 37 years or for at least 6 months for participants above 38 years Regular menstrual cycles of 21-35 days. Exclusion Criteria: Known condition of not functioning ovaries Known advanced endometriosis (stage III/IV) Considered unsuitable for controlled ovarian stimulation with a dosing regimen corresponding to approximately 225 IU/day gonadotropin, as judged by the investigator History of previous episode of OHSS or exuberant ovarian response to gonadotropins, and polycystic ovarian syndrome Any known hormonal or metabolic abnormalities which can compromise participation in the trial Known tumors of the ovary, breast, uterus, adrenal gland, pituitary or hypothalamus

Ages Eligible for Study
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Minimum Age: 18 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: REKOVELLE (Follitropin Delta)<br> | Drug: REKOVELLE (Follitropin Delta)<br>* REKOVELLE administered as single daily subcutaneous injections in the abdomen. The starting dose of REKOVELLE is 15 μg fixed for the first four stimulation days. Dose adjustments may be implemented on the day of starting the gonadotropin-releasing hormone (GnRH) antagonist (stimulation day 5 or day 6) or later, can occur no more frequently than every second day. At each dose adjustment, the daily REKOVELLE dose can be increased or decreased by 5 μg based on the subject's response. The minimum REKOVELLE dose is 5 μg and the maximum REKOVELLE is 20 μg. Subjects can be treated for a maximum of 20 days.<br>|
| Active Comparator: GONAL-F (Follitropin Alfa)<br> | Other: GONAL-F (Follitropin Alfa)<br>* GONAL-F administered as single daily subcutaneous injections in the abdomen. The starting dose of GONAL-F is 225 IU fixed for the first four stimulation days. Dose adjustments may be implemented on the day of starting the GnRH antagonist (stimulation day 5 or day 6) or later, can occur no more frequently than every second day. At each dose adjustment, the daily GONAL-F dose may be adjusted by 75 IU based on the subject's response. The minimum GONAL-F dose is 75 IU and the maximum GONAL-F dose is 300 IU. Subjects can be treated for a maximum of 20 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of oocytes retrieved | The number of oocytes retrieved will be recorded at the oocyte retrieval visit. | 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) at end-of-stimulation | Counted by ultrasound for the right and left ovary for each subject. | At end-of-stimulation (up to 20 stimulation days) | 
| Size of the follicles at end-of-stimulation | Counted by ultrasound for the right and left ovary for each subject. | At end-of-stimulation (up to 20 stimulation days) | 
| Serum concentrations of estradiol at end-of-stimulation | Blood samples for analysis of circulating concentrations of estradiol will be drawn. | At end-of-stimulation (up to 20 stimulation days) | 
| Serum concentrations of progesterone at end-of-stimulation | Blood samples for analysis of circulating concentrations of progesterone will be drawn. | At end-of-stimulation (up to 20 stimulation days) | 
| Number of fertilized oocytes | The number of pronuclei will be counted after insemination. Fertilized oocytes with 2 pronuclei (2PN) will be regarded as correctly fertilized. | On day 1 after oocyte retrieval (up to 23 days after start of stimulation) | 
| Fertilization rate | The fertilization rate was defined as the number of oocytes with 2PN divided by the number of oocytes retrieved. | On day 1 after oocyte retrieval (up to 23 days after start of stimulation) | 
| Number of Blastocysts and Number of Good Quality Blastocysts | Number of blastocysts and number of good quality blastocysts on Day 5 or 6 will be presented. The quality evaluation of blastocysts consisted of assessment of three parameters, as per the Gardner & Schoolcraft system: blastocyst expansion and hatching status (graded: 1-6), inner cell mass (graded: A-D) and trophectoderm (graded: A-D). A good-quality blastocyst was defined as a blastocyst of grade 3BB or higher. | On Day 5 or Day 6 (as applicable) after oocyte retrieval (up to 27 or 28 days after start of stimulation) | 
| Total gonadotropin dose | Calculated by start dates, end dates and daily dose of investigational medicinal product (IMP). | Up to 20 stimulation days | 
| Number of stimulation days | Calculated by start dates and end dates. | Up to 20 stimulation days | 
| Proportion of subjects with early ovarian hyperstimulation syndrome (OHSS) (overall and by grade) and/or preventive interventions for early OHSS | Early OHSS is defined as OHSS with onset ≤9 days after triggering of final follicular maturation. Classification of grade was according to Golan's classification system, and all OHSS cases were graded as mild, moderate or severe. | Up to 9 days after triggering of final follicular maturation |