Dose-Finding Study of Recombinant FSH Following Corifollitropin Alfa in Subfertility Patients Undergoing IVF/ICSI with GnRH Antagonist Protocol

The primary objective of this study is to compare the mean serum **progesterone** level (ng/mL) on the day of human chorionic gonadotropin (hCG) administration between the study groups. This is clinically relevant as serum progesterone levels can influence the success rates of in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) treatments, particularly in patients with subfertility requiring ICSI treatment.

Secondary objectives include assessing the number of retrieved oocytes, the number of mature oocytes, and the number of top-quality embryos on Day 3. Additionally, the study aims to evaluate the clinical pregnancy rate, defined as the number of viable pregnancies at 6 weeks of gestation per intention-to-treat (ITT) and per-protocol (PP) analyses, and the ongoing pregnancy rate, defined as the number of viable pregnancies at 12 weeks of gestation per ITT and PP. The study will also assess the miscarriage rate and the percentage of patients with a progesterone value above 1.5 ng/mL on the day of hCG administration. These secondary objectives are important for understanding the broader impacts of recombinant follicle-stimulating hormone (FSH) dosing on reproductive outcomes in the context of a GnRH antagonist protocol.

The clinical trial focuses on **subfertility** in need of ICSI treatment, involving a study population exclusively composed of female participants. The age range for participants is greater than 18 and less than 40 years. Participants are required to have a body mass index (BMI) of 29 kg/m² or less, with specific weight criteria based on age: those 36 years or younger must weigh more than 60 kg, while those older than 36 years must weigh more than 50 kg. Participants must have regular normo-ovulatory menstrual cycles, with a cycle length of 26 to 35 days, and meet specific hormonal criteria, including basal FSH levels below 10 IU/l, basal E2 levels below 60 pg/ml, and basal progesterone levels below 1.5 ng/mL. Additionally, a normal ultrasound scan confirming the presence of both ovaries without abnormalities within the past six months is required, along with an antral follicle count (AFC) between 7 and 20. The trial does not include male subjects or vulnerable populations. The sponsor has not provided information regarding the total number of participants in the study.

The clinical trial is designed to evaluate the optimal dosing of recombinant **FSH** following **corifollitropin alfa** in patients undergoing **IVF/ICSI** treatment within a **GnRH antagonist** protocol. This study is a randomized, controlled, dose-finding trial with a double-blind design to ensure unbiased results. The trial is expected to run from June 24, 2019, to June 30, 2026, with the primary objective of comparing the mean serum progesterone level on the day of **hCG** administration between study groups. Secondary endpoints include the number of **COCs** retrieved, clinical pregnancy rate, ongoing pregnancy rate, miscarriage rate, and live birth rate.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as age, body mass index, and hormonal levels. The inclusion criteria specify that participants must be females aged 18 to 40 years, with a body mass index of ≤29 kg/m², and must not have undergone hormonal pre-treatment within the month before the start of the treatment cycle. Regular follow-up visits will be scheduled to monitor the participants' response to the treatment, with the end-of-study visit marking the conclusion of their involvement. The expected length of participant involvement is up to five treatment cycles, with each cycle lasting a maximum of five days for **follitropin beta** and one day for **corifollitropin alfa**.

Participants may be subject to early termination from the study if they experience adverse reactions, fail to comply with the study protocol, or withdraw consent. The trial will utilize **Puregon** and **Elonva** solutions for injection, administered via subcutaneous injection, with dosing tailored to individual patient needs. The study aims to provide valuable insights into the optimal dosing strategy for enhancing the success rates of **IVF/ICSI** treatments in subfertile patients.

The clinical trial involves the administration of several **experimental medications** in the form of solutions for injection. The primary experimental medication is **Puregon**, which contains the active substance **follitropin beta**. This medication is available in three different dosages: 900 IU/1.08 mL, 600 IU/0.72 mL, and 300 IU/0.36 mL. Each formulation is administered via **subcutaneous injection**. The maximum daily dose for Puregon is 250 IU, with a total maximum dose of 1250 IU over a treatment period of up to 5 days. The pharmaceutical form is a solution for injection, and the medication is not a pediatric formulation. The active substance, follitropin beta, is a protein of non-human origin, and the product is manufactured by N.V. Organon.

Another experimental medication used in the trial is **Elonva**, which contains the active substance **corifollitropin alfa**. This medication is provided as a 150 micrograms solution for injection and is also administered via subcutaneous injection. The maximum daily and total dose for Elonva is 150 micrograms, with a treatment period limited to a single day. Similar to Puregon, Elonva is not a pediatric formulation and is produced by N.V. Organon. The active substance, corifollitropin alfa, is also a protein of non-human origin.

In this clinical trial, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The study focuses on evaluating the effects of these experimental medications in patients undergoing IVF/ICSI in a GnRH antagonist protocol. Participant compliance with the dosing schedule is monitored to ensure adherence to the prescribed treatment regimen.

Efficacy in this clinical trial will be assessed by evaluating both primary and secondary endpoints. The primary endpoint is the mean serum **progesterone** level on the day of human chorionic gonadotropin (hCG) administration. This parameter will be measured to compare the efficacy of different dosing regimens of recombinant follicle-stimulating hormone (FSH) following corifollitropin alfa in patients undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) within a GnRH antagonist protocol.

Secondary endpoints include the number of cumulus-oocyte complexes (COCs) retrieved, the number of patients who underwent follicular aspiration (FA), clinical pregnancy rate, ongoing pregnancy rate, miscarriage rate, and live birth rate. These parameters will provide additional insights into the treatment's efficacy. The collection and analysis of these endpoints will be conducted at specified timepoints throughout the trial, ensuring a comprehensive evaluation of the treatment's impact on reproductive outcomes.