A randomised, controlled, assessor-blind, parallel groups, multicentre, multinational trial comparing the ovarian response after controlled ovarian stimulation with mixed protocols of follitropin delta (REKOVELLE) and highly purified human menopausal gonadotropin (MENOPUR) in women undergoing an assisted reproductive technology programme
- Trial ID
- 2022-500308-23-00
- Sponsor
- Ferring Pharmaceuticals A/S
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to compare the **ovarian response** after controlled ovarian stimulation using different mixed protocols of REKOVELLE and MENOPUR in women undergoing assisted reproductive technology (ART) programs. This is clinically relevant as optimizing ovarian response can enhance the success rates of ART procedures such as in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI), thereby addressing infertility in women.
Secondary objectives include:
- Evaluating the **follicular development** and endocrine profile associated with different mixed protocols of REKOVELLE and MENOPUR.
- Describing the **embryo development** associated with these protocols.
- Assessing the treatment efficiency and safety profile of the mixed protocols.
Participants
The clinical trial involves a total of **36 participants** who are pre-menopausal females aged between **18 and 40 years**. The study population consists exclusively of women diagnosed with **infertility** undergoing assisted reproductive technologies such as in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). Participants were selected based on their good physical and mental health, as assessed by the investigator, and their ability to comply with the trial protocol. The trial includes women with regular menstrual cycles presumed to be ovulatory, and those with documented transvaginal ultrasound showing the presence and adequate visualization of both ovaries without significant abnormalities. The study population is characterized by a lifestyle that supports regular menstrual cycles, and participants have been diagnosed with infertility for at least one year before randomization if they are 37 years or younger, or for at least six months if they are 38 years or older, unless they have tubal or severe male factor infertility. The trial does not include male subjects, and the population is considered vulnerable due to the nature of the medical condition being studied.
Plans and Procedures
The clinical trial is designed as a **randomized**, controlled, assessor-blind, parallel-group, multicenter, multinational study. The primary objective is to compare the ovarian response after controlled ovarian stimulation using mixed protocols of **follitropin delta** (REKOVELLE) and highly purified human menopausal gonadotropin (MENOPUR) in women undergoing assisted reproductive technology (ART) programs. The trial is expected to commence recruitment on December 1, 2022, and conclude by March 31, 2024, with an estimated duration of 16 months.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on specific criteria, including age, health status, and infertility diagnosis. The inclusion criteria require participants to be pre-menopausal females aged 18 to 40 years, with a diagnosis of infertility due to various factors such as tubal infertility or endometriosis, and eligible for in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). Regular menstrual cycles and specific serum levels of follicle-stimulating hormone (FSH) are also required. The screening visit will include a transvaginal ultrasound to ensure the presence and adequate visualization of both ovaries.
Following the screening, eligible participants will be randomized to receive either the investigational product or the control. The trial involves multiple follow-up visits to monitor the ovarian response and collect data on the primary endpoint, which is the number of fertilized oocytes at 19±2 hours post-insemination. The end-of-study visit will occur after the completion of the treatment period, which varies depending on the specific protocol but does not exceed 20 days for any participant.
Participant involvement is expected to last for the duration of the treatment period, with additional time allocated for follow-up assessments. Conditions that may lead to early termination from the study include non-compliance with the trial protocol, adverse events, or withdrawal of consent. The trial is conducted under strict adherence to ethical guidelines, ensuring the safety and well-being of all participants throughout the study duration.
Treatment
The clinical trial involves the administration of several experimental medications, each with specific pharmaceutical forms, dosages, and administration routes. **Fyremadel** is a solution for injection containing **ganirelix** as the active substance. It is provided in a pre-filled syringe with a concentration of 0.25 mg/0.5 mL. The medication is administered via subcutaneous injection, with a maximum daily dose of 0.25 mg and a total dose of 3.75 mg over a treatment period of up to 16 days. The product is manufactured by Sun Pharmaceutical Industries Europe B.V. and is labeled specifically for the trial.
**Decapeptyl** is another solution for injection, containing **triptorelin acetate**. It is administered subcutaneously at a maximum daily and total dose of 0.2 mg, with a treatment period limited to 1 day. This product is manufactured by Ferring B.V. and has been repackaged and labeled specifically for the trial.
**Menopur** is a solution for injection containing **menotrophin**. It is administered via subcutaneous use, with a maximum daily dose of 150 IU and a total dose of 3000 IU over a treatment period of up to 20 days. The product is manufactured by Ferring Lægemidler A/S and is labeled specifically for the trial.
**Ovitrelle** is a solution for injection containing **choriogonadotropin alfa**. It is available in two forms: a pre-filled syringe and a pre-filled pen, both with a concentration of 250 micrograms/0.5 mL. The medication is administered via subcutaneous use, with a maximum daily and total dose of 250 micrograms, and a treatment period of 1 day. The product is manufactured by Merck Europe B.V. and is labeled specifically for the trial.
**REKOVELLE** is a solution for injection in a pre-filled pen containing **follitropin delta**. It is administered via subcutaneous injection, with a maximum daily dose of 10 micrograms and a total dose of 200 micrograms over a treatment period of up to 20 days. The product is manufactured by Ferring Pharmaceuticals A/S and is labeled specifically for the trial.
All medications are administered via subcutaneous routes, and participant compliance is monitored throughout the trial. The trial involves mixed protocols of **follitropin delta** and highly purified human menopausal gonadotropin to compare ovarian responses in women undergoing an assisted reproductive technology program. Each product is authorized for use in the trial and has been specifically labeled for this purpose.
Efficacy
Efficacy in this clinical trial will be assessed by evaluating the primary endpoint, which is the number of fertilized oocytes with two pronuclei (2PN) at 19±2 hours after insemination. This endpoint is critical for determining the ovarian response following controlled ovarian stimulation with mixed protocols of **follitropin delta** (REKOVELLE) and highly purified human menopausal gonadotropin (MENOPUR) in women undergoing an assisted reproductive technology program. The measurement of fertilized oocytes will be conducted using standardized laboratory procedures to ensure accuracy and consistency across trial sites. Data collection will occur at the specified timepoint of 19±2 hours post-insemination, allowing for a precise assessment of the fertilization process. The analysis of these efficacy parameters will be performed using appropriate statistical methods to compare the outcomes between the different treatment groups, ensuring that the trial's objectives are met with scientific rigor.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Informed Consent Form signed prior to screening evaluations.
- In good physical and mental health as judged by the investigator, and willing and able to comply with the trial protocol.
- Pre-menopausal females between the ages of 18 and 40 years. The subjects must be at least 18 years (including the 18th birthday) when they sign the informed consent and no more than 40 years (up to the day before the 41st birthday) at the time of randomisation.
- 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) and/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 ≤37 years or for at least 6 months for subjects ≥38 years (not applicable in case of tubal or severe male factor infertility).
- Regular menstrual cycles of 21-35 days (both inclusive), presumed to be ovulatory.
- Transvaginal ultrasound documenting presence and adequate visualisation of both ovaries, without evidence of significant abnormality (e.g. no endometrioma greater than 3 cm, and no enlarged ovaries or ovarian cyst not due to polycystic ovarian syndrome, which would contraindicate the use of gonadotropins) and normal adnexa (e.g. no hydrosalpinx) within 1 year prior to randomisation. Both ovaries must be accessible for oocyte retrieval.
- Early follicular phase (cycle day 2-4) serum levels of FSH between 1 and 15 IU/L (results obtained within 3 months prior to randomisation).
Exclusion Criteria
- Primary ovarian failure.
- Known 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.egnancy.
- One or more follicles ≥10 mm (including cysts) observed on the transvaginal ultrasound prior to randomisation on stimulation day 1 (puncture of cysts is allowed prior to randomisation).
- Any 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.
- Active arterial or venous thromboembolism.
- Currently breast-feeding.
- Undiagnosed vaginal bleeding.
- Findings at the gynaecological examination at screening which preclude gonadotropin stimulation or are associated with a reduced chance of pregnancy, e.g. congenital uterine abnormalities or retained intrauterine device.
- Pregnancy (negative urinary pregnancy tests must be documented at screening and prior to randomisation) or contraindication to pregnancy.e exception of controlled thyroid function disease.
- Use of fertility modifiers during the last menstrual cycle before randomisation, including dehydroepiandrosterone (DHEA) or cycle programming with oral contraceptives, progestogen or estrogen preparations.ns.
- Hypersensitivity to any active ingredient or excipients in the medicinal products used in the trial.
- Previous participation in the trial.
- Use of any non-registered investigational drugs during the last 3 months prior to randomisation.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Italy | Not Recruiting | 01 Dec 2022 | 35 |
 Spain | Not Recruiting | 01 Dec 2022 | 80 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Fyremadel, 0,25 mg/0,5 ml oplossing voor injectie in voorgevulde spuit | Other | OPLOSSING VOOR INJECTIE IN VOORGEVULDE SPUIT | SUBCUTANEOUS INJECTION | 0.25 | 16 | PRD985672 |
Decapeptyl 0,1 mg/1 ml, oplossing voor injectie | Other | OPLOSSING VOOR INJECTIE | SUBCUTANEOUS INJECTION | 0.2 | 1 | PRD469221 |
Menopur | Test | INJEKTIONSVÆSKE, OPLØSNING | SUBCUTANEOUS USE | 150 | 20 | PRD9063581 |
Ovitrelle 250 micrograms/0.5 mL solution for injection in pre-filled syringe | Other | SOLUTION FOR INJECTION IN PRE-FILLED SYRINGE | SUBCUTANEOUS USE | 250 | 1 | PRD3312177 |
REKOVELLE 72 micrograms/2.16 mL solution for injection in a pre-filled pen | Test | SOLUTION FOR INJECTION IN A PRE-FILLED PEN | SUBCUTANEOUS INJECTION | 10 | 20 | PRD5098780 |
Menopur | Test | SOLUTION FOR INJECTION | SUBCUTANEOUS USE | 150 | 20 | PRD9063630 |
Ovitrelle 250 micrograms solution for injection in pre-filled pen | Other | SOLUTION FOR INJECTION IN PRE-FILLED PEN | SUBCUTANEOUS USE | 250 | 1 | PRD3312175 |