Infertility, Female
Conditions
Keywords
Assisted Reproductive Technology (ART), oocyte donors undergoing controlled ovarian hyperstimulation for assisted reproductive technologies
Brief summary
The main purpose of this clinical research study is to investigate if degarelix can synchronise the growth of the egg sacs in the ovaries and if degarelix has any effect on the lining of the womb.
Detailed description
For the primary end-point (data collected on Stimulation Day 1), the study will compare degarelix 2.5 mg administered in the mid-luteal phase to placebo administered in the mid-luteal phase. After Stimulation Day 1 the placebo group will be split into two groups: a degarelix 2.5 mg follicular group and a ganirelix 0.25 mg group.
Interventions
DRUGDegarelix mid-luteal, 2.5 mg
Degarelix 2.5 mg will be injected subcutaneously (SC) 7 days after luteinizing hormone (LH) peak and on Stimulation Day 6. Placebo will be injected SC on Stimulation Day 1.
DRUGPlacebo
Placebo will be injected subcutaneously (SC) 7 days after luteinizing hormone (LH) peak. Degarelix 2.5 mg will be injected SC on Stimulation Day 1 and Stimulation Day 6. or Placebo will be injected SC 7 days after LH peak and on Stimulation Day 1. Ganirelix 0.25 mg will be injected SC daily from Stimulation Day 6 until the last stimulation day.
Sponsors
Ferring Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 35 Years
Healthy volunteers
Yes
Inclusion criteria
* Signed Informed Consent Form, prior to screening evaluations * In good physical and mental health * Pre-menopausal females between the ages of 18-35 years (both inclusive) at the time of randomisation * Regular menstrual cycles of 26-35 days duration (both inclusive), presumed to be ovulatory * Body mass index (BMI) between 18 and 29 kg/m2 (both inclusive) * Willing to donate the retrieved oocytes * Willing to use an adequate barrier method of contraception from informed consent to Day hCG injection +7 and to use an adequate barrier or hormonal method of contraception from Day hCG injection +7 to the end-of-study visit
Exclusion criteria
* Abnormal karyotype * Any known clinically significant systemic disease (e.g., insulin dependent diabetes) * Any known endocrine or metabolic abnormalities (pituitary, adrenal, pancreas, liver or kidney) which can compromise participation in the study * Diagnosed with polycystic ovarian syndrome or endometriosis stage III/IV * Diagnosed as poor responder * History of recurrent miscarriage (defined as three consecutive spontaneous losses before weeks 24 of pregnancy) * Pregnancy or lactation * Use of any investigational drug during 3 months prior to start of the current COH cycle * Previous participation in the study * Hypersensitivity to any trial product
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Coefficient of Variation of Follicular Sizes on Stimulation Day 1 (Follicles ≥ 2 mm) | Stimulation Day 1 | Explanation of the term coefficient of variation: The coefficient of variation is a normalized measure of dispersion of a probability distribution. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of Oocyte Donors With Adequate Secretory Transformation at the Endometrial Histology Evaluation 7 Days After Injection With Human Chorionic Gonadotrophin (hCG) | 7 days after hCG injection | An adequate secretory endometrium 7 days after hCG injection was defined as secretory in the histological classification and with endometrial dating corresponding to the expected cycle day ±1 day. |
Countries
Belgium, Czechia, Spain
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Degarelix Mid-luteal, 2.5 mg Degarelix 2.5 mg will be injected subcutaneously (SC) 7 days after luteinizing hormone (LH) peak and on Stimulation Day 6. Placebo will be injected SC on Stimulation Day 1. | 39 |
| Placebo Placebo will be injected subcutaneously (SC) 7 days after luteinizing hormone (LH) peak. Degarelix 2.5 mg will be injected SC on Stimulation Day 1 and Stimulation Day 6.
or Placebo will be injected SC 7 days after LH peak and on Stimulation Day 1. Ganirelix 0.25 mg will be injected SC daily from Stimulation Day 6 until the last stimulation day. | 39 |
| Total | 78 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Large follicle size | 2 | 2 |
| Overall Study | loss of subject contact | 1 | 1 |
| Overall Study | Low follicular response. | 1 | 2 |
| Overall Study | Non-compliance with protocol | 0 | 1 |
| Overall Study | Personal reasons | 1 | 1 |
| Overall Study | Travelling of subject. | 1 | 0 |
Baseline characteristics
| Characteristic | Degarelix Mid-luteal, 2.5 mg | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 39 Participants | 39 Participants | 78 Participants |
| Age Continuous | 28.9 years STANDARD_DEVIATION 4.1 | 28.0 years STANDARD_DEVIATION 3.9 | 28.4 years STANDARD_DEVIATION 4 |
| Region of Enrollment Belgium | 5 participants | 6 participants | 11 participants |
| Region of Enrollment Czech Republic | 7 participants | 7 participants | 14 participants |
| Region of Enrollment Spain | 27 participants | 26 participants | 53 participants |
| Sex: Female, Male Female | 39 Participants | 39 Participants | 78 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 7 / 63 | 4 / 22 |
| serious Total, serious adverse events | 1 / 63 | 0 / 22 |
Outcome results
Primary
Coefficient of Variation of Follicular Sizes on Stimulation Day 1 (Follicles ≥ 2 mm)
Explanation of the term coefficient of variation: The coefficient of variation is a normalized measure of dispersion of a probability distribution.
Time frame: Stimulation Day 1
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Degarelix Mid-luteal, 2.5 mg | Coefficient of Variation of Follicular Sizes on Stimulation Day 1 (Follicles ≥ 2 mm) | 36.7 Percentage | Standard Deviation 5.6 |
| Placebo | Coefficient of Variation of Follicular Sizes on Stimulation Day 1 (Follicles ≥ 2 mm) | 39.2 Percentage | Standard Deviation 9.5 |
Secondary
Frequency of Oocyte Donors With Adequate Secretory Transformation at the Endometrial Histology Evaluation 7 Days After Injection With Human Chorionic Gonadotrophin (hCG)
An adequate secretory endometrium 7 days after hCG injection was defined as secretory in the histological classification and with endometrial dating corresponding to the expected cycle day ±1 day.
Time frame: 7 days after hCG injection
Population: Subjects with evaluable endometrial biopsies 7 days after injection with hCG.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Degarelix Mid-luteal, 2.5 mg | Frequency of Oocyte Donors With Adequate Secretory Transformation at the Endometrial Histology Evaluation 7 Days After Injection With Human Chorionic Gonadotrophin (hCG) | 31 Participants |
| Placebo | Frequency of Oocyte Donors With Adequate Secretory Transformation at the Endometrial Histology Evaluation 7 Days After Injection With Human Chorionic Gonadotrophin (hCG) | 11 Participants |
| Ganirelix, 0.25 mg | Frequency of Oocyte Donors With Adequate Secretory Transformation at the Endometrial Histology Evaluation 7 Days After Injection With Human Chorionic Gonadotrophin (hCG) | 14 Participants |