Infertility
Conditions
Brief summary
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.
Interventions
REKOVELLE administered as single daily subcutaneous injections in the abdomen. The starting dose of REKOVELLE was 15 μg fixed for the first four stimulation days. Dose adjustments could be implemented on the day of starting the gonadotropin-releasing hormone (GnRH) antagonist (stimulation day 5 or day 6) or later, could occur no more frequently than every second day. At each dose adjustment, the daily REKOVELLE dose could be increased or decreased by 5 μg based on the participant's response. The minimum REKOVELLE dose was 5 μg and the maximum REKOVELLE was 20 μg. Participants could be treated for a maximum of 20 days.
GONAL-F administered as single daily subcutaneous injections in the abdomen. The starting dose of GONAL-F was 225 IU fixed for the first four stimulation days. Dose adjustments could be implemented on the day of starting the GnRH antagonist (stimulation day 5 or day 6) or later, could occur no more frequently than every second day. At each dose adjustment, the daily GONAL-F dose could be adjusted by 75 IU based on the participant's response. The minimum GONAL-F dose was 75 IU and the maximum GONAL-F dose was 300 IU. Participants could be treated for a maximum of 20 days.
Sponsors
Ferring Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 40 Years
Healthy volunteers
No
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 eligible for in vitro fertilization (IVF) and/or intracytoplasmic sperm injection (ICSI) * Infertility for at least one year for participants ≤ 37 years or for at least 6 months for participants ≥ 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Oocytes Retrieved | On day of oocyte retrieval (Up to 22 days after start of stimulation) | The number of oocytes retrieved was recorded at the oocyte retrieval visit. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Size of the Follicles at End-of-stimulation | At end-of-stimulation (up to 20 stimulation days) | Counted by ultrasound for the right and left ovary for each subject. |
| Serum Concentrations of Estradiol at End-of-stimulation | At end-of-stimulation (up to 20 stimulation days) | Blood samples for analysis of circulating concentrations of estradiol were drawn. |
| Serum Concentrations of Progesterone at End-of-stimulation | At end-of-stimulation (up to 20 stimulation days) | Blood samples for analysis of circulating concentrations of progesterone were drawn. |
| Number of Fertilized Oocytes | On day 1 after oocyte retrieval (up to 23 days after start of stimulation) | The number of pronuclei were counted after insemination. Fertilized oocytes with 2 pronuclei (2PN) were regarded as correctly fertilized. |
| Number of Follicles (Total) at End-of-stimulation | At end-of-stimulation (up to 20 stimulation days) | Counted by transvaginal ultrasound for the right and left ovary for each subject. |
| Number of Blastocysts and Number of Good Quality Blastocysts | On Day 5 or Day 6 (as applicable) after oocyte retrieval (up to 27 or 28 days after start of stimulation) | Number of blastocysts and number of good quality blastocysts on Day 5 or 6 were 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. |
| Total Gonadotropin Dose | Up to 20 stimulation days | Calculated by start dates, end dates and daily dose of investigational medicinal product (IMP). |
| Number of Stimulation Days | Up to 20 stimulation days | Calculated by start dates and end dates. |
| Proportion of Subjects With Early Ovarian Hyperstimulation Syndrome (OHSS) (Overall and by Grade) and/or Preventive Interventions for Early OHSS | Up to 9 days after triggering of final follicular maturation | 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. |
| Fertilization Rate | On day 1 after oocyte retrieval (up to 23 days after start of stimulation) | The fertilization rate was defined as the number of oocytes with 2PN divided by the number of oocytes retrieved. |
Countries
Austria, France, Italy, Spain, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| REKOVELLE (Follitropin Delta) REKOVELLE (Follitropin Delta): 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. | 200 |
| GONAL-F (Follitropin Alfa) GONAL-F (Follitropin Alfa): 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. | 100 |
| Total | 300 |
Baseline characteristics
| Characteristic | REKOVELLE (Follitropin Delta) | GONAL-F (Follitropin Alfa) | Total |
|---|---|---|---|
| Age, Continuous | 34.5 years STANDARD_DEVIATION 3.8 | 34.5 years STANDARD_DEVIATION 3.4 | 34.5 years STANDARD_DEVIATION 3.7 |
| Age, Customized 35 - 37 Years | 74 Participants | 39 Participants | 113 Participants |
| Age, Customized <35 Years | 83 Participants | 43 Participants | 126 Participants |
| Age, Customized 38 - 40 Years | 43 Participants | 18 Participants | 61 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 27 Participants | 20 Participants | 47 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 173 Participants | 80 Participants | 253 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 7 Participants | 0 Participants | 7 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 191 Participants | 98 Participants | 289 Participants |
| Region of Enrollment Austria | 46 participants | 22 participants | 68 participants |
| Region of Enrollment France | 5 participants | 3 participants | 8 participants |
| Region of Enrollment Italy | 35 participants | 15 participants | 50 participants |
| Region of Enrollment Spain | 85 participants | 47 participants | 132 participants |
| Region of Enrollment United Kingdom | 29 participants | 13 participants | 42 participants |
| Sex: Female, Male Female | 200 Participants | 100 Participants | 300 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 | 0 / 200 | 0 / 100 |
| other Total, other adverse events | 24 / 200 | 11 / 100 |
| serious Total, serious adverse events | 0 / 200 | 2 / 100 |
Outcome results
Primary
Number of Oocytes Retrieved
The number of oocytes retrieved was recorded at the oocyte retrieval visit.
Time frame: On day of oocyte retrieval (Up to 22 days after start of stimulation)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| REKOVELLE (Follitropin Delta) | Number of Oocytes Retrieved | 9.0 Oocytes Retrieved |
| GONAL-F (Follitropin Alfa) | Number of Oocytes Retrieved | 9.0 Oocytes Retrieved |
Secondary
Fertilization Rate
The fertilization rate was defined as the number of oocytes with 2PN divided by the number of oocytes retrieved.
Time frame: On day 1 after oocyte retrieval (up to 23 days after start of stimulation)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| REKOVELLE (Follitropin Delta) | Fertilization Rate | 54.5 percentage of oocytes fertilised |
| GONAL-F (Follitropin Alfa) | Fertilization Rate | 57.7 percentage of oocytes fertilised |
Secondary
Number of Blastocysts and Number of Good Quality Blastocysts
Number of blastocysts and number of good quality blastocysts on Day 5 or 6 were 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.
Time frame: On Day 5 or Day 6 (as applicable) after oocyte retrieval (up to 27 or 28 days after start of stimulation)
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| REKOVELLE (Follitropin Delta) | Number of Blastocysts and Number of Good Quality Blastocysts | Number of Blastocysts | 2.0 Blastocysts |
| REKOVELLE (Follitropin Delta) | Number of Blastocysts and Number of Good Quality Blastocysts | Number of good quality blastocysts | 2.0 Blastocysts |
| GONAL-F (Follitropin Alfa) | Number of Blastocysts and Number of Good Quality Blastocysts | Number of Blastocysts | 3.0 Blastocysts |
| GONAL-F (Follitropin Alfa) | Number of Blastocysts and Number of Good Quality Blastocysts | Number of good quality blastocysts | 2.0 Blastocysts |
Secondary
Number of Fertilized Oocytes
The number of pronuclei were counted after insemination. Fertilized oocytes with 2 pronuclei (2PN) were regarded as correctly fertilized.
Time frame: On day 1 after oocyte retrieval (up to 23 days after start of stimulation)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| REKOVELLE (Follitropin Delta) | Number of Fertilized Oocytes | 5.0 Oocytes |
| GONAL-F (Follitropin Alfa) | Number of Fertilized Oocytes | 5.0 Oocytes |
Secondary
Number of Follicles (Total) at End-of-stimulation
Counted by transvaginal ultrasound for the right and left ovary for each subject.
Time frame: At end-of-stimulation (up to 20 stimulation days)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| REKOVELLE (Follitropin Delta) | Number of Follicles (Total) at End-of-stimulation | 12.0 Follicles |
| GONAL-F (Follitropin Alfa) | Number of Follicles (Total) at End-of-stimulation | 12.0 Follicles |
Secondary
Number of Stimulation Days
Calculated by start dates and end dates.
Time frame: Up to 20 stimulation days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| REKOVELLE (Follitropin Delta) | Number of Stimulation Days | 9.0 days |
| GONAL-F (Follitropin Alfa) | Number of Stimulation Days | 9.0 days |
Secondary
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.
Time frame: Up to 9 days after triggering of final follicular maturation
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| REKOVELLE (Follitropin Delta) | Proportion of Subjects With Early Ovarian Hyperstimulation Syndrome (OHSS) (Overall and by Grade) and/or Preventive Interventions for Early OHSS | Early OHSS (moderate/severe) | 1 Participants |
| REKOVELLE (Follitropin Delta) | Proportion of Subjects With Early Ovarian Hyperstimulation Syndrome (OHSS) (Overall and by Grade) and/or Preventive Interventions for Early OHSS | Early OHSS (any grade) and / or preventative interventions | 33 Participants |
| REKOVELLE (Follitropin Delta) | Proportion of Subjects With Early Ovarian Hyperstimulation Syndrome (OHSS) (Overall and by Grade) and/or Preventive Interventions for Early OHSS | Early OHSS (moderate/severe) and / or preventative interventions | 30 Participants |
| REKOVELLE (Follitropin Delta) | Proportion of Subjects With Early Ovarian Hyperstimulation Syndrome (OHSS) (Overall and by Grade) and/or Preventive Interventions for Early OHSS | Early OHSS (any grade) | 5 Participants |
| GONAL-F (Follitropin Alfa) | Proportion of Subjects With Early Ovarian Hyperstimulation Syndrome (OHSS) (Overall and by Grade) and/or Preventive Interventions for Early OHSS | Early OHSS (moderate/severe) and / or preventative interventions | 16 Participants |
| GONAL-F (Follitropin Alfa) | Proportion of Subjects With Early Ovarian Hyperstimulation Syndrome (OHSS) (Overall and by Grade) and/or Preventive Interventions for Early OHSS | Early OHSS (any grade) | 3 Participants |
| GONAL-F (Follitropin Alfa) | Proportion of Subjects With Early Ovarian Hyperstimulation Syndrome (OHSS) (Overall and by Grade) and/or Preventive Interventions for Early OHSS | Early OHSS (any grade) and / or preventative interventions | 17 Participants |
| GONAL-F (Follitropin Alfa) | Proportion of Subjects With Early Ovarian Hyperstimulation Syndrome (OHSS) (Overall and by Grade) and/or Preventive Interventions for Early OHSS | Early OHSS (moderate/severe) | 1 Participants |
Secondary
Serum Concentrations of Estradiol at End-of-stimulation
Blood samples for analysis of circulating concentrations of estradiol were drawn.
Time frame: At end-of-stimulation (up to 20 stimulation days)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| REKOVELLE (Follitropin Delta) | Serum Concentrations of Estradiol at End-of-stimulation | 6085.0 pmol/L |
| GONAL-F (Follitropin Alfa) | Serum Concentrations of Estradiol at End-of-stimulation | 5853.5 pmol/L |
Secondary
Serum Concentrations of Progesterone at End-of-stimulation
Blood samples for analysis of circulating concentrations of progesterone were drawn.
Time frame: At end-of-stimulation (up to 20 stimulation days)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| REKOVELLE (Follitropin Delta) | Serum Concentrations of Progesterone at End-of-stimulation | 2.9 nmol/L |
| GONAL-F (Follitropin Alfa) | Serum Concentrations of Progesterone at End-of-stimulation | 2.5 nmol/L |
Secondary
Size of the Follicles at End-of-stimulation
Counted by ultrasound for the right and left ovary for each subject.
Time frame: At end-of-stimulation (up to 20 stimulation days)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| REKOVELLE (Follitropin Delta) | Size of the Follicles at End-of-stimulation | 15.7 mm |
| GONAL-F (Follitropin Alfa) | Size of the Follicles at End-of-stimulation | 16.0 mm |
Secondary
Total Gonadotropin Dose
Calculated by start dates, end dates and daily dose of investigational medicinal product (IMP).
Time frame: Up to 20 stimulation days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| REKOVELLE (Follitropin Delta) | Total Gonadotropin Dose | 135 ug |
| GONAL-F (Follitropin Alfa) | Total Gonadotropin Dose | 148.5 ug |