Infertility
Conditions
Brief summary
This trial investigates the effects of several doses of FE 999049 in women undergoing IVF/ICSI (in-vitro fertilisation/intracytoplasmic sperm injection) treatment.
Interventions
DRUGFE 999049
DRUGGonal - F
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 37 Years
Healthy volunteers
No
Inclusion criteria
* Women diagnosed with tubal infertility, unexplained infertility, infertility related to endometriosis stage I/II or with partners diagnosed with male factor infertility * Women eligible for IVF (in-vitro fertilisation) and/or ICSI (intracytoplasmic sperm injection) treatment * Women aged 18-37 years * Women with body mass index (BMI) of 18.5-32.0 kg/m2
Exclusion criteria
* Women with polycystic ovary syndrome (PCOS) associated with anovulation, endometriosis stage III/IV * Women with history of recurrent miscarriage * Women with contraindications to controlled ovarian stimulation with gonadotropins * Women with three or more controlled ovarian stimulation cycles
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Oocytes Retrieved | Day of oocyte retrieval (up to Day 18 after start of stimulation) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Endocrine Profile | End of stimulation (up to 16 stimulation days) | Estradiol at end of stimulation |
| Total IMP Dose | End of stimulation (up to 16 stimulation days) | — |
| Number of Fertilised Oocytes | Day 1 after insemination | An oocyte with 2 pronuclei was regarded as correctly fertilised |
| Number and Size of Follicles During Stimulation | End of stimulation (up to 16 stimulation days) | Follicular volume at end of stimulation |
| Clinical Pregnancy With Fetal Heart Beat Rate | 5-6 weeks after transfer | Clinical pregnancy with fetal heart beat was defined as at least one intrauterine gestational sac with fetal heart beat |
| Frequency and Intensity of Adverse Events | From signing informed consent form until end of trial visit (up to 5 months) | — |
| Number and Quality of Blastocysts on Day 5 | Day 5 after oocyte retrieval | Number of blastocysts (total and good-quality) on Day 5 are presented. A good-quality blastocyst was defined as a blastocyst of grade 3BB or higher |
Countries
Belgium, Czechia, Denmark, Spain
Participant flow
Recruitment details
A total of 7 sites randomised subjects to the trial: 1 in Belgium, 1 in Czech Republic, 1 in Denmark and 4 in Spain.
Pre-assignment details
In total 334 subjects were screened. Of these, 69 were screening failures and 265 were randomised. All randomised subjects were exposed to investigational medicinal product (IMP).
Participants by arm
| Arm | Count |
|---|---|
| FE 999049 5.2 µg Subjects received single daily subcutaneous injections of 5.2 µg FE 999049, for a maximum of 16 days | 42 |
| FE 999049 6.9 µg Subjects received single daily subcutaneous injections of 6.9 µg FE 999049, for a maximum of 16 days | 45 |
| FE 999049 8.6 µg Subjects received single daily subcutaneous injections of 8.6 µg FE 999049, for a maximum of 16 days | 44 |
| FE 999049 10.3 µg Subjects received single daily subcutaneous injections of 10.3 µg FE 999049, for a maximum of 16 days | 44 |
| FE 999049 12.1 µg Subjects received single daily subcutaneous injections of 12.1 µg FE 999049, for a maximum of 16 days | 47 |
| GONAL-F 11 µg Subjects received single daily subcutaneous injections of 11 µg GONAL-F, for a maximum of 16 days | 43 |
| Total | 265 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Did not attend scheduled visit | 1 | 4 | 0 | 0 | 2 | 1 |
| Overall Study | Personal reasons | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Poor response | 2 | 1 | 2 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | FE 999049 5.2 µg | FE 999049 6.9 µg | FE 999049 8.6 µg | FE 999049 10.3 µg | FE 999049 12.1 µg | GONAL-F 11 µg | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 33.6 years STANDARD_DEVIATION 2.24 | 32.3 years STANDARD_DEVIATION 3.51 | 32.8 years STANDARD_DEVIATION 2.44 | 32.3 years STANDARD_DEVIATION 3.21 | 32.6 years STANDARD_DEVIATION 2.97 | 32.4 years STANDARD_DEVIATION 3.04 | 32.7 years STANDARD_DEVIATION 2.95 |
| Sex: Female, Male Female | 42 Participants | 45 Participants | 44 Participants | 44 Participants | 47 Participants | 43 Participants | 265 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 42 | 0 / 45 | 0 / 44 | 0 / 44 | 0 / 47 | 0 / 43 |
| other Total, other adverse events | 11 / 42 | 9 / 45 | 11 / 44 | 12 / 44 | 11 / 47 | 4 / 43 |
| serious Total, serious adverse events | 0 / 42 | 0 / 45 | 0 / 44 | 1 / 44 | 0 / 47 | 0 / 43 |
Outcome results
Primary
Number of Oocytes Retrieved
Time frame: Day of oocyte retrieval (up to Day 18 after start of stimulation)
Population: Modified Intention-to-treat (mITT) population (all randomised and exposed subjects). This is equivalent to the Full Analysis Set (FAS)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FE 999049 5.2 µg | Number of Oocytes Retrieved | 5.2 Oocytes | Standard Deviation 3.3 |
| FE 999049 6.9 µg | Number of Oocytes Retrieved | 7.9 Oocytes | Standard Deviation 5.9 |
| FE 999049 8.6 µg | Number of Oocytes Retrieved | 9.2 Oocytes | Standard Deviation 4.6 |
| FE 999049 10.3 µg | Number of Oocytes Retrieved | 10.5 Oocytes | Standard Deviation 7 |
| FE 999049 12.1 µg | Number of Oocytes Retrieved | 12.2 Oocytes | Standard Deviation 5.9 |
| GONAL-F 11 µg | Number of Oocytes Retrieved | 10.4 Oocytes | Standard Deviation 5.2 |
Comparison: The dose-response relationship was analysed using an analysis of covariance (ANCOVA) modelp-value: <0.00195% CI: [5.69, 10.18]ANCOVA
Secondary
Clinical Pregnancy With Fetal Heart Beat Rate
Clinical pregnancy with fetal heart beat was defined as at least one intrauterine gestational sac with fetal heart beat
Time frame: 5-6 weeks after transfer
Population: mITT population (all randomised and exposed subjects). This is equivalent to the FAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FE 999049 5.2 µg | Clinical Pregnancy With Fetal Heart Beat Rate | 36 percentage |
| FE 999049 6.9 µg | Clinical Pregnancy With Fetal Heart Beat Rate | 40 percentage |
| FE 999049 8.6 µg | Clinical Pregnancy With Fetal Heart Beat Rate | 36 percentage |
| FE 999049 10.3 µg | Clinical Pregnancy With Fetal Heart Beat Rate | 25 percentage |
| FE 999049 12.1 µg | Clinical Pregnancy With Fetal Heart Beat Rate | 40 percentage |
| GONAL-F 11 µg | Clinical Pregnancy With Fetal Heart Beat Rate | 51 percentage |
p-value: 0.248Chi-squared
Secondary
Endocrine Profile
Estradiol at end of stimulation
Time frame: End of stimulation (up to 16 stimulation days)
Population: mITT population (all randomised and exposed subjects). This is equivalent to the FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FE 999049 5.2 µg | Endocrine Profile | 3641.9 pmol/L | Standard Deviation 2954.6 |
| FE 999049 6.9 µg | Endocrine Profile | 5221.1 pmol/L | Standard Deviation 3378.8 |
| FE 999049 8.6 µg | Endocrine Profile | 5689.5 pmol/L | Standard Deviation 3995.7 |
| FE 999049 10.3 µg | Endocrine Profile | 6171.8 pmol/L | Standard Deviation 3855.9 |
| FE 999049 12.1 µg | Endocrine Profile | 6442.0 pmol/L | Standard Deviation 3195.2 |
| GONAL-F 11 µg | Endocrine Profile | 5750.7 pmol/L | Standard Deviation 3709.7 |
Comparison: The dose-response relationship was analysed using an analysis of covariance (ANCOVA) modelp-value: <0.00195% CI: [0.56, 1.11]ANCOVA
Secondary
Frequency and Intensity of Adverse Events
Time frame: From signing informed consent form until end of trial visit (up to 5 months)
Population: Safety population (all randomised and exposed subjects). This is equivalent to the mITT
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FE 999049 5.2 µg | Frequency and Intensity of Adverse Events | Any moderate adverse events | 2 participants |
| FE 999049 5.2 µg | Frequency and Intensity of Adverse Events | Any mild adverse events | 15 participants |
| FE 999049 5.2 µg | Frequency and Intensity of Adverse Events | Any severe adverse events | 0 participants |
| FE 999049 6.9 µg | Frequency and Intensity of Adverse Events | Any moderate adverse events | 6 participants |
| FE 999049 6.9 µg | Frequency and Intensity of Adverse Events | Any mild adverse events | 17 participants |
| FE 999049 6.9 µg | Frequency and Intensity of Adverse Events | Any severe adverse events | 0 participants |
| FE 999049 8.6 µg | Frequency and Intensity of Adverse Events | Any moderate adverse events | 5 participants |
| FE 999049 8.6 µg | Frequency and Intensity of Adverse Events | Any mild adverse events | 17 participants |
| FE 999049 8.6 µg | Frequency and Intensity of Adverse Events | Any severe adverse events | 0 participants |
| FE 999049 10.3 µg | Frequency and Intensity of Adverse Events | Any moderate adverse events | 9 participants |
| FE 999049 10.3 µg | Frequency and Intensity of Adverse Events | Any mild adverse events | 18 participants |
| FE 999049 10.3 µg | Frequency and Intensity of Adverse Events | Any severe adverse events | 1 participants |
| FE 999049 12.1 µg | Frequency and Intensity of Adverse Events | Any moderate adverse events | 8 participants |
| FE 999049 12.1 µg | Frequency and Intensity of Adverse Events | Any mild adverse events | 15 participants |
| FE 999049 12.1 µg | Frequency and Intensity of Adverse Events | Any severe adverse events | 0 participants |
| GONAL-F 11 µg | Frequency and Intensity of Adverse Events | Any mild adverse events | 11 participants |
| GONAL-F 11 µg | Frequency and Intensity of Adverse Events | Any severe adverse events | 0 participants |
| GONAL-F 11 µg | Frequency and Intensity of Adverse Events | Any moderate adverse events | 2 participants |
Secondary
Number and Quality of Blastocysts on Day 5
Number of blastocysts (total and good-quality) on Day 5 are presented. A good-quality blastocyst was defined as a blastocyst of grade 3BB or higher
Time frame: Day 5 after oocyte retrieval
Population: Subjects with oocytes retrieved
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FE 999049 5.2 µg | Number and Quality of Blastocysts on Day 5 | Total blastocysts | 2.3 Blastocysts | Standard Deviation 1.7 |
| FE 999049 5.2 µg | Number and Quality of Blastocysts on Day 5 | Good quality blastocysts | 0.9 Blastocysts | Standard Deviation 1.2 |
| FE 999049 6.9 µg | Number and Quality of Blastocysts on Day 5 | Total blastocysts | 3.1 Blastocysts | Standard Deviation 2.7 |
| FE 999049 6.9 µg | Number and Quality of Blastocysts on Day 5 | Good quality blastocysts | 1.4 Blastocysts | Standard Deviation 1.7 |
| FE 999049 8.6 µg | Number and Quality of Blastocysts on Day 5 | Total blastocysts | 2.7 Blastocysts | Standard Deviation 2 |
| FE 999049 8.6 µg | Number and Quality of Blastocysts on Day 5 | Good quality blastocysts | 1.2 Blastocysts | Standard Deviation 1.2 |
| FE 999049 10.3 µg | Number and Quality of Blastocysts on Day 5 | Total blastocysts | 2.8 Blastocysts | Standard Deviation 2.8 |
| FE 999049 10.3 µg | Number and Quality of Blastocysts on Day 5 | Good quality blastocysts | 1.4 Blastocysts | Standard Deviation 1.5 |
| FE 999049 12.1 µg | Number and Quality of Blastocysts on Day 5 | Total blastocysts | 3.2 Blastocysts | Standard Deviation 2.2 |
| FE 999049 12.1 µg | Number and Quality of Blastocysts on Day 5 | Good quality blastocysts | 1.3 Blastocysts | Standard Deviation 1.3 |
| GONAL-F 11 µg | Number and Quality of Blastocysts on Day 5 | Total blastocysts | 3.5 Blastocysts | Standard Deviation 2.5 |
| GONAL-F 11 µg | Number and Quality of Blastocysts on Day 5 | Good quality blastocysts | 1.6 Blastocysts | Standard Deviation 1.6 |
Secondary
Number and Size of Follicles During Stimulation
Follicular volume at end of stimulation
Time frame: End of stimulation (up to 16 stimulation days)
Population: mITT population (all randomised and exposed subjects). This is equivalent to the FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FE 999049 5.2 µg | Number and Size of Follicles During Stimulation | 19.2 cm^3 | Standard Deviation 7 |
| FE 999049 6.9 µg | Number and Size of Follicles During Stimulation | 23.0 cm^3 | Standard Deviation 10.5 |
| FE 999049 8.6 µg | Number and Size of Follicles During Stimulation | 25.0 cm^3 | Standard Deviation 9.2 |
| FE 999049 10.3 µg | Number and Size of Follicles During Stimulation | 27.9 cm^3 | Standard Deviation 15.6 |
| FE 999049 12.1 µg | Number and Size of Follicles During Stimulation | 28.2 cm^3 | Standard Deviation 9.5 |
| GONAL-F 11 µg | Number and Size of Follicles During Stimulation | 26.7 cm^3 | Standard Deviation 9.2 |
Comparison: The dose-response relationship was analysed using an analysis of covariance (ANCOVA) modelp-value: <0.00195% CI: [6.78, 15.48]ANCOVA
Secondary
Number of Fertilised Oocytes
An oocyte with 2 pronuclei was regarded as correctly fertilised
Time frame: Day 1 after insemination
Population: Subjects with oocytes retrieved
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FE 999049 5.2 µg | Number of Fertilised Oocytes | 3.7 Fertilised oocytes | Standard Deviation 2.5 |
| FE 999049 6.9 µg | Number of Fertilised Oocytes | 5.4 Fertilised oocytes | Standard Deviation 3.8 |
| FE 999049 8.6 µg | Number of Fertilised Oocytes | 4.9 Fertilised oocytes | Standard Deviation 2.7 |
| FE 999049 10.3 µg | Number of Fertilised Oocytes | 6.1 Fertilised oocytes | Standard Deviation 5.1 |
| FE 999049 12.1 µg | Number of Fertilised Oocytes | 6.7 Fertilised oocytes | Standard Deviation 3.5 |
| GONAL-F 11 µg | Number of Fertilised Oocytes | 6.4 Fertilised oocytes | Standard Deviation 3.5 |
Comparison: The dose-response relationship was analysed using an analysis of covariance (ANCOVA) modelp-value: <0.00195% CI: [1.71, 4.78]ANCOVA
Secondary
Total IMP Dose
Time frame: End of stimulation (up to 16 stimulation days)
Population: mITT population (all randomised and exposed subjects). This is equivalent to the FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FE 999049 5.2 µg | Total IMP Dose | 50.0 µg | Standard Deviation 11.6 |
| FE 999049 6.9 µg | Total IMP Dose | 61.9 µg | Standard Deviation 13.7 |
| FE 999049 8.6 µg | Total IMP Dose | 71.9 µg | Standard Deviation 14.1 |
| FE 999049 10.3 µg | Total IMP Dose | 81.0 µg | Standard Deviation 14.2 |
| FE 999049 12.1 µg | Total IMP Dose | 97.8 µg | Standard Deviation 22 |
| GONAL-F 11 µg | Total IMP Dose | 94.7 µg | Standard Deviation 18.1 |