Infertility
Conditions
Brief summary
This trial is investigating the efficacy and safety of highly purified human chorionic gonadotropin (HP-hCG) and recombinant human chorionic gonadotropin (rhCG) for triggering of final follicular maturation in women undergoing controlled ovarian stimulation
Interventions
DRUGhighly purified human chorionic gonadotropin
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 39 Years
Healthy volunteers
No
Inclusion criteria
* Pre-menopausal females between the ages of 18 and 39 years * Documented history of infertility * Body mass index (BMI) between 17.5 and 32.0 kg/m2 * Regular menstrual cycles
Exclusion criteria
* Known endometriosis stage III and IV * Known polycystic ovarian syndrome (PCOS) * History of recurrent miscarriage * History of more than three previous controlled ovarian stimulation cycles
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Oocytes Retrieved | Approximately 36 hours after hCG administration | Oocyte retrieval took place 36 h (±2h) after hCG administration. At oocyte retrieval the number of oocytes retrieved was recorded. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Fertilized (2 Pronuclei (2PN)) Oocytes | One day after oocyte retrieval | Fertilization was assessed by counting the number of pronuclei, which was recorded as 0, 1, 2 or \>2. Correct fertilization was defined as oocytes with 2PN. |
| Positive β Unit of Human Chorionic Gonadotropin (βhCG) Rate | 13-15 days after transfer | Defined as percentage of subjects with positive beta hCG. A positive β hCG was confirmed by a blood test obtained 13-15 days after transfer. |
| Number of Metaphase II (MII) Oocytes | Prior to insemination (within 6 hours after oocyte retrieval) | Only applicable for insemination using intracytoplasmic sperm injection (ICSI). The MII oocytes were counted prior to insemination. |
| Frequency of Adverse Events (AEs) | AEs were collected from signing informed consent until end of trial visit = maximum period approximately 5 months. However, only TEAEs are presented | The number of treatment-emergent AEs (TEAEs) in each treatment group will be presented. |
| Intensity of AEs | AEs were collected from signing informed consent until end of trial visit = maximum period approximately 5 months. However, only TEAEs are presented. | The intensity of an TEAE would be classified using the following 3-point scale: mild (awareness of signs or symptoms, but no disruption of usual activity), moderate (event sufficient to affect usual activity \[disturbing\]) or severe (inability to work or perform usual activities \[unacceptable\]). |
| Clinical Pregnancy Rate | 5-6 weeks after transfer | Defined as percentage of subjects with clinical pregnancy. Clinical pregnancy was defined as at least one gestational sac 5-6 weeks after transfer. |
Countries
Brazil
Participant flow
Recruitment details
A total of 4 sites in Brazil randomized subjects to the trial.
Pre-assignment details
In total 245 subjects were screened. Of these, 69 were screening failures and 176 were randomized. All randomized subjects were exposed to investigational medicinal product (IMP).
Participants by arm
| Arm | Count |
|---|---|
| HP-hCG IM Highly purified human chorionic gonadotropin 5000 international units (IU), intramuscularly (IM)
Highly purified human chorionic gonadotropin | 58 |
| HP-hCG SC Highly purified human chorionic gonadotropin, 5000 IU subcutaneously (SC)
Highly purified human chorionic gonadotropin | 58 |
| rhCG SC Recombinant human chorionic gonadotropin 250 µg SC
Recombinant human chorionic gonadotropin | 60 |
| Total | 176 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 2 | 0 |
| Overall Study | Protocol Violation | 0 | 4 | 1 |
Baseline characteristics
| Characteristic | Total | HP-hCG IM | HP-hCG SC | rhCG SC |
|---|---|---|---|---|
| Age, Customized 35-37 years | 65 Participants | 20 Participants | 23 Participants | 22 Participants |
| Age, Customized <35 years | 100 Participants | 35 Participants | 33 Participants | 32 Participants |
| Age, Customized >=38 years | 11 Participants | 3 Participants | 2 Participants | 6 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 1 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 23 Participants | 8 Participants | 5 Participants | 10 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 150 Participants | 49 Participants | 51 Participants | 50 Participants |
| Region of Enrollment Brazil | 176 Participants | 58 Participants | 58 Participants | 60 Participants |
| Sex: Female, Male Female | 176 Participants | 58 Participants | 58 Participants | 60 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 58 | 0 / 58 | 0 / 60 |
| other Total, other adverse events | 12 / 58 | 12 / 58 | 11 / 60 |
| serious Total, serious adverse events | 1 / 58 | 1 / 58 | 2 / 60 |
Outcome results
Primary
Number of Oocytes Retrieved
Oocyte retrieval took place 36 h (±2h) after hCG administration. At oocyte retrieval the number of oocytes retrieved was recorded.
Time frame: Approximately 36 hours after hCG administration
Population: The ITT analysis set was defined as all randomized subjects. Subjects were analyzed according to planned (randomized) treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HP-hCG IM | Number of Oocytes Retrieved | 7.1 Number of oocytes | Standard Deviation 4.6 |
| HP-hCG SC | Number of Oocytes Retrieved | 7.3 Number of oocytes | Standard Deviation 4.8 |
| rhCG SC | Number of Oocytes Retrieved | 6.6 Number of oocytes | Standard Deviation 4.1 |
Comparison: Mean number of oocytes retrieved for the treatment comparison of HP-hCG IM versus rhCG SC95% CI: [-0.6, 1.8]
Comparison: Mean number of oocytes retrieved for the treatment comparison of HP-hCG SC versus rhCG SC95% CI: [-0.5, 2]
Secondary
Clinical Pregnancy Rate
Defined as percentage of subjects with clinical pregnancy. Clinical pregnancy was defined as at least one gestational sac 5-6 weeks after transfer.
Time frame: 5-6 weeks after transfer
Population: The ITT analysis set was defined as all randomized subjects. Subjects were analyzed according to planned (randomized) treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HP-hCG IM | Clinical Pregnancy Rate | 46.6 percentage of participants |
| HP-hCG SC | Clinical Pregnancy Rate | 27.6 percentage of participants |
| rhCG SC | Clinical Pregnancy Rate | 31.7 percentage of participants |
Secondary
Frequency of Adverse Events (AEs)
The number of treatment-emergent AEs (TEAEs) in each treatment group will be presented.
Time frame: AEs were collected from signing informed consent until end of trial visit = maximum period approximately 5 months. However, only TEAEs are presented
Population: Safety was summarized based on the safety analysis set.The safety analysis set included all 176 subjects. Subjects were analyzed according to their actual treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HP-hCG IM | Frequency of Adverse Events (AEs) | 22 Number of AEs |
| HP-hCG SC | Frequency of Adverse Events (AEs) | 25 Number of AEs |
| rhCG SC | Frequency of Adverse Events (AEs) | 25 Number of AEs |
Secondary
Intensity of AEs
The intensity of an TEAE would be classified using the following 3-point scale: mild (awareness of signs or symptoms, but no disruption of usual activity), moderate (event sufficient to affect usual activity \[disturbing\]) or severe (inability to work or perform usual activities \[unacceptable\]).
Time frame: AEs were collected from signing informed consent until end of trial visit = maximum period approximately 5 months. However, only TEAEs are presented.
Population: Safety was summarized based on the safety analysis set.The safety analysis set included all 176 subjects. Subjects were analyzed according to their actual treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| HP-hCG IM | Intensity of AEs | Any moderate AE | 8 Participants |
| HP-hCG IM | Intensity of AEs | Any mild AE | 14 Participants |
| HP-hCG IM | Intensity of AEs | Any severe AE | 0 Participants |
| HP-hCG SC | Intensity of AEs | Any moderate AE | 6 Participants |
| HP-hCG SC | Intensity of AEs | Any mild AE | 18 Participants |
| HP-hCG SC | Intensity of AEs | Any severe AE | 1 Participants |
| rhCG SC | Intensity of AEs | Any mild AE | 22 Participants |
| rhCG SC | Intensity of AEs | Any severe AE | 0 Participants |
| rhCG SC | Intensity of AEs | Any moderate AE | 3 Participants |
Secondary
Number of Fertilized (2 Pronuclei (2PN)) Oocytes
Fertilization was assessed by counting the number of pronuclei, which was recorded as 0, 1, 2 or \>2. Correct fertilization was defined as oocytes with 2PN.
Time frame: One day after oocyte retrieval
Population: The ITT analysis set was defined as all randomized subjects. Subjects were analyzed according to planned (randomized) treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HP-hCG IM | Number of Fertilized (2 Pronuclei (2PN)) Oocytes | 4.4 Number of fertilized oocytes | Standard Deviation 3.3 |
| HP-hCG SC | Number of Fertilized (2 Pronuclei (2PN)) Oocytes | 4.7 Number of fertilized oocytes | Standard Deviation 3.4 |
| rhCG SC | Number of Fertilized (2 Pronuclei (2PN)) Oocytes | 4.2 Number of fertilized oocytes | Standard Deviation 2.7 |
Comparison: Number of fertilized (2 pronuclei (2PN)) oocytes for the treatment comparison of HP-hCG IM versus rhCG SC95% CI: [-0.6, 1.3]
Comparison: Number of fertilized (2 pronuclei (2PN)) oocytes for the treatment comparison of HP-hCG SC versus rhCG SC.95% CI: [-0.5, 1.4]
Secondary
Number of Metaphase II (MII) Oocytes
Only applicable for insemination using intracytoplasmic sperm injection (ICSI). The MII oocytes were counted prior to insemination.
Time frame: Prior to insemination (within 6 hours after oocyte retrieval)
Population: The ITT analysis set was defined as all randomized subjects. Subjects were analyzed according to planned (randomized) treatment.~Note that only subjects with ICSI were included in this analysis, i.e. 58 subjects in the HP-hCG IM group, 55 subjects in the HP-hCG SC group and 57 subjects in the rhCG SC group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HP-hCG IM | Number of Metaphase II (MII) Oocytes | 5.9 Number of MII oocytes | Standard Deviation 3.7 |
| HP-hCG SC | Number of Metaphase II (MII) Oocytes | 6.2 Number of MII oocytes | Standard Deviation 3.5 |
| rhCG SC | Number of Metaphase II (MII) Oocytes | 5.6 Number of MII oocytes | Standard Deviation 3.3 |
Comparison: Number of MII oocytes retrieved for the treatment comparison of HP-hCG IM versus rhCG SC95% CI: [-0.6, 1.5]
Comparison: Number of Mll oocytes retrieved for the treatment comparison of HP-hCG SC versus rhCG SC95% CI: [-0.4, 1.6]
Secondary
Positive β Unit of Human Chorionic Gonadotropin (βhCG) Rate
Defined as percentage of subjects with positive beta hCG. A positive β hCG was confirmed by a blood test obtained 13-15 days after transfer.
Time frame: 13-15 days after transfer
Population: The ITT analysis set was defined as all randomized subjects. Subjects were analyzed according to planned (randomized) treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HP-hCG IM | Positive β Unit of Human Chorionic Gonadotropin (βhCG) Rate | 50.0 percentage of participants |
| HP-hCG SC | Positive β Unit of Human Chorionic Gonadotropin (βhCG) Rate | 37.9 percentage of participants |
| rhCG SC | Positive β Unit of Human Chorionic Gonadotropin (βhCG) Rate | 36.7 percentage of participants |