Infertility, Ovulation Induction, In-Vitro Fertilization
Conditions
Keywords
Infertility, Ovulation induction, Gonal-F, Follitropin alpha, Controlled ovarian stimulation
Brief summary
This was a prospective, open-label, non-comparative, Phase IIIb trial to assess the convenience, safety and efficacy of the new Gonal-F fbm \[recombinant follicle stimulating hormone (r-FSH)\] liquid formulation, in common setting for ovulation induction (OI) and also in in-vitro fertilization (IVF).
Interventions
DRUGGONAL-f®
GONAL-f® will be administered subcutaneously to subjects between Day 2 and Day 5 of their cycle with a starting dose of 75 International Units (IU) per day for subjects who undergo ovulation induction (OI)/artificial insemination (IUI) and between 150 and 225 IU per day for subjects who undergo in-vitro fertilization (IVF). For subjects who undergo OI/IUI, the dose will be increased by 37.5 IU after Day 14 up to Week 4 if no ovarian response is observed.
Sponsors
Merck KGaA, Darmstadt, Germany
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 43 Years
Healthy volunteers
No
Inclusion criteria
* Female subjects aged between 18 and 43 years * Ambulatory subjects * Subjects who are willing to get pregnant and are infertile, that justifies ovarian stimulation treatment for mono-/pauci-follicular development (OI or IUI) or multiple follicular development for IVF/Intracytoplasmic Sperm Injection (ICSI) procedures * Subjects who are able to communicate well with the investigator and to comply with the requirements of the entire study * Subjects who have given written informed consent, prior to treatment
Exclusion criteria
* Subjects with enlarged ovaries or cysts unrelated to polycystic ovaries * Subjects with extra-uterine pregnancy during the last 3 months * Subjects with several endometriosis (Grade III & IV) * Subjects with history of severe ovarian hyperstimulation syndrome * Subjects with history of thromboembolic event * Subjects with malformative uterine pathology that could disturb either implantation or pregnancy processes * Subjects with premature menopause * Subjects with gynecological bleeding of unknown origin * Subjects with ovarian, uterine, or mammary cancer * Subjects with tumors of the hypothalamus or the pituitary glands * Subjects with history of serious allergy or atopic asthma disease * Subjects with known allergic reaction against one of the Follicle Stimulating Hormone (FSH) and ingredients, * Ongoing pregnant, or breast feeding subjects * Subjects who have participated in a trial during the last 3 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Who Self-administered the Investigational Medicinal Product (IMP) | Up to 1 year | Number of subjects who self-administered the IMP were presented in this outcome measure. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluation of the Information Given to the Subjects on the Pen's Utilization | Up to 1 year | Subjects were provided with the information on Pen's utilization via training session and in the form of information brochure. Subjects assessed both the methods using the following responses: satisfactory, satisfactory, unsatisfactory and very unsatisfactory. |
| Duration of Ovarian Stimulation With GONAL-f® | Up to 1 year | Stimulation duration was defined as the duration (in days) for which subjects underwent GONAL-f® treatment. |
| Mean Number of Embryos Transferred | End of Stimulation period (up to a maximum 26 days) | — |
| Total and Average Daily Dose of GONAL-f® | Up to 26 days | — |
| Global Evaluation of the GONAL-f® Prefilled Pen by the Investigator | Up to 1 year | Investigator evaluated the use of GONAL-f® prefilled pen in subjects as very satisfactory, satisfactory and average satisfaction. |
| Number of Subjects With Live Birth | End of Gestation period, assessed up to a maximum of 1 year | Number of subjects whose stimulation with the IMP resulted in the birth of a baby were reported. |
| Number of Subjects With Local Tolerance at GONAL-f ® Injection Site as Assessed by Investigator | Up to 1 year | Local tolerance at the GONAL-f ® injection site was assessed for the presence of pain, swelling/welt, redness, itch and haematoma. |
| Number of Subjects With at Least 1 Adverse Event | Up to 1 year | An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerged or worsened relative to baseline (i.e. present at the initial study visit) during a clinical study with an investigational product, regardless of causal relationship and even if no investigational product has been administered. |
| Number of Subjects Taking at Least 1 Concomitant Treatment | Up to 1 year | — |
| Pregnancy Rate in Subjects Receiving Stimulation by Ovulation Induction (OI) or Artificial Insemination (IUI) | Up to 20 Weeks of Gestation | Pregnancy rate was defined as the percentage of subjects with diagnosis of pregnancy, who underwent OI/IUI. Clinical pregnancy: Evidence of pregnancy by clinical or ultrasound parameters at 12 weeks after fertilization. Biochemical pregnancy: Evidence of conception based only on biochemical data in the serum or urine before ultrasound evidence of a gestational sac. Ongoing pregnancy was defined when the pregnancy had completed 20 weeks of gestation. |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| GONAL-f® GONAL-f® was administered subcutaneously to subjects between Day 2 and Day 5 of their cycle with a starting dose of 75 International Units (IU) per day for subjects who underwent ovulation induction (OI)/ artificial insemination (IUI) and between 150 and 225 IU per day for subjects who underwent in-vitro fertilization (IVF). For subjects who underwent OI/ IUI the dose was increased by 37.5 IU after Day 14 up to Week 4 if no ovarian response was observed. | 204 |
| Total | 204 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Protocol Violation | 115 |
| Overall Study | Subject Questionnaires not returned | 5 |
| Overall Study | Subjects enrolled, but not treated | 11 |
| Overall Study | Withdrawal by Subject | 19 |
Baseline characteristics
| Characteristic | GONAL-f® |
|---|---|
| Age, Continuous | 30.0 years STANDARD_DEVIATION 3.3 |
| Sex: Female, Male Female | 204 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 36 / 215 |
| serious Total, serious adverse events | 6 / 215 |
Outcome results
Primary
Number of Subjects Who Self-administered the Investigational Medicinal Product (IMP)
Number of subjects who self-administered the IMP were presented in this outcome measure.
Time frame: Up to 1 year
Population: The ITT population included all the subjects who received at least 1 dose of the IMP.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GONAL-f® | Number of Subjects Who Self-administered the Investigational Medicinal Product (IMP) | 159 subjects |
Secondary
Duration of Ovarian Stimulation With GONAL-f®
Stimulation duration was defined as the duration (in days) for which subjects underwent GONAL-f® treatment.
Time frame: Up to 1 year
Population: The ITT population included all the subjects who received, at least 1 dose of the IMP.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| GONAL-f® | Duration of Ovarian Stimulation With GONAL-f® | 10 days |
Secondary
Evaluation of the Information Given to the Subjects on the Pen's Utilization
Subjects were provided with the information on Pen's utilization via training session and in the form of information brochure. Subjects assessed both the methods using the following responses: satisfactory, satisfactory, unsatisfactory and very unsatisfactory.
Time frame: Up to 1 year
Population: The ITT population. Here Overall Number of Subjects Analyzed signifies those subjects who were evaluable for this outcome and Number Analyzed signifies those who were evaluable for the specified category.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GONAL-f® | Evaluation of the Information Given to the Subjects on the Pen's Utilization | Training Session: Unsatisfactory | 5 subjects |
| GONAL-f® | Evaluation of the Information Given to the Subjects on the Pen's Utilization | Training Session: Very unsatisfactory | 1 subjects |
| GONAL-f® | Evaluation of the Information Given to the Subjects on the Pen's Utilization | Information brochure: Very satisfactory | 95 subjects |
| GONAL-f® | Evaluation of the Information Given to the Subjects on the Pen's Utilization | Information brochure: Satisfactory | 89 subjects |
| GONAL-f® | Evaluation of the Information Given to the Subjects on the Pen's Utilization | Information brochure: Unsatisfactory | 9 subjects |
| GONAL-f® | Evaluation of the Information Given to the Subjects on the Pen's Utilization | Information brochure: Very unsatisfactory | 2 subjects |
| GONAL-f® | Evaluation of the Information Given to the Subjects on the Pen's Utilization | Training Session: Very satisfactory | 89 subjects |
| GONAL-f® | Evaluation of the Information Given to the Subjects on the Pen's Utilization | Training Session: Satisfactory | 95 subjects |
Secondary
Global Evaluation of the GONAL-f® Prefilled Pen by the Investigator
Investigator evaluated the use of GONAL-f® prefilled pen in subjects as very satisfactory, satisfactory and average satisfaction.
Time frame: Up to 1 year
Population: The ITT population included all the subjects who received at least 1 dose of the IMP. Here Overall Number of Subjects Analyzed signifies those subjects who were evaluable for this outcome.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GONAL-f® | Global Evaluation of the GONAL-f® Prefilled Pen by the Investigator | Very satisfactory | 101 subjects |
| GONAL-f® | Global Evaluation of the GONAL-f® Prefilled Pen by the Investigator | Satisfactory | 93 subjects |
| GONAL-f® | Global Evaluation of the GONAL-f® Prefilled Pen by the Investigator | Average satisfaction | 1 subjects |
Secondary
Mean Number of Embryos Transferred
Time frame: End of Stimulation period (up to a maximum 26 days)
Population: The ITT population included all the subjects who received at least 1 dose of the IMP. Here Number of Participants Analyzed signifies those subjects who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GONAL-f® | Mean Number of Embryos Transferred | 1.8 embryos | Standard Deviation 0.7 |
Secondary
Number of Subjects Taking at Least 1 Concomitant Treatment
Time frame: Up to 1 year
Population: The tolerance analysis set included of all the subjects who were presented at the inclusion visit.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GONAL-f® | Number of Subjects Taking at Least 1 Concomitant Treatment | 28 subjects |
Secondary
Number of Subjects With at Least 1 Adverse Event
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerged or worsened relative to baseline (i.e. present at the initial study visit) during a clinical study with an investigational product, regardless of causal relationship and even if no investigational product has been administered.
Time frame: Up to 1 year
Population: The tolerance analysis set included of all the subjects who were presented at the inclusion visit.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GONAL-f® | Number of Subjects With at Least 1 Adverse Event | 36 subjects |
Secondary
Number of Subjects With Live Birth
Number of subjects whose stimulation with the IMP resulted in the birth of a baby were reported.
Time frame: End of Gestation period, assessed up to a maximum of 1 year
Population: Per Protocol (PP) population was defined as the group of subjects who completed the study, having returned their completed questionnaire and who did not present any major protocol deviations.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GONAL-f® | Number of Subjects With Live Birth | 41 subjects |
Secondary
Number of Subjects With Local Tolerance at GONAL-f ® Injection Site as Assessed by Investigator
Local tolerance at the GONAL-f ® injection site was assessed for the presence of pain, swelling/welt, redness, itch and haematoma.
Time frame: Up to 1 year
Population: ITT population included all the subjects who received at least 1 dose of the investigational medicinal product.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GONAL-f® | Number of Subjects With Local Tolerance at GONAL-f ® Injection Site as Assessed by Investigator | Pain | 32 subjects |
| GONAL-f® | Number of Subjects With Local Tolerance at GONAL-f ® Injection Site as Assessed by Investigator | Swelling/welt | 3 subjects |
| GONAL-f® | Number of Subjects With Local Tolerance at GONAL-f ® Injection Site as Assessed by Investigator | Redness | 34 subjects |
| GONAL-f® | Number of Subjects With Local Tolerance at GONAL-f ® Injection Site as Assessed by Investigator | Itch | 8 subjects |
| GONAL-f® | Number of Subjects With Local Tolerance at GONAL-f ® Injection Site as Assessed by Investigator | Haematoma | 41 subjects |
Secondary
Pregnancy Rate in Subjects Receiving Stimulation by Ovulation Induction (OI) or Artificial Insemination (IUI)
Pregnancy rate was defined as the percentage of subjects with diagnosis of pregnancy, who underwent OI/IUI. Clinical pregnancy: Evidence of pregnancy by clinical or ultrasound parameters at 12 weeks after fertilization. Biochemical pregnancy: Evidence of conception based only on biochemical data in the serum or urine before ultrasound evidence of a gestational sac. Ongoing pregnancy was defined when the pregnancy had completed 20 weeks of gestation.
Time frame: Up to 20 Weeks of Gestation
Population: The ITT population included all the subjects who received, at least 1 dose of the IMP. Number of Participants Analyzed signifies ITT (OI/IUI) subjects who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GONAL-f® | Pregnancy Rate in Subjects Receiving Stimulation by Ovulation Induction (OI) or Artificial Insemination (IUI) | Clinical pregnancy | 16.5 Percentage of subjects |
| GONAL-f® | Pregnancy Rate in Subjects Receiving Stimulation by Ovulation Induction (OI) or Artificial Insemination (IUI) | Biochemical pregnancy | 16.5 Percentage of subjects |
| GONAL-f® | Pregnancy Rate in Subjects Receiving Stimulation by Ovulation Induction (OI) or Artificial Insemination (IUI) | Ongoing pregnancy | 16.5 Percentage of subjects |
Secondary
Total and Average Daily Dose of GONAL-f®
Time frame: Up to 26 days
Population: The ITT population included all the subjects who received at least 1 dose of the IMP.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GONAL-f® | Total and Average Daily Dose of GONAL-f® | Total dose | 1527 International Units (IU) | Standard Deviation 964 |
| GONAL-f® | Total and Average Daily Dose of GONAL-f® | Daily dose | 149.5 International Units (IU) | Standard Deviation 75.9 |