Infertility
Conditions
Brief summary
This trial investigates the immunogenicity of FE 999049 in repeated cycles.
Interventions
Sponsors
Ferring Pharmaceuticals
Study design
Allocation
NON_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
* Informed Consent Documents signed prior to screening evaluations related to this protocol * Participation in the pivotal efficacy trial (trial 000004/ESTHER-1) * Anti-FSH antibody results from baseline and at least one post-dosing assessment in the previous cycle(s) available. * Having undergone the oocyte retrieval procedure, or having had cycle cancellation prior to oocyte retrieval due to poor ovarian response or excessive ovarian response, in the previous cycle(s). * Failure to achieve ongoing pregnancy in the previous cycle(s).
Exclusion criteria
* Non-compliance to protocol compliance in the previous cycle(s). * Having undergone any stimulation with gonadotropins since the end-of-trial / end-of-cycle visit in the previous cycle * One or more follicles ≥10 mm observed on the transvaginal ultrasound prior to start of dosing on stimulation day 1 * Severe OHSS in a previous cycle. * Any clinically relevant change to any of the eligibility criteria in the previous cycle(s). * Clinically relevant medical history since the previous cycle which precludes gonadotropin stimulation or is associated with a reduced chance of pregnancy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion (Percentage) of Subjects With Treatment-induced Anti-Follicle-Stimulating Hormone (FSH) Antibodies After up to Two Repeated Controlled Ovarian Stimulation Cycles | Stimulation day 1, 7-10 days after last FE 999049 or GONAL-F dose and 21-28 days after last FE 999049 or GONAL-F dose | The proportion (percentage) of participants with at least one treatment-induced anti-FSH antibody response at any time point is presented. The cumulative incidences in COS cycle 2 and COS cycle 3 divided by participants in COS cycle 2 are presented. Participants with observations in both cycles are only counted once. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion (Percentage) of Subjects With Treatment-induced Anti-FSH Antibodies With Neutralising Capacity After up to Two Repeated Controlled Ovarian Stimulation Cycles | Stimulation day 1, 7-10 days after last FE 999049 or GONAL-F dose and 21-28 days after last FE 999049 or GONAL-F dose | The proportion (percentage) of participants with treatment-induced anti-FSH antibodies with neutralising capacity at any time point is presented. The cumulative incidences in COS cycle 2 and COS cycle 3 divided by participants in COS cycle 2 are presented. Participants with observations in both cycles are only counted once. |
| Proportion (Percentage) of Subjects With Treatment-induced Anti-FSH Antibodies, Overall as Well as With Neutralising Capacity, After One and After Two Repeated Controlled Ovarian Stimulation Cycles | Stimulation day 1, 7-10 days after last FE 999049 or GONAL-F dose and 21-28 days after last FE 999049 or GONAL-F dose | The proportion (percentage) of participants with treatment-induced anti-FSH antibodies, overall as well as with neutralising capacity, after one and after two repeated COS cycles is presented. |
| Proportion (Percentage) of Subjects With Early Ovarian Hyperstimulation Syndrome (OHSS) (Including OHSS of Moderate/Severe Grade) and/or Preventive Interventions for Early OHSS for Each Controlled Ovarian Stimulation Cycle | ≤9 days after triggering of final follicular maturation. | The proportion (percentage) of participants with early OHSS, early OHSS of moderate or severe grade, preventive interventions for early OHSS, early OHSS and/or preventive interventions for early OHSS, and early OHSS of moderate or severe grade and/or preventive interventions for early OHSS are presented. |
| Proportion (Percentage) of Subject With Cycle Cancellation Due to Poor Ovarian Response or Excessive Ovarian Response for Each Controlled Ovarian Stimulation Cycle | End-of-stimulation (up to 20 stimulation days) | Proportion (percentage) of participants with cycle cancellation due to poor ovarian response, excessive ovarian response, and triggering with gonadotropin-releasing hormone (GnRH) agonist are presented. |
| Implantation Rate for Each Controlled Ovarian Stimulation Cycle | 5-6 weeks after blastocyst transfer | Implantation rate was defined as the number of gestational sacs 5-6 weeks after transfer divided by number of blastocysts transferred. |
| Vital Pregnancy Rate for Each Controlled Ovarian Stimulation Cycle | 5-6 weeks after blastocyst transfer | Vital pregnancy was defined as at least one intrauterine gestational sac with fetal heart beat 5-6 weeks after blastocyst transfer. |
| Ongoing Implantation Rate for Each Controlled Ovarian Stimulation Cycle | 10-11 weeks after blastocyst transfer | Ongoing implantation rate was defined as the number of intrauterine viable fetuses 10-11 weeks after transfer divided by number of blastocysts transferred. |
| Frequency of Injection Site Reactions (Redness, Pain, Itching, Swelling and Bruising) Assessed by the Subject During the Stimulation Period for Each Controlled Ovarian Stimulation Cycle | End-of-stimulation (up to 20 stimulation days) | Participants self-assessed injection site reactions (redness, itching, pain, swelling and bruising) immediately, 30 minutes and 24 hours after each injection. The injection site reactions were assessed as none, mild, moderate and severe. The frequency of injection site reactions (mild, moderate or severe) based on all assessment performed is presented. |
| Proportion (Percentage) of Subjects With Late OHSS (Including OHSS of Moderate/Severe Grade) for Each Controlled Ovarian Stimulation Cycle | >9 days after triggering of final follicular maturation | Late OHSS was defined as OHSS with onset \>9 days after triggering of final follicular maturation. |
| Technical Malfunctions of the Administration Pen for Each Controlled Ovarian Stimulation Cycle | End-of-stimulation (up to 20 stimulation days) | Incidences of confirmed technical malfunction of administration pen are presented. |
| Ongoing Pregnancy Rate for Each Controlled Ovarian Stimulation Cycle | 10-11 weeks after blastocyst transfer | Ongoing pregnancy rate was defined as at least one intrauterine viable fetus 10-11 weeks after blastocyst transfer. |
Countries
Belgium, Brazil, Canada, Czechia, Denmark, France, Italy, Poland, Russia, Spain, United Kingdom
Participant flow
Recruitment details
A total of 32 investigational sites included participants to the trial : 3 in Belgium, 3 in Brazil, 3 in Canada, 3 in the Czech Republic, 2 in Denmark, 2 in Italy, 2 in Poland, 2 in Russia, 10 in Spain and 2 in United Kingdom.
Pre-assignment details
Participants who participated in Trial 000004 (NCT01956110) (controlled ovarian stimulation \[COS\] cycle 1) & failed to achieve ongoing pregnancy were eligible for the trial. For COS cycle 2, 520 participants were screened and 513 enrolled. For COS cycle 3, 190 participants were screened and 189 enrolled. Participants were exposed to the same IMP as in COS cycle 1.
Participants by arm
| Arm | Count |
|---|---|
| FE 999049 (COS Cycle 2) FE 999049 was administered as single daily subcutaneous injections in the abdomen. The dose was determined based on the ovarian response in COS cycle 1. The daily FE 999049 dose was fixed throughout the stimulation period and maximum allowed daily dose was 18 μg. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days. | 252 |
| GONAL-F (COS Cycle 2) GONAL-F was administered as single daily subcutaneous injections in the abdomen. The starting dose was determined based on the ovarian response in COS cycle 1. The GONAL-F starting dose was fixed for the first 5 days after which it could be adjusted by 75 IU based on the individual response. The maximum allowed daily dose was 450 IU. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days. | 261 |
| Total | 513 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| COS Cycle 2 | Adverse Event | 3 | 4 | 0 | 0 |
| COS Cycle 2 | Personal Reasons | 2 | 0 | 0 | 0 |
| COS Cycle 2 | Protocol Violation | 8 | 3 | 0 | 0 |
| COS Cycle 2 | Withdrawal by Subject | 1 | 0 | 0 | 0 |
| COS Cycle 3 | Adverse Event | 0 | 0 | 3 | 0 |
| COS Cycle 3 | Personal Reasons | 0 | 0 | 1 | 0 |
| COS Cycle 3 | Protocol Violation | 0 | 0 | 2 | 1 |
| COS Cycle 3 | Withdrawal by Subject | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | FE 999049 (COS Cycle 2) | GONAL-F (COS Cycle 2) | Total |
|---|---|---|---|
| Age, Categorical COS cycle 2 <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical COS cycle 2 >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical COS cycle 2 Between 18 and 65 years | 252 Participants | 261 Participants | 513 Participants |
| Age, Categorical COS cycle 3 <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical COS cycle 3 >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical COS cycle 3 Between 18 and 65 years | 95 Participants | 93 Participants | 188 Participants |
| Sex: Female, Male COS cycle 2 Female | 252 Participants | 261 Participants | 513 Participants |
| Sex: Female, Male COS cycle 2 Male | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male COS cycle 3 Female | 95 Participants | 93 Participants | 188 Participants |
| Sex: Female, Male COS cycle 3 Male | 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 |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 252 | 0 / 261 | 0 / 95 | 0 / 93 |
| other Total, other adverse events | 70 / 252 | 77 / 261 | 26 / 95 | 34 / 93 |
| serious Total, serious adverse events | 4 / 252 | 4 / 261 | 0 / 95 | 1 / 93 |
Outcome results
Primary
Proportion (Percentage) of Subjects With Treatment-induced Anti-Follicle-Stimulating Hormone (FSH) Antibodies After up to Two Repeated Controlled Ovarian Stimulation Cycles
The proportion (percentage) of participants with at least one treatment-induced anti-FSH antibody response at any time point is presented. The cumulative incidences in COS cycle 2 and COS cycle 3 divided by participants in COS cycle 2 are presented. Participants with observations in both cycles are only counted once.
Time frame: Stimulation day 1, 7-10 days after last FE 999049 or GONAL-F dose and 21-28 days after last FE 999049 or GONAL-F dose
Population: Safety analysis set (all exposed participants).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FE 999049 (COS Cycle 2) | Proportion (Percentage) of Subjects With Treatment-induced Anti-Follicle-Stimulating Hormone (FSH) Antibodies After up to Two Repeated Controlled Ovarian Stimulation Cycles | 0.79 Percentage of participants |
| GONAL-F (COS Cycle 2) | Proportion (Percentage) of Subjects With Treatment-induced Anti-Follicle-Stimulating Hormone (FSH) Antibodies After up to Two Repeated Controlled Ovarian Stimulation Cycles | 0.38 Percentage of participants |
Secondary
Frequency of Injection Site Reactions (Redness, Pain, Itching, Swelling and Bruising) Assessed by the Subject During the Stimulation Period for Each Controlled Ovarian Stimulation Cycle
Participants self-assessed injection site reactions (redness, itching, pain, swelling and bruising) immediately, 30 minutes and 24 hours after each injection. The injection site reactions were assessed as none, mild, moderate and severe. The frequency of injection site reactions (mild, moderate or severe) based on all assessment performed is presented.
Time frame: End-of-stimulation (up to 20 stimulation days)
Population: Safety analysis set (all exposed participants).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FE 999049 (COS Cycle 2) | Frequency of Injection Site Reactions (Redness, Pain, Itching, Swelling and Bruising) Assessed by the Subject During the Stimulation Period for Each Controlled Ovarian Stimulation Cycle | 3.0 Percentage of events |
| GONAL-F (COS Cycle 2) | Frequency of Injection Site Reactions (Redness, Pain, Itching, Swelling and Bruising) Assessed by the Subject During the Stimulation Period for Each Controlled Ovarian Stimulation Cycle | 2.4 Percentage of events |
| FE 999049 (COS Cycle 3) | Frequency of Injection Site Reactions (Redness, Pain, Itching, Swelling and Bruising) Assessed by the Subject During the Stimulation Period for Each Controlled Ovarian Stimulation Cycle | 2.8 Percentage of events |
| GONAL-F (COS Cycle 3) | Frequency of Injection Site Reactions (Redness, Pain, Itching, Swelling and Bruising) Assessed by the Subject During the Stimulation Period for Each Controlled Ovarian Stimulation Cycle | 2.3 Percentage of events |
Secondary
Implantation Rate for Each Controlled Ovarian Stimulation Cycle
Implantation rate was defined as the number of gestational sacs 5-6 weeks after transfer divided by number of blastocysts transferred.
Time frame: 5-6 weeks after blastocyst transfer
Population: Participants with blastocyst transfer. In COS cycle 2, a total of 254 and 271 blastocysts were transferred in the FE 999049 and GONAL-F groups, respectively. In COS cycle 3, a total of 132 and 121 blastocysts were transferred in the FE 999049 and GONAL-F groups, respectively.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FE 999049 (COS Cycle 2) | Implantation Rate for Each Controlled Ovarian Stimulation Cycle | 34.6 Percentage |
| GONAL-F (COS Cycle 2) | Implantation Rate for Each Controlled Ovarian Stimulation Cycle | 30.6 Percentage |
| FE 999049 (COS Cycle 3) | Implantation Rate for Each Controlled Ovarian Stimulation Cycle | 28.8 Percentage |
| GONAL-F (COS Cycle 3) | Implantation Rate for Each Controlled Ovarian Stimulation Cycle | 32.2 Percentage |
Secondary
Ongoing Implantation Rate for Each Controlled Ovarian Stimulation Cycle
Ongoing implantation rate was defined as the number of intrauterine viable fetuses 10-11 weeks after transfer divided by number of blastocysts transferred.
Time frame: 10-11 weeks after blastocyst transfer
Population: Participants with blastocyst transfer. In COS cycle 2, a total of 254 and 271 blastocysts were transferred in the FE 999049 and GONAL-F groups, respectively. In COS cycle 3, a total of 132 and 121 blastocysts were transferred in the FE 999049 and GONAL-F groups, respectively.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FE 999049 (COS Cycle 2) | Ongoing Implantation Rate for Each Controlled Ovarian Stimulation Cycle | 28.7 Percentage |
| GONAL-F (COS Cycle 2) | Ongoing Implantation Rate for Each Controlled Ovarian Stimulation Cycle | 25.5 Percentage |
| FE 999049 (COS Cycle 3) | Ongoing Implantation Rate for Each Controlled Ovarian Stimulation Cycle | 25.0 Percentage |
| GONAL-F (COS Cycle 3) | Ongoing Implantation Rate for Each Controlled Ovarian Stimulation Cycle | 28.9 Percentage |
Secondary
Ongoing Pregnancy Rate for Each Controlled Ovarian Stimulation Cycle
Ongoing pregnancy rate was defined as at least one intrauterine viable fetus 10-11 weeks after blastocyst transfer.
Time frame: 10-11 weeks after blastocyst transfer
Population: mITT analysis set (all exposed participants). This is equivalent to FAS.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FE 999049 (COS Cycle 2) | Ongoing Pregnancy Rate for Each Controlled Ovarian Stimulation Cycle | 27.8 Percentage of participants |
| GONAL-F (COS Cycle 2) | Ongoing Pregnancy Rate for Each Controlled Ovarian Stimulation Cycle | 25.7 Percentage of participants |
| FE 999049 (COS Cycle 3) | Ongoing Pregnancy Rate for Each Controlled Ovarian Stimulation Cycle | 27.4 Percentage of participants |
| GONAL-F (COS Cycle 3) | Ongoing Pregnancy Rate for Each Controlled Ovarian Stimulation Cycle | 28 Percentage of participants |
Secondary
Proportion (Percentage) of Subjects With Early Ovarian Hyperstimulation Syndrome (OHSS) (Including OHSS of Moderate/Severe Grade) and/or Preventive Interventions for Early OHSS for Each Controlled Ovarian Stimulation Cycle
The proportion (percentage) of participants with early OHSS, early OHSS of moderate or severe grade, preventive interventions for early OHSS, early OHSS and/or preventive interventions for early OHSS, and early OHSS of moderate or severe grade and/or preventive interventions for early OHSS are presented.
Time frame: ≤9 days after triggering of final follicular maturation.
Population: Modified intention-to-treat (mITT) analysis set (all exposed participants). This is equivalent to the full analysis set (FAS).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FE 999049 (COS Cycle 2) | Proportion (Percentage) of Subjects With Early Ovarian Hyperstimulation Syndrome (OHSS) (Including OHSS of Moderate/Severe Grade) and/or Preventive Interventions for Early OHSS for Each Controlled Ovarian Stimulation Cycle | Early OHSS (any grade) / preventive | 2.0 Percentage of participants |
| FE 999049 (COS Cycle 2) | Proportion (Percentage) of Subjects With Early Ovarian Hyperstimulation Syndrome (OHSS) (Including OHSS of Moderate/Severe Grade) and/or Preventive Interventions for Early OHSS for Each Controlled Ovarian Stimulation Cycle | Early OHSS (moderate/severe) | 0.0 Percentage of participants |
| FE 999049 (COS Cycle 2) | Proportion (Percentage) of Subjects With Early Ovarian Hyperstimulation Syndrome (OHSS) (Including OHSS of Moderate/Severe Grade) and/or Preventive Interventions for Early OHSS for Each Controlled Ovarian Stimulation Cycle | Early OHSS (moderate/severe) / preventive | 1.6 Percentage of participants |
| FE 999049 (COS Cycle 2) | Proportion (Percentage) of Subjects With Early Ovarian Hyperstimulation Syndrome (OHSS) (Including OHSS of Moderate/Severe Grade) and/or Preventive Interventions for Early OHSS for Each Controlled Ovarian Stimulation Cycle | Any preventive intervention | 1.6 Percentage of participants |
| FE 999049 (COS Cycle 2) | Proportion (Percentage) of Subjects With Early Ovarian Hyperstimulation Syndrome (OHSS) (Including OHSS of Moderate/Severe Grade) and/or Preventive Interventions for Early OHSS for Each Controlled Ovarian Stimulation Cycle | Early OHSS (any grade) | 0.8 Percentage of participants |
| GONAL-F (COS Cycle 2) | Proportion (Percentage) of Subjects With Early Ovarian Hyperstimulation Syndrome (OHSS) (Including OHSS of Moderate/Severe Grade) and/or Preventive Interventions for Early OHSS for Each Controlled Ovarian Stimulation Cycle | Any preventive intervention | 1.9 Percentage of participants |
| GONAL-F (COS Cycle 2) | Proportion (Percentage) of Subjects With Early Ovarian Hyperstimulation Syndrome (OHSS) (Including OHSS of Moderate/Severe Grade) and/or Preventive Interventions for Early OHSS for Each Controlled Ovarian Stimulation Cycle | Early OHSS (any grade) / preventive | 3.8 Percentage of participants |
| GONAL-F (COS Cycle 2) | Proportion (Percentage) of Subjects With Early Ovarian Hyperstimulation Syndrome (OHSS) (Including OHSS of Moderate/Severe Grade) and/or Preventive Interventions for Early OHSS for Each Controlled Ovarian Stimulation Cycle | Early OHSS (moderate/severe) / preventive | 3.8 Percentage of participants |
| GONAL-F (COS Cycle 2) | Proportion (Percentage) of Subjects With Early Ovarian Hyperstimulation Syndrome (OHSS) (Including OHSS of Moderate/Severe Grade) and/or Preventive Interventions for Early OHSS for Each Controlled Ovarian Stimulation Cycle | Early OHSS (moderate/severe) | 1.9 Percentage of participants |
| GONAL-F (COS Cycle 2) | Proportion (Percentage) of Subjects With Early Ovarian Hyperstimulation Syndrome (OHSS) (Including OHSS of Moderate/Severe Grade) and/or Preventive Interventions for Early OHSS for Each Controlled Ovarian Stimulation Cycle | Early OHSS (any grade) | 2.3 Percentage of participants |
| FE 999049 (COS Cycle 3) | Proportion (Percentage) of Subjects With Early Ovarian Hyperstimulation Syndrome (OHSS) (Including OHSS of Moderate/Severe Grade) and/or Preventive Interventions for Early OHSS for Each Controlled Ovarian Stimulation Cycle | Any preventive intervention | 0.0 Percentage of participants |
| FE 999049 (COS Cycle 3) | Proportion (Percentage) of Subjects With Early Ovarian Hyperstimulation Syndrome (OHSS) (Including OHSS of Moderate/Severe Grade) and/or Preventive Interventions for Early OHSS for Each Controlled Ovarian Stimulation Cycle | Early OHSS (any grade) | 1.1 Percentage of participants |
| FE 999049 (COS Cycle 3) | Proportion (Percentage) of Subjects With Early Ovarian Hyperstimulation Syndrome (OHSS) (Including OHSS of Moderate/Severe Grade) and/or Preventive Interventions for Early OHSS for Each Controlled Ovarian Stimulation Cycle | Early OHSS (moderate/severe) | 0.0 Percentage of participants |
| FE 999049 (COS Cycle 3) | Proportion (Percentage) of Subjects With Early Ovarian Hyperstimulation Syndrome (OHSS) (Including OHSS of Moderate/Severe Grade) and/or Preventive Interventions for Early OHSS for Each Controlled Ovarian Stimulation Cycle | Early OHSS (any grade) / preventive | 1.1 Percentage of participants |
| FE 999049 (COS Cycle 3) | Proportion (Percentage) of Subjects With Early Ovarian Hyperstimulation Syndrome (OHSS) (Including OHSS of Moderate/Severe Grade) and/or Preventive Interventions for Early OHSS for Each Controlled Ovarian Stimulation Cycle | Early OHSS (moderate/severe) / preventive | 0.0 Percentage of participants |
| GONAL-F (COS Cycle 3) | Proportion (Percentage) of Subjects With Early Ovarian Hyperstimulation Syndrome (OHSS) (Including OHSS of Moderate/Severe Grade) and/or Preventive Interventions for Early OHSS for Each Controlled Ovarian Stimulation Cycle | Early OHSS (any grade) / preventive | 1.1 Percentage of participants |
| GONAL-F (COS Cycle 3) | Proportion (Percentage) of Subjects With Early Ovarian Hyperstimulation Syndrome (OHSS) (Including OHSS of Moderate/Severe Grade) and/or Preventive Interventions for Early OHSS for Each Controlled Ovarian Stimulation Cycle | Early OHSS (moderate/severe) | 0.0 Percentage of participants |
| GONAL-F (COS Cycle 3) | Proportion (Percentage) of Subjects With Early Ovarian Hyperstimulation Syndrome (OHSS) (Including OHSS of Moderate/Severe Grade) and/or Preventive Interventions for Early OHSS for Each Controlled Ovarian Stimulation Cycle | Early OHSS (any grade) | 0.0 Percentage of participants |
| GONAL-F (COS Cycle 3) | Proportion (Percentage) of Subjects With Early Ovarian Hyperstimulation Syndrome (OHSS) (Including OHSS of Moderate/Severe Grade) and/or Preventive Interventions for Early OHSS for Each Controlled Ovarian Stimulation Cycle | Any preventive intervention | 1.1 Percentage of participants |
| GONAL-F (COS Cycle 3) | Proportion (Percentage) of Subjects With Early Ovarian Hyperstimulation Syndrome (OHSS) (Including OHSS of Moderate/Severe Grade) and/or Preventive Interventions for Early OHSS for Each Controlled Ovarian Stimulation Cycle | Early OHSS (moderate/severe) / preventive | 1.1 Percentage of participants |
Secondary
Proportion (Percentage) of Subjects With Late OHSS (Including OHSS of Moderate/Severe Grade) for Each Controlled Ovarian Stimulation Cycle
Late OHSS was defined as OHSS with onset \>9 days after triggering of final follicular maturation.
Time frame: >9 days after triggering of final follicular maturation
Population: Safety analysis set (all exposed participants).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FE 999049 (COS Cycle 2) | Proportion (Percentage) of Subjects With Late OHSS (Including OHSS of Moderate/Severe Grade) for Each Controlled Ovarian Stimulation Cycle | Late OHSS (any grade) | 0.4 Percentage of participants |
| FE 999049 (COS Cycle 2) | Proportion (Percentage) of Subjects With Late OHSS (Including OHSS of Moderate/Severe Grade) for Each Controlled Ovarian Stimulation Cycle | Late OHSS (moderate/severe) | 0.0 Percentage of participants |
| GONAL-F (COS Cycle 2) | Proportion (Percentage) of Subjects With Late OHSS (Including OHSS of Moderate/Severe Grade) for Each Controlled Ovarian Stimulation Cycle | Late OHSS (moderate/severe) | 0.8 Percentage of participants |
| GONAL-F (COS Cycle 2) | Proportion (Percentage) of Subjects With Late OHSS (Including OHSS of Moderate/Severe Grade) for Each Controlled Ovarian Stimulation Cycle | Late OHSS (any grade) | 0.8 Percentage of participants |
| FE 999049 (COS Cycle 3) | Proportion (Percentage) of Subjects With Late OHSS (Including OHSS of Moderate/Severe Grade) for Each Controlled Ovarian Stimulation Cycle | Late OHSS (any grade) | 1.1 Percentage of participants |
| FE 999049 (COS Cycle 3) | Proportion (Percentage) of Subjects With Late OHSS (Including OHSS of Moderate/Severe Grade) for Each Controlled Ovarian Stimulation Cycle | Late OHSS (moderate/severe) | 0.0 Percentage of participants |
| GONAL-F (COS Cycle 3) | Proportion (Percentage) of Subjects With Late OHSS (Including OHSS of Moderate/Severe Grade) for Each Controlled Ovarian Stimulation Cycle | Late OHSS (any grade) | 1.1 Percentage of participants |
| GONAL-F (COS Cycle 3) | Proportion (Percentage) of Subjects With Late OHSS (Including OHSS of Moderate/Severe Grade) for Each Controlled Ovarian Stimulation Cycle | Late OHSS (moderate/severe) | 1.1 Percentage of participants |
Secondary
Proportion (Percentage) of Subjects With Treatment-induced Anti-FSH Antibodies, Overall as Well as With Neutralising Capacity, After One and After Two Repeated Controlled Ovarian Stimulation Cycles
The proportion (percentage) of participants with treatment-induced anti-FSH antibodies, overall as well as with neutralising capacity, after one and after two repeated COS cycles is presented.
Time frame: Stimulation day 1, 7-10 days after last FE 999049 or GONAL-F dose and 21-28 days after last FE 999049 or GONAL-F dose
Population: Safety analysis set (all exposed participants).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FE 999049 (COS Cycle 2) | Proportion (Percentage) of Subjects With Treatment-induced Anti-FSH Antibodies, Overall as Well as With Neutralising Capacity, After One and After Two Repeated Controlled Ovarian Stimulation Cycles | Treatment-induced anti-FSH antibodies | 0.79 Percentage of participants |
| FE 999049 (COS Cycle 2) | Proportion (Percentage) of Subjects With Treatment-induced Anti-FSH Antibodies, Overall as Well as With Neutralising Capacity, After One and After Two Repeated Controlled Ovarian Stimulation Cycles | Antibodies with neutralising capacity | 0.00 Percentage of participants |
| GONAL-F (COS Cycle 2) | Proportion (Percentage) of Subjects With Treatment-induced Anti-FSH Antibodies, Overall as Well as With Neutralising Capacity, After One and After Two Repeated Controlled Ovarian Stimulation Cycles | Antibodies with neutralising capacity | 0.00 Percentage of participants |
| GONAL-F (COS Cycle 2) | Proportion (Percentage) of Subjects With Treatment-induced Anti-FSH Antibodies, Overall as Well as With Neutralising Capacity, After One and After Two Repeated Controlled Ovarian Stimulation Cycles | Treatment-induced anti-FSH antibodies | 0.38 Percentage of participants |
| FE 999049 (COS Cycle 3) | Proportion (Percentage) of Subjects With Treatment-induced Anti-FSH Antibodies, Overall as Well as With Neutralising Capacity, After One and After Two Repeated Controlled Ovarian Stimulation Cycles | Treatment-induced anti-FSH antibodies | 1.05 Percentage of participants |
| FE 999049 (COS Cycle 3) | Proportion (Percentage) of Subjects With Treatment-induced Anti-FSH Antibodies, Overall as Well as With Neutralising Capacity, After One and After Two Repeated Controlled Ovarian Stimulation Cycles | Antibodies with neutralising capacity | 0.00 Percentage of participants |
| GONAL-F (COS Cycle 3) | Proportion (Percentage) of Subjects With Treatment-induced Anti-FSH Antibodies, Overall as Well as With Neutralising Capacity, After One and After Two Repeated Controlled Ovarian Stimulation Cycles | Treatment-induced anti-FSH antibodies | 1.08 Percentage of participants |
| GONAL-F (COS Cycle 3) | Proportion (Percentage) of Subjects With Treatment-induced Anti-FSH Antibodies, Overall as Well as With Neutralising Capacity, After One and After Two Repeated Controlled Ovarian Stimulation Cycles | Antibodies with neutralising capacity | 0.00 Percentage of participants |
Secondary
Proportion (Percentage) of Subjects With Treatment-induced Anti-FSH Antibodies With Neutralising Capacity After up to Two Repeated Controlled Ovarian Stimulation Cycles
The proportion (percentage) of participants with treatment-induced anti-FSH antibodies with neutralising capacity at any time point is presented. The cumulative incidences in COS cycle 2 and COS cycle 3 divided by participants in COS cycle 2 are presented. Participants with observations in both cycles are only counted once.
Time frame: Stimulation day 1, 7-10 days after last FE 999049 or GONAL-F dose and 21-28 days after last FE 999049 or GONAL-F dose
Population: Safety analysis set (all exposed participants).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FE 999049 (COS Cycle 2) | Proportion (Percentage) of Subjects With Treatment-induced Anti-FSH Antibodies With Neutralising Capacity After up to Two Repeated Controlled Ovarian Stimulation Cycles | 0.00 Percentage of participants |
| GONAL-F (COS Cycle 2) | Proportion (Percentage) of Subjects With Treatment-induced Anti-FSH Antibodies With Neutralising Capacity After up to Two Repeated Controlled Ovarian Stimulation Cycles | 0.00 Percentage of participants |
Secondary
Proportion (Percentage) of Subject With Cycle Cancellation Due to Poor Ovarian Response or Excessive Ovarian Response for Each Controlled Ovarian Stimulation Cycle
Proportion (percentage) of participants with cycle cancellation due to poor ovarian response, excessive ovarian response, and triggering with gonadotropin-releasing hormone (GnRH) agonist are presented.
Time frame: End-of-stimulation (up to 20 stimulation days)
Population: mITT analysis set (all exposed participants). This is equivalent to the FAS.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FE 999049 (COS Cycle 2) | Proportion (Percentage) of Subject With Cycle Cancellation Due to Poor Ovarian Response or Excessive Ovarian Response for Each Controlled Ovarian Stimulation Cycle | Cycle cancelled due to poor ovarian response | 2.0 Percentage of participants |
| FE 999049 (COS Cycle 2) | Proportion (Percentage) of Subject With Cycle Cancellation Due to Poor Ovarian Response or Excessive Ovarian Response for Each Controlled Ovarian Stimulation Cycle | Triggering with GnRH agonist | 0.4 Percentage of participants |
| FE 999049 (COS Cycle 2) | Proportion (Percentage) of Subject With Cycle Cancellation Due to Poor Ovarian Response or Excessive Ovarian Response for Each Controlled Ovarian Stimulation Cycle | Cycle cancelled due to excessive ovarian response | 0.4 Percentage of participants |
| GONAL-F (COS Cycle 2) | Proportion (Percentage) of Subject With Cycle Cancellation Due to Poor Ovarian Response or Excessive Ovarian Response for Each Controlled Ovarian Stimulation Cycle | Cycle cancelled due to poor ovarian response | 3.8 Percentage of participants |
| GONAL-F (COS Cycle 2) | Proportion (Percentage) of Subject With Cycle Cancellation Due to Poor Ovarian Response or Excessive Ovarian Response for Each Controlled Ovarian Stimulation Cycle | Triggering with GnRH agonist | 0.8 Percentage of participants |
| GONAL-F (COS Cycle 2) | Proportion (Percentage) of Subject With Cycle Cancellation Due to Poor Ovarian Response or Excessive Ovarian Response for Each Controlled Ovarian Stimulation Cycle | Cycle cancelled due to excessive ovarian response | 0.0 Percentage of participants |
| FE 999049 (COS Cycle 3) | Proportion (Percentage) of Subject With Cycle Cancellation Due to Poor Ovarian Response or Excessive Ovarian Response for Each Controlled Ovarian Stimulation Cycle | Cycle cancelled due to excessive ovarian response | 0.0 Percentage of participants |
| FE 999049 (COS Cycle 3) | Proportion (Percentage) of Subject With Cycle Cancellation Due to Poor Ovarian Response or Excessive Ovarian Response for Each Controlled Ovarian Stimulation Cycle | Cycle cancelled due to poor ovarian response | 2.1 Percentage of participants |
| FE 999049 (COS Cycle 3) | Proportion (Percentage) of Subject With Cycle Cancellation Due to Poor Ovarian Response or Excessive Ovarian Response for Each Controlled Ovarian Stimulation Cycle | Triggering with GnRH agonist | 0.0 Percentage of participants |
| GONAL-F (COS Cycle 3) | Proportion (Percentage) of Subject With Cycle Cancellation Due to Poor Ovarian Response or Excessive Ovarian Response for Each Controlled Ovarian Stimulation Cycle | Cycle cancelled due to poor ovarian response | 2.2 Percentage of participants |
| GONAL-F (COS Cycle 3) | Proportion (Percentage) of Subject With Cycle Cancellation Due to Poor Ovarian Response or Excessive Ovarian Response for Each Controlled Ovarian Stimulation Cycle | Triggering with GnRH agonist | 1.1 Percentage of participants |
| GONAL-F (COS Cycle 3) | Proportion (Percentage) of Subject With Cycle Cancellation Due to Poor Ovarian Response or Excessive Ovarian Response for Each Controlled Ovarian Stimulation Cycle | Cycle cancelled due to excessive ovarian response | 0.0 Percentage of participants |
Secondary
Technical Malfunctions of the Administration Pen for Each Controlled Ovarian Stimulation Cycle
Incidences of confirmed technical malfunction of administration pen are presented.
Time frame: End-of-stimulation (up to 20 stimulation days)
Population: Safety analysis set (all exposed participants).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FE 999049 (COS Cycle 2) | Technical Malfunctions of the Administration Pen for Each Controlled Ovarian Stimulation Cycle | 0.0 Percentage of participants |
| GONAL-F (COS Cycle 2) | Technical Malfunctions of the Administration Pen for Each Controlled Ovarian Stimulation Cycle | 0.0 Percentage of participants |
| FE 999049 (COS Cycle 3) | Technical Malfunctions of the Administration Pen for Each Controlled Ovarian Stimulation Cycle | 0.0 Percentage of participants |
| GONAL-F (COS Cycle 3) | Technical Malfunctions of the Administration Pen for Each Controlled Ovarian Stimulation Cycle | 0.0 Percentage of participants |
Secondary
Vital Pregnancy Rate for Each Controlled Ovarian Stimulation Cycle
Vital pregnancy was defined as at least one intrauterine gestational sac with fetal heart beat 5-6 weeks after blastocyst transfer.
Time frame: 5-6 weeks after blastocyst transfer
Population: mITT analysis set (all exposed participants). This is equivalent to the FAS.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FE 999049 (COS Cycle 2) | Vital Pregnancy Rate for Each Controlled Ovarian Stimulation Cycle | 29.4 Percentage of participants |
| GONAL-F (COS Cycle 2) | Vital Pregnancy Rate for Each Controlled Ovarian Stimulation Cycle | 27.2 Percentage of participants |
| FE 999049 (COS Cycle 3) | Vital Pregnancy Rate for Each Controlled Ovarian Stimulation Cycle | 27.4 Percentage of participants |
| GONAL-F (COS Cycle 3) | Vital Pregnancy Rate for Each Controlled Ovarian Stimulation Cycle | 29.0 Percentage of participants |