Trial Outcomes & Findings for Evidence-based Stimulation Trial With Human rFSH in Europe and Rest of World 2 (NCT NCT01956123)
NCT ID: NCT01956123
Last Updated: 2023-09-06
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
513 participants
Primary outcome timeframe
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
Results posted on
2023-09-06
Participant Flow
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.
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.
Participant milestones
| Measure |
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.
|
GONAL-F (COS Cycle 2)
Follitropin Alfa (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 international units (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.
|
FE 999049 (COS Cycle 3)
FE 999049 was administered as single daily subcutaneous injections in the abdomen. The dose was determined based on the ovarian response in COS cycle 2. The daily FE 999049 dose was fixed throughout the stimulation period and maximum allowed daily dose was 24 μg. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.
|
GONAL-F (COS Cycle 3)
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 2. 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.
|
|---|---|---|---|---|
|
COS Cycle 2
STARTED
|
252
|
261
|
0
|
0
|
|
COS Cycle 2
COMPLETED
|
238
|
254
|
0
|
0
|
|
COS Cycle 2
NOT COMPLETED
|
14
|
7
|
0
|
0
|
|
COS Cycle 3
STARTED
|
0
|
0
|
95
|
93
|
|
COS Cycle 3
COMPLETED
|
0
|
0
|
89
|
91
|
|
COS Cycle 3
NOT COMPLETED
|
0
|
0
|
6
|
2
|
Reasons for withdrawal
| Measure |
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.
|
GONAL-F (COS Cycle 2)
Follitropin Alfa (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 international units (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.
|
FE 999049 (COS Cycle 3)
FE 999049 was administered as single daily subcutaneous injections in the abdomen. The dose was determined based on the ovarian response in COS cycle 2. The daily FE 999049 dose was fixed throughout the stimulation period and maximum allowed daily dose was 24 μg. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.
|
GONAL-F (COS Cycle 3)
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 2. 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.
|
|---|---|---|---|---|
|
COS Cycle 2
Protocol Violation
|
8
|
3
|
0
|
0
|
|
COS Cycle 2
Adverse Event
|
3
|
4
|
0
|
0
|
|
COS Cycle 2
Personal Reasons
|
2
|
0
|
0
|
0
|
|
COS Cycle 2
Withdrawal by Subject
|
1
|
0
|
0
|
0
|
|
COS Cycle 3
Protocol Violation
|
0
|
0
|
2
|
1
|
|
COS Cycle 3
Adverse Event
|
0
|
0
|
3
|
0
|
|
COS Cycle 3
Personal Reasons
|
0
|
0
|
1
|
0
|
|
COS Cycle 3
Withdrawal by Subject
|
0
|
0
|
0
|
1
|
Baseline Characteristics
Only participants who participated in COS cycle 2 but failed to achieve an ongoing pregnancy could undergo COS cycle 3.
Baseline characteristics by cohort
| Measure |
FE 999049 (COS Cycle 2)
n=252 Participants
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.
|
GONAL-F (COS Cycle 2)
n=261 Participants
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.
|
Total
n=513 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
COS cycle 2 · <=18 years
|
0 Participants
n=252 Participants • Only participants who participated in COS cycle 2 but failed to achieve an ongoing pregnancy could undergo COS cycle 3.
|
0 Participants
n=261 Participants • Only participants who participated in COS cycle 2 but failed to achieve an ongoing pregnancy could undergo COS cycle 3.
|
0 Participants
n=513 Participants • Only participants who participated in COS cycle 2 but failed to achieve an ongoing pregnancy could undergo COS cycle 3.
|
|
Age, Categorical
COS cycle 2 · Between 18 and 65 years
|
252 Participants
n=252 Participants • Only participants who participated in COS cycle 2 but failed to achieve an ongoing pregnancy could undergo COS cycle 3.
|
261 Participants
n=261 Participants • Only participants who participated in COS cycle 2 but failed to achieve an ongoing pregnancy could undergo COS cycle 3.
|
513 Participants
n=513 Participants • Only participants who participated in COS cycle 2 but failed to achieve an ongoing pregnancy could undergo COS cycle 3.
|
|
Age, Categorical
COS cycle 2 · >=65 years
|
0 Participants
n=252 Participants • Only participants who participated in COS cycle 2 but failed to achieve an ongoing pregnancy could undergo COS cycle 3.
|
0 Participants
n=261 Participants • Only participants who participated in COS cycle 2 but failed to achieve an ongoing pregnancy could undergo COS cycle 3.
|
0 Participants
n=513 Participants • Only participants who participated in COS cycle 2 but failed to achieve an ongoing pregnancy could undergo COS cycle 3.
|
|
Age, Categorical
COS cycle 3 · <=18 years
|
0 Participants
n=95 Participants • Only participants who participated in COS cycle 2 but failed to achieve an ongoing pregnancy could undergo COS cycle 3.
|
0 Participants
n=93 Participants • Only participants who participated in COS cycle 2 but failed to achieve an ongoing pregnancy could undergo COS cycle 3.
|
0 Participants
n=188 Participants • Only participants who participated in COS cycle 2 but failed to achieve an ongoing pregnancy could undergo COS cycle 3.
|
|
Age, Categorical
COS cycle 3 · Between 18 and 65 years
|
95 Participants
n=95 Participants • Only participants who participated in COS cycle 2 but failed to achieve an ongoing pregnancy could undergo COS cycle 3.
|
93 Participants
n=93 Participants • Only participants who participated in COS cycle 2 but failed to achieve an ongoing pregnancy could undergo COS cycle 3.
|
188 Participants
n=188 Participants • Only participants who participated in COS cycle 2 but failed to achieve an ongoing pregnancy could undergo COS cycle 3.
|
|
Age, Categorical
COS cycle 3 · >=65 years
|
0 Participants
n=95 Participants • Only participants who participated in COS cycle 2 but failed to achieve an ongoing pregnancy could undergo COS cycle 3.
|
0 Participants
n=93 Participants • Only participants who participated in COS cycle 2 but failed to achieve an ongoing pregnancy could undergo COS cycle 3.
|
0 Participants
n=188 Participants • Only participants who participated in COS cycle 2 but failed to achieve an ongoing pregnancy could undergo COS cycle 3.
|
|
Sex: Female, Male
COS cycle 2 · Female
|
252 Participants
n=252 Participants • Only participants who participated in COS cycle 2 but failed to achieve an ongoing pregnancy could undergo COS cycle 3.
|
261 Participants
n=261 Participants • Only participants who participated in COS cycle 2 but failed to achieve an ongoing pregnancy could undergo COS cycle 3.
|
513 Participants
n=513 Participants • Only participants who participated in COS cycle 2 but failed to achieve an ongoing pregnancy could undergo COS cycle 3.
|
|
Sex: Female, Male
COS cycle 2 · Male
|
0 Participants
n=252 Participants • Only participants who participated in COS cycle 2 but failed to achieve an ongoing pregnancy could undergo COS cycle 3.
|
0 Participants
n=261 Participants • Only participants who participated in COS cycle 2 but failed to achieve an ongoing pregnancy could undergo COS cycle 3.
|
0 Participants
n=513 Participants • Only participants who participated in COS cycle 2 but failed to achieve an ongoing pregnancy could undergo COS cycle 3.
|
|
Sex: Female, Male
COS cycle 3 · Female
|
95 Participants
n=95 Participants • Only participants who participated in COS cycle 2 but failed to achieve an ongoing pregnancy could undergo COS cycle 3.
|
93 Participants
n=93 Participants • Only participants who participated in COS cycle 2 but failed to achieve an ongoing pregnancy could undergo COS cycle 3.
|
188 Participants
n=188 Participants • Only participants who participated in COS cycle 2 but failed to achieve an ongoing pregnancy could undergo COS cycle 3.
|
|
Sex: Female, Male
COS cycle 3 · Male
|
0 Participants
n=95 Participants • Only participants who participated in COS cycle 2 but failed to achieve an ongoing pregnancy could undergo COS cycle 3.
|
0 Participants
n=93 Participants • Only participants who participated in COS cycle 2 but failed to achieve an ongoing pregnancy could undergo COS cycle 3.
|
0 Participants
n=188 Participants • Only participants who participated in COS cycle 2 but failed to achieve an ongoing pregnancy could undergo COS cycle 3.
|
PRIMARY outcome
Timeframe: 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 dosePopulation: Safety analysis set (all exposed participants).
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.
Outcome measures
| Measure |
FE 999049 (COS Cycle 2)
n=252 Participants
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.
|
GONAL-F (COS Cycle 2)
n=261 Participants
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.
|
FE 999049 (COS Cycle 3)
FE 999049 was administered as single daily subcutaneous injections in the abdomen. The dose was determined based on the ovarian response in COS cycle 2. The daily FE 999049 dose was fixed throughout the stimulation period and maximum allowed daily dose was 24 μg. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.
|
GONAL-F (COS Cycle 3)
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 2. 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.
|
|---|---|---|---|---|
|
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
Interval 0.1 to 2.84
|
0.38 Percentage of participants
Interval 0.01 to 2.12
|
—
|
—
|
SECONDARY outcome
Timeframe: 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 dosePopulation: Safety analysis set (all exposed participants).
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.
Outcome measures
| Measure |
FE 999049 (COS Cycle 2)
n=252 Participants
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.
|
GONAL-F (COS Cycle 2)
n=261 Participants
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.
|
FE 999049 (COS Cycle 3)
FE 999049 was administered as single daily subcutaneous injections in the abdomen. The dose was determined based on the ovarian response in COS cycle 2. The daily FE 999049 dose was fixed throughout the stimulation period and maximum allowed daily dose was 24 μg. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.
|
GONAL-F (COS Cycle 3)
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 2. 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.
|
|---|---|---|---|---|
|
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
Interval 0.0 to 1.45
|
0.00 Percentage of participants
Interval 0.0 to 1.4
|
—
|
—
|
SECONDARY outcome
Timeframe: 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 dosePopulation: Safety analysis set (all exposed participants).
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.
Outcome measures
| Measure |
FE 999049 (COS Cycle 2)
n=252 Participants
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.
|
GONAL-F (COS Cycle 2)
n=261 Participants
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.
|
FE 999049 (COS Cycle 3)
n=95 Participants
FE 999049 was administered as single daily subcutaneous injections in the abdomen. The dose was determined based on the ovarian response in COS cycle 2. The daily FE 999049 dose was fixed throughout the stimulation period and maximum allowed daily dose was 24 μg. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.
|
GONAL-F (COS Cycle 3)
n=93 Participants
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 2. 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.
|
|---|---|---|---|---|
|
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
Interval 0.1 to 2.84
|
0.38 Percentage of participants
Interval 0.01 to 2.12
|
1.05 Percentage of participants
Interval 0.03 to 5.73
|
1.08 Percentage of participants
Interval 0.03 to 5.85
|
|
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
Interval 0.0 to 1.45
|
0.00 Percentage of participants
Interval 0.0 to 1.4
|
0.00 Percentage of participants
Interval 0.0 to 3.81
|
0.00 Percentage of participants
Interval 0.0 to 3.89
|
SECONDARY outcome
Timeframe: ≤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).
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.
Outcome measures
| Measure |
FE 999049 (COS Cycle 2)
n=252 Participants
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.
|
GONAL-F (COS Cycle 2)
n=261 Participants
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.
|
FE 999049 (COS Cycle 3)
n=95 Participants
FE 999049 was administered as single daily subcutaneous injections in the abdomen. The dose was determined based on the ovarian response in COS cycle 2. The daily FE 999049 dose was fixed throughout the stimulation period and maximum allowed daily dose was 24 μg. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.
|
GONAL-F (COS Cycle 3)
n=93 Participants
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 2. 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.
|
|---|---|---|---|---|
|
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
|
2.3 Percentage of participants
|
1.1 Percentage of participants
|
0.0 Percentage of participants
|
|
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
|
1.9 Percentage of participants
|
0.0 Percentage of participants
|
0.0 Percentage of participants
|
|
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
|
1.9 Percentage of participants
|
0.0 Percentage of participants
|
1.1 Percentage of participants
|
|
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
|
3.8 Percentage of participants
|
1.1 Percentage of participants
|
1.1 Percentage of participants
|
|
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
|
3.8 Percentage of participants
|
0.0 Percentage of participants
|
1.1 Percentage of participants
|
SECONDARY outcome
Timeframe: End-of-stimulation (up to 20 stimulation days)Population: mITT analysis set (all exposed participants). This is equivalent to the FAS.
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.
Outcome measures
| Measure |
FE 999049 (COS Cycle 2)
n=252 Participants
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.
|
GONAL-F (COS Cycle 2)
n=261 Participants
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.
|
FE 999049 (COS Cycle 3)
n=95 Participants
FE 999049 was administered as single daily subcutaneous injections in the abdomen. The dose was determined based on the ovarian response in COS cycle 2. The daily FE 999049 dose was fixed throughout the stimulation period and maximum allowed daily dose was 24 μg. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.
|
GONAL-F (COS Cycle 3)
n=93 Participants
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 2. 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.
|
|---|---|---|---|---|
|
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
|
3.8 Percentage of participants
|
2.1 Percentage of participants
|
2.2 Percentage of participants
|
|
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
|
0.0 Percentage of participants
|
0.0 Percentage of participants
|
0.0 Percentage of participants
|
|
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
|
0.8 Percentage of participants
|
0.0 Percentage of participants
|
1.1 Percentage of participants
|
SECONDARY outcome
Timeframe: 5-6 weeks after blastocyst transferPopulation: mITT analysis set (all exposed participants). This is equivalent to the FAS.
Vital pregnancy was defined as at least one intrauterine gestational sac with fetal heart beat 5-6 weeks after blastocyst transfer.
Outcome measures
| Measure |
FE 999049 (COS Cycle 2)
n=252 Participants
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.
|
GONAL-F (COS Cycle 2)
n=261 Participants
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.
|
FE 999049 (COS Cycle 3)
n=95 Participants
FE 999049 was administered as single daily subcutaneous injections in the abdomen. The dose was determined based on the ovarian response in COS cycle 2. The daily FE 999049 dose was fixed throughout the stimulation period and maximum allowed daily dose was 24 μg. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.
|
GONAL-F (COS Cycle 3)
n=93 Participants
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 2. 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.
|
|---|---|---|---|---|
|
Vital Pregnancy Rate for Each Controlled Ovarian Stimulation Cycle
|
29.4 Percentage of participants
Interval 23.8 to 35.4
|
27.2 Percentage of participants
Interval 21.9 to 33.0
|
27.4 Percentage of participants
Interval 18.7 to 37.5
|
29.0 Percentage of participants
Interval 20.1 to 39.4
|
SECONDARY outcome
Timeframe: 5-6 weeks after blastocyst transferPopulation: 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.
Implantation rate was defined as the number of gestational sacs 5-6 weeks after transfer divided by number of blastocysts transferred.
Outcome measures
| Measure |
FE 999049 (COS Cycle 2)
n=211 Participants
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.
|
GONAL-F (COS Cycle 2)
n=221 Participants
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.
|
FE 999049 (COS Cycle 3)
n=82 Participants
FE 999049 was administered as single daily subcutaneous injections in the abdomen. The dose was determined based on the ovarian response in COS cycle 2. The daily FE 999049 dose was fixed throughout the stimulation period and maximum allowed daily dose was 24 μg. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.
|
GONAL-F (COS Cycle 3)
n=75 Participants
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 2. 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.
|
|---|---|---|---|---|
|
Implantation Rate for Each Controlled Ovarian Stimulation Cycle
|
34.6 Percentage
Interval 28.8 to 40.8
|
30.6 Percentage
Interval 25.2 to 36.5
|
28.8 Percentage
Interval 21.2 to 37.3
|
32.2 Percentage
Interval 24.0 to 41.3
|
SECONDARY outcome
Timeframe: 10-11 weeks after blastocyst transferPopulation: mITT analysis set (all exposed participants). This is equivalent to FAS.
Ongoing pregnancy rate was defined as at least one intrauterine viable fetus 10-11 weeks after blastocyst transfer.
Outcome measures
| Measure |
FE 999049 (COS Cycle 2)
n=252 Participants
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.
|
GONAL-F (COS Cycle 2)
n=261 Participants
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.
|
FE 999049 (COS Cycle 3)
n=95 Participants
FE 999049 was administered as single daily subcutaneous injections in the abdomen. The dose was determined based on the ovarian response in COS cycle 2. The daily FE 999049 dose was fixed throughout the stimulation period and maximum allowed daily dose was 24 μg. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.
|
GONAL-F (COS Cycle 3)
n=93 Participants
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 2. 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.
|
|---|---|---|---|---|
|
Ongoing Pregnancy Rate for Each Controlled Ovarian Stimulation Cycle
|
27.8 Percentage of participants
Interval 22.3 to 33.7
|
25.7 Percentage of participants
Interval 20.5 to 31.4
|
27.4 Percentage of participants
Interval 18.7 to 37.5
|
28 Percentage of participants
Interval 19.1 to 38.2
|
SECONDARY outcome
Timeframe: 10-11 weeks after blastocyst transferPopulation: 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.
Ongoing implantation rate was defined as the number of intrauterine viable fetuses 10-11 weeks after transfer divided by number of blastocysts transferred.
Outcome measures
| Measure |
FE 999049 (COS Cycle 2)
n=211 Participants
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.
|
GONAL-F (COS Cycle 2)
n=221 Participants
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.
|
FE 999049 (COS Cycle 3)
n=82 Participants
FE 999049 was administered as single daily subcutaneous injections in the abdomen. The dose was determined based on the ovarian response in COS cycle 2. The daily FE 999049 dose was fixed throughout the stimulation period and maximum allowed daily dose was 24 μg. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.
|
GONAL-F (COS Cycle 3)
n=75 Participants
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 2. 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.
|
|---|---|---|---|---|
|
Ongoing Implantation Rate for Each Controlled Ovarian Stimulation Cycle
|
28.7 Percentage
Interval 23.3 to 34.7
|
25.5 Percentage
Interval 20.4 to 31.1
|
25.0 Percentage
Interval 17.9 to 33.3
|
28.9 Percentage
Interval 21.0 to 37.9
|
SECONDARY outcome
Timeframe: End-of-stimulation (up to 20 stimulation days)Population: Safety analysis set (all exposed participants).
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.
Outcome measures
| Measure |
FE 999049 (COS Cycle 2)
n=252 Participants
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.
|
GONAL-F (COS Cycle 2)
n=261 Participants
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.
|
FE 999049 (COS Cycle 3)
n=95 Participants
FE 999049 was administered as single daily subcutaneous injections in the abdomen. The dose was determined based on the ovarian response in COS cycle 2. The daily FE 999049 dose was fixed throughout the stimulation period and maximum allowed daily dose was 24 μg. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.
|
GONAL-F (COS Cycle 3)
n=93 Participants
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 2. 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.
|
|---|---|---|---|---|
|
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
|
2.4 Percentage of events
|
2.8 Percentage of events
|
2.3 Percentage of events
|
SECONDARY outcome
Timeframe: >9 days after triggering of final follicular maturationPopulation: Safety analysis set (all exposed participants).
Late OHSS was defined as OHSS with onset \>9 days after triggering of final follicular maturation.
Outcome measures
| Measure |
FE 999049 (COS Cycle 2)
n=252 Participants
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.
|
GONAL-F (COS Cycle 2)
n=261 Participants
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.
|
FE 999049 (COS Cycle 3)
n=95 Participants
FE 999049 was administered as single daily subcutaneous injections in the abdomen. The dose was determined based on the ovarian response in COS cycle 2. The daily FE 999049 dose was fixed throughout the stimulation period and maximum allowed daily dose was 24 μg. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.
|
GONAL-F (COS Cycle 3)
n=93 Participants
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 2. 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.
|
|---|---|---|---|---|
|
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
|
0.8 Percentage of participants
|
1.1 Percentage of participants
|
1.1 Percentage of participants
|
|
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
|
0.8 Percentage of participants
|
0.0 Percentage of participants
|
1.1 Percentage of participants
|
SECONDARY outcome
Timeframe: End-of-stimulation (up to 20 stimulation days)Population: Safety analysis set (all exposed participants).
Incidences of confirmed technical malfunction of administration pen are presented.
Outcome measures
| Measure |
FE 999049 (COS Cycle 2)
n=252 Participants
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.
|
GONAL-F (COS Cycle 2)
n=261 Participants
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.
|
FE 999049 (COS Cycle 3)
n=95 Participants
FE 999049 was administered as single daily subcutaneous injections in the abdomen. The dose was determined based on the ovarian response in COS cycle 2. The daily FE 999049 dose was fixed throughout the stimulation period and maximum allowed daily dose was 24 μg. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.
|
GONAL-F (COS Cycle 3)
n=93 Participants
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 2. 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.
|
|---|---|---|---|---|
|
Technical Malfunctions of the Administration Pen for Each Controlled Ovarian Stimulation Cycle
|
0.0 Percentage of participants
|
0.0 Percentage of participants
|
0.0 Percentage of participants
|
0.0 Percentage of participants
|
Adverse Events
FE 999049 (COS Cycle 2)
Serious events: 4 serious events
Other events: 70 other events
Deaths: 0 deaths
GONAL-F (COS Cycle 2)
Serious events: 4 serious events
Other events: 77 other events
Deaths: 0 deaths
FE 999049 (COS Cycle 3)
Serious events: 0 serious events
Other events: 26 other events
Deaths: 0 deaths
GONAL-F (COS Cycle 3)
Serious events: 1 serious events
Other events: 34 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
FE 999049 (COS Cycle 2)
n=252 participants at risk
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.
|
GONAL-F (COS Cycle 2)
n=261 participants at risk
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.
|
FE 999049 (COS Cycle 3)
n=95 participants at risk
FE 999049 was administered as single daily subcutaneous injections in the abdomen. The dose was determined based on the ovarian response in COS cycle 2. The daily FE 999049 dose was fixed throughout the stimulation period and maximum allowed daily dose was 24 μg. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.
|
GONAL-F (COS Cycle 3)
n=93 participants at risk
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 2. 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.
|
|---|---|---|---|---|
|
Pregnancy, puerperium and perinatal conditions
Ectopic pregnancy
|
0.40%
1/252 • Number of events 1 • Adverse events (AEs) were recorded from signed informed consent to the end-of-cycle visit for COS cycle 2 (up to approximately 4.5 months) and again from screening to the end-of-cycle visit for COS cycle 3 (up to approximately 4.5 months).
AEs with onset after start of first administration of IMP and before the end-of-cycle were considered treatment-emergent and are presented for the safety analysis set.
|
0.77%
2/261 • Number of events 2 • Adverse events (AEs) were recorded from signed informed consent to the end-of-cycle visit for COS cycle 2 (up to approximately 4.5 months) and again from screening to the end-of-cycle visit for COS cycle 3 (up to approximately 4.5 months).
AEs with onset after start of first administration of IMP and before the end-of-cycle were considered treatment-emergent and are presented for the safety analysis set.
|
0.00%
0/95 • Adverse events (AEs) were recorded from signed informed consent to the end-of-cycle visit for COS cycle 2 (up to approximately 4.5 months) and again from screening to the end-of-cycle visit for COS cycle 3 (up to approximately 4.5 months).
AEs with onset after start of first administration of IMP and before the end-of-cycle were considered treatment-emergent and are presented for the safety analysis set.
|
0.00%
0/93 • Adverse events (AEs) were recorded from signed informed consent to the end-of-cycle visit for COS cycle 2 (up to approximately 4.5 months) and again from screening to the end-of-cycle visit for COS cycle 3 (up to approximately 4.5 months).
AEs with onset after start of first administration of IMP and before the end-of-cycle were considered treatment-emergent and are presented for the safety analysis set.
|
|
Pregnancy, puerperium and perinatal conditions
Haemorrhage in pregnancy
|
0.40%
1/252 • Number of events 1 • Adverse events (AEs) were recorded from signed informed consent to the end-of-cycle visit for COS cycle 2 (up to approximately 4.5 months) and again from screening to the end-of-cycle visit for COS cycle 3 (up to approximately 4.5 months).
AEs with onset after start of first administration of IMP and before the end-of-cycle were considered treatment-emergent and are presented for the safety analysis set.
|
0.38%
1/261 • Number of events 1 • Adverse events (AEs) were recorded from signed informed consent to the end-of-cycle visit for COS cycle 2 (up to approximately 4.5 months) and again from screening to the end-of-cycle visit for COS cycle 3 (up to approximately 4.5 months).
AEs with onset after start of first administration of IMP and before the end-of-cycle were considered treatment-emergent and are presented for the safety analysis set.
|
0.00%
0/95 • Adverse events (AEs) were recorded from signed informed consent to the end-of-cycle visit for COS cycle 2 (up to approximately 4.5 months) and again from screening to the end-of-cycle visit for COS cycle 3 (up to approximately 4.5 months).
AEs with onset after start of first administration of IMP and before the end-of-cycle were considered treatment-emergent and are presented for the safety analysis set.
|
0.00%
0/93 • Adverse events (AEs) were recorded from signed informed consent to the end-of-cycle visit for COS cycle 2 (up to approximately 4.5 months) and again from screening to the end-of-cycle visit for COS cycle 3 (up to approximately 4.5 months).
AEs with onset after start of first administration of IMP and before the end-of-cycle were considered treatment-emergent and are presented for the safety analysis set.
|
|
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous
|
0.40%
1/252 • Number of events 1 • Adverse events (AEs) were recorded from signed informed consent to the end-of-cycle visit for COS cycle 2 (up to approximately 4.5 months) and again from screening to the end-of-cycle visit for COS cycle 3 (up to approximately 4.5 months).
AEs with onset after start of first administration of IMP and before the end-of-cycle were considered treatment-emergent and are presented for the safety analysis set.
|
0.00%
0/261 • Adverse events (AEs) were recorded from signed informed consent to the end-of-cycle visit for COS cycle 2 (up to approximately 4.5 months) and again from screening to the end-of-cycle visit for COS cycle 3 (up to approximately 4.5 months).
AEs with onset after start of first administration of IMP and before the end-of-cycle were considered treatment-emergent and are presented for the safety analysis set.
|
0.00%
0/95 • Adverse events (AEs) were recorded from signed informed consent to the end-of-cycle visit for COS cycle 2 (up to approximately 4.5 months) and again from screening to the end-of-cycle visit for COS cycle 3 (up to approximately 4.5 months).
AEs with onset after start of first administration of IMP and before the end-of-cycle were considered treatment-emergent and are presented for the safety analysis set.
|
0.00%
0/93 • Adverse events (AEs) were recorded from signed informed consent to the end-of-cycle visit for COS cycle 2 (up to approximately 4.5 months) and again from screening to the end-of-cycle visit for COS cycle 3 (up to approximately 4.5 months).
AEs with onset after start of first administration of IMP and before the end-of-cycle were considered treatment-emergent and are presented for the safety analysis set.
|
|
Pregnancy, puerperium and perinatal conditions
Vomiting in pregnancy
|
0.40%
1/252 • Number of events 1 • Adverse events (AEs) were recorded from signed informed consent to the end-of-cycle visit for COS cycle 2 (up to approximately 4.5 months) and again from screening to the end-of-cycle visit for COS cycle 3 (up to approximately 4.5 months).
AEs with onset after start of first administration of IMP and before the end-of-cycle were considered treatment-emergent and are presented for the safety analysis set.
|
0.00%
0/261 • Adverse events (AEs) were recorded from signed informed consent to the end-of-cycle visit for COS cycle 2 (up to approximately 4.5 months) and again from screening to the end-of-cycle visit for COS cycle 3 (up to approximately 4.5 months).
AEs with onset after start of first administration of IMP and before the end-of-cycle were considered treatment-emergent and are presented for the safety analysis set.
|
0.00%
0/95 • Adverse events (AEs) were recorded from signed informed consent to the end-of-cycle visit for COS cycle 2 (up to approximately 4.5 months) and again from screening to the end-of-cycle visit for COS cycle 3 (up to approximately 4.5 months).
AEs with onset after start of first administration of IMP and before the end-of-cycle were considered treatment-emergent and are presented for the safety analysis set.
|
0.00%
0/93 • Adverse events (AEs) were recorded from signed informed consent to the end-of-cycle visit for COS cycle 2 (up to approximately 4.5 months) and again from screening to the end-of-cycle visit for COS cycle 3 (up to approximately 4.5 months).
AEs with onset after start of first administration of IMP and before the end-of-cycle were considered treatment-emergent and are presented for the safety analysis set.
|
|
Reproductive system and breast disorders
Ovarian hyperstimulation syndrome
|
0.00%
0/252 • Adverse events (AEs) were recorded from signed informed consent to the end-of-cycle visit for COS cycle 2 (up to approximately 4.5 months) and again from screening to the end-of-cycle visit for COS cycle 3 (up to approximately 4.5 months).
AEs with onset after start of first administration of IMP and before the end-of-cycle were considered treatment-emergent and are presented for the safety analysis set.
|
0.38%
1/261 • Number of events 1 • Adverse events (AEs) were recorded from signed informed consent to the end-of-cycle visit for COS cycle 2 (up to approximately 4.5 months) and again from screening to the end-of-cycle visit for COS cycle 3 (up to approximately 4.5 months).
AEs with onset after start of first administration of IMP and before the end-of-cycle were considered treatment-emergent and are presented for the safety analysis set.
|
0.00%
0/95 • Adverse events (AEs) were recorded from signed informed consent to the end-of-cycle visit for COS cycle 2 (up to approximately 4.5 months) and again from screening to the end-of-cycle visit for COS cycle 3 (up to approximately 4.5 months).
AEs with onset after start of first administration of IMP and before the end-of-cycle were considered treatment-emergent and are presented for the safety analysis set.
|
1.1%
1/93 • Number of events 1 • Adverse events (AEs) were recorded from signed informed consent to the end-of-cycle visit for COS cycle 2 (up to approximately 4.5 months) and again from screening to the end-of-cycle visit for COS cycle 3 (up to approximately 4.5 months).
AEs with onset after start of first administration of IMP and before the end-of-cycle were considered treatment-emergent and are presented for the safety analysis set.
|
|
Renal and urinary disorders
Nephrolithiasis
|
0.40%
1/252 • Number of events 1 • Adverse events (AEs) were recorded from signed informed consent to the end-of-cycle visit for COS cycle 2 (up to approximately 4.5 months) and again from screening to the end-of-cycle visit for COS cycle 3 (up to approximately 4.5 months).
AEs with onset after start of first administration of IMP and before the end-of-cycle were considered treatment-emergent and are presented for the safety analysis set.
|
0.00%
0/261 • Adverse events (AEs) were recorded from signed informed consent to the end-of-cycle visit for COS cycle 2 (up to approximately 4.5 months) and again from screening to the end-of-cycle visit for COS cycle 3 (up to approximately 4.5 months).
AEs with onset after start of first administration of IMP and before the end-of-cycle were considered treatment-emergent and are presented for the safety analysis set.
|
0.00%
0/95 • Adverse events (AEs) were recorded from signed informed consent to the end-of-cycle visit for COS cycle 2 (up to approximately 4.5 months) and again from screening to the end-of-cycle visit for COS cycle 3 (up to approximately 4.5 months).
AEs with onset after start of first administration of IMP and before the end-of-cycle were considered treatment-emergent and are presented for the safety analysis set.
|
0.00%
0/93 • Adverse events (AEs) were recorded from signed informed consent to the end-of-cycle visit for COS cycle 2 (up to approximately 4.5 months) and again from screening to the end-of-cycle visit for COS cycle 3 (up to approximately 4.5 months).
AEs with onset after start of first administration of IMP and before the end-of-cycle were considered treatment-emergent and are presented for the safety analysis set.
|
Other adverse events
| Measure |
FE 999049 (COS Cycle 2)
n=252 participants at risk
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.
|
GONAL-F (COS Cycle 2)
n=261 participants at risk
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.
|
FE 999049 (COS Cycle 3)
n=95 participants at risk
FE 999049 was administered as single daily subcutaneous injections in the abdomen. The dose was determined based on the ovarian response in COS cycle 2. The daily FE 999049 dose was fixed throughout the stimulation period and maximum allowed daily dose was 24 μg. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.
|
GONAL-F (COS Cycle 3)
n=93 participants at risk
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 2. 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.
|
|---|---|---|---|---|
|
Injury, poisoning and procedural complications
Procedural pain
|
5.2%
13/252 • Number of events 14 • Adverse events (AEs) were recorded from signed informed consent to the end-of-cycle visit for COS cycle 2 (up to approximately 4.5 months) and again from screening to the end-of-cycle visit for COS cycle 3 (up to approximately 4.5 months).
AEs with onset after start of first administration of IMP and before the end-of-cycle were considered treatment-emergent and are presented for the safety analysis set.
|
6.5%
17/261 • Number of events 20 • Adverse events (AEs) were recorded from signed informed consent to the end-of-cycle visit for COS cycle 2 (up to approximately 4.5 months) and again from screening to the end-of-cycle visit for COS cycle 3 (up to approximately 4.5 months).
AEs with onset after start of first administration of IMP and before the end-of-cycle were considered treatment-emergent and are presented for the safety analysis set.
|
5.3%
5/95 • Number of events 6 • Adverse events (AEs) were recorded from signed informed consent to the end-of-cycle visit for COS cycle 2 (up to approximately 4.5 months) and again from screening to the end-of-cycle visit for COS cycle 3 (up to approximately 4.5 months).
AEs with onset after start of first administration of IMP and before the end-of-cycle were considered treatment-emergent and are presented for the safety analysis set.
|
8.6%
8/93 • Number of events 8 • Adverse events (AEs) were recorded from signed informed consent to the end-of-cycle visit for COS cycle 2 (up to approximately 4.5 months) and again from screening to the end-of-cycle visit for COS cycle 3 (up to approximately 4.5 months).
AEs with onset after start of first administration of IMP and before the end-of-cycle were considered treatment-emergent and are presented for the safety analysis set.
|
|
Nervous system disorders
Headache
|
7.5%
19/252 • Number of events 24 • Adverse events (AEs) were recorded from signed informed consent to the end-of-cycle visit for COS cycle 2 (up to approximately 4.5 months) and again from screening to the end-of-cycle visit for COS cycle 3 (up to approximately 4.5 months).
AEs with onset after start of first administration of IMP and before the end-of-cycle were considered treatment-emergent and are presented for the safety analysis set.
|
10.3%
27/261 • Number of events 34 • Adverse events (AEs) were recorded from signed informed consent to the end-of-cycle visit for COS cycle 2 (up to approximately 4.5 months) and again from screening to the end-of-cycle visit for COS cycle 3 (up to approximately 4.5 months).
AEs with onset after start of first administration of IMP and before the end-of-cycle were considered treatment-emergent and are presented for the safety analysis set.
|
11.6%
11/95 • Number of events 12 • Adverse events (AEs) were recorded from signed informed consent to the end-of-cycle visit for COS cycle 2 (up to approximately 4.5 months) and again from screening to the end-of-cycle visit for COS cycle 3 (up to approximately 4.5 months).
AEs with onset after start of first administration of IMP and before the end-of-cycle were considered treatment-emergent and are presented for the safety analysis set.
|
14.0%
13/93 • Number of events 15 • Adverse events (AEs) were recorded from signed informed consent to the end-of-cycle visit for COS cycle 2 (up to approximately 4.5 months) and again from screening to the end-of-cycle visit for COS cycle 3 (up to approximately 4.5 months).
AEs with onset after start of first administration of IMP and before the end-of-cycle were considered treatment-emergent and are presented for the safety analysis set.
|
|
Pregnancy, puerperium and perinatal conditions
Biochemical pregnancy
|
5.2%
13/252 • Number of events 13 • Adverse events (AEs) were recorded from signed informed consent to the end-of-cycle visit for COS cycle 2 (up to approximately 4.5 months) and again from screening to the end-of-cycle visit for COS cycle 3 (up to approximately 4.5 months).
AEs with onset after start of first administration of IMP and before the end-of-cycle were considered treatment-emergent and are presented for the safety analysis set.
|
3.1%
8/261 • Number of events 8 • Adverse events (AEs) were recorded from signed informed consent to the end-of-cycle visit for COS cycle 2 (up to approximately 4.5 months) and again from screening to the end-of-cycle visit for COS cycle 3 (up to approximately 4.5 months).
AEs with onset after start of first administration of IMP and before the end-of-cycle were considered treatment-emergent and are presented for the safety analysis set.
|
9.5%
9/95 • Number of events 9 • Adverse events (AEs) were recorded from signed informed consent to the end-of-cycle visit for COS cycle 2 (up to approximately 4.5 months) and again from screening to the end-of-cycle visit for COS cycle 3 (up to approximately 4.5 months).
AEs with onset after start of first administration of IMP and before the end-of-cycle were considered treatment-emergent and are presented for the safety analysis set.
|
4.3%
4/93 • Number of events 4 • Adverse events (AEs) were recorded from signed informed consent to the end-of-cycle visit for COS cycle 2 (up to approximately 4.5 months) and again from screening to the end-of-cycle visit for COS cycle 3 (up to approximately 4.5 months).
AEs with onset after start of first administration of IMP and before the end-of-cycle were considered treatment-emergent and are presented for the safety analysis set.
|
|
Pregnancy, puerperium and perinatal conditions
Haemorrhage in pregnancy
|
5.2%
13/252 • Number of events 15 • Adverse events (AEs) were recorded from signed informed consent to the end-of-cycle visit for COS cycle 2 (up to approximately 4.5 months) and again from screening to the end-of-cycle visit for COS cycle 3 (up to approximately 4.5 months).
AEs with onset after start of first administration of IMP and before the end-of-cycle were considered treatment-emergent and are presented for the safety analysis set.
|
3.8%
10/261 • Number of events 11 • Adverse events (AEs) were recorded from signed informed consent to the end-of-cycle visit for COS cycle 2 (up to approximately 4.5 months) and again from screening to the end-of-cycle visit for COS cycle 3 (up to approximately 4.5 months).
AEs with onset after start of first administration of IMP and before the end-of-cycle were considered treatment-emergent and are presented for the safety analysis set.
|
3.2%
3/95 • Number of events 3 • Adverse events (AEs) were recorded from signed informed consent to the end-of-cycle visit for COS cycle 2 (up to approximately 4.5 months) and again from screening to the end-of-cycle visit for COS cycle 3 (up to approximately 4.5 months).
AEs with onset after start of first administration of IMP and before the end-of-cycle were considered treatment-emergent and are presented for the safety analysis set.
|
2.2%
2/93 • Number of events 2 • Adverse events (AEs) were recorded from signed informed consent to the end-of-cycle visit for COS cycle 2 (up to approximately 4.5 months) and again from screening to the end-of-cycle visit for COS cycle 3 (up to approximately 4.5 months).
AEs with onset after start of first administration of IMP and before the end-of-cycle were considered treatment-emergent and are presented for the safety analysis set.
|
|
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous
|
4.0%
10/252 • Number of events 10 • Adverse events (AEs) were recorded from signed informed consent to the end-of-cycle visit for COS cycle 2 (up to approximately 4.5 months) and again from screening to the end-of-cycle visit for COS cycle 3 (up to approximately 4.5 months).
AEs with onset after start of first administration of IMP and before the end-of-cycle were considered treatment-emergent and are presented for the safety analysis set.
|
3.4%
9/261 • Number of events 9 • Adverse events (AEs) were recorded from signed informed consent to the end-of-cycle visit for COS cycle 2 (up to approximately 4.5 months) and again from screening to the end-of-cycle visit for COS cycle 3 (up to approximately 4.5 months).
AEs with onset after start of first administration of IMP and before the end-of-cycle were considered treatment-emergent and are presented for the safety analysis set.
|
5.3%
5/95 • Number of events 5 • Adverse events (AEs) were recorded from signed informed consent to the end-of-cycle visit for COS cycle 2 (up to approximately 4.5 months) and again from screening to the end-of-cycle visit for COS cycle 3 (up to approximately 4.5 months).
AEs with onset after start of first administration of IMP and before the end-of-cycle were considered treatment-emergent and are presented for the safety analysis set.
|
4.3%
4/93 • Number of events 4 • Adverse events (AEs) were recorded from signed informed consent to the end-of-cycle visit for COS cycle 2 (up to approximately 4.5 months) and again from screening to the end-of-cycle visit for COS cycle 3 (up to approximately 4.5 months).
AEs with onset after start of first administration of IMP and before the end-of-cycle were considered treatment-emergent and are presented for the safety analysis set.
|
|
Reproductive system and breast disorders
Pelvic pain
|
5.6%
14/252 • Number of events 14 • Adverse events (AEs) were recorded from signed informed consent to the end-of-cycle visit for COS cycle 2 (up to approximately 4.5 months) and again from screening to the end-of-cycle visit for COS cycle 3 (up to approximately 4.5 months).
AEs with onset after start of first administration of IMP and before the end-of-cycle were considered treatment-emergent and are presented for the safety analysis set.
|
4.2%
11/261 • Number of events 12 • Adverse events (AEs) were recorded from signed informed consent to the end-of-cycle visit for COS cycle 2 (up to approximately 4.5 months) and again from screening to the end-of-cycle visit for COS cycle 3 (up to approximately 4.5 months).
AEs with onset after start of first administration of IMP and before the end-of-cycle were considered treatment-emergent and are presented for the safety analysis set.
|
3.2%
3/95 • Number of events 3 • Adverse events (AEs) were recorded from signed informed consent to the end-of-cycle visit for COS cycle 2 (up to approximately 4.5 months) and again from screening to the end-of-cycle visit for COS cycle 3 (up to approximately 4.5 months).
AEs with onset after start of first administration of IMP and before the end-of-cycle were considered treatment-emergent and are presented for the safety analysis set.
|
5.4%
5/93 • Number of events 5 • Adverse events (AEs) were recorded from signed informed consent to the end-of-cycle visit for COS cycle 2 (up to approximately 4.5 months) and again from screening to the end-of-cycle visit for COS cycle 3 (up to approximately 4.5 months).
AEs with onset after start of first administration of IMP and before the end-of-cycle were considered treatment-emergent and are presented for the safety analysis set.
|
|
Reproductive system and breast disorders
Pelvic discomfort
|
2.4%
6/252 • Number of events 6 • Adverse events (AEs) were recorded from signed informed consent to the end-of-cycle visit for COS cycle 2 (up to approximately 4.5 months) and again from screening to the end-of-cycle visit for COS cycle 3 (up to approximately 4.5 months).
AEs with onset after start of first administration of IMP and before the end-of-cycle were considered treatment-emergent and are presented for the safety analysis set.
|
5.0%
13/261 • Number of events 14 • Adverse events (AEs) were recorded from signed informed consent to the end-of-cycle visit for COS cycle 2 (up to approximately 4.5 months) and again from screening to the end-of-cycle visit for COS cycle 3 (up to approximately 4.5 months).
AEs with onset after start of first administration of IMP and before the end-of-cycle were considered treatment-emergent and are presented for the safety analysis set.
|
0.00%
0/95 • Adverse events (AEs) were recorded from signed informed consent to the end-of-cycle visit for COS cycle 2 (up to approximately 4.5 months) and again from screening to the end-of-cycle visit for COS cycle 3 (up to approximately 4.5 months).
AEs with onset after start of first administration of IMP and before the end-of-cycle were considered treatment-emergent and are presented for the safety analysis set.
|
6.5%
6/93 • Number of events 7 • Adverse events (AEs) were recorded from signed informed consent to the end-of-cycle visit for COS cycle 2 (up to approximately 4.5 months) and again from screening to the end-of-cycle visit for COS cycle 3 (up to approximately 4.5 months).
AEs with onset after start of first administration of IMP and before the end-of-cycle were considered treatment-emergent and are presented for the safety analysis set.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The only disclosure restriction on the PI is that the sponsor can review the draft manuscript prior to publication and can request delay of publication where any contents are deemed patentable by the sponsor or confidential to the sponsor. Comments will be given within four weeks from receipt of the draft manuscript. Additional time may be required to allow Ferring to seek patent protection of the invention.
- Publication restrictions are in place
Restriction type: OTHER