Trial Outcomes & Findings for Follitropin Delta in Long GnRH Agonist and GnRH Antagonist Protocols (BEYOND) (NCT NCT03809429)
NCT ID: NCT03809429
Last Updated: 2024-05-13
Results Overview
The number of oocytes retrieved was recorded at the oocyte retrieval visit.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
437 participants
Primary outcome timeframe
On day of oocyte retrieval (up to 22 days after start of stimulation)
Results posted on
2024-05-13
Participant Flow
The trial was opened for recruitment in April 2019, and participants were assessed at 16 investigational sites in 7 countries between May 2019 and Feb 2022.
In total, 532 participants were screened of which 437 were randomized. Of the 437 participants, 435 participants were included in the Full Analysis Set (FAS): 220 participants to long GnRH agonist and 215 participants to GnRH antagonist. 406 participants were exposed to the investigational medicinal product (IMP): 202 participants to long GnRH agonist and 204 participants to GnRH antagonist. Two participants discontinued before the start of stimulation with FE999049 due to COVID-19 pandemic.
Participant milestones
| Measure |
FE 999049 + GnRH Agonist (GONAPEPTYL)
FE 999049 + GnRH agonist (GONAPEPTYL): Pre-filled injection pen
|
FE 999049 + GnRH Antagonist (CETROTIDE)
FE 999049 + GnRH antagonist (CETROTIDE): Powder and solvent for solution for injection
|
|---|---|---|
|
Overall Study
STARTED
|
220
|
215
|
|
Overall Study
COMPLETED
|
192
|
195
|
|
Overall Study
NOT COMPLETED
|
28
|
20
|
Reasons for withdrawal
| Measure |
FE 999049 + GnRH Agonist (GONAPEPTYL)
FE 999049 + GnRH agonist (GONAPEPTYL): Pre-filled injection pen
|
FE 999049 + GnRH Antagonist (CETROTIDE)
FE 999049 + GnRH antagonist (CETROTIDE): Powder and solvent for solution for injection
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
7
|
3
|
|
Overall Study
Adverse Event
|
6
|
9
|
|
Overall Study
COVID-19
|
3
|
1
|
|
Overall Study
Participant was discontinued by investigator
|
12
|
7
|
Baseline Characteristics
Follitropin Delta in Long GnRH Agonist and GnRH Antagonist Protocols (BEYOND)
Baseline characteristics by cohort
| Measure |
FE 999049 + GnRH Agonist (GONAPEPTYL)
n=220 Participants
FE 999049 + GnRH agonist (GONAPEPTYL): Pre-filled injection pen
|
FE 999049 + GnRH Antagonist (CETROTIDE)
n=215 Participants
FE 999049 + GnRH antagonist (CETROTIDE): Powder and solvent for solution for injection
|
Total
n=435 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
32.3 years
STANDARD_DEVIATION 4.4 • n=5 Participants
|
32.4 years
STANDARD_DEVIATION 4.2 • n=7 Participants
|
32.3 years
STANDARD_DEVIATION 4.3 • n=5 Participants
|
|
Age, Customized
<35 years
|
143 Participants
n=5 Participants
|
141 Participants
n=7 Participants
|
284 Participants
n=5 Participants
|
|
Age, Customized
35-37 years
|
47 Participants
n=5 Participants
|
48 Participants
n=7 Participants
|
95 Participants
n=5 Participants
|
|
Age, Customized
38-40 years
|
30 Participants
n=5 Participants
|
26 Participants
n=7 Participants
|
56 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
220 Participants
n=5 Participants
|
215 Participants
n=7 Participants
|
435 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
9 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
19 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
211 Participants
n=5 Participants
|
205 Participants
n=7 Participants
|
416 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
9 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
208 Participants
n=5 Participants
|
202 Participants
n=7 Participants
|
410 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
Austria
|
29 participants
n=5 Participants
|
31 participants
n=7 Participants
|
60 participants
n=5 Participants
|
|
Region of Enrollment
Netherlands
|
31 participants
n=5 Participants
|
26 participants
n=7 Participants
|
57 participants
n=5 Participants
|
|
Region of Enrollment
Norway
|
117 participants
n=5 Participants
|
114 participants
n=7 Participants
|
231 participants
n=5 Participants
|
|
Region of Enrollment
Denmark
|
15 participants
n=5 Participants
|
16 participants
n=7 Participants
|
31 participants
n=5 Participants
|
|
Region of Enrollment
Italy
|
9 participants
n=5 Participants
|
12 participants
n=7 Participants
|
21 participants
n=5 Participants
|
|
Region of Enrollment
Israel
|
13 participants
n=5 Participants
|
12 participants
n=7 Participants
|
25 participants
n=5 Participants
|
|
Region of Enrollment
Switzerland
|
6 participants
n=5 Participants
|
4 participants
n=7 Participants
|
10 participants
n=5 Participants
|
|
Body Mass Index (BMI)
|
24.36 kg/m^2
STANDARD_DEVIATION 3.50 • n=5 Participants
|
24.39 kg/m^2
STANDARD_DEVIATION 3.55 • n=7 Participants
|
24.37 kg/m^2
STANDARD_DEVIATION 3.52 • n=5 Participants
|
PRIMARY outcome
Timeframe: On day of oocyte retrieval (up to 22 days after start of stimulation)Population: Participants analyzed for this endpoint represent participants who were evaluable for this outcome measure.
The number of oocytes retrieved was recorded at the oocyte retrieval visit.
Outcome measures
| Measure |
FE 999049 + GnRH Agonist (GONAPEPTYL)
n=202 Participants
FE 999049 + GnRH agonist (GONAPEPTYL): Pre-filled injection pen
|
FE 999049 + GnRH Antagonist (CETROTIDE)
n=204 Participants
FE 999049 + GnRH antagonist (CETROTIDE): Powder and solvent for solution for injection
|
|---|---|---|
|
Number of Oocytes Retrieved
|
11.1 Oocytes
Standard Deviation 5.9
|
9.6 Oocytes
Standard Deviation 5.5
|
SECONDARY outcome
Timeframe: At end-of-stimulation (up to 20 days)Population: Participants analyzed for this endpoint represent participants who were evaluable for this outcome measure.
For each participant, the reason for cycle cancellation was recorded
Outcome measures
| Measure |
FE 999049 + GnRH Agonist (GONAPEPTYL)
n=202 Participants
FE 999049 + GnRH agonist (GONAPEPTYL): Pre-filled injection pen
|
FE 999049 + GnRH Antagonist (CETROTIDE)
n=204 Participants
FE 999049 + GnRH antagonist (CETROTIDE): Powder and solvent for solution for injection
|
|---|---|---|
|
Proportion of Subjects With Cycle Cancellation Due to Poor Ovarian Response or Excessive Ovarian Response
Excessive response
|
2 participants
|
3 participants
|
|
Proportion of Subjects With Cycle Cancellation Due to Poor Ovarian Response or Excessive Ovarian Response
Poor response
|
1 participants
|
3 participants
|
|
Proportion of Subjects With Cycle Cancellation Due to Poor Ovarian Response or Excessive Ovarian Response
Other reason
|
1 participants
|
1 participants
|
SECONDARY outcome
Timeframe: At end of transfer (up to 4 weeks)Population: Participants analyzed for this endpoint represent participants with blastocyst transfer cancellation.
For each participant, the reason for blastocyst transfer cancellation was recorded.
Outcome measures
| Measure |
FE 999049 + GnRH Agonist (GONAPEPTYL)
n=27 Participants
FE 999049 + GnRH agonist (GONAPEPTYL): Pre-filled injection pen
|
FE 999049 + GnRH Antagonist (CETROTIDE)
n=30 Participants
FE 999049 + GnRH antagonist (CETROTIDE): Powder and solvent for solution for injection
|
|---|---|---|
|
Proportion of Subjects With Blastocyst Transfer Cancellation After Oocyte Retrieval Due to (Risk of) Ovarian Hyperstimulation Syndrome (OHSS)
Transfer cancellation
|
27 participants
|
30 participants
|
|
Proportion of Subjects With Blastocyst Transfer Cancellation After Oocyte Retrieval Due to (Risk of) Ovarian Hyperstimulation Syndrome (OHSS)
Reason for transfer cancellation: Adverse Event
|
5 participants
|
8 participants
|
|
Proportion of Subjects With Blastocyst Transfer Cancellation After Oocyte Retrieval Due to (Risk of) Ovarian Hyperstimulation Syndrome (OHSS)
Reason for transfer cancellation: Risk of OHSS
|
1 participants
|
1 participants
|
|
Proportion of Subjects With Blastocyst Transfer Cancellation After Oocyte Retrieval Due to (Risk of) Ovarian Hyperstimulation Syndrome (OHSS)
Reason for transfer cancellation: No blastocyst
|
13 participants
|
18 participants
|
|
Proportion of Subjects With Blastocyst Transfer Cancellation After Oocyte Retrieval Due to (Risk of) Ovarian Hyperstimulation Syndrome (OHSS)
Reason for transfer cancellation: COVID-19
|
3 participants
|
1 participants
|
|
Proportion of Subjects With Blastocyst Transfer Cancellation After Oocyte Retrieval Due to (Risk of) Ovarian Hyperstimulation Syndrome (OHSS)
Reason for transfer cancellation: Other reason
|
5 participants
|
2 participants
|
SECONDARY outcome
Timeframe: On stimulation day 6 and at end-of-stimulation (up to 20 days)Population: Participants analyzed for this endpoint represent participants who were evaluable for this outcome measure.
The total number of follicles and the number of follicles per size category will be reported
Outcome measures
| Measure |
FE 999049 + GnRH Agonist (GONAPEPTYL)
n=202 Participants
FE 999049 + GnRH agonist (GONAPEPTYL): Pre-filled injection pen
|
FE 999049 + GnRH Antagonist (CETROTIDE)
n=204 Participants
FE 999049 + GnRH antagonist (CETROTIDE): Powder and solvent for solution for injection
|
|---|---|---|
|
Number of Follicles
Total number of follicles at Stimulation Day 6
|
15.2 Number of follicles
Standard Deviation 6.3
|
14.9 Number of follicles
Standard Deviation 6.3
|
|
Number of Follicles
Follicles >= 10 mm at Stimulation Day 6
|
4.6 Number of follicles
Standard Deviation 4.3
|
7.1 Number of follicles
Standard Deviation 3.6
|
|
Number of Follicles
Follicles >= 12 mm at Stimulation Day 6
|
1.6 Number of follicles
Standard Deviation 2.7
|
3.8 Number of follicles
Standard Deviation 2.9
|
|
Number of Follicles
Total number of follicles at End-of-stimulation visit
|
18.3 Number of follicles
Standard Deviation 7.1
|
17.1 Number of follicles
Standard Deviation 8.0
|
|
Number of Follicles
Follicles >= 10 mm at End-of-stimulation visit
|
14.8 Number of follicles
Standard Deviation 6.4
|
13.3 Number of follicles
Standard Deviation 6.1
|
|
Number of Follicles
Follicles >= 12 mm at End-of-stimulation visit
|
12.2 Number of follicles
Standard Deviation 5.3
|
10.9 Number of follicles
Standard Deviation 5.1
|
|
Number of Follicles
Follicles >= 15 mm at End-of-stimulation visit
|
7.9 Number of follicles
Standard Deviation 3.7
|
7.2 Number of follicles
Standard Deviation 3.3
|
|
Number of Follicles
Follicles >= 17 mm at End-of-stimulation visit
|
4.8 Number of follicles
Standard Deviation 2.1
|
4.6 Number of follicles
Standard Deviation 2.0
|
SECONDARY outcome
Timeframe: On day of oocyte retrieval (up to 22 days after start of stimulation)Population: Participants analyzed for this endpoint represent participants who were evaluable for this outcome measure.
Grouped according to number of oocytes
Outcome measures
| Measure |
FE 999049 + GnRH Agonist (GONAPEPTYL)
n=202 Participants
FE 999049 + GnRH agonist (GONAPEPTYL): Pre-filled injection pen
|
FE 999049 + GnRH Antagonist (CETROTIDE)
n=204 Participants
FE 999049 + GnRH antagonist (CETROTIDE): Powder and solvent for solution for injection
|
|---|---|---|
|
Proportion of Subjects With <4, 4-7, 8-14, 15-19 and ≥20 Oocytes Retrieved
4-7 Oocytes Retrieved
|
47 Participants
|
56 Participants
|
|
Proportion of Subjects With <4, 4-7, 8-14, 15-19 and ≥20 Oocytes Retrieved
<4 Oocytes Retrieved
|
13 Participants
|
26 Participants
|
|
Proportion of Subjects With <4, 4-7, 8-14, 15-19 and ≥20 Oocytes Retrieved
8-14 Oocytes Retrieved
|
84 Participants
|
82 Participants
|
|
Proportion of Subjects With <4, 4-7, 8-14, 15-19 and ≥20 Oocytes Retrieved
15-19 Oocytes Retrieved
|
42 Participants
|
29 Participants
|
|
Proportion of Subjects With <4, 4-7, 8-14, 15-19 and ≥20 Oocytes Retrieved
>=20 Oocytes Retrieved
|
16 Participants
|
11 Participants
|
SECONDARY outcome
Timeframe: On day of oocyte retrieval (up to 22 days after start of stimulation)Population: Participants analyzed for this endpoint represent participants who were evaluable for this outcome measure.
Only applicable for those inseminated using ICSI
Outcome measures
| Measure |
FE 999049 + GnRH Agonist (GONAPEPTYL)
n=96 Participants
FE 999049 + GnRH agonist (GONAPEPTYL): Pre-filled injection pen
|
FE 999049 + GnRH Antagonist (CETROTIDE)
n=99 Participants
FE 999049 + GnRH antagonist (CETROTIDE): Powder and solvent for solution for injection
|
|---|---|---|
|
Number of Metaphase II Oocytes
|
9.2 MII oocytes
Standard Deviation 4.8
|
7.9 MII oocytes
Standard Deviation 4.7
|
SECONDARY outcome
Timeframe: On day 1 after oocyte retrieval (up to 23 days after start of stimulation)Population: Participants analyzed for this endpoint represent participants who were evaluable for this outcome measure.
Measured by the number of pronuclei. Fertilized oocytes with 2 pronuclei were regarded as correctly fertilized
Outcome measures
| Measure |
FE 999049 + GnRH Agonist (GONAPEPTYL)
n=197 Participants
FE 999049 + GnRH agonist (GONAPEPTYL): Pre-filled injection pen
|
FE 999049 + GnRH Antagonist (CETROTIDE)
n=197 Participants
FE 999049 + GnRH antagonist (CETROTIDE): Powder and solvent for solution for injection
|
|---|---|---|
|
Fertilization Rate
|
53.8 percentage of fertilized oocytes
Standard Deviation 24.1
|
54.4 percentage of fertilized oocytes
Standard Deviation 26.8
|
SECONDARY outcome
Timeframe: On day 3 after oocyte retrieval (up to 25 days after start of stimulation)Population: Participants analyzed for this endpoint represent participants who were evaluable for this outcome measure.
The number of embryos (total and good-quality) was reported. Embryo quality is determined by combined assessment of cleavage stage (number of blastomeres/compaction status) and embryo morphology parameters
Outcome measures
| Measure |
FE 999049 + GnRH Agonist (GONAPEPTYL)
n=202 Participants
FE 999049 + GnRH agonist (GONAPEPTYL): Pre-filled injection pen
|
FE 999049 + GnRH Antagonist (CETROTIDE)
n=204 Participants
FE 999049 + GnRH antagonist (CETROTIDE): Powder and solvent for solution for injection
|
|---|---|---|
|
Number of Embryos
Total number of embryos
|
5.7 Embryos
Standard Deviation 3.9
|
5.0 Embryos
Standard Deviation 3.9
|
|
Number of Embryos
Number of good-quality embryos
|
4.0 Embryos
Standard Deviation 3.2
|
3.9 Embryos
Standard Deviation 3.3
|
SECONDARY outcome
Timeframe: On day 5 after oocyte retrieval (up to 27 days after start of stimulation)Population: Participants analyzed for this endpoint represent participants who were evaluable for this outcome measure.
The number of blastocysts (total and good-quality) was reported. Blastocyst quality is assessed by blastocyst expansion and hatching status, blastocyst inner cell mass grading, and trophectoderm grading. The scoring is based on the classification system by Gardner and Schoolcraft, with additional categories for inner cell mass (degenerative or no inner cell mass) and trophectoderm (degenerative or very large cells)
Outcome measures
| Measure |
FE 999049 + GnRH Agonist (GONAPEPTYL)
n=202 Participants
FE 999049 + GnRH agonist (GONAPEPTYL): Pre-filled injection pen
|
FE 999049 + GnRH Antagonist (CETROTIDE)
n=204 Participants
FE 999049 + GnRH antagonist (CETROTIDE): Powder and solvent for solution for injection
|
|---|---|---|
|
Number of Blastocysts
Total Number of blastocysts
|
3.8 Blastocysts
Standard Deviation 3.1
|
3.3 Blastocysts
Standard Deviation 2.9
|
|
Number of Blastocysts
Number of good-quality blastocysts
|
2.3 Blastocysts
Standard Deviation 2.3
|
2.1 Blastocysts
Standard Deviation 2.2
|
SECONDARY outcome
Timeframe: On stimulation day 6, at end-of-stimulation (up to 20 days after start of stimulation) and at oocyte retrieval (up to 22 days after start of stimulation)Population: Participants analyzed for this endpoint represent participants who were evaluable for this outcome measure.
Blood samples for analysis of circulating concentrations of FSH were drawn.
Outcome measures
| Measure |
FE 999049 + GnRH Agonist (GONAPEPTYL)
n=199 Participants
FE 999049 + GnRH agonist (GONAPEPTYL): Pre-filled injection pen
|
FE 999049 + GnRH Antagonist (CETROTIDE)
n=200 Participants
FE 999049 + GnRH antagonist (CETROTIDE): Powder and solvent for solution for injection
|
|---|---|---|
|
Circulating Concentrations of Follicle-stimulating Hormone (FSH)
Stimulation Day 6
|
15.5 IU/L
Standard Deviation 4.3
|
16.7 IU/L
Standard Deviation 4.5
|
|
Circulating Concentrations of Follicle-stimulating Hormone (FSH)
End-of-stimulation
|
16.2 IU/L
Standard Deviation 4.4
|
15.8 IU/L
Standard Deviation 4.0
|
|
Circulating Concentrations of Follicle-stimulating Hormone (FSH)
Oocyte retrieval
|
9.4 IU/L
Standard Deviation 2.8
|
9.8 IU/L
Standard Deviation 2.9
|
SECONDARY outcome
Timeframe: On stimulation day 6, at end-of-stimulation (up to 20 days after start of stimulation) and at oocyte retrieval (up to 22 days after start of stimulation)Population: Participants analyzed for this endpoint represent participants who were evaluable for this outcome measure.
Blood samples for analysis of circulating concentrations of LH were drawn
Outcome measures
| Measure |
FE 999049 + GnRH Agonist (GONAPEPTYL)
n=199 Participants
FE 999049 + GnRH agonist (GONAPEPTYL): Pre-filled injection pen
|
FE 999049 + GnRH Antagonist (CETROTIDE)
n=200 Participants
FE 999049 + GnRH antagonist (CETROTIDE): Powder and solvent for solution for injection
|
|---|---|---|
|
Circulating Concentrations of Luteinizing Hormone (LH)
Stimulation Day 6
|
1.5 IU/L
Standard Deviation 0.9
|
5.6 IU/L
Standard Deviation 6.0
|
|
Circulating Concentrations of Luteinizing Hormone (LH)
End-of-stimulation
|
1.8 IU/L
Standard Deviation 0.9
|
1.8 IU/L
Standard Deviation 1.5
|
|
Circulating Concentrations of Luteinizing Hormone (LH)
Oocyte retrieval
|
0.2 IU/L
Standard Deviation 0.2
|
2.0 IU/L
Standard Deviation 2.1
|
SECONDARY outcome
Timeframe: On stimulation day 6, at end-of-stimulation (up to 20 days after start of stimulation) and at oocyte retrieval (up to 22 days after start of stimulation)Population: Participants analyzed for this endpoint represent participants who were evaluable for this outcome measure.
Blood samples for analysis of circulating concentrations of estradiol were drawn
Outcome measures
| Measure |
FE 999049 + GnRH Agonist (GONAPEPTYL)
n=199 Participants
FE 999049 + GnRH agonist (GONAPEPTYL): Pre-filled injection pen
|
FE 999049 + GnRH Antagonist (CETROTIDE)
n=201 Participants
FE 999049 + GnRH antagonist (CETROTIDE): Powder and solvent for solution for injection
|
|---|---|---|
|
Circulating Concentrations of Estradiol
Stimulation Day 6
|
1190.1 pmol/L
Standard Deviation 1101.2
|
2675.8 pmol/L
Standard Deviation 1544.3
|
|
Circulating Concentrations of Estradiol
End-of-stimulation
|
7542.7 pmol/L
Standard Deviation 4106.8
|
6487.7 pmol/L
Standard Deviation 3960.2
|
|
Circulating Concentrations of Estradiol
Oocyte retrieval
|
3485.1 pmol/L
Standard Deviation 2129.0
|
3163.5 pmol/L
Standard Deviation 1865.0
|
SECONDARY outcome
Timeframe: On stimulation day 6, at end-of-stimulation (up to 20 days after start of stimulation) and at oocyte retrieval (up to 22 days after start of stimulation)Population: Participants analyzed for this endpoint represent participants who were evaluable for this outcome measure.
Blood samples for analysis of circulating concentrations of progesterone were drawn
Outcome measures
| Measure |
FE 999049 + GnRH Agonist (GONAPEPTYL)
n=200 Participants
FE 999049 + GnRH agonist (GONAPEPTYL): Pre-filled injection pen
|
FE 999049 + GnRH Antagonist (CETROTIDE)
n=200 Participants
FE 999049 + GnRH antagonist (CETROTIDE): Powder and solvent for solution for injection
|
|---|---|---|
|
Circulating Concentrations of Progesterone
Stimulation Day 6
|
1.8 nmol/L
Standard Deviation 1.0
|
2.6 nmol/L
Standard Deviation 1.5
|
|
Circulating Concentrations of Progesterone
End-of-stimulation
|
3.1 nmol/L
Standard Deviation 1.4
|
3.5 nmol/L
Standard Deviation 2.0
|
|
Circulating Concentrations of Progesterone
Oocyte retrieval
|
25.9 nmol/L
Standard Deviation 12.9
|
26.0 nmol/L
Standard Deviation 13.2
|
SECONDARY outcome
Timeframe: On stimulation day 6, at end-of-stimulation (up to 20 days after start of stimulation) and at oocyte retrieval (up to 22 days after start of stimulation)Population: Participants analyzed for this endpoint represent participants who were evaluable for this outcome measure.
Blood samples for analysis of circulating concentrations of Inhibin B were drawn
Outcome measures
| Measure |
FE 999049 + GnRH Agonist (GONAPEPTYL)
n=196 Participants
FE 999049 + GnRH agonist (GONAPEPTYL): Pre-filled injection pen
|
FE 999049 + GnRH Antagonist (CETROTIDE)
n=198 Participants
FE 999049 + GnRH antagonist (CETROTIDE): Powder and solvent for solution for injection
|
|---|---|---|
|
Circulating Concentrations of Inhibin B
Stimulation Day 6
|
690.4 pg/mL
Standard Deviation 419.1
|
808.2 pg/mL
Standard Deviation 428.5
|
|
Circulating Concentrations of Inhibin B
End-of-stimulation
|
1032.6 pg/mL
Standard Deviation 605.2
|
938.1 pg/mL
Standard Deviation 570.0
|
|
Circulating Concentrations of Inhibin B
Oocyte retrieval
|
416.6 pg/mL
Standard Deviation 253.9
|
389.0 pg/mL
Standard Deviation 226.6
|
SECONDARY outcome
Timeframe: Up to 20 daysPopulation: Participants analyzed for this endpoint represent participants who were evaluable for this outcome measure.
Calculated by start dates, end dates and daily dose of investigational medicinal product
Outcome measures
| Measure |
FE 999049 + GnRH Agonist (GONAPEPTYL)
n=202 Participants
FE 999049 + GnRH agonist (GONAPEPTYL): Pre-filled injection pen
|
FE 999049 + GnRH Antagonist (CETROTIDE)
n=204 Participants
FE 999049 + GnRH antagonist (CETROTIDE): Powder and solvent for solution for injection
|
|---|---|---|
|
Total Gonadotropin Dose
|
112.2 ug
Standard Deviation 28.9
|
96.5 ug
Standard Deviation 26.0
|
SECONDARY outcome
Timeframe: Up to 20 daysPopulation: Participants analyzed for this endpoint represent participants who were evaluable for this outcome measure.
Calculated by start dates and end dates
Outcome measures
| Measure |
FE 999049 + GnRH Agonist (GONAPEPTYL)
n=202 Participants
FE 999049 + GnRH agonist (GONAPEPTYL): Pre-filled injection pen
|
FE 999049 + GnRH Antagonist (CETROTIDE)
n=204 Participants
FE 999049 + GnRH antagonist (CETROTIDE): Powder and solvent for solution for injection
|
|---|---|---|
|
Number of Stimulation Days
|
10.4 Days
Standard Deviation 1.9
|
8.8 Days
Standard Deviation 1.8
|
SECONDARY outcome
Timeframe: 13-15 days after transfer (up to approximately 1.5 months after start of stimulation)Population: Participants analyzed for this endpoint represent participants who were evaluable for this outcome measure.
Defined as positive serum βhCG test
Outcome measures
| Measure |
FE 999049 + GnRH Agonist (GONAPEPTYL)
n=202 Participants
FE 999049 + GnRH agonist (GONAPEPTYL): Pre-filled injection pen
|
FE 999049 + GnRH Antagonist (CETROTIDE)
n=204 Participants
FE 999049 + GnRH antagonist (CETROTIDE): Powder and solvent for solution for injection
|
|---|---|---|
|
Positive Beta Human Chorionic Gonadotropin (βhCG) Rate
Positive βhCG test
|
91 Participants
|
79 Participants
|
|
Positive Beta Human Chorionic Gonadotropin (βhCG) Rate
Negative βhCG test
|
111 Participants
|
125 Participants
|
SECONDARY outcome
Timeframe: 5-6 weeks after transfer (up to approximately 2.5 months after start of stimulation)Population: Participants analyzed for this endpoint represent participants who were evaluable for this outcome measure.
Defined as the number of gestational sacs after transfer divided by number of blastocysts transferred
Outcome measures
| Measure |
FE 999049 + GnRH Agonist (GONAPEPTYL)
n=173 Participants
FE 999049 + GnRH agonist (GONAPEPTYL): Pre-filled injection pen
|
FE 999049 + GnRH Antagonist (CETROTIDE)
n=167 Participants
FE 999049 + GnRH antagonist (CETROTIDE): Powder and solvent for solution for injection
|
|---|---|---|
|
Implantation Rate
|
82 Embryos
|
68 Embryos
|
SECONDARY outcome
Timeframe: 5-6 weeks after transfer (up to approximately 2.5 months after start of stimulation)Population: Participants analyzed for this endpoint represent participants who were evaluable for this outcome measure.
Defined as at least one gestational sac
Outcome measures
| Measure |
FE 999049 + GnRH Agonist (GONAPEPTYL)
n=202 Participants
FE 999049 + GnRH agonist (GONAPEPTYL): Pre-filled injection pen
|
FE 999049 + GnRH Antagonist (CETROTIDE)
n=204 Participants
FE 999049 + GnRH antagonist (CETROTIDE): Powder and solvent for solution for injection
|
|---|---|---|
|
Clinical Pregnancy Rate
Positive
|
81 Participants
|
68 Participants
|
|
Clinical Pregnancy Rate
Negtaive
|
121 Participants
|
136 Participants
|
SECONDARY outcome
Timeframe: 5-6 weeks after transfer (up to approximately 2.5 months after start of stimulation)Population: Participants analyzed for this endpoint represent participants who were evaluable for this outcome measure.
Defined as at least one intrauterine gestational sac with fetal heart beat
Outcome measures
| Measure |
FE 999049 + GnRH Agonist (GONAPEPTYL)
n=202 Participants
FE 999049 + GnRH agonist (GONAPEPTYL): Pre-filled injection pen
|
FE 999049 + GnRH Antagonist (CETROTIDE)
n=204 Participants
FE 999049 + GnRH antagonist (CETROTIDE): Powder and solvent for solution for injection
|
|---|---|---|
|
Vital Pregnancy Rate
Positive
|
77 Participants
|
62 Participants
|
|
Vital Pregnancy Rate
Negative
|
125 Participants
|
142 Participants
|
SECONDARY outcome
Timeframe: 10-11 weeks after transfer (up to approximately 4 months after start of stimulation)Population: Participants analyzed for this endpoint represent participants who were evaluable for this outcome measure.
At least one intrauterine viable fetus
Outcome measures
| Measure |
FE 999049 + GnRH Agonist (GONAPEPTYL)
n=202 Participants
FE 999049 + GnRH agonist (GONAPEPTYL): Pre-filled injection pen
|
FE 999049 + GnRH Antagonist (CETROTIDE)
n=204 Participants
FE 999049 + GnRH antagonist (CETROTIDE): Powder and solvent for solution for injection
|
|---|---|---|
|
Ongoing Pregnancy Rate
Positive
|
73 Participants
|
60 Participants
|
|
Ongoing Pregnancy Rate
Negative
|
129 Participants
|
144 Participants
|
SECONDARY outcome
Timeframe: 10-11 weeks after transfer (up to approximately 4 months after start of stimulation)Population: Participants analyzed for this endpoint represent participants who were evaluable for this outcome measure.
Defined as number of intrauterine viable fetuses divided by the number of blastocysts transferred
Outcome measures
| Measure |
FE 999049 + GnRH Agonist (GONAPEPTYL)
n=173 Participants
FE 999049 + GnRH agonist (GONAPEPTYL): Pre-filled injection pen
|
FE 999049 + GnRH Antagonist (CETROTIDE)
n=167 Participants
FE 999049 + GnRH antagonist (CETROTIDE): Powder and solvent for solution for injection
|
|---|---|---|
|
Ongoing Implantation Rate
|
74 Embryos
|
60 Embryos
|
SECONDARY outcome
Timeframe: Up to 9 days after triggering of final follicular maturationPopulation: Participants analyzed for this endpoint represent participants who were evaluable for this outcome measure.
Classification of grade was according to Golan's classification system, and all OHSS cases were graded as mild, moderate or severe.
Outcome measures
| Measure |
FE 999049 + GnRH Agonist (GONAPEPTYL)
n=202 Participants
FE 999049 + GnRH agonist (GONAPEPTYL): Pre-filled injection pen
|
FE 999049 + GnRH Antagonist (CETROTIDE)
n=204 Participants
FE 999049 + GnRH antagonist (CETROTIDE): Powder and solvent for solution for injection
|
|---|---|---|
|
Proportion of Subjects With Early OHSS (Including OHSS of Moderate/Severe Grade)
|
8 Participants
|
5 Participants
|
SECONDARY outcome
Timeframe: >9 days after triggering of final follicular maturationPopulation: Participants analyzed for this endpoint represent participants who were evaluable for this outcome measure.
Classification of grade was according to Golan's classification system, and all OHSS cases were graded as mild, moderate or severe.
Outcome measures
| Measure |
FE 999049 + GnRH Agonist (GONAPEPTYL)
n=202 Participants
FE 999049 + GnRH agonist (GONAPEPTYL): Pre-filled injection pen
|
FE 999049 + GnRH Antagonist (CETROTIDE)
n=204 Participants
FE 999049 + GnRH antagonist (CETROTIDE): Powder and solvent for solution for injection
|
|---|---|---|
|
Proportion of Subjects With Late OHSS (Including OHSS of Moderate/Severe Grade)
|
4 Participants
|
6 Participants
|
SECONDARY outcome
Timeframe: From time of signing informed consent until the end-of-trial (approximately 7 months)Population: Participants analyzed for this endpoint represent participants who were evaluable for this outcome measure.
Any untoward medical occurrence
Outcome measures
| Measure |
FE 999049 + GnRH Agonist (GONAPEPTYL)
n=202 Participants
FE 999049 + GnRH agonist (GONAPEPTYL): Pre-filled injection pen
|
FE 999049 + GnRH Antagonist (CETROTIDE)
n=204 Participants
FE 999049 + GnRH antagonist (CETROTIDE): Powder and solvent for solution for injection
|
|---|---|---|
|
Frequency of Adverse Events
|
112 Participants
|
109 Participants
|
SECONDARY outcome
Timeframe: From time of signing informed consent until the end-of-trial (approximately 7 months)Population: Participants analyzed for this endpoint represent participants who were evaluable for this outcome measure.
Categorized as mild, moderate or severe
Outcome measures
| Measure |
FE 999049 + GnRH Agonist (GONAPEPTYL)
n=202 Participants
FE 999049 + GnRH agonist (GONAPEPTYL): Pre-filled injection pen
|
FE 999049 + GnRH Antagonist (CETROTIDE)
n=204 Participants
FE 999049 + GnRH antagonist (CETROTIDE): Powder and solvent for solution for injection
|
|---|---|---|
|
Intensity of Adverse Events
Mild adverse events
|
42.6 Percentage of participants
|
41.7 Percentage of participants
|
|
Intensity of Adverse Events
Moderate adverse events
|
18.8 Percentage of participants
|
16.7 Percentage of participants
|
|
Intensity of Adverse Events
Severe adverse events
|
4.0 Percentage of participants
|
3.4 Percentage of participants
|
SECONDARY outcome
Timeframe: Up to 20 daysPopulation: Participants analyzed for this endpoint represent participants who were evaluable for this outcome measure.
Incidences of technical malfunctions of the pre-filled injection pen were recorded
Outcome measures
| Measure |
FE 999049 + GnRH Agonist (GONAPEPTYL)
n=202 Participants
FE 999049 + GnRH agonist (GONAPEPTYL): Pre-filled injection pen
|
FE 999049 + GnRH Antagonist (CETROTIDE)
n=204 Participants
FE 999049 + GnRH antagonist (CETROTIDE): Powder and solvent for solution for injection
|
|---|---|---|
|
Technical Malfunctions of the Pre-filled Injection Pen
|
2 Participants
|
0 Participants
|
Adverse Events
FE 999049 + GnRH Agonist (GONAPEPTYL)
Serious events: 4 serious events
Other events: 68 other events
Deaths: 0 deaths
FE 999049 + GnRH Antagonist (CETROTIDE)
Serious events: 6 serious events
Other events: 69 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
FE 999049 + GnRH Agonist (GONAPEPTYL)
n=202 participants at risk
FE 999049 + GnRH agonist (GONAPEPTYL): Pre-filled injection pen
|
FE 999049 + GnRH Antagonist (CETROTIDE)
n=204 participants at risk
FE 999049 + GnRH antagonist (CETROTIDE): Powder and solvent for solution for injection
|
|---|---|---|
|
Infections and infestations
Appendicitis
|
0.50%
1/202 • Number of events 1 • Adverse events were recorded from signing of the informed consent until end-of-trial (approximately 7 months).
Adverse events were recorded from signing of the informed consent until end-of-trial (approximately 7 months).
|
0.00%
0/204 • Adverse events were recorded from signing of the informed consent until end-of-trial (approximately 7 months).
Adverse events were recorded from signing of the informed consent until end-of-trial (approximately 7 months).
|
|
Infections and infestations
Bacterial abdominal infection
|
0.50%
1/202 • Number of events 1 • Adverse events were recorded from signing of the informed consent until end-of-trial (approximately 7 months).
Adverse events were recorded from signing of the informed consent until end-of-trial (approximately 7 months).
|
0.00%
0/204 • Adverse events were recorded from signing of the informed consent until end-of-trial (approximately 7 months).
Adverse events were recorded from signing of the informed consent until end-of-trial (approximately 7 months).
|
|
Pregnancy, puerperium and perinatal conditions
Hyperemesis gravidarum
|
0.00%
0/202 • Adverse events were recorded from signing of the informed consent until end-of-trial (approximately 7 months).
Adverse events were recorded from signing of the informed consent until end-of-trial (approximately 7 months).
|
0.49%
1/204 • Number of events 1 • Adverse events were recorded from signing of the informed consent until end-of-trial (approximately 7 months).
Adverse events were recorded from signing of the informed consent until end-of-trial (approximately 7 months).
|
|
Reproductive system and breast disorders
Ovarian hyperstimulation syndrome
|
0.99%
2/202 • Number of events 2 • Adverse events were recorded from signing of the informed consent until end-of-trial (approximately 7 months).
Adverse events were recorded from signing of the informed consent until end-of-trial (approximately 7 months).
|
2.0%
4/204 • Number of events 4 • Adverse events were recorded from signing of the informed consent until end-of-trial (approximately 7 months).
Adverse events were recorded from signing of the informed consent until end-of-trial (approximately 7 months).
|
|
Reproductive system and breast disorders
Adnexal torsion
|
0.00%
0/202 • Adverse events were recorded from signing of the informed consent until end-of-trial (approximately 7 months).
Adverse events were recorded from signing of the informed consent until end-of-trial (approximately 7 months).
|
0.49%
1/204 • Number of events 1 • Adverse events were recorded from signing of the informed consent until end-of-trial (approximately 7 months).
Adverse events were recorded from signing of the informed consent until end-of-trial (approximately 7 months).
|
Other adverse events
| Measure |
FE 999049 + GnRH Agonist (GONAPEPTYL)
n=202 participants at risk
FE 999049 + GnRH agonist (GONAPEPTYL): Pre-filled injection pen
|
FE 999049 + GnRH Antagonist (CETROTIDE)
n=204 participants at risk
FE 999049 + GnRH antagonist (CETROTIDE): Powder and solvent for solution for injection
|
|---|---|---|
|
Injury, poisoning and procedural complications
Procedural pain
|
9.9%
20/202 • Number of events 20 • Adverse events were recorded from signing of the informed consent until end-of-trial (approximately 7 months).
Adverse events were recorded from signing of the informed consent until end-of-trial (approximately 7 months).
|
5.9%
12/204 • Number of events 12 • Adverse events were recorded from signing of the informed consent until end-of-trial (approximately 7 months).
Adverse events were recorded from signing of the informed consent until end-of-trial (approximately 7 months).
|
|
Nervous system disorders
Headache
|
13.4%
27/202 • Number of events 31 • Adverse events were recorded from signing of the informed consent until end-of-trial (approximately 7 months).
Adverse events were recorded from signing of the informed consent until end-of-trial (approximately 7 months).
|
14.2%
29/204 • Number of events 30 • Adverse events were recorded from signing of the informed consent until end-of-trial (approximately 7 months).
Adverse events were recorded from signing of the informed consent until end-of-trial (approximately 7 months).
|
|
Pregnancy, puerperium and perinatal conditions
Biochemical pregnancy
|
5.0%
10/202 • Number of events 10 • Adverse events were recorded from signing of the informed consent until end-of-trial (approximately 7 months).
Adverse events were recorded from signing of the informed consent until end-of-trial (approximately 7 months).
|
5.4%
11/204 • Number of events 11 • Adverse events were recorded from signing of the informed consent until end-of-trial (approximately 7 months).
Adverse events were recorded from signing of the informed consent until end-of-trial (approximately 7 months).
|
|
Reproductive system and breast disorders
Pelvic pain
|
6.9%
14/202 • Number of events 15 • Adverse events were recorded from signing of the informed consent until end-of-trial (approximately 7 months).
Adverse events were recorded from signing of the informed consent until end-of-trial (approximately 7 months).
|
5.4%
11/204 • Number of events 12 • Adverse events were recorded from signing of the informed consent until end-of-trial (approximately 7 months).
Adverse events were recorded from signing of the informed consent until end-of-trial (approximately 7 months).
|
|
Reproductive system and breast disorders
Ovarian hyperstimulation syndrome
|
5.9%
12/202 • Number of events 12 • Adverse events were recorded from signing of the informed consent until end-of-trial (approximately 7 months).
Adverse events were recorded from signing of the informed consent until end-of-trial (approximately 7 months).
|
5.4%
11/204 • Number of events 11 • Adverse events were recorded from signing of the informed consent until end-of-trial (approximately 7 months).
Adverse events were recorded from signing of the informed consent until end-of-trial (approximately 7 months).
|
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