CompletedNCT01956110ESTHER-1Updated Jan 13, 2022Results posted

Evidence-based Stimulation Trial With Human rFSH in Europe and Rest of World 1

A Phase 3 interventional study of Follitropin Delta (FE 999049) and Follitropin Alfa (GONAL-F) in Infertility, sponsored by Ferring Pharmaceuticals. Completed at 13 sites in 11 countries. Open to female participants aged 18 Years to 40 Years. Per ClinicalTrials.gov, last updated 2022-01-13.

Sponsored by Ferring Pharmaceuticals · Phase 3, Interventional, and Treatment

Phase: Phase 3
Study type: Interventional
Enrollment: 1,329
Allocation: Randomized
Ages: 18 Years to 40 Years
Sex: Female

Study summary

This trial investigates the effects of FE 999049 compared to GONAL-F.

Conditions studied

Infertility

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Infertility 2,506

In context

Infertility

2,506 studies on the registry are indexed under Infertility; 407 are open to participants now.

This study's enrollment of 1,329 is above the median of 120 across 1,698 interventional studies indexed under Infertility.

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Lead sponsor

Ferring Pharmaceuticals is the lead sponsor of 244 studies on the registry; 4 are open to participants now.

Of its 14 completed or terminated interventional studies of FDA-regulated products, 13 (93%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years to 40 Years
Sexes eligible: Female
Accepts healthy volunteers: No

Inclusion criteria

Informed Consent Documents signed prior to screening evaluations
In good physical and mental health
Pre-menopausal females between the ages of 18 and 40 years
Infertile women diagnosed with tubal infertility, unexplained infertility, endometriosis stage I/II or with partners diagnosed with male factor infertility, eligible for in vitro fertilisation (IVF) and/or intracytoplasmic sperm injection (ICSI) using fresh or frozen ejaculated sperm from male partner or sperm donor
Infertility for at least one year before randomisation for subjects ≤37 years or for at least 6 months for subjects ≥38 years (not applicable in case of tubal or severe male factor infertility)
The trial cycle will be the subject's first controlled ovarian stimulation cycle for IVF/ICSI
Hysterosalpingography, hysteroscopy, saline infusion sonography, or transvaginal ultrasound documenting a uterus consistent with expected normal function (e.g. no evidence of clinically interfering uterine fibroids defined as submucous or intramural fibroids larger than 3 cm in diameter, no polyps and no congenital structural abnormalities which are associated with a reduced chance of pregnancy) within 1 year prior to randomisation
Transvaginal ultrasound documenting presence and adequate visualisation of both ovaries, without evidence of significant abnormality (e.g. no endometrioma greater than 3 cm or enlarged ovaries which would contraindicate the use of gonadotropins) and normal adnexa (e.g. no hydrosalpinx) within 1 year prior to randomisation. Both ovaries must be accessible for oocyte retrieval.
Early follicular phase (cycle day 2-4) serum levels of FSH between 1 and 15 IU/L (results obtained within 3 months prior to randomisation)
Body mass index (BMI) between 17.5 and 32.0 kg/m2 (both inclusive) at screening

Exclusion criteria

Exclusion Criteria:

Known endometriosis stage III-IV
One or more follicles ≥10 mm observed on the transvaginal ultrasound prior to randomisation on stimulation day 1
Known history of recurrent miscarriage (defined as three consecutive losses after ultrasound confirmation of pregnancy (excl. ectopic pregnancy) and before week 24 of pregnancy)
Known abnormal karyotype of subject or of her partner/sperm donor, as applicable, depending on source of sperm used for insemination in this trial.
Any known clinically significant systemic disease (e.g. insulin-dependent diabetes)
Any known endocrine or metabolic abnormalities (pituitary, adrenal, pancreas, liver or kidney) which can compromise participation in the trial with the exception of controlled thyroid function disease
Known tumours of the ovary, breast, uterus, adrenal gland, pituitary or hypothalamus which would contraindicate the use of gonadotropins.

Study design

Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Single (Outcomes assessor)
Enrollment: 1,329 participants (actual)

Study arms

Experimental
A
Follitropin Delta (FE 999049)
Drug: Follitropin Delta (FE 999049)
Active comparator
B
Follitropin Alfa (GONAL-F)
Drug: Follitropin Alfa (GONAL-F)

Interventions

DrugFollitropin Delta (FE 999049)
DrugFollitropin Alfa (GONAL-F)

What researchers measure

Primary outcomes

Ongoing Pregnancy Rate
Ongoing pregnancy was defined as at least one intrauterine viable fetus 10-11 weeks after blastocyst transfer.
Time frame: 10-11 weeks after blastocyst transfer
Ongoing Implantation Rate
Ongoing implantation rate was defined as the number of intrauterine viable fetuses 10-11 weeks after transfer divided by number of blastocysts transferred.
Time frame: 10-11 weeks after blastocyst transfer

Secondary outcomes

Vital Pregnancy Rate
Vital pregnancy was defined as at least one intrauterine gestational sac with fetal heart beat 5-6 weeks after blastocyst transfer.
Time frame: 5-6 weeks after blastocyst transfer
Implantation Rate
Implantation rate was defined as the number of gestational sacs 5-6 weeks after transfer divided by number of blastocysts transferred.
Time frame: 5-6 weeks after blastocyst transfer
Proportion of Subjects With Extreme Ovarian Responses, Defined as <4, ≥15 or ≥20 Oocytes Retrieved
Time frame: Day of oocyte retrieval
Proportion of Subjects With Early OHSS (Ovarian Hyperstimulation Syndrome) and/or Preventive Interventions for Early OHSS
The proportion of subjects with early OHSS, early OHSS of moderate or severe grade, preventive interventions for early OHSS, early OHSS and/or preventive interventions for early OHSS, and early OHSS of moderate or severe grade and/or preventive interventions for early OHSS are presented.
Time frame: ≤9 days after triggering of final follicular maturation
Proportion of Subjects With Cycle Cancellation Due to Poor Ovarian Response or Excessive Ovarian Response
Proportion of subjects with cycle cancellation due to poor ovarian response, excessive ovarian response, and triggering with gonadotropin-releasing hormone (GnRH) agonist are presented.
Time frame: End-of-stimulation (up to 20 stimulation days)
Number of Oocytes Retrieved
Time frame: Day of oocyte retrieval
Proportion of Subjects With <4, 4-7, 8-14, 15-19 and ≥20 Oocytes Retrieved
Time frame: Day of oocyte retrieval
Percentage of Metaphase II Oocytes (Oocytes Inseminated Using ICSI [Intracytoplasmic Sperm Injection])
Number of oocytes in metaphase II prior to ICSI insemination is presented.
Time frame: Prior to insemination
Fertilisation Rate
Fertilisation rate was defined as the number of oocytes with 2 pronuclei divided by the number of oocytes retrieved.
Time frame: Day 1 after insemination
Number and Quality of Embryos on Day 3
Number of embryos (total and good-quality) on Day 3 are presented. A good-quality embryo was defined as an embryo with ≥6 blastomeres and fragmentation ≤20% on Day 3.
Time frame: On day 3 after oocyte retrieval
Number and Quality of Blastocysts on Day 5
Number of blastocysts (total and good-quality) on Day 5 are presented. A good-quality blastocyst was defined as a blastocyst of grade 3BB or higher.
Time frame: On day 5 after oocyte retrieval
Total Gonadotropin Dose
The total gonadotropin dose was recorded.
Time frame: End-of-stimulation (up to 20 stimulation days)
Number of Stimulation Days
Time frame: End-of-stimulation (up to 20 stimulation days)
Proportion of Subjects With Investigator-requested Gonadotropin Dose Adjustments
Time frame: End-of-stimulation (up to 20 stimulation days)
Frequency of Injection Site Reactions (Redness, Pain, Itching, Swelling and Bruising) Assessed by the Subject During the Stimulation Period
Subjects 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 assessments performed is presented.
Time frame: End-of-stimulation (up to 20 stimulation days)
Abdominal Discomfort Related to Controlled Ovarian Stimulation as Assessed by a Visual Analogue Scale (VAS)
The subject self-assessed abdominal discomfort related to controlled ovarian stimulation using a VAS going from 0 mm (no abdominal discomfort) to 100 mm (worst imaginable abdominal discomfort).
Time frame: End-of-stimulation and day of blastocyst transfer
Changes in Body Weight
Change in body weight from baseline to end-of-stimulation and from baseline to day of blastocyst transfer.
Time frame: End-of-stimulation and day of blastocyst transfer
Changes in Maximum Abdominal Circumference
Change in maximum abdominal circumference from baseline to end-of-stimulation and from baseline to day of blastocyst transfer.
Time frame: End-of-stimulation and day of blastocyst transfer
Proportion of Subjects With Treatment-induced Anti-follicle-stimulating Hormone (FSH) Antibodies
The proportion of subjects with at least one treatment-induced anti-FSH antibody response at any time point.
Time frame: Stimulation day 1, 7-10 days after last FE 999049 or GONAL-F dose and 21-28 days after last FE 999049 or GONAL-F dose
Proportion of Subjects With Late OHSS
Late OHSS was defined as OHSS with onset \>9 days after triggering of final follicular maturation.The proportion of subjects with late OHSS, and late OHSS of moderate or severe grade are presented.
Time frame: >9 days after triggering of final follicular maturation
Technical Malfunctions of the Administration Pen
Confirmed technical malfunction of administration pen.
Time frame: End-of-stimulation (up to 20 stimulation days)

Results

Posted Sep 25, 2018

Participant flow

A total of 37 sites randomised subjects into the trial : 3 in Belgium, 3 in Brazil, 3 in Canada, 4 in the Czech Republic, 2 in Denmark, 2 in France, 2 in Italy, 2 in Poland, 4 in Russia, 10 in Spain and 2 in United Kingdom.

Participant flow — Overall Study
Milestone	FE 999049	GONAL-F
Started	665	661
Completed	630	639
Not completed	35	22
Withdrew: Protocol violation	25	11
Withdrew: Adverse event	9	10
Withdrew: Personal reasons	1	1

Outcome measures

PrimaryOngoing Pregnancy Rate

Ongoing pregnancy was defined as at least one intrauterine viable fetus 10-11 weeks after blastocyst transfer.

Time frame:: 10-11 weeks after blastocyst transfer
Reported as:: Number · Percentage of subjects

Ongoing Pregnancy Rate
Percentage of subjects	FE 999049	GONAL-F
Ongoing Pregnancy Rate	30.7	31.6

Statistical analysis

FE 999049 vs GONAL-F · Treatment difference: -0.9 · 95% CI -5.9 to 4.1

PrimaryOngoing Implantation Rate

Ongoing implantation rate was defined as the number of intrauterine viable fetuses 10-11 weeks after transfer divided by number of blastocysts transferred.

Time frame:: 10-11 weeks after blastocyst transfer
Reported as:: Number · Percentage

Ongoing Implantation Rate
Percentage	FE 999049	GONAL-F
Ongoing Implantation Rate	35.2	35.8

Statistical analysis

FE 999049 vs GONAL-F · Treatment difference: -0.6 · 95% CI -6.1 to 4.8

SecondaryVital Pregnancy Rate

Vital pregnancy was defined as at least one intrauterine gestational sac with fetal heart beat 5-6 weeks after blastocyst transfer.

Time frame:: 5-6 weeks after blastocyst transfer
Reported as:: Number · Percentage of subjects

Vital Pregnancy Rate
Percentage of subjects	FE 999049	GONAL-F
Vital Pregnancy Rate	31.7	33.4

Statistical analysis

FE 999049 vs GONAL-F · Treatment difference: -1.6 · 95% CI -6.7 to 3.4

SecondaryImplantation Rate

Implantation rate was defined as the number of gestational sacs 5-6 weeks after transfer divided by number of blastocysts transferred.

Time frame:: 5-6 weeks after blastocyst transfer
Reported as:: Number · Percentage

Implantation Rate
Percentage	FE 999049	GONAL-F
Implantation Rate	39.8	41.3

Statistical analysis

FE 999049 vs GONAL-F · Treatment difference: -1.4 · 95% CI -7.0 to 4.2

SecondaryProportion of Subjects With Extreme Ovarian Responses, Defined as <4, ≥15 or ≥20 Oocytes Retrieved

Time frame:: Day of oocyte retrieval
Reported as:: Number · Percentage of subjects

Proportion of Subjects With Extreme Ovarian Responses, Defined as <4, ≥15 or ≥20 Oocytes Retrieved
Percentage of subjects	FE 999049	GONAL-F
<4 or >=15 oocytes retrieved	26.6	31.3
<4 or >=20 oocytes retrieved	14.5	18.4

Statistical analysis

FE 999049 vs GONAL-F · Likelihood ratio test · p = =0.001 (Inclusion of treatment provides a better fit to the data.)Likelihood ratio test comparing the reduced model including only AMH to the full model including AMH, treatment group and interactions.
FE 999049 vs GONAL-F · Likelihood ratio test · p = =0.002 (Inclusion of treatment provides a better fit to the data.)Likelihood ratio test comparing the reduced model including only AMH to the full model including AMH, treatment group and interactions.

SecondaryProportion of Subjects With Early OHSS (Ovarian Hyperstimulation Syndrome) and/or Preventive Interventions for Early OHSS

The proportion of subjects with early OHSS, early OHSS of moderate or severe grade, preventive interventions for early OHSS, early OHSS and/or preventive interventions for early OHSS, and early OHSS of moderate or severe grade and/or preventive interventions for early OHSS are presented.

Time frame:: ≤9 days after triggering of final follicular maturation
Reported as:: Number · Percentage of subjects

Proportion of Subjects With Early OHSS (Ovarian Hyperstimulation Syndrome) and/or Preventive Interventions for Early OHSS
Percentage of subjects	FE 999049	GONAL-F
Early OHSS (any grade)	2.6	3.0
Early OHSS (moderate/severe)	1.4	1.4
Any preventive intervention	2.3	4.5
Early OHSS (any grade) / preventive interventions	4.7	6.2
Early OHSS (mod/severe) / preventive interventions	3.6	5.1

Statistical analysis

FE 999049 vs GONAL-F · Likelihood ratio test · p = =0.291 (Inclusion of treatment does not provide a better fit to the data.)Likelihood ratio test comparing the reduced model including only AMH to the full model including AMH, treatment group and interactions.
FE 999049 vs GONAL-F · Likelihood ratio test · p = =0.644 (Inclusion of treatment does not provide a better fit to the data.)Likelihood ratio test comparing the reduced model including only AMH to the full model including AMH, treatment group and interactions.
FE 999049 vs GONAL-F · Likelihood ratio test · p = =0.005 (Inclusion of treatment does not provide a better fit to the data.)Likelihood ratio test comparing the reduced model including only AMH to the full model including AMH, treatment group and interactions.
FE 999049 vs GONAL-F · Likelihood ratio test · p = =0.046 (Inclusion of treatment does not provide a better fit to the data.)Likelihood ratio test comparing the reduced model including only AMH to the full model including AMH, treatment group and interactions.
FE 999049 vs GONAL-F · Likelihood ratio test · p = =0.019 (Inclusion of treatment does not provide a better fit to the data.)Likelihood ratio test comparing the reduced model including only AMH to the full model including AMH, treatment group and interactions.

SecondaryProportion of Subjects With Cycle Cancellation Due to Poor Ovarian Response or Excessive Ovarian Response

Proportion of subjects with cycle cancellation due to poor ovarian response, excessive ovarian response, and triggering with gonadotropin-releasing hormone (GnRH) agonist are presented.

Time frame:: End-of-stimulation (up to 20 stimulation days)
Reported as:: Number · Percentage of subjects

Proportion of Subjects With Cycle Cancellation Due to Poor Ovarian Response or Excessive Ovarian Response
Percentage of subjects	FE 999049	GONAL-F
Cycle cancelled due to poor ovarian response	3.8	2.7
Cycle cancelled due to excessive ovarian response	0	0
Triggering with GnRH agonist	1.5	3.5

Statistical analysis

FE 999049 vs GONAL-F · Likelihood ratio test · p = =0.302 (P-value corresponds to test for treatment difference.) · Odds ratio (or): 1.38 · 95% CI 0.74 to 2.57
FE 999049 vs GONAL-F · Likelihood ratio test · p = 0.019 (P-value corresponds to test for treatment difference.) · Odds ratio (or): 0.42 · 95% CI 0.2 to 0.9

SecondaryNumber of Oocytes Retrieved

Time frame:: Day of oocyte retrieval
Reported as:: Mean · Oocytes retrieved

Number of Oocytes Retrieved
Oocytes retrieved	FE 999049	GONAL-F
Number of Oocytes Retrieved	10.0 ± 5.6	10.4 ± 6.5

Statistical analysis

FE 999049 vs GONAL-F · van Elteren · p = =0.692

SecondaryProportion of Subjects With <4, 4-7, 8-14, 15-19 and ≥20 Oocytes Retrieved

Time frame:: Day of oocyte retrieval
Reported as:: Number · Percentage of subjects

Proportion of Subjects With <4, 4-7, 8-14, 15-19 and ≥20 Oocytes Retrieved
Percentage of subjects	FE 999049	GONAL-F
Low response (<4 oocytes)	8.0	9.6
Moderate response (4-7 oocytes)	30.1	30.3
Targeted response (8-14 oocytes)	43.3	38.4
Hyperresponse (15-19 oocytes)	12.1	12.9
Severe hyperresponse (≥ 20 oocytes)	6.5	8.7

Statistical analysis

FE 999049 vs GONAL-F · Likelihood ratio test · p = =0.019 (Inclusion of treatment provides a better fit to the data)Likelihood ratio test comparing the reduced model including only AMH to the full model including AMH, treatment group and interactions.

SecondaryPercentage of Metaphase II Oocytes (Oocytes Inseminated Using ICSI [Intracytoplasmic Sperm Injection])

Number of oocytes in metaphase II prior to ICSI insemination is presented.

Time frame:: Prior to insemination
Reported as:: Mean · Number of oocytes

Percentage of Metaphase II Oocytes (Oocytes Inseminated Using ICSI [Intracytoplasmic Sperm Injection])
Number of oocytes	FE 999049	GONAL-F
Percentage of Metaphase II Oocytes (Oocytes Inseminated Using ICSI [Intracytoplasmic Sperm Injection])	7.4 ± 4.3	7.7 ± 5.2

Statistical analysis

FE 999049 vs GONAL-F · van Elteren · p = =0.909

SecondaryFertilisation Rate

Fertilisation rate was defined as the number of oocytes with 2 pronuclei divided by the number of oocytes retrieved.

Time frame:: Day 1 after insemination
Reported as:: Mean · Percentage of oocytes

Fertilisation Rate
Percentage of oocytes	FE 999049	GONAL-F
Fertilisation Rate	56 ± 24.5	57 ± 23.8

Statistical analysis

FE 999049 vs GONAL-F · van Elteren · p = 0.53

SecondaryNumber and Quality of Embryos on Day 3

Number of embryos (total and good-quality) on Day 3 are presented. A good-quality embryo was defined as an embryo with ≥6 blastomeres and fragmentation ≤20% on Day 3.

Time frame:: On day 3 after oocyte retrieval
Reported as:: Mean · Number of embryos

Number and Quality of Embryos on Day 3
Number of embryos	FE 999049	GONAL-F
Number of embryos	5.4 ± 3.7	5.7 ± 4.3
Number of good-quality embryos	4.2 ± 3.3	4.5 ± 3.7

Statistical analysis

FE 999049 vs GONAL-F · van Elteren · p = =0.59
FE 999049 vs GONAL-F · van Elteren · p = =0.414

SecondaryNumber and Quality of Blastocysts on Day 5

Number of blastocysts (total and good-quality) on Day 5 are presented. A good-quality blastocyst was defined as a blastocyst of grade 3BB or higher.

Time frame:: On day 5 after oocyte retrieval
Reported as:: Mean · Number of blastocytss

Number and Quality of Blastocysts on Day 5
Number of blastocytss	FE 999049	GONAL-F
Number of blastocysts	3.3 ± 2.8	3.5 ± 3.2
Number of good-quality blastocysts	2.0 ± 2.2	2.1 ± 2.4

Statistical analysis

FE 999049 vs GONAL-F · van Elteren · p = = 0.344
FE 999049 vs GONAL-F · van Elteren · p = = 0.58

SecondaryTotal Gonadotropin Dose

The total gonadotropin dose was recorded.

Time frame:: End-of-stimulation (up to 20 stimulation days)
Reported as:: Mean · µg of dose

Total Gonadotropin Dose
µg of dose	FE 999049	GONAL-F
Total Gonadotropin Dose	90 ± 25.3	103.7 ± 33.6

Statistical analysis

FE 999049 vs GONAL-F · van Elteren · p = <0.001

SecondaryNumber of Stimulation Days

Time frame:: End-of-stimulation (up to 20 stimulation days)
Reported as:: Mean · Days

Number of Stimulation Days
Days	FE 999049	GONAL-F
Number of Stimulation Days	8.9 ± 1.9	8.6 ± 1.7

Statistical analysis

FE 999049 vs GONAL-F · van Elteren · p = =0.062

SecondaryProportion of Subjects With Investigator-requested Gonadotropin Dose Adjustments

Time frame:: End-of-stimulation (up to 20 stimulation days)
Reported as:: Number · Percentage of subjects

Proportion of Subjects With Investigator-requested Gonadotropin Dose Adjustments
Percentage of subjects	FE 999049	GONAL-F
Proportion of Subjects With Investigator-requested Gonadotropin Dose Adjustments	33.2	36.8

Statistical analysis

FE 999049 vs GONAL-F · Chi-squared · p = =0.178

SecondaryFrequency of Injection Site Reactions (Redness, Pain, Itching, Swelling and Bruising) Assessed by the Subject During the Stimulation Period

Subjects 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 assessments performed is presented.

Time frame:: End-of-stimulation (up to 20 stimulation days)
Reported as:: Number · Percentage of events

Frequency of Injection Site Reactions (Redness, Pain, Itching, Swelling and Bruising) Assessed by the Subject During the Stimulation Period
Percentage of events	FE 999049	GONAL-F
Frequency of Injection Site Reactions (Redness, Pain, Itching, Swelling and Bruising) Assessed by the Subject During the Stimulation Period	3.4	3.5

SecondaryAbdominal Discomfort Related to Controlled Ovarian Stimulation as Assessed by a Visual Analogue Scale (VAS)

The subject self-assessed abdominal discomfort related to controlled ovarian stimulation using a VAS going from 0 mm (no abdominal discomfort) to 100 mm (worst imaginable abdominal discomfort).

Time frame:: End-of-stimulation and day of blastocyst transfer
Reported as:: Mean · Millimeter

Abdominal Discomfort Related to Controlled Ovarian Stimulation as Assessed by a Visual Analogue Scale (VAS)
Millimeter	FE 999049	GONAL-F
End of stimulation visit	16.1 ± 18.14	15.9 ± 17.36
Transfer visit	17.2 ± 20.02	16.1 ± 19.37

SecondaryChanges in Body Weight

Change in body weight from baseline to end-of-stimulation and from baseline to day of blastocyst transfer.

Time frame:: End-of-stimulation and day of blastocyst transfer
Reported as:: Mean · Kg

Changes in Body Weight
Kg	FE 999049	GONAL-F
End of stimulation visit	0.3 ± 1.11	0.2 ± 0.78
Transfer visit	0.0 ± 1.03	0.0 ± 0.98

SecondaryChanges in Maximum Abdominal Circumference

Change in maximum abdominal circumference from baseline to end-of-stimulation and from baseline to day of blastocyst transfer.

Time frame:: End-of-stimulation and day of blastocyst transfer
Reported as:: Mean · Centimeter

Changes in Maximum Abdominal Circumference
Centimeter	FE 999049	GONAL-F
End of stimulation visit	0.3 ± 4.41	0.1 ± 5.03
Transfer visit	0.6 ± 4.79	-0.1 ± 5.23

SecondaryProportion of Subjects With Treatment-induced Anti-follicle-stimulating Hormone (FSH) Antibodies

The proportion of subjects with at least one treatment-induced anti-FSH antibody response at any time point.

Time frame:: Stimulation day 1, 7-10 days after last FE 999049 or GONAL-F dose and 21-28 days after last FE 999049 or GONAL-F dose
Reported as:: Number · Percentage of subjects

Proportion of Subjects With Treatment-induced Anti-follicle-stimulating Hormone (FSH) Antibodies
Percentage of subjects	FE 999049	GONAL-F
Proportion of Subjects With Treatment-induced Anti-follicle-stimulating Hormone (FSH) Antibodies	1.05 (0.42 to 2.16)	0.76 (0.25 to 1.76)

SecondaryProportion of Subjects With Late OHSS

Late OHSS was defined as OHSS with onset \>9 days after triggering of final follicular maturation.The proportion of subjects with late OHSS, and late OHSS of moderate or severe grade are presented.

Time frame:: >9 days after triggering of final follicular maturation
Reported as:: Number · Percentage of subjects

Proportion of Subjects With Late OHSS
Percentage of subjects	FE 999049	GONAL-F
Late OHSS (any grade)	0.9	1.8
Late OHSS (moderate/severe)	0.8	1.5

Statistical analysis

FE 999049 vs GONAL-F · Likelihood ratio test · p = 0.320 (Inclusion of treatment does not provide a better fit to the data.)Likelihood ratio test comparing the reduced model including only AMH to the full model including AMH, treatment group and interactions.
FE 999049 vs GONAL-F · Likelihood ratio test · p = 0.390 (Inclusion of treatment does not provide a better fit to the data.)Likelihood ratio test comparing the reduced model including only AMH to the full model including AMH, treatment group and interactions.

SecondaryTechnical Malfunctions of the Administration Pen

Confirmed technical malfunction of administration pen.

Time frame:: End-of-stimulation (up to 20 stimulation days)
Reported as:: Number · Percentage of subjects

Technical Malfunctions of the Administration Pen
Percentage of subjects	FE 999049	GONAL-F
Technical Malfunctions of the Administration Pen	0.15	0.00

Adverse events

Collected over Adverse events (AEs) were recorded from signed informed consent to the end-of-trial (up to approximately 5.5 months).. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
FE 999049	—	16/665 (2.4%)	168/665 (25.3%)
GONAL-F	—	10/661 (1.5%)	159/661 (24.1%)

Most frequent serious events

Showing 10 of 11

Most frequent serious events
Event	FE 999049	GONAL-F
Ovarian hyperstimulation syndromeReproductive system and breast disorders	3/665	6/661
Haemorrhage in pregnancyPregnancy, puerperium and perinatal conditions	5/665	1/661
Biochemical pregnancyPregnancy, puerperium and perinatal conditions	1/665	2/661
Post procedural haemorrhageInjury, poisoning and procedural complications	2/665	0/661
Abortion spontaneousPregnancy, puerperium and perinatal conditions	2/665	1/661
Hyperemesis gravidarumPregnancy, puerperium and perinatal conditions	0/665	1/661
Post procedural infectionInfections and infestations	0/665	1/661
Abortion threatenedPregnancy, puerperium and perinatal conditions	1/665	0/661
Affect labilityPsychiatric disorders	1/665	0/661
Colitis ulcerativeGastrointestinal disorders	1/665	0/661

Most frequent other events

Most frequent other events
Event	FE 999049	GONAL-F
HeadacheNervous system disorders	97/665	88/661
Procedural painInjury, poisoning and procedural complications	49/665	52/661
Pelvic painReproductive system and breast disorders	46/665	41/661
Pelvic discomfortReproductive system and breast disorders	38/665	25/661

Baseline characteristics

Of the 1,329 randomised subjects, 1,326 were exposed to IMP: FE 999049 (665 subjects) and GONAL-F (661 subjects). The 3 subjects who were not exposed to IMP were randomisation failures; 2 subjects (1 in each treatment group) did not fulfil an inclusion criterion, and 1 subject (in the GONAL-F group) withdrew due to personal reasons.

Age, Categorical
Age, Categorical(Participants)	FE 999049	GONAL-F	Total
<=18 years	0	0	0
Between 18 and 65 years	665	661	1326
>=65 years	0	0	0

Sex: Female, Male
Sex: Female, Male(Participants)	FE 999049	GONAL-F	Total
Female	665	661	1326
Male	0	0	0

Study locations

13 sites

UZ Brussel (there may be other sites in this country)
Brussels, Belgium
Fertilitat and PUC-RS (there may be other sites in this country)
Porto Alegre, Brazil
Pacific Centre for Reproductive Medicine
Burnaby, British Columbia, Canada
Olive Fertility Centre
Vancouver, British Columbia, Canada
Ottawa Fertility Centre
Ottawa, Ontario, Canada
IVF CUBE SE (there may be other sites in this country)
Prague, Czechia
Rigshospitalet Fertilitetsklinikken (there may be other sites in this country)
Copenhagen, Denmark
Department of Endocrine Gynaecology and Reproductive Medicine, Hôpital Jeanne de Flandre (there may be other sites in this country)
Lille, France
Centro Natalità San Raffaele (there may be other sites in this country)
Milano, Italy
The nOvum Clinic (there may be other sites in this country)
Warszawa, Poland
IVF & Reproductive Genetics Center (there may be other sites in this country)
Moscow, Russian Federation
IVI Sevilla (there may be other sites in this country)
Sevilla, Spain
Glasgow Centre for Reproductive Medicine Ltd. (there may be other sites in this country)
Glasgow, United Kingdom

References and documents

Publications

Arce JC, Larsson P, Garcia-Velasco JA. Establishing the follitropin delta dose that provides a comparable ovarian response to 150 IU/day follitropin alfa. Reprod Biomed Online. 2020 Oct;41(4):616-622. doi: 10.1016/j.rbmo.2020.07.006. Epub 2020 Jul 15. PubMed 32819842 ↗
Havelock J, Aaris Henningsen AK, Mannaerts B, Arce JC; ESTHER-1 and ESTHER-2 Trial Groups. Pregnancy and neonatal outcomes in fresh and frozen cycles using blastocysts derived from ovarian stimulation with follitropin delta. J Assist Reprod Genet. 2021 Oct;38(10):2651-2661. doi: 10.1007/s10815-021-02271-5. Epub 2021 Jul 13. PubMed 34254211 ↗
Ishihara O, Nelson SM, Arce JC. Comparison of ovarian response to follitropin delta in Japanese and White IVF/ICSI patients. Reprod Biomed Online. 2022 Jan;44(1):177-184. doi: 10.1016/j.rbmo.2021.09.014. Epub 2021 Sep 23. PubMed 34799275 ↗
Nelson SM, Larsson P, Mannaerts BMJL, Nyboe Andersen A, Fauser BCJM. Anti-Mullerian hormone variability and its implications for the number of oocytes retrieved following individualized dosing with follitropin delta. Clin Endocrinol (Oxf). 2019 May;90(5):719-726. doi: 10.1111/cen.13956. Epub 2019 Mar 18. PubMed 30801744 ↗
Nyboe Andersen A, Nelson SM, Fauser BC, Garcia-Velasco JA, Klein BM, Arce JC; ESTHER-1 study group. Individualized versus conventional ovarian stimulation for in vitro fertilization: a multicenter, randomized, controlled, assessor-blinded, phase 3 noninferiority trial. Fertil Steril. 2017 Feb;107(2):387-396.e4. doi: 10.1016/j.fertnstert.2016.10.033. Epub 2016 Nov 29. PubMed 27912901 ↗

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Jan 13, 2022, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT01956110
Lead sponsor: Ferring Pharmaceuticals
Responsible party: Sponsor
First posted: Oct 8, 2013
Start date: Oct 2013
Primary completion: May 2015
Completion: Jan 3, 2017
Results posted: Sep 25, 2018
Last update: Jan 13, 2022

Study contacts

Clinical Development Support

study director · Ferring Pharmaceuticals

Oversight

Data monitoring committee: No

View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Sep 2018. You cannot join it, but the record below documents what was studied.

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