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

Phase 3

Completed

Conditions: Infertility

Interventions: Drug: Follitropin Delta (FE 999049)
Drug: Follitropin Alfa (GONAL-F)

Registration Number: NCT01956110

Lead Sponsor: Ferring Pharmaceuticals

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

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 1329

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

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

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
A	Follitropin Delta (FE 999049)	Follitropin Delta (FE 999049)
B	Follitropin Alfa (GONAL-F)	Follitropin Alfa (GONAL-F)

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Vital Pregnancy Rate	5-6 weeks after blastocyst transfer	Vital pregnancy was defined as at least one intrauterine gestational sac with fetal heart beat 5-6 weeks after blastocyst transfer.
Implantation Rate	5-6 weeks after blastocyst transfer	Implantation rate was defined as the number of gestational sacs 5-6 weeks after transfer divided by number of blastocysts transferred.
Proportion of Subjects With Extreme Ovarian Responses, Defined as <4, ≥15 or ≥20 Oocytes Retrieved	Day of oocyte retrieval
Proportion of Subjects With Early OHSS (Ovarian Hyperstimulation Syndrome) and/or Preventive Interventions for Early OHSS	≤9 days after triggering of final follicular maturation	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.
Proportion of Subjects With Cycle Cancellation Due to Poor Ovarian Response or Excessive Ovarian Response	End-of-stimulation (up to 20 stimulation days)	Proportion of subjects with cycle cancellation due to poor ovarian response, excessive ovarian response, and triggering with gonadotropin-releasing hormone (GnRH) agonist are presented.
Number of Oocytes Retrieved	Day of oocyte retrieval
Proportion of Subjects With <4, 4-7, 8-14, 15-19 and ≥20 Oocytes Retrieved	Day of oocyte retrieval
Proportion of Subjects With Investigator-requested Gonadotropin Dose Adjustments	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	End-of-stimulation (up to 20 stimulation days)	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.
Abdominal Discomfort Related to Controlled Ovarian Stimulation as Assessed by a Visual Analogue Scale (VAS)	End-of-stimulation and day of blastocyst transfer	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).
Changes in Body Weight	End-of-stimulation and day of blastocyst transfer	Change in body weight from baseline to end-of-stimulation and from baseline to day of blastocyst transfer.
Changes in Maximum Abdominal Circumference	End-of-stimulation and day of blastocyst transfer	Change in maximum abdominal circumference from baseline to end-of-stimulation and from baseline to day of blastocyst transfer.
Proportion of Subjects With Treatment-induced Anti-follicle-stimulating Hormone (FSH) Antibodies	Stimulation day 1, 7-10 days after last FE 999049 or GONAL-F dose and 21-28 days after last FE 999049 or GONAL-F dose	The proportion of subjects with at least one treatment-induced anti-FSH antibody response at any time point.
Proportion of Subjects With Late OHSS	>9 days after triggering of final follicular maturation	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.
Technical Malfunctions of the Administration Pen	End-of-stimulation (up to 20 stimulation days)	Confirmed technical malfunction of administration pen.
Percentage of Metaphase II Oocytes (Oocytes Inseminated Using ICSI [Intracytoplasmic Sperm Injection])	Prior to insemination	Number of oocytes in metaphase II prior to ICSI insemination is presented.
Fertilisation Rate	Day 1 after insemination	Fertilisation rate was defined as the number of oocytes with 2 pronuclei divided by the number of oocytes retrieved.
Number and Quality of Embryos on Day 3	On day 3 after oocyte retrieval	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.
Number and Quality of Blastocysts on Day 5	On day 5 after oocyte retrieval	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.
Total Gonadotropin Dose	End-of-stimulation (up to 20 stimulation days)	The total gonadotropin dose was recorded.
Number of Stimulation Days	End-of-stimulation (up to 20 stimulation days)

Trial Locations

Locations (13): Department of Endocrine Gynaecology and Reproductive Medicine, Hôpital Jeanne de Flandre (there may be other sites in this country)
🇫🇷
Lille, France
Ottawa Fertility Centre
🇨🇦
Ottawa, Ontario, Canada
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
Pacific Centre for Reproductive Medicine
🇨🇦
Burnaby, British Columbia, Canada
Fertilitat and PUC-RS (there may be other sites in this country)
🇧🇷
Porto Alegre, Brazil
UZ Brussel (there may be other sites in this country)
🇧🇪
Brussels, Belgium
Olive Fertility Centre
🇨🇦
Vancouver, British Columbia, Canada
Rigshospitalet Fertilitetsklinikken (there may be other sites in this country)
🇩🇰
Copenhagen, Denmark
Centro Natalità San Raffaele (there may be other sites in this country)
🇮🇹
Milano, Italy
Glasgow Centre for Reproductive Medicine Ltd. (there may be other sites in this country)
🇬🇧
Glasgow, United Kingdom
IVF CUBE SE (there may be other sites in this country)
🇨🇿
Prague, Czechia
IVI Sevilla (there may be other sites in this country)
🇪🇸
Sevilla, Spain