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

NCT01956110 | Completed Phase 3 Results

• 3 other identifiers: 0000042013-001669-17U1111-1147-6826
• Study Type: interventional
• Target: 1,329
• Locations: 11 countries
• Sites: 13

Brief Summary

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

Conditions

Infertility

Outcome Measures

Primary Outcomes (2)

• Ongoing Pregnancy Rate

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

  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.

  10-11 weeks after blastocyst transfer

Secondary Outcomes (21)

• Vital Pregnancy Rate

  5-6 weeks after blastocyst transfer

• Implantation Rate

  5-6 weeks after blastocyst transfer

• 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

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

  End-of-stimulation (up to 20 stimulation days)

Study Arms (2)

A

EXPERIMENTAL

Follitropin Delta (FE 999049)

Drug: Follitropin Delta (FE 999049)

B

ACTIVE COMPARATOR

Follitropin Alfa (GONAL-F)

Drug: Follitropin Alfa (GONAL-F)

Interventions

Follitropin Delta (FE 999049) DRUG

A

Follitropin Alfa (GONAL-F) DRUG

B

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ferring Pharmaceuticals: lead

Study Sites (13)

UZ Brussel (there may be other sites in this country)

Brussels, Belgium

Location

Fertilitat and PUC-RS (there may be other sites in this country)

Porto Alegre, Brazil

Location

Pacific Centre for Reproductive Medicine

Burnaby, British Columbia, Canada

Location

Olive Fertility Centre

Vancouver, British Columbia, Canada

Location

Ottawa Fertility Centre

Ottawa, Ontario, Canada

Location

IVF CUBE SE (there may be other sites in this country)

Prague, Czechia

Location

Rigshospitalet Fertilitetsklinikken (there may be other sites in this country)

Copenhagen, Denmark

Location

Department of Endocrine Gynaecology and Reproductive Medicine, Hôpital Jeanne de Flandre (there may be other sites in this country)

Lille, France

Location

Centro Natalità San Raffaele (there may be other sites in this country)

Milan, Italy

Location

The nOvum Clinic (there may be other sites in this country)

Warsaw, Poland

Location

IVF & Reproductive Genetics Center (there may be other sites in this country)

Moscow, Russia

Location

IVI Sevilla (there may be other sites in this country)

Seville, Spain

Location

Glasgow Centre for Reproductive Medicine Ltd. (there may be other sites in this country)

Glasgow, United Kingdom

Location

Related Publications (5)

• 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.

  PMID: 32819842 RESULT

• 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.

  PMID: 34254211 RESULT

• 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.

  PMID: 34799275 RESULT

• 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.

  PMID: 30801744 DERIVED

• 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.

  PMID: 27912901 DERIVED

MeSH Terms

Conditions

Infertility

Interventions

follitropin delta; FE 999049; follitropin alfa

Condition Hierarchy (Ancestors)

Genital Diseases; Urogenital Diseases

Results Point of Contact

• Title: Global Clinical Compliance
• Organization: Ferring Pharmaceuticals

DK0-Disclosure@ferring.com

Study Officials

• Clinical Development Support

  Ferring Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 16, 2013
• First Posted: October 8, 2013
• Study Start: October 1, 2013
• Primary Completion: May 1, 2015
• Study Completion: January 3, 2017
• Last Updated: January 13, 2022
• Results First Posted: September 25, 2018

Record last verified: 2018-09

Locations

BR (1); CA (3); PL (1); GB (1); IT (1); FR (1); CZ (1); ES (1); RU (1); BE (1); DK (1)