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

January 4, 2022 updated by: Ferring Pharmaceuticals

A Randomised, Controlled, Assessor-blind, Parallel Groups, Multicentre, Multinational Trial Comparing the Efficacy and Safety of FE 999049 With Follitropin Alfa (GONAL-F) in Controlled Ovarian Stimulation in Women Undergoing an Assisted Reproductive Technology Programme

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

1329

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 40 years (ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: SINGLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: A
Follitropin Delta (FE 999049)
Drug: Follitropin Delta (FE 999049)
ACTIVE_COMPARATOR: B
Follitropin Alfa (GONAL-F)
Drug: Follitropin Alfa (GONAL-F)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Ongoing Pregnancy Rate
Time Frame: 10-11 weeks after blastocyst transfer
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
Time Frame: 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.
10-11 weeks after blastocyst transfer

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Stimulation Days
Time Frame: End-of-stimulation (up to 20 stimulation days)
End-of-stimulation (up to 20 stimulation days)
Vital Pregnancy Rate
Time Frame: 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.
5-6 weeks after blastocyst transfer
Implantation Rate
Time Frame: 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.
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
Day of oocyte retrieval
Proportion of Subjects With Early OHSS (Ovarian Hyperstimulation Syndrome) and/or Preventive Interventions for Early OHSS
Time Frame: ≤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.
≤9 days after triggering of final follicular maturation
Proportion of Subjects With Cycle Cancellation Due to Poor Ovarian Response or Excessive Ovarian Response
Time Frame: 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.
End-of-stimulation (up to 20 stimulation days)
Number of Oocytes Retrieved
Time Frame: Day of oocyte retrieval
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
Day of oocyte retrieval
Percentage of Metaphase II Oocytes (Oocytes Inseminated Using ICSI [Intracytoplasmic Sperm Injection])
Time Frame: Prior to insemination
Number of oocytes in metaphase II prior to ICSI insemination is presented.
Prior to insemination
Fertilisation Rate
Time Frame: Day 1 after insemination
Fertilisation rate was defined as the number of oocytes with 2 pronuclei divided by the number of oocytes retrieved.
Day 1 after insemination
Number and Quality of Embryos on Day 3
Time Frame: 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.
On day 3 after oocyte retrieval
Number and Quality of Blastocysts on Day 5
Time Frame: 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.
On day 5 after oocyte retrieval
Total Gonadotropin Dose
Time Frame: End-of-stimulation (up to 20 stimulation days)
The total gonadotropin dose was recorded.
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)
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
Time Frame: 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.
End-of-stimulation (up to 20 stimulation days)
Abdominal Discomfort Related to Controlled Ovarian Stimulation as Assessed by a Visual Analogue Scale (VAS)
Time Frame: 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).
End-of-stimulation and day of blastocyst transfer
Changes in Body Weight
Time Frame: 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.
End-of-stimulation and day of blastocyst transfer
Changes in Maximum Abdominal Circumference
Time Frame: 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.
End-of-stimulation and day of blastocyst transfer
Proportion of Subjects With Treatment-induced Anti-follicle-stimulating Hormone (FSH) Antibodies
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
The proportion of subjects with at least one treatment-induced anti-FSH antibody response at any time point.
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
Time Frame: >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.
>9 days after triggering of final follicular maturation
Technical Malfunctions of the Administration Pen
Time Frame: End-of-stimulation (up to 20 stimulation days)
Confirmed technical malfunction of administration pen.
End-of-stimulation (up to 20 stimulation days)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ferring Pharmaceuticals

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2013

Primary Completion (ACTUAL)

May 1, 2015

Study Completion (ACTUAL)

January 3, 2017

Study Registration Dates

First Submitted

August 16, 2013

First Submitted That Met QC Criteria

October 7, 2013

First Posted (ESTIMATE)

October 8, 2013

Study Record Updates

Last Update Posted (ACTUAL)

January 13, 2022

Last Update Submitted That Met QC Criteria

January 4, 2022

Last Verified

September 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 000004
  • 2013-001669-17 (EUDRACT_NUMBER)
  • U1111-1147-6826 (OTHER: WHO)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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