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InfertilityPhase 3ESTHER-2NCT01956123

Evidence-based Stimulation Trial With Human rFSH in Europe and Rest of World 2

A Phase 3 study testing Follitropin Delta (FE 999049) and Follitropin Alfa (GONAL-F) in people with Infertility, run by Ferring Pharmaceuticals at 13 sites in 11 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This trial investigates the immunogenicity of FE 999049 in repeated cycles. Read more about this study

Who is it for?
Ages 18 to 40 years, women only
Conditions the study is for
Infertility
What is being tested?
Follitropin Delta (FE 999049) and Follitropin Alfa (GONAL-F)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
513 participants
Where
13 sitesin 11 countries
Study dates
26 Mar 2014to 3 Jan 2017
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 40 years
  • Women only
  • No healthy volunteers
  • Adult

Who may be able to join

  • Informed Consent Documents signed prior to screening evaluations related to this protocol
  • Participation in the pivotal efficacy trial (trial 000004/ESTHER-1)
  • Anti-FSH antibody results from baseline and at least one post-dosing assessment in the previous cycle(s) available.
  • Having undergone the oocyte retrieval procedure, or having had cycle cancellation prior to oocyte retrieval due to poor ovarian response or excessive ovarian response, in the previous cycle(s).
  • Failure to achieve ongoing pregnancy in the previous cycle(s).

Who cannot join

  • Non-compliance to protocol compliance in the previous cycle(s).
  • Having undergone any stimulation with gonadotropins since the end-of-trial / end-of-cycle visit in the previous cycle
  • One or more follicles ≥10 mm observed on the transvaginal ultrasound prior to start of dosing on stimulation day 1
  • Severe OHSS in a previous cycle.
  • Any clinically relevant change to any of the eligibility criteria in the previous cycle(s).
  • Clinically relevant medical history since the previous cycle which precludes gonadotropin stimulation or is associated with a reduced chance of pregnancy.

Trial locations and contacts

13 sites in 11 countries.

13 sites in 11 countries

Canada3 sites

  • Pacific Centre for Reproductive Medicine

    Burnaby, British Columbia

  • Ottawa Fertility Centre

    Ottawa, Ontario

  • Olive Fertility Centre

    Vancouver, British Columbia

Other trials in Canada

Belgium1 site

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

    Brussels

Other trials in Belgium

Brazil1 site

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

    Porto Alegre

Other trials in Brazil

Czechia1 site

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

    Prague

Other trials in Czechia

Denmark1 site

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

    Copenhagen

Other trials in Denmark

France1 site

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

    Lille

Other trials in France

Italy1 site

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

    Milan

Other trials in Italy

Poland1 site

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

    Warsaw

Other trials in Poland

Russia1 site

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

    Moscow

Other trials in Russia

Spain1 site

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

    Seville

Other trials in Spain

United Kingdom1 site

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

    Glasgow

Other trials in United Kingdom

About this study

Official title: A Controlled, Assessor-blind, Parallel Groups, Multicentre, Multinational Trial Evaluating the Immunogenicity of FE 999049 in Repeated Cycles of Controlled Ovarian Stimulation in Women Undergoing an Assisted Reproductive Technology Programme

This trial investigates the immunogenicity of FE 999049 in repeated cycles.

Conditions
Infertility
Being tested
Follitropin Delta (FE 999049), Follitropin Alfa (GONAL-F)
Medical subject headings
Infertility

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Follitropin Delta (FE 999049)Drug

  • Follitropin Alfa (GONAL-F)Drug

Study groups in NCT01956123
Study groupRoleWhat they receive
AExperimentalFollitropin Delta (FE 999049) (COS cycle 2)
Receives: Drug: Follitropin Delta (FE 999049)
BActive comparatorFollitropin Alfa (GONAL-F) (COS cycle 2)
Receives: Drug: Follitropin Alfa (GONAL-F)
CExperimentalFollitropin Delta (FE 999049) (COS cycle 3)
Receives: Drug: Follitropin Delta (FE 999049)
DActive comparatorFollitropin Alfa (GONAL-F) (COS cycle 3)
Receives: Drug: Follitropin Alfa (GONAL-F)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Proportion (Percentage) of Subjects With Treatment-induced Anti-Follicle-Stimulating Hormone (FSH) Antibodies After up to Two Repeated Controlled Ovarian Stimulation Cycles

    The proportion (percentage) of participants with at least one treatment-induced anti-FSH antibody response at any time point is presented. The cumulative incidences in COS cycle 2 and COS cycle 3 divided by participants in COS cycle 2 are presented. Participants with observations in both cycles are only counted once.

    Measured: 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

Secondary outcomes (11)

  1. Proportion (Percentage) of Subjects With Treatment-induced Anti-FSH Antibodies With Neutralising Capacity After up to Two Repeated Controlled Ovarian Stimulation Cycles

    The proportion (percentage) of participants with treatment-induced anti-FSH antibodies with neutralising capacity at any time point is presented. The cumulative incidences in COS cycle 2 and COS cycle 3 divided by participants in COS cycle 2 are presented. Participants with observations in both cycles are only counted once.

    Measured: 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

  2. Proportion (Percentage) of Subjects With Treatment-induced Anti-FSH Antibodies, Overall as Well as With Neutralising Capacity, After One and After Two Repeated Controlled Ovarian Stimulation Cycles

    The proportion (percentage) of participants with treatment-induced anti-FSH antibodies, overall as well as with neutralising capacity, after one and after two repeated COS cycles is presented.

    Measured: 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

  3. Proportion (Percentage) of Subjects With Early Ovarian Hyperstimulation Syndrome (OHSS) (Including OHSS of Moderate/Severe Grade) and/or Preventive Interventions for Early OHSS for Each Controlled Ovarian Stimulation Cycle

    The proportion (percentage) of participants 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.

    Measured: ≤9 days after triggering of final follicular maturation.

  4. Proportion (Percentage) of Subject With Cycle Cancellation Due to Poor Ovarian Response or Excessive Ovarian Response for Each Controlled Ovarian Stimulation Cycle

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

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

  5. Vital Pregnancy Rate for Each Controlled Ovarian Stimulation Cycle

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

    Measured: 5-6 weeks after blastocyst transfer

  6. Implantation Rate for Each Controlled Ovarian Stimulation Cycle

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

    Measured: 5-6 weeks after blastocyst transfer

  7. Ongoing Pregnancy Rate for Each Controlled Ovarian Stimulation Cycle

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

    Measured: 10-11 weeks after blastocyst transfer

  8. Ongoing Implantation Rate for Each Controlled Ovarian Stimulation Cycle

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

    Measured: 10-11 weeks after blastocyst transfer

  9. Frequency of Injection Site Reactions (Redness, Pain, Itching, Swelling and Bruising) Assessed by the Subject During the Stimulation Period for Each Controlled Ovarian Stimulation Cycle

    Participants 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 assessment performed is presented.

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

  10. Proportion (Percentage) of Subjects With Late OHSS (Including OHSS of Moderate/Severe Grade) for Each Controlled Ovarian Stimulation Cycle

    Late OHSS was defined as OHSS with onset >9 days after triggering of final follicular maturation.

    Measured: >9 days after triggering of final follicular maturation

  11. Technical Malfunctions of the Administration Pen for Each Controlled Ovarian Stimulation Cycle

    Incidences of confirmed technical malfunction of administration pen are presented.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Oct 2013 (estimated)
  2. Study start26 Mar 2014
  3. Primary completionMay 2015
  4. Study completion3 Jan 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
513 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01956123
Sponsor's protocol ID
000071
Other IDs
2013-001616-30, U1111-1147-6922
Acronym
ESTHER-2
Status last verified
Aug 2018
First submitted
16 Aug 2013
Last updated
6 Sep 2023
Data monitoring committee
No

Publications

  • 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

  • Fernandez-Sanchez M, Fatemi H, Garcia-Velasco JA, Heiser PW, Daftary GS, Mannaerts B. Incidence and severity of ovarian hyperstimulation syndrome (OHSS) in high responders after gonadotropin-releasing hormone (GnRH) agonist trigger in "freeze-all" approach. Gynecol Endocrinol. 2023 Dec;39(1):2205952. doi: 10.1080/09513590.2023.2205952.

    PubMed 37156263

  • 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

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Follitropin Delta (FE 999049) and Follitropin Alfa (GONAL-F) in people with Infertility, run by Ferring Pharmaceuticals at 13 sites in 11 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites in Canada, Belgium, Brazil, Czechia, Denmark and 6 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 21 Sep 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Proportion (Percentage) of Subjects With Treatment-induced Anti-Follicle-Stimulating Hormone (FSH) Antibodies After up to Two Repeated Controlled Ovarian Stimulation Cycles (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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01956123, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Sep 2023.

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