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

August 9, 2023 updated by: Ferring Pharmaceuticals

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

513

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

Description

Inclusion Criteria:

  • 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).

Exclusion Criteria:

  • 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.

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: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: A
Follitropin Delta (FE 999049) (COS cycle 2)
Drug: Follitropin Delta (FE 999049)
Active Comparator: B
Follitropin Alfa (GONAL-F) (COS cycle 2)
Drug: Follitropin Alfa (GONAL-F)
Experimental: C
Follitropin Delta (FE 999049) (COS cycle 3)
Drug: Follitropin Delta (FE 999049)
Active Comparator: D
Follitropin Alfa (GONAL-F) (COS cycle 3)
Drug: Follitropin Alfa (GONAL-F)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
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.
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Vital Pregnancy Rate for Each Controlled Ovarian Stimulation Cycle
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 for Each Controlled Ovarian Stimulation Cycle
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
Ongoing Pregnancy Rate for Each Controlled Ovarian Stimulation Cycle
Time Frame: 10-11 weeks after blastocyst transfer
Ongoing pregnancy rate was defined as at least one intrauterine viable fetus 10-11 weeks after blastocyst transfer.
10-11 weeks after blastocyst transfer
Ongoing Implantation Rate for Each Controlled Ovarian Stimulation Cycle
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
Proportion (Percentage) of Subjects With Late OHSS (Including OHSS of Moderate/Severe Grade) for Each Controlled Ovarian Stimulation Cycle
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.
>9 days after triggering of final follicular maturation
Technical Malfunctions of the Administration Pen for Each Controlled Ovarian Stimulation Cycle
Time Frame: End-of-stimulation (up to 20 stimulation days)
Incidences of confirmed technical malfunction of administration pen are presented.
End-of-stimulation (up to 20 stimulation days)
Proportion (Percentage) of Subjects With Treatment-induced Anti-FSH Antibodies With Neutralising Capacity 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
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.
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 (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
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 (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.
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 (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
Time Frame: ≤9 days after triggering of final follicular maturation.
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.
≤9 days after triggering of final follicular maturation.
Proportion (Percentage) of Subject With Cycle Cancellation Due to Poor Ovarian Response or Excessive Ovarian Response for Each Controlled Ovarian Stimulation Cycle
Time Frame: End-of-stimulation (up to 20 stimulation days)
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.
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 for Each Controlled Ovarian Stimulation Cycle
Time Frame: End-of-stimulation (up to 20 stimulation days)
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.
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

Investigators

  • Study Director: Clinical Development Support, 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 (Actual)

March 26, 2014

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 1, 2013

First Posted (Estimated)

October 8, 2013

Study Record Updates

Last Update Posted (Actual)

September 6, 2023

Last Update Submitted That Met QC Criteria

August 9, 2023

Last Verified

August 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 000071
  • 2013-001616-30 (EudraCT Number)
  • U1111-1147-6922 (Other Identifier: 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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