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

Infertility Clinical Trial

— ESTHER-2  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01956123
• Other study ID #: 000071
• Secondary ID: 2013-001616-30U1
• Status: Completed
• Phase: Phase 3
• Start date: March 26, 2014
• Est. completion date: January 3, 2017

Study information

• Verified date: August 2018
• Source: Ferring Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 513
• Est. completion date: January 3, 2017
• Est. primary completion date: May 2015
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 40 Years

Eligibility

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.

Related Conditions & MeSH terms

• Infertility

Intervention

Drug:
• Follitropin Delta (FE 999049)

• Follitropin Alfa (GONAL-F)

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Ferring Pharmaceuticals

Countries where clinical trial is conducted

Belgium,  Brazil,  Canada,  Czechia,  Denmark,  France,  Italy,  Poland,  Russian Federation,  Spain,  United Kingdom, 

References & Publications (2)

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" approac — View Citation

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 Oc — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	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	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.	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	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.	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	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.	=9 days after triggering of final follicular maturation.
Secondary	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.	End-of-stimulation (up to 20 stimulation days)
Secondary	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.	5-6 weeks after blastocyst transfer
Secondary	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.	5-6 weeks after blastocyst transfer
Secondary	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.	10-11 weeks after blastocyst transfer
Secondary	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.	10-11 weeks after blastocyst transfer
Secondary	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.	End-of-stimulation (up to 20 stimulation days)
Secondary	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.	>9 days after triggering of final follicular maturation
Secondary	Technical Malfunctions of the Administration Pen for Each Controlled Ovarian Stimulation Cycle	Incidences of confirmed technical malfunction of administration pen are presented.	End-of-stimulation (up to 20 stimulation days)