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

Phase 3
Completed
Conditions
Infertility
Interventions
Registration Number
NCT01956123
Lead Sponsor
Ferring Pharmaceuticals
Brief Summary

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

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
513
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
CFollitropin Delta (FE 999049)Follitropin Delta (FE 999049) (COS cycle 3)
DFollitropin Alfa (GONAL-F)Follitropin Alfa (GONAL-F) (COS cycle 3)
BFollitropin Alfa (GONAL-F)Follitropin Alfa (GONAL-F) (COS cycle 2)
AFollitropin Delta (FE 999049)Follitropin Delta (FE 999049) (COS cycle 2)
Primary Outcome Measures
NameTimeMethod
Proportion (Percentage) of Subjects With Treatment-induced Anti-Follicle-Stimulating Hormone (FSH) Antibodies After up to Two Repeated Controlled Ovarian Stimulation CyclesStimulation 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.

Secondary Outcome Measures
NameTimeMethod
Ongoing Pregnancy Rate for Each Controlled Ovarian Stimulation Cycle10-11 weeks after blastocyst transfer

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

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

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

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 CyclesStimulation 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.

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≤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.

Vital Pregnancy Rate for Each Controlled Ovarian Stimulation Cycle5-6 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.

Implantation Rate for Each Controlled Ovarian Stimulation Cycle5-6 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.

Ongoing Implantation Rate for Each Controlled Ovarian Stimulation Cycle10-11 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.

Proportion (Percentage) of Subjects With Late OHSS (Including OHSS of Moderate/Severe Grade) for Each Controlled Ovarian Stimulation Cycle>9 days after triggering of final follicular maturation

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

Technical Malfunctions of the Administration Pen for Each Controlled Ovarian Stimulation CycleEnd-of-stimulation (up to 20 stimulation days)

Incidences of confirmed technical malfunction of administration pen are presented.

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

Trial Locations

Locations (13)

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

🇮🇹

Milano, Italy

Pacific Centre for Reproductive Medicine

🇨🇦

Burnaby, British Columbia, Canada

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

🇨🇿

Prague, Czechia

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

🇵🇱

Warszawa, Poland

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

🇪🇸

Sevilla, Spain

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

🇧🇷

Porto Alegre, Brazil

Ottawa Fertility Centre

🇨🇦

Ottawa, Ontario, Canada

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

🇫🇷

Lille, France

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

🇩🇰

Copenhagen, Denmark

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

🇬🇧

Glasgow, United Kingdom

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

🇧🇪

Brussels, Belgium

Olive Fertility Centre

🇨🇦

Vancouver, British Columbia, Canada

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

🇷🇺

Moscow, Russian Federation

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