Clinical trial NCT01956123: Evidence-based Stimulation Trial With Human rFSH in Europe and Rest of World 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Infertility
Lead sponsor: Ferring Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2013-10-08
Enrollment: 513
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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.

Primary outcomes:
measure: Proportion (Percentage) of Subjects With Treatment-induced Anti-Follicle-Stimulating Hormone (FSH) Antibodies After up to Two Repeated Controlled Ovarian Stimulation Cycles
timeFrame: 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:
measure: Proportion (Percentage) of Subjects With Treatment-induced Anti-FSH Antibodies With Neutralising Capacity After up to Two Repeated Controlled Ovarian Stimulation Cycles
timeFrame: 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
measure: 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
timeFrame: 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
measure: 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
timeFrame: ≤9 days after triggering of final follicular maturation.
measure: Proportion (Percentage) of Subject With Cycle Cancellation Due to Poor Ovarian Response or Excessive Ovarian Response for Each Controlled Ovarian Stimulation Cycle
timeFrame: End-of-stimulation (up to 20 stimulation days)
measure: Vital Pregnancy Rate for Each Controlled Ovarian Stimulation Cycle
timeFrame: 5-6 weeks after blastocyst transfer
measure: Implantation Rate for Each Controlled Ovarian Stimulation Cycle
timeFrame: 5-6 weeks after blastocyst transfer
measure: Ongoing Pregnancy Rate for Each Controlled Ovarian Stimulation Cycle
timeFrame: 10-11 weeks after blastocyst transfer
measure: Ongoing Implantation Rate for Each Controlled Ovarian Stimulation Cycle
timeFrame: 10-11 weeks after blastocyst transfer
measure: 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
timeFrame: End-of-stimulation (up to 20 stimulation days)
measure: Proportion (Percentage) of Subjects With Late OHSS (Including OHSS of Moderate/Severe Grade) for Each Controlled Ovarian Stimulation Cycle
timeFrame: >9 days after triggering of final follicular maturation
measure: Technical Malfunctions of the Administration Pen for Each Controlled Ovarian Stimulation Cycle
timeFrame: End-of-stimulation (up to 20 stimulation days)
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: UZ Brussel (there may be other sites in this country)
city: Porto Alegre
country: Brazil
facility: Fertilitat and PUC-RS (there may be other sites in this country)
city: Burnaby
country: Canada
facility: Pacific Centre for Reproductive Medicine
state: British Columbia
city: Vancouver
country: Canada
facility: Olive Fertility Centre
state: British Columbia
city: Ottawa
country: Canada
facility: Ottawa Fertility Centre
state: Ontario
city: Prague
country: Czechia
facility: IVF CUBE SE (there may be other sites in this country)
city: Copenhagen
country: Denmark
facility: Rigshospitalet Fertilitetsklinikken (there may be other sites in this country)
city: Lille
country: France
facility: Department of Endocrine Gynaecology and Reproductive Medicine, Hôpital Jeanne de Flandre (there may be other sites in this country)
city: Milano
country: Italy
facility: Centro Natalità San Raffaele (there may be other sites in this country)
city: Warszawa
country: Poland
facility: The nOvum Clinic (there may be other sites in this country)
city: Moscow
country: Russian Federation
facility: IVF & Reproductive Genetics Center (there may be other sites in this country)
city: Sevilla
country: Spain
facility: IVI Sevilla (there may be other sites in this country)
city: Glasgow
country: United Kingdom
facility: Glasgow Centre for Reproductive Medicine Ltd. (there may be other sites in this country)
Study officials:
affiliation: Ferring Pharmaceuticals
name: Clinical Development Support
role: STUDY_DIRECTOR
References:
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 Oct;38(10):2651-2661. doi: 10.1007/s10815-021-02271-5. Epub 2021 Jul 13.
citation: 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.
citation: 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.