Clinical trial NCT03564509: A Trial to Investigate the Efficacy and Safety of FE 999302 as add-on Treatment to Follitropin Delta (REKOVELLE) in Women Undergoing Controlled Ovarian Stimulation.
Official title: A Randomised, Double-blind, Placebo-controlled, Parallel-group, Dose-range Trial to Investigate the Efficacy and Safety of FE 999302 as add-on Treatment to Follitropin Delta (REKOVELLE) in Women Undergoing Controlled Ovarian Stimulation in a Long GnRH Agonist Protocol
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Controlled Ovarian Stimulation
Keywords: Human Chorionic Gonadotropin (hCG)
Recombinant Human Chorionic Gonadotropin (rhCG)
Controlled Ovarian Stimulation (COS)
Assisted Reproductive Technologies (ART)
Lead sponsor: Ferring Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2018-06-21
Enrollment: 620
Sex: FEMALE
Minimum age (years): 30
Maximum age (years): 42
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this phase 2 dose-ranging trial is to investigate the effects of FE 999302 on parameters influencing pregnancy rates in women undergoing Controlled Ovarian Stimulation (COS) with follitropin delta in a long gonadotropin releasing hormone (GnRH) agonist protocol.

Furthermore, the study intends:

* To investigate the safety of FE 999302 in women undergoing COS with follitropin delta in a long GnRH agonist protocol.
* To investigate the potential immunogenicity of FE 999302 in subjects undergoing COS with follitropin delta in a long GnRH agonist protocol.
* To estimate the impact of body weight on FE 999302 exposure in subjects undergoing COS with follitropin delta in a long GnRH agonist protocol.


Eligibility criteria: Inclusion Criteria:

* Informed consent documents signed prior to screening evaluations.
* In good physical and mental health as judged by the investigator.
* Anti-Müllerian hormone (AMH) levels at screening of 5.0-35.0 pmol/L (as measured by Elecsys® AMH Plus Immunoassay \[Roche Diagnostics\] at central laboratory).
* Pre-menopausal women between the ages of 30 and 42 years. The subjects must be at least 30 years (including the 30th birthday) and no more than 42 years (up to the day before the 43rd birthday) when they sign the informed consent.
* Infertile women diagnosed with tubal infertility, unexplained infertility, endometriosis stage I/II or with partners diagnosed with male factor infertility, eligible for in vitro fertilisation and/or intracytoplasmic sperm injection using fresh or frozen ejaculated sperm from male partner or sperm donor.
* Infertility for at least 1 year before screening for subjects less than 35 years or for at least 6 months for subjects greater than equal to (≥)35 years (not applicable in case of tubal or severe male factor infertility).

Exclusion Criteria:

* Known polycystic ovary syndrome (PCOS) associated with anovulation or known endometriosis stage III-IV (defined by the revised American Society for Reproductive Medicine \[ASRM\] classification, 1996).
* One or more follicles ≥10 mm (including cysts) observed on the transvaginal ultrasound after down-regulation prior to randomisation on stimulation day 1 (puncture of cysts is allowed prior to randomisation).
* Pregnancy (negative pregnancy tests must be documented at screening and prior to start of down-regulation) or contraindication to pregnancy.

Primary outcomes:
measure: Number of good-quality blastocysts on Day 5 after oocyte retrieval
timeFrame: On Day 5 after oocyte retrieval
Secondary outcomes:
measure: Number of subjects with at least one good-quality blastocyst on Day 5 after oocyte retrieval
timeFrame: On Day 5 after oocyte retrieval
measure: Number of subjects with at least two good-quality blastocysts on Day 5 after oocyte retrieval
timeFrame: On Day 5 after oocyte retrieval
measure: Number and quality of embryos on Day 3 after oocyte retrieval
timeFrame: On Day 3 after oocyte retrieval
measure: Number and quality of blastocysts on Day 5 after oocyte retrieval
timeFrame: On Day 5 after oocyte retrieval
measure: Changes in serum hormone levels
timeFrame: Stimulation Day 1 (baseline), stimulation Day 6, stimulation Day 8, end-of-stimulation (up to 20 stimulation days), and oocyte retrieval
measure: Number and size of follicles on stimulation Day 6
timeFrame: On stimulation Day 6
measure: Number and size of follicles at end-of-stimulation
timeFrame: At end-of-stimulation (up to 20 stimulation days)
measure: Positive beta human chorionic gonadotropin (βhCG) rate
timeFrame: 13-15 days after blastocyst transfer
measure: Clinical pregnancy rate
timeFrame: 5-6 weeks after blastocyst transfer
measure: Vital pregnancy rate
timeFrame: 5-6 weeks after blastocyst transfer
measure: Ongoing pregnancy rate
timeFrame: 10-11 weeks after blastocyst transfer
measure: Number of oocytes retrieved
timeFrame: On the day of oocyte retrieval
measure: Number of metaphase II oocytes
timeFrame: On the day of oocyte retrieval
measure: Number of fertilised 2 pronuclei (2PN) oocytes
timeFrame: On day 1 after insemination
measure: Total gonadotropin dose
timeFrame: At end-of-stimulation (up to 20 stimulation days)
measure: Total number of stimulation days
timeFrame: At end-of-stimulation (up to 20 stimulation days)
measure: Incidence of cycle cancellation
timeFrame: At end-of-stimulation (up to 20 stimulation days)
measure: Serum concentrations of FE 999302
timeFrame: On stimulation Day 1 (prior to first dose of FE 999302 or placebo), stimulation Day 6, stimulation Day 8, end-of-stimulation (up to 20 stimulation days)
measure: Incidence of ovarian hyperstimulation syndrome (OHSS) (early or late, any grade)
timeFrame: From stimulation Day 1 to end-of-trial (estimated maximum of 4 months from start of stimulation)
measure: Incidence and intensity of adverse events (AEs)
timeFrame: From screening to end-of-trial (estimated maximum of 4 months from start of stimulation)
measure: Changes in circulating levels of clinical chemistry and haematology parameters
timeFrame: At screening, on stimulation Day 1, end-of-stimulation (up to 20 stimulation days), end-of-trial (estimated maximum of 4 months from start of stimulation)
measure: Incidence and intensity of injection site reactions after FE 999302 administration (redness, pain, itching, swelling and bruising) assessed by the subject during the stimulation period
timeFrame: Immediately after injection of FE 999302 or placebo, 30 minutes after injection, and 24 hours after injection
measure: Incidence of treatment-induced anti-FE 999302 antibodies, overall as well as with neutralising capacity
timeFrame: On stimulation Day 1, end-of-stimulation (up to 20 stimulation days), 19-28 days after the last FE999302 or placebo dose
measure: Incidence of multi-fetal gestation
timeFrame: 5 to 6 weeks after transfer
measure: Incidence of biochemical pregnancy
timeFrame: Up to 5 to 6 weeks after transfer
measure: Incidence of spontaneous abortion (with and without medical/surgical intervention)
timeFrame: Up to 10 to 11 weeks after transfer
measure: Incidence of ectopic pregnancy (with and without medical/surgical intervention)
timeFrame: Up to 5 to 6 weeks after transfer
measure: Incidence of vanishing twins
timeFrame: Up to 10 to 11 weeks after transfer
Other outcomes:
Locations:
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent (UZ Gent)
city: Jette
country: Belgium
facility: Universitair Ziekenhuis Brussel
city: Karlovy Vary
country: Czechia
facility: Institut fur Reproduktionsmedizin und Genetik
city: Olomouc
country: Czechia
facility: Fertimed
city: Praha
country: Czechia
facility: GYNEM
city: Praha
country: Czechia
facility: IVF CUBE
city: Aalborg
country: Denmark
facility: Aalborg University Hospital
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Frederiksberg
country: Denmark
facility: Dansk Fertilitetsklinik
city: Hvidovre
country: Denmark
facility: Hvidovre Hospital
city: Barcelona
country: Spain
facility: Dexeus Woman's Health
city: Leioa
country: Spain
facility: Instituto Valenciano de Infertilidad (IVI) - Bilbao
city: Madrid
country: Spain
facility: GINEFIV - Clinica Belen Location
city: Madrid
country: Spain
facility: Instituto Valenciano de Infertilidad (IVI) - Madrid
city: Sevilla
country: Spain
facility: Instituto Valenciano de Infertilidad (IVI) - Sevilla
city: Valencia
country: Spain
facility: Instituto Valenciano de Infertilidad (IVI) - Valencia
city: Glasgow
country: United Kingdom
facility: Glasgow Royal Infirmary
city: Liverpool
country: United Kingdom
facility: Liverpool Women's Hospital
city: London
country: United Kingdom
facility: Guy's and St Thomas' NHS Trust
city: London
country: United Kingdom
facility: Kings College (Assisted Conception Unit)
Study officials:
affiliation: Ferring Pharmaceuticals
name: Global Clinical Compliance
role: STUDY_DIRECTOR
References:
citation: Sanchez MF, Larsson P, Serrano MF, Bosch E, Velasco JAG, Lopez ES, Mannaerts B. Live birth rates following individualized dosing algorithm of follitropin delta in a long GnRH agonist protocol. Reprod Biol Endocrinol. 2023 May 16;21(1):45. doi: 10.1186/s12958-023-01090-w.