NCT03564509

Completed

Phase 2

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

Ferring Pharmaceuticals20 sites in 5 countries620 target enrollmentMay 14, 2018

ConditionsControlled Ovarian Stimulation

InterventionsFE 999302 (1 μg) and follitropin delta FE 999302 (2 μg) and follitropin delta FE 999302 (4 μg) and follitropin delta FE 999302 (8 μg) and follitropin delta FE 999302 (12 μg) and follitropin delta Placebo and follitropin delta

DrugsFE 999302 (1 μg) and follitropin delta FE 999302 (2 μg) and follitropin delta FE 999302 (4 μg) and follitropin delta FE 999302 (8 μg) and follitropin delta FE 999302 (12 μg) and follitropin delta

Overview

Phase: Phase 2
Intervention: FE 999302 (1 μg) and follitropin delta
Conditions: Controlled Ovarian Stimulation
Sponsor: Ferring Pharmaceuticals
Enrollment: 620
Locations: 20
Primary Endpoint: Number of good-quality blastocysts on Day 5 after oocyte retrieval
Status: Completed
Last Updated: 2 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

May 14, 2018

End Date

January 8, 2020

Last Updated

2 years ago

Study Type

Interventional

Study Design

Parallel

Sex

Female

Investigators

Sponsor

Ferring Pharmaceuticals

Responsible Party

Sponsor

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.

Arms & Interventions

FE 999302 (1 μg) and follitropin delta

Intervention: FE 999302 (1 μg) and follitropin delta

FE 999302 (2 μg) and follitropin delta

Intervention: FE 999302 (2 μg) and follitropin delta

FE 999302 (4 μg) and follitropin delta

Intervention: FE 999302 (4 μg) and follitropin delta

FE 999302 (8 μg) and follitropin delta

Intervention: FE 999302 (8 μg) and follitropin delta

FE 999302 (12 μg) and follitropin delta

Intervention: FE 999302 (12 μg) and follitropin delta

Placebo and follitropin delta

Intervention: Placebo and follitropin delta

Outcomes

Primary Outcomes

Number of good-quality blastocysts on Day 5 after oocyte retrieval

Time Frame: On Day 5 after oocyte retrieval

Quality of blastocysts was assessed by blastocyst expansion and hatching status, blastocyst inner cell mass grading, and trophectoderm grading. The scoring was based on the classification system by Gardner and Schoolcraft, with additional categories for inner cell mass (degenerative or no inner cell mass) and trophectoderm (degenerative or very large cell).

Secondary Outcomes

Total number of stimulation days(At end-of-stimulation (up to 20 stimulation days))
Clinical pregnancy rate(5-6 weeks after blastocyst transfer)
Number of fertilised 2 pronuclei (2PN) oocytes(On day 1 after insemination)
Number and size of follicles on stimulation Day 6(On stimulation Day 6)
Total gonadotropin dose(At end-of-stimulation (up to 20 stimulation days))
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(Immediately after injection of FE 999302 or placebo, 30 minutes after injection, and 24 hours after injection)
Incidence of biochemical pregnancy(Up to 5 to 6 weeks after transfer)
Number and quality of blastocysts on Day 5 after oocyte retrieval(On Day 5 after oocyte retrieval)
Changes in serum hormone levels(Stimulation Day 1 (baseline), stimulation Day 6, stimulation Day 8, end-of-stimulation (up to 20 stimulation days), and oocyte retrieval)
Number and size of follicles at end-of-stimulation(At end-of-stimulation (up to 20 stimulation days))
Number of oocytes retrieved(On the day of oocyte retrieval)
Incidence and intensity of adverse events (AEs)(From screening to end-of-trial (estimated maximum of 4 months from start of stimulation))
Incidence of multi-fetal gestation(5 to 6 weeks after transfer)
Incidence of ectopic pregnancy (with and without medical/surgical intervention)(Up to 5 to 6 weeks after transfer)
Positive beta human chorionic gonadotropin (βhCG) rate(13-15 days after blastocyst transfer)
Incidence of cycle cancellation(At end-of-stimulation (up to 20 stimulation days))
Changes in circulating levels of clinical chemistry and haematology parameters(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))
Incidence of spontaneous abortion (with and without medical/surgical intervention)(Up to 10 to 11 weeks after transfer)
Incidence of vanishing twins(Up to 10 to 11 weeks after transfer)
Incidence of treatment-induced anti-FE 999302 antibodies, overall as well as with neutralising capacity(On stimulation Day 1, end-of-stimulation (up to 20 stimulation days), 19-28 days after the last FE999302 or placebo dose)
Number of subjects with at least one good-quality blastocyst on Day 5 after oocyte retrieval(On Day 5 after oocyte retrieval)
Number of subjects with at least two good-quality blastocysts on Day 5 after oocyte retrieval(On Day 5 after oocyte retrieval)
Number and quality of embryos on Day 3 after oocyte retrieval(On Day 3 after oocyte retrieval)
Vital pregnancy rate(5-6 weeks after blastocyst transfer)
Ongoing pregnancy rate(10-11 weeks after blastocyst transfer)
Number of metaphase II oocytes(On the day of oocyte retrieval)
Serum concentrations of FE 999302(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))
Incidence of ovarian hyperstimulation syndrome (OHSS) (early or late, any grade)(From stimulation Day 1 to end-of-trial (estimated maximum of 4 months from start of stimulation))