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Completed

NCT Number: 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.

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.

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Key information

Conditions

Controlled Ovarian Stimulation

Age range

30 year–42 year

Sex eligibility

Female

Study type

Interventional

Phase

Phase 2

Primary location

Universitair Ziekenhuis Gent (UZ Gent), Ghent, Belgium

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

FE 999302 (1 μg) and follitropin delta

Drug

Daily dose of 1 μg of FE 999302, a recombinant human chorionic gonadotropin (rhCG) solution for subcutaneous injection; individualized follitropin delta dose.

Other names: Choriogonadotropin beta

FE 999302 (2 μg) and follitropin delta

Drug

Daily dose of 2 μg of FE 999302, a rhCG solution for subcutaneous injection; individualized follitropin delta dose.

Other names: Choriogonadotropin beta

FE 999302 (4 μg) and follitropin delta

Drug

Daily dose of 4 μg of FE 999302, a rhCG solution for subcutaneous injection; individualized follitropin delta dose.

Other names: Choriogonadotropin beta

FE 999302 (8 μg) and follitropin delta

Drug

Daily dose of 8 μg of FE 999302, a rhCG solution for subcutaneous injection; individualized follitropin delta dose.

Other names: Choriogonadotropin beta

FE 999302 (12 μg) and follitropin delta

Drug

Daily dose of 12 μg of FE 999302, a rhCG solution for subcutaneous injection; individualized follitropin delta dose.

Other names: Choriogonadotropin beta

Placebo and follitropin delta

Other

Daily dose of placebo; individualized follitropin delta dose.

Primary outcomes

  1. 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

  1. Number of subjects with at least one good-quality blastocyst 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).

  2. Number of subjects with at least two 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).

  3. Number and quality of embryos on Day 3 after oocyte retrieval

    Time frame: On Day 3 after oocyte retrieval

    Embryo quality was assessed by cleavage stage and embryo morphology parameters. The total number of embryos and the number of embryos per quality category were reported.

  4. Number and quality of blastocysts on Day 5 after oocyte retrieval

    Time frame: On Day 5 after oocyte retrieval

    Blastocyst quality 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 cells).

    The total number of blastocysts and the number of blastocysts per quality category will be reported.

  5. Changes in serum hormone levels

    Time frame: Stimulation Day 1 (baseline), stimulation Day 6, stimulation Day 8, end-of-stimulation (up to 20 stimulation days), and oocyte retrieval

    Blood samples for analysis of hormone concentrations were drawn at stimulation Day 1, stimulation Day 6, stimulation Day 8, last day of stimulation, and at oocyte retrieval.

  6. Number and size of follicles on stimulation Day 6

    Time frame: On stimulation Day 6

    Number and size of follicles assessed using transvaginal ultrasound. The total number of follicles and the number of follicles per size category were reported.

  7. Number and size of follicles at end-of-stimulation

    Time frame: At end-of-stimulation (up to 20 stimulation days)

    Number and size of follicles assessed using transvaginal ultrasound. The total number of follicles and the number of follicles per size category were reported.

  8. Positive beta human chorionic gonadotropin (βhCG) rate

    Time frame: 13-15 days after blastocyst transfer

    Proportion of patients with positive blood βhCG confirmed by a blood test.

  9. Clinical pregnancy rate

    Time frame: 5-6 weeks after blastocyst transfer

    Clinical pregnancy was defined as at least one gestational sac, either intrauterine or ectopic.

  10. Vital pregnancy rate

    Time frame: 5-6 weeks after blastocyst transfer

    Vital pregnancy was defined as at least one intrauterine gestational sac with fetal heart beat, as assessed by transvaginal ultrasound.

  11. Ongoing pregnancy rate

    Time frame: 10-11 weeks after blastocyst transfer

    Ongoing pregnancy was defined as at least one intrauterine viable fetus, assessed using transvaginal or abdominal ultrasound.

  12. Number of oocytes retrieved

    Time frame: On the day of oocyte retrieval

  13. Number of metaphase II oocytes

    Time frame: On the day of oocyte retrieval

  14. Number of fertilised 2 pronuclei (2PN) oocytes

    Time frame: On day 1 after insemination

  15. Total gonadotropin dose

    Time frame: At end-of-stimulation (up to 20 stimulation days)

    The daily dose of FE 999302 or placebo, and follitropin delta were recorded.

  16. Total number of stimulation days

    Time frame: At end-of-stimulation (up to 20 stimulation days)

    The start and end dates of administration of FE 999302 or placebo, and follitropin delta were recorded.

  17. Incidence of cycle cancellation

    Time frame: At end-of-stimulation (up to 20 stimulation days)

    Cycle cancellation due to poor ovarian response or excessive ovarian response.

  18. Serum concentrations of FE 999302

    Time frame: 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)

  19. Incidence of ovarian hyperstimulation syndrome (OHSS) (early or late, any grade)

    Time frame: From stimulation Day 1 to end-of-trial (estimated maximum of 4 months from start of stimulation)

    Early OHSS was defined as OHSS with onset less than equal to 9 days after triggering of final follicular maturation.

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

    All OHSS cases were graded as mild, moderate or severe.

  20. Incidence and intensity of adverse events (AEs)

    Time frame: From screening to end-of-trial (estimated maximum of 4 months from start of stimulation)

  21. Changes in circulating levels of clinical chemistry and haematology parameters

    Time frame: 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)

  22. 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

    Time frame: Immediately after injection of FE 999302 or placebo, 30 minutes after injection, and 24 hours after injection

  23. Incidence of treatment-induced anti-FE 999302 antibodies, overall as well as with neutralising capacity

    Time frame: On stimulation Day 1, end-of-stimulation (up to 20 stimulation days), 19-28 days after the last FE999302 or placebo dose

    The proportion of subjects with treatment-induced anti-FE999302 antibodies as well as the proportion of subjects with treatment-induced anti-FE999302 antibodies with neutralizing capacity were reported.

  24. Incidence of multi-fetal gestation

    Time frame: 5 to 6 weeks after transfer

  25. Incidence of biochemical pregnancy

    Time frame: Up to 5 to 6 weeks after transfer

    Biochemical pregnancy was defined as positive βhCG test but no gestational sac was observed on transvaginal ultrasound conducted later, or menstruation is

    was reported.

  26. Incidence of spontaneous abortion (with and without medical/surgical intervention)

    Time frame: Up to 10 to 11 weeks after transfer

    Spontaneous abortion was defined as positive βhCG test but all intrauterine gestational sacs without fetal heart beat as documented by ultrasound, or there were no viable fetuses observed by ultrasound.

  27. Incidence of ectopic pregnancy (with and without medical/surgical intervention)

    Time frame: Up to 5 to 6 weeks after transfer

    Ectopic pregnancy was defined as extrauterine gestational sac with or without fetal heart beat as documented by ultrasound or surgery.

  28. Incidence of vanishing twins

    Time frame: Up to 10 to 11 weeks after transfer

    Vanishing twin was defined as spontaneous disappearance of an intrauterine gestational sac with or without heart beat in a pregnancy where one viable fetus remained as documented by ultrasound.

Sponsors and collaborators

Lead sponsor

Ferring Pharmaceuticals

Industry

Registry information

Official study 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

Acronym: RAINBOW

Important dates

Study start
2018
Primary completion
2019
Study completion
2020
First posted
Jun 21, 2018
Registry last updated
Aug 31, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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