Efficacy and Safety of FE 999049 in Controlled Ovarian Stimulation in Japanese Women

NCT ID: NCT03228680

Last Updated: 2023-08-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 373 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-07-29
• Study Completion Date: 2019-07-08

Brief Summary

To demonstrate non-inferiority of FE 999049 compared to FOLLISTIM with respect to number of oocytes retrieved in Japanese IVF/ICSI patients undergoing controlled ovarian stimulation.

Conditions

Infertility

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Follitropin delta

FE 999049 was administered as single daily subcutaneous injections in the abdomen. Participants randomized to FE 999049 had their individual dose determined on the basis of their anti-Müllerian hormone (AMH) level at screening and their body weight at randomization. The daily FE 999049 dose was fixed throughout the stimulation period. The minimum allowed daily FE 999049 dose was 6 μg and maximum allowed daily dose was 12 μg. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.

Group Type: EXPERIMENTAL

Follitropin delta

Intervention Type: DRUG

Single daily subcutaneous administration through pre-filled injection pen

Follitropin beta

FOLLISTIM was administered as single daily subcutaneous injections in the abdomen. The starting dose of FOLLISTIM was 150 IU and fixed for the first five stimulation days, after which it could be adjusted by 75 IU based on the individual response. The maximum allowed daily dose was 375 IU. Dosing continued until the criterion for triggering of final follicular maturation was met. Participants could be treated for a maximum of 20 days.

Group Type: ACTIVE_COMPARATOR

Follitropin beta

Intervention Type: DRUG

Single daily subcutaneous injection in the abdomen

Interventions

Follitropin delta

Single daily subcutaneous administration through pre-filled injection pen

Intervention Type: DRUG

Follitropin beta

Single daily subcutaneous injection in the abdomen

Intervention Type: DRUG

Other Intervention Names

FE 999049; REKOVELLE; FOLLISTIM

Eligibility Criteria

Inclusion Criteria

• Informed Consent Documents signed prior to any trial-related procedures.
• In good physical and mental health.
• Japanese females between the ages of 20 and 40 years.
• Infertile women diagnosed with tubal infertility, unexplained infertility, endometriosis stage I/II (defined by the revised American Society for Reproductive Medicine (ASRM) classification) or with partners diagnosed with male factor infertility, eligible for in vitro fertilization (IVF) and/or intracytoplasmic sperm injection (ICSI) treatment using ejaculated sperm from male partner.
• Infertility for at least 1 year before randomization (not applicable in case of tubal or severe male factor infertility).
• The trial cycle will be the participant's first controlled ovarian stimulation cycle for IVF/ICSI.
• Hysterosalpingography, hysteroscopy, saline infusion sonography or transvaginal ultrasound documenting a uterus consistent with expected normal function (e.g. no evidence of clinically interfering uterine fibroids defined as submucous or intramural fibroids larger than 3 cm in diameter, no polyps and no congenital structural abnormalities which are associated with a reduced chance of pregnancy) within 1 year prior to screening. This also includes women who have been diagnosed with any of the above medical conditions but have had them surgically corrected within 1 year prior to screening.
• Transvaginal ultrasound documenting presence and adequate visualization of both ovaries, without evidence of significant abnormality (e.g. no endometrioma greater than 3 cm or enlarged ovaries which would contraindicate the use of gonadotropins) and fallopian tubes and surrounding tissue without evidence of significant abnormality (e.g. no hydrosalpinx) within 1 year prior to screening. Both ovaries must be accessible for oocyte retrieval.
• Early follicular phase (cycle day 2-4) serum levels of follicle stimulating hormone (FSH) between 1 and 15 IU/L (results obtained within 3 months prior to screening).
• Body mass index (BMI) between 17.5 and 32.0 kg/m^2 (both inclusive) at screening.

Exclusion Criteria

• Known endometriosis stage III-IV (defined by the revised ASRM classification).
• One or more follicles >10 mm (including cysts) observed on the transvaginal ultrasound prior to start of stimulation on stimulation day 1 (puncture of cysts prior randomization is allowed).
• Known history of recurrent miscarriage (defined as three consecutive losses after ultrasound confirmation of pregnancy (excl. ectopic pregnancy) and before week 24 of pregnancy).
• Known abnormal karyotype of participant or of her partner. In case the sperm production is severely impaired (concentration <1 million/mL), normal karyotype, including no Y chromosome microdeletion, must be documented.
• Active arterial or venous thromboembolism or severe thrombophlebitis, or a history of these events.
• Any known clinically significant systemic disease (e.g. insulin-dependent diabetes).
• Any known endocrine or metabolic abnormalities (pituitary, adrenal, pancreas, liver or kidney) which can compromise participation in the trial with the exception of controlled thyroid function disease.
• Known tumours of the ovary, breast, uterus, adrenal gland, pituitary or hypothalamus which would contraindicate the use of gonadotropins.

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Ferring Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Global Clinical Compliance

Role: STUDY_DIRECTOR

Ferring Pharmaceuticals

Locations

Yachiyo Hospital

Anjo, Aichi-ken, Japan

Investigational Site 8121

Chiba, Chiba, Japan

Yokota Maternity Hospital

Maebashi, Gunma, Japan

Sophia Ladies Clinic

Sagamihara, Kanagawa, Japan

Investigational Site 8122

Sendai, Miyagi, Japan

Investigational Site 8123

Higashiōsaka-shi, Osaka, Japan

Investigational Site 8120

Osaka, Osaka, Japan

Ladies Clinic Kitahama

Osaka, Osaka, Japan

Investigational Site 8125

Saitama-shi, Saitama, Japan

Investigational Site 8124

Shinjuku-Ku, Tokyo, Japan

Akita University Hospital

Akita, , Japan

Yamashita Ladies' Clinic

Hyōgo, , Japan

Investigational Site 8126

Saitama, , Japan

Omiya Ladies Clinic

Saitama, , Japan

Saint Women's Clinic

Saitama, , Japan

Women's Clinic Fujimino

Saitama, , Japan

Tokushima University Hospital

Tokushima, , Japan

Countries

Japan

References

Ishihara O, Arce JC; Japanese Follitropin Delta Phase 3 Trial (STORK) Group. Individualized follitropin delta dosing reduces OHSS risk in Japanese IVF/ICSI patients: a randomized controlled trial. Reprod Biomed Online. 2021 May;42(5):909-918. doi: 10.1016/j.rbmo.2021.01.023. Epub 2021 Feb 9.

Reference Type: RESULT

PMID: 33722477 (View on PubMed)

Ishihara O, Nelson SM, Arce JC. Comparison of ovarian response to follitropin delta in Japanese and White IVF/ICSI patients. Reprod Biomed Online. 2022 Jan;44(1):177-184. doi: 10.1016/j.rbmo.2021.09.014. Epub 2021 Sep 23.

Reference Type: RESULT

PMID: 34799275 (View on PubMed)

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.

Reference Type: RESULT

PMID: 37156263 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

000273

Identifier Type: -

Identifier Source: org_study_id