Efficacy and Safety of FE 999049 in Controlled Ovarian Stimulation in Pan-Asian Women

NCT03296527 | Completed Phase 3 Results

• 1 other identifier: 000145
• Study Type: interventional
• Target: 1,011
• Locations: 4 countries
• Sites: 26

Brief Summary

To demonstrate non-inferiority of FE 999049 compared with GONAL-F with respect to ongoing pregnancy rate in women undergoing controlled ovarian stimulation.

Conditions

Controlled Ovarian Simulation

Outcome Measures

Primary Outcomes (1)

• Ongoing Pregnancy Rate

  Defined as at least one intrauterine viable fetus 10-11 weeks after transfer.

  10-11 weeks after transfer

Secondary Outcomes (60)

• Positive Beta Unit of Human Chorionic Gonadotropin (βhCG) Rate

  13-15 days after transfer

• Clinical Pregnancy Rate

  5-6 weeks after transfer

• Vital Pregnancy Rate

  5-6 weeks after transfer

• Implantation Rate

  5-6 weeks after transfer

• Ongoing Implantation Rate

  10-11 weeks after transfer

Study Arms (2)

Follitropin delta

EXPERIMENTAL

Recombinant follicle-stimulating hormone (rFSH). Follitropin delta for subcutaneous injection

Drug: Follitropin delta

Gonal-F

ACTIVE COMPARATOR

rFSH. Follitropin alfa for subcutaneous injection

Drug: Follitropin alfa

Interventions

Follitropin alfa DRUG

GONAL-F dose was fixed for the first 5 stimulation days.

Also known as: GONAL-F

Gonal-F

Follitropin delta DRUG

REKOVELLE (FE 999049) was fixed throughout the stimulation period.

Also known as: FE 999049, REKOVELLE

Follitropin delta

Eligibility Criteria

• Age: 20 Years - 40 Years
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Informed Consent Documents signed prior to screening evaluations.
• In good physical and mental health in the judgement of the investigator.
• Asian pre-menopausal females between the ages of 20 and 40 years. The participants must be at least 20 years (including the 20th birthday) when they sign the informed consent and no more than 40 years (up to the day before the 41st birthday) at the time of randomization.
• Infertile women diagnosed with tubal infertility, unexplained infertility, endometriosis stage I/II (defined by the revised American Society for Reproductive Medicine \[ASRM\] classification, 1996) or with partners diagnosed with male factor infertility, eligible for in vitro fertilisation (IVF) and/or intracytoplasmic sperm injection (ICSI) using fresh or frozen ejaculated sperm from male partner or sperm donor.
• Infertility for at least one year before randomization for participants \<35 years or for at least 6 months for participants ≥35 years (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.
• Regular menstrual cycles of 24-35 days (both inclusive), presumed to be ovulatory.
• 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 randomization.
• Transvaginal ultrasound documenting presence and adequate visualisation of both ovaries, without evidence of significant abnormality (e.g. enlarged ovaries which would contraindicate the use of gonadotropins) and normal adnexa (e.g. no hydrosalpinx) within 1 year prior to randomization. Both ovaries must be accessible for oocyte retrieval.
• Early follicular phase (cycle day 2-4) serum levels of FSH between 1 and 15 IU/L (results obtained within 3 months prior to randomization).
• Negative serum Hepatitis B Surface Antigen (HBsAg), Hepatitis C Virus (HCV) and Human Immunodeficiency Virus (HIV) antibody tests within 2 years prior to randomization.
• Body mass index (BMI) between 17.5 and 32.0 kg/m2 (both inclusive) at screening.
• Willing to accept transfer of 1-2 embryos.

You may not qualify if:

• Known endometriosis stage III-IV (defined by the revised ASRM classification, 1996).
• One or more follicles ≥10 mm (including cysts) observed on the transvaginal ultrasound prior to randomization on stimulation day 1 (puncture of cysts is allowed prior to randomization).
• 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 / sperm donor, as applicable, depending on source of sperm used for insemination in this trial.
• Any known clinically significant systemic disease (e.g. insulin-dependent diabetes).
• Known inherited or acquired thrombophilia disease.
• Active arterial or venous thromboembolism or severe thrombophlebitis, or a history of these events.
• Known porphyria.
• Any known endocrine or metabolic abnormalities (pituitary, adrenal, pancreas, liver or kidney) with the exception of controlled thyroid function disease.
• Known presence of anti-FSH antibodies (based on the information available in the participant's medical records; i.e. not based on the anti-FSH antibody analyses conducted in the trial).
• Known tumours of the ovary, breast, uterus, adrenal gland, pituitary or hypothalamus which would contraindicate the use of gonadotropins.
• Known moderate or severe impairment of renal or hepatic function.
• Any abnormal finding of clinical chemistry, haematology or vital signs at screening which is clinically significant as judged by the investigator.
• Currently breast-feeding.
• Undiagnosed vaginal bleeding.

Sponsors & Collaborators

• Ferring Pharmaceuticals: lead

Study Sites (26)

Beijing Obstetrics and Gynecology Hospital,Capital Medical University

Beijing, China

Location

Medical Center for Human Reproduction, Peking University Third Hospital

Beijing, China

Location

Peking University First Hospital

Beijing, China

Location

West China Second University Hospital of Sichuan University

Chengdu, China

Location

Sun Yat-sen Memorial Hospital, Sun Yat-sen University

Guangzhou, China

Location

The Sixth Affiliated Hospital of Sun Yat-sen University

Guangzhou, China

Location

The Third Affiliated Hospital of Guangzhou Medical University

Guangzhou, China

Location

The First Affiliated Hospital of An'hui Medical University

Hefei, China

Location

Jiangsu Province Hospital

Nanjing, China

Location

ShengJing Hospital of China Medical University

Shenyang, China

Location

Peking University Shenzhen Hospital

Shenzhen, China

Location

Tianjin Central Hospital of Gynaecology and Obstetrics

Tianjin, China

Location

Tianjin Medical University General Hospital

Tianjin, China

Location

Renmin Hospital of Wuhan University

Wuhan, China

Location

Tongji Hospital,Tongji Medical College, Huazhong University of Science & Technology

Wuhan, China

Location

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, China

Location

Seoul National University Bundang Hospital

Seongnam-si, South Korea

Location

Asan Medical Center

Seoul, South Korea

Location

Samsung Medical Center

Seoul, South Korea

Location

Seoul National University Hospital

Seoul, South Korea

Location

Taichung Veterans General Hospital

Taichung, Taiwan

Location

National Taiwan University Hospital

Taipei, Taiwan

Location

Taipei Medical University Hospital

Taipei, Taiwan

Location

Chang Gung Memorial Hospital

Taoyuan District, Taiwan

Location

National Center for Assisted Reproductive Technology

Hanoi, Vietnam

Location

My Duc Hospital

Ho Chi Minh City, Vietnam

Location

Related Publications (3)

• Qiao J, Zhang Y, Liang X, Ho T, Huang HY, Kim SH, Goethberg M, Mannaerts B, Arce JC. A randomised controlled trial to clinically validate follitropin delta in its individualised dosing regimen for ovarian stimulation in Asian IVF/ICSI patients. Hum Reprod. 2021 Aug 18;36(9):2452-2462. doi: 10.1093/humrep/deab155.

  PMID: 34179971 RESULT

• Yang R, Zhang Y, Liang X, Song X, Wei Z, Liu J, Yang Y, Tan J, Zhang Q, Sun Y, Wang W, Qian W, Jin L, Wang S, Xu Y, Yang J, Goethberg M, Mannaerts B, Wu W, Zheng Z, Qiao J. Comparative clinical outcome following individualized follitropin delta dosing in Chinese women undergoing ovarian stimulation for in vitro fertilization /intracytoplasmic sperm injection. Reprod Biol Endocrinol. 2022 Oct 4;20(1):147. doi: 10.1186/s12958-022-01016-y.

  PMID: 36195924 RESULT

• 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.

  PMID: 37156263 RESULT

MeSH Terms

Interventions

follitropin alfa; follitropin delta; FE 999049

Results Point of Contact

• Title: Global Clinical Compliance
• Organization: Ferring Pharmaceuticals

DK0-Disclosure@ferring.com

-

Study Officials

• Global Clinical Compliance

  Ferring Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 14, 2017
• First Posted: September 28, 2017
• Study Start: December 1, 2017
• Primary Completion: January 3, 2020
• Study Completion: July 26, 2020
• Last Updated: August 24, 2023
• Results First Posted: June 1, 2021

Record last verified: 2021-04

Locations

CN (16); KR (4); TW (4); VN (2)