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

NCT ID: NCT03296527

Last Updated: 2023-08-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 1011 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-12-01
• Study Completion Date: 2020-07-26

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

Study Design

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

Study Groups

Follitropin delta

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

Group Type: EXPERIMENTAL

Follitropin delta

Intervention Type: DRUG

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

Gonal-F

rFSH. Follitropin alfa for subcutaneous injection

Group Type: ACTIVE_COMPARATOR

Follitropin alfa

Intervention Type: DRUG

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

Interventions

Follitropin alfa

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

Intervention Type: DRUG

Follitropin delta

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

Intervention Type: DRUG

Other Intervention Names

GONAL-F; FE 999049; REKOVELLE

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.
• Known abnormal cervical cytology of clinical significance observed within three years prior to randomization (unless the clinical significance has been resolved).
• Findings at the gynaecological examination at screening which preclude gonadotropin stimulation or are associated with a reduced chance of pregnancy, e.g. congenital uterine abnormalities or retained intrauterine device.
• Pregnancy (negative urinary pregnancy tests must be documented at screening and prior to randomization) or contraindication to pregnancy.
• Known current active pelvic inflammatory disease.
• Use of fertility modifiers during the last menstrual cycle before randomization, including dehydroepiandrosterone (DHEA), metformin or cycle programming with oral contraceptives, progestogen or estrogen preparations.
• Use of hormonal preparations (except for thyroid medication) during the last menstrual cycle before randomization.
• Known history of chemotherapy (except for gestational conditions) or radiotherapy.
• Current or past (1 year prior to randomization) abuse of alcohol or drugs.
• Current (last month) intake of more than 14 units of alcohol per week.
• Current or past (3 months prior to randomization) smoking habit of more than 10 cigarettes per day.
• Hypersensitivity to any active ingredient or excipients in the medicinal products used in the trial.
• Previous participation in the trial.
• Use of any non-registered investigational drugs during the last 3 months prior to randomization.

• 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

Beijing Obstetrics and Gynecology Hospital,Capital Medical University

Beijing, , China

Medical Center for Human Reproduction, Peking University Third Hospital

Beijing, , China

Peking University First Hospital

Beijing, , China

West China Second University Hospital of Sichuan University

Chengdu, , China

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

Guangzhou, , China

The Sixth Affiliated Hospital of Sun Yat-sen University

Guangzhou, , China

The Third Affiliated Hospital of Guangzhou Medical University

Guangzhou, , China

The First Affiliated Hospital of An'hui Medical University

Hefei, , China

Jiangsu Province Hospital

Nanjing, , China

ShengJing Hospital of China Medical University

Shenyang, , China

Peking University Shenzhen Hospital

Shenzhen, , China

Tianjin Central Hospital of Gynaecology and Obstetrics

Tianjin, , China

Tianjin Medical University General Hospital

Tianjin, , China

Renmin Hospital of Wuhan University

Wuhan, , China

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

Wuhan, , China

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, , China

Seoul National University Bundang Hospital

Seongnam-si, , South Korea

Asan Medical Center

Seoul, , South Korea

Samsung Medical Center

Seoul, , South Korea

Seoul National University Hospital

Seoul, , South Korea

Taichung Veterans General Hospital

Taichung, , Taiwan

National Taiwan University Hospital

Taipei, , Taiwan

Taipei Medical University Hospital

Taipei, , Taiwan

Chang Gung Memorial Hospital

Taoyuan District, , Taiwan

National Center for Assisted Reproductive Technology

Hanoi, , Vietnam

My Duc Hospital

Ho Chi Minh City, , Vietnam

Countries

China; South Korea; Taiwan; Vietnam

References

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.

Reference Type: RESULT

PMID: 34179971 (View on PubMed)

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.

Reference Type: RESULT

PMID: 36195924 (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: Protocol excluding mainland China

View Document

Document Type: Study Protocol: Protocol specific for mainland China

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

000145

Identifier Type: -

Identifier Source: org_study_id