To Investigate Efficacy and Safety of a Single Injection of GenSci094 for Ovarian Stimulation Using Daily Recombinant FSH as Reference

Study Overview
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Brief Summary
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To investigate the efficacy and safety of a single injection of GenSci094 to induce multi-follicular development for controlled ovarian stimulation using daily recombinant FSH (recFSH) as a reference. The primary hypothesis is that a single injection of GenSci094 is non-inferior to daily treatment with recFSH in initiating multi-follicular growth.

Official Title
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A Multicenter, Double-blind, Non-inferiority, Phase 3 RCT Comparing GenSci094 and Recombinant FSH During the First Seven Days of Ovarian Stimulation in Chinese ART Patients

Conditions
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Infertility

Intervention / Treatment
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* Drug: GenSci094
* Drug: Placebo RecFSH / follitropin alfa
* Biological: Biological: RecFSH / Follitropin alfa (Days 1 to 7)
* Drug: Placebo GenSci094
* Biological: RecFSH / Follitropin alfa (Days 8 to hCG)
* Drug: Ganirelix
* Biological: hCG
* Drug: Progesterone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Females of couples with an indication for Controlled Ovarian Stimulation (COS) and in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI); >=20 and <40 years of age at the time of signing informed consent; Body weight >=50 kg and body mass index (BMI) >=18 and <=28 kg/m^2; AMH<4.0 and>=1.1μg/L FSH<10 IU/L Willing and able to sign informed consent. Exclusion Criteria: History of ovarian hyper-response or ovarian hyperstimulation syndrome (OHSS); History of/or current polycystic ovary syndrome (PCOS); More than 20 basal antral follicles <11 mm (both ovaries combined) as measured on ultrasound scan (USS) in the early follicular phase (menstrual cycle day 2-4); Presence of unilateral or bilateral hydrosalphinx (visible on USS); Presence of any clinically relevant pathology affecting the uterine cavity or fibroids >4 cm; More than three unsuccessful IVF cycles since the last established ongoing pregnancy (if applicable); History of non- or low ovarian response to FSH/ human menopausal gonadotropin (hMG) treatment; History of recurrent miscarriage (3 or more, even when unexplained); Any clinically relevant abnormal laboratory value based on a sample taken during the screening phase; Contraindications for the use of gonadotropins (e.g. tumors, pregnancy/lactation, undiagnosed vaginal bleeding, hypersensitivity, ovarian cysts); Recent history of/or current epilepsy, human immunodeficiency virus (HIV) infection, diabetes, cardiovascular, gastro-intestinal, hepatic, renal or pulmonary disease; Use of hormonal preparations within 1 month prior to randomization; Hypersensitivity to any of the concomitant medication prescribed as part of the treatment regimen in this protocol; Administration of investigational drugs within three months prior to signing informed consent.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 39 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GenSci094<br>Participants received a single subcutaneous (SC) injection of 150 µg or 100µg GenSci094 on day 2 or 3 of the menstrual cycle (Stimulation Day 1); 7 daily SC injections from Stimulation Days 1 to 7 with placebo-recFSH; followed by daily SC injections with 150 IU or225IU recFSH up to the day of hCG. Daily SC injections of Ganirelix were administered from Stimulation Day 5 to the day of hCG; at which time a single dose of hCG was given when 3 follicles >= 17 mm. On the day of oocyte pick up (OPU) daily doses of progesterone were started and continued for up to 6 weeks or menses. | Drug: GenSci094<br>* On the morning of day 2 or 3 of the menstrual cycle (Stimulation Day 1), a single SC injection of 150 μg or 100μg (0.5 mL) GenSci094 was administered in the abdominal wall.<br>Drug: Placebo RecFSH / follitropin alfa<br>* powder-injection, but without the active ingedient, SC injection . Daily SC injections were started on Stimulation Day 1 and continued up to and including Stimulation Day 7.<br>Biological: RecFSH / Follitropin alfa (Days 8 to hCG)<br>* From Stimulation Day 8 onwards a daily SC dose 75IU～300 IU recFSH was administered up to and including the Day of hCG.<br>Drug: Ganirelix<br>* On Stimulation Day 5 a daily SC injection of 0.25 mg was started, which continued up to and including the day of hCG<br>Biological: hCG<br>* When 3 follicles >= 17 mm were observed by USS, a single dose of 10,000 IU/USP hCG was administered; or, for those at risk for Ovarian Hyperstimulation Syndrome (OHSS), a lower dose of 5,000 IU/USP<br>Drug: Progesterone<br>* On the day of OPU, luteal phase support was started by administering micronized progesterone of at least 400 mg/day vaginally, and 40mg/d oral, which continued for at least 6 weeks, or up to menses.<br>|
| Active Comparator: recFSH<br>Participants received a single SC injection of placebo GenSci094 on day 2 or 3 of the menstrual cycle (Stimulation Day 1); 7 daily SC injections with 150 IU or 225IU recFSH from Stimulation Days 1 to 7; followed by daily SC injections with 200 IU recFSH up to the day of hCG. Daily SC injections of Ganirelix were given from Stimulation Day 5 to the day of hCG; at which time a single dose of hCG was administered when 3 follicles >= 17 mm. On the day of OPU daily doses of progesterone were started and continued for up to 6 weeks or menses. | Biological: Biological: RecFSH / Follitropin alfa (Days 1 to 7)<br>* Daily SC injections with 150IU or 225IU recFSH were started on Stimulation Day 1 and continued up to and including Stimulation Day 7.<br>Drug: Placebo GenSci094<br>* Pre-filled syringe containing an identical solution when compared to GenSci094. On the morning of day 2 or 3 of the menstrual cycle (Stimulation Day 1), a single SC injection was administered in the abdominal wall.<br>Biological: RecFSH / Follitropin alfa (Days 8 to hCG)<br>* From Stimulation Day 8 onwards a daily SC dose 75IU～300 IU recFSH was administered up to and including the Day of hCG.<br>Drug: Ganirelix<br>* On Stimulation Day 5 a daily SC injection of 0.25 mg was started, which continued up to and including the day of hCG<br>Biological: hCG<br>* When 3 follicles >= 17 mm were observed by USS, a single dose of 10,000 IU/USP hCG was administered; or, for those at risk for Ovarian Hyperstimulation Syndrome (OHSS), a lower dose of 5,000 IU/USP<br>Drug: Progesterone<br>* On the day of OPU, luteal phase support was started by administering micronized progesterone of at least 400 mg/day vaginally, and 40mg/d oral, which continued for at least 6 weeks, or up to menses.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Number of Oocytes Retrieved |  | Approximately Day 10-14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With an Ongoing Pregnancy (Ongoing Pregnancy Rate) |  | Assessed at least 10 weeks after embryo transfer | 
| Percentage of Fertilized Oocytes (Fertilization Rate) |  | Up to 18 hours after start of fertilization | 
| Number of Embryos Obtained on Day 3 Categorized by Quality |  | Post fertilization Day 3 | 
| Percentage of Gestational Sacs (Implantation Rate) |  | Up to 6 weeks after embryo transfer | 
| Percentage of Participants With a Biochemical Pregnancy Per Embryo Transfer |  | Two weeks after embryo transfe | 
| Percentage of Participants With a early miscarriage（early miscarriage rate）Per Clinical Pregnancy |  | Up to 12 weeks after embryo transfer |