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

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

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.

Study Overview

• Status: Completed
• Conditions: Infertility
• Intervention / Treatment: Drug: Ganirelix; Biological: hCG; Drug: GenSci094; Drug: Placebo RecFSH / follitropin alfa; Biological: RecFSH / Follitropin alfa (Days 8 to hCG); Drug: Progesterone; Biological: Biological: RecFSH / Follitropin alfa (Days 1 to 7); Drug: Placebo GenSci094

• Study Type: Interventional
• Enrollment (Actual): 176
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510610
      • The Sixth Affiliated Hospital, Sun Yat-sen University Guangdong Gastrointestinal Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GenSci094; 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: Ganirelix; On Stimulation Day 5 a daily SC injection of 0.25 mg was started, which continued up to and including the day of hCG; Biological: hCG; 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; Drug: GenSci094; 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.; Drug: Placebo RecFSH / follitropin alfa; 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.; Biological: RecFSH / Follitropin alfa (Days 8 to hCG); From Stimulation Day 8 onwards a daily SC dose 75IU～300 IU recFSH was administered up to and including the Day of hCG.; Drug: Progesterone; 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.
Active Comparator: recFSH; 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.	Drug: Ganirelix; On Stimulation Day 5 a daily SC injection of 0.25 mg was started, which continued up to and including the day of hCG; Biological: hCG; 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; Biological: RecFSH / Follitropin alfa (Days 8 to hCG); From Stimulation Day 8 onwards a daily SC dose 75IU～300 IU recFSH was administered up to and including the Day of hCG.; Drug: Progesterone; 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.; Biological: Biological: RecFSH / Follitropin alfa (Days 1 to 7); Daily SC injections with 150IU or 225IU recFSH were started on Stimulation Day 1 and continued up to and including Stimulation Day 7.; Drug: Placebo GenSci094; 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.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Changchun GeneScience Pharmaceutical Co., Ltd.
• Collaborators: Sixth Affiliated Hospital, Sun Yat-sen University
• Investigators: Study Chair: Xiaoyan Liang, doctor, The Sixth Affiliated Hospital, Sun Yat-sen University Guangdong Gastrointestinal Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 24, 2023
• Primary Completion (Actual): December 25, 2023
• Study Completion (Actual): January 29, 2024

Study Registration Dates

• First Submitted: August 8, 2023
• First Submitted That Met QC Criteria: October 17, 2023
• First Posted (Actual): October 19, 2023

Study Record Updates

• Last Update Posted (Actual): December 3, 2024
• Last Update Submitted That Met QC Criteria: December 1, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Infertility; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Progestins; Follicle Stimulating Hormone; Progesterone; Ganirelix
• Other Study ID Numbers: GenSci094-301

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No