Identify Effective Doses of SHR7280 Tablets in Controlled Ovarian Hyperstimulation (COH) for Female Subjects Undergoing Assisted Reproductive Technology (ART)

NCT05082233 | Completed Phase 2

• 1 other identifier: SHR7280-201
• Study Type: interventional
• Target: 85
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a multicentre, open-label phase II dose-finding clinical trial that will recruit approximately 120 female subjects undergoing COH for in vitro fertilization (IVF) or intracytoplasmic single sperm injection (ICSI). We set up three SHR7280 tablets dose groups of 300 mg BID, 200 mg BID, and 200 mg QD with 40 subjects in each group, besides, a group of 400mg bid is set as an alternative.

Conditions

Female Subjects Undergoing COH in ART to Prevent Early Ovulation

Outcome Measures

Primary Outcomes (1)

• Inhibition rate of early LH serge with different oral doses of SHR7280 tablets from the 1st day of study drug administration to the date of hCG injection

  Through the whole period of oral administration of SHR7280, generally 5-7 days)

Secondary Outcomes (7)

• The proportion of embryos with 2 protoplasts in the cytoplasm 16-18 hours (h) after fertilization (2PN rates).

  On embryo transfer day, 3 days after oocyte retrieval

• Quality embryo rates

  On embryo transfer day, 3 days after oocyte retrieval.

• Clinical pregnancy rates.

  On pregnancy test day

• Total dose of gonadotropin (Gn) administered and duration of gonadotropin treatment

  Through the whole period of controlled ovarian stimulation, generally 9-11 days

• Adverse drug events

  Through study completion, follow-up period may be up to 40 weeks if the patient gets a successful clinical pregnancy and a full term delivery

Study Arms (1)

SHR7280 tablets

EXPERIMENTAL

Treatment group A: oral SHR7280 tablets; 300mg bid p.o.; Treatment group B: oral SHR7280 tablets; 200mg bid p.o.; Treatment group C: oral SHR7280 tablets; 200mg qd p.o.; Treatment group D: oral SHR7280 tablets; 400mg bid p.o.; as an alternative.

Drug: SHR7280 tablets

Interventions

SHR7280 tablets DRUG

Treatment group A:SHR7280 tablets ; 300mg BID； Treatment group B:SHR7280 tablets ; 200mg BID； Treatment group C:SHR7280 tablets ; 200mg QD； Treatment group D:SHR7280 tablets ; 400mg BID；

SHR7280 tablets

Eligibility Criteria

• Age: 20 Years - 39 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Married infertile female subjects aged 20 to 39 years with indications for in vitro fertilization-embryo transfer (IVF-ET) or intracytoplasmic monosperm microinjection (ICSI) techniques.
• Body mass index (BMI) of 18 to 28 kg/m2.
• Regular menstrual cycle (24 to 35 days) for the last 3 months prior to screening.
• Screening serum sex hormone levels must be performed on day 2 to 3 in the menstrual cycle and meet basal serum follicle stimulating hormone (FSH) \< 10 IU/L; LH, estradiol (E2), progesterone (P), prolactin (PRL), and total testosterone levels within the normal laboratory range, or the investigator considers the abnormality without clinical significance; 1.2 ng/mL \< anti-müllerian hormone (AMH) \< 4.0 ng/mL.
• Expected normal ovarian response.
• Clinical feasible and willingness of the subject to undergo fresh cycle transfer with one or two embryos at a time in the first IVF-ET cycle.
• Able and willing to provide a written informed consent.

You may not qualify if:

• Subjects underwent 3 or more controlled ovarian stimulation cycles of IVF/ICSI-ET prior to screening without achieving clinical pregnancy.
• Previous IVF or ART failure due to sperm/fertilization problems and no improvement in related medical condition.
• Subjects had spontaneous abortion≥2 times.
• Subjects at high risk of OHSS, judged by the investigator according to the Golan classification (e.g., those with moderate to severe OHSS during previous superovulatory cycles, polycystic ovary syndrome (PCOS) \[refer to the 2018 Chinese PCOS guidelines\] \[1\], or with previous cancelled cycles due to OHSS).
• Note: The 2018 Chinese PCOS guideline specifies the diagnostic criteria as meeting 1 of the following 2 items: ① hyperandrogenic manifestations or irregular menstruation: scanty or amenorrhea menstruation or irregular uterine bleeding are required for the diagnosis. ②Other diseases that may cause hyperandrogenism or abnormal ovulation should be excluded.
• Subjects with low ovarian function meeting at least one of the following items: poor previous ovarian response (≤3 ovums obtained with previous conventional adequate Gn stimulation regimen); less than 7 follicles of 2-9 mm diameter (AFC) count visible on vaginal ultrasound in both ovaries; anti-mullerian hormone (AMH) \< 1.1 ng/mL.
• Any pregnancy that occurred within 3 months prior to screening date.
• Subjects with clinically significant abnormal cervical findings within 6 months prior to screening (TCT).
• Note: Human papillomavirus (HPV) testing may be used as an adjunct in subjects with atypical squamous cells of undefined significance (ASC-US). Subjects may be included in the study if only the high-risk HPV strains test was negative.
• Unexplained abnormal vaginal bleeding.
• Persons who have donated blood or blood components within 1 month prior to screening, or have lost at least the equivalent of 200 mL of blood, or have received a blood transfusion within 2 months.
• Subjects had a serious infection, severe trauma or major surgical procedure within 6 months prior to screening.
• Use of clomiphene citrate, letrozole, gonadotropins (Gn), metformin, or oral contraceptives within 1 month prior to receiving ovarian stimulation.
• Abnormal blood alanine aminotransferase (ALT) and aspartate aminotransferase (AST) values on screening visit or ovarian stimulation day 1 visit.
• Positive serum beta-hCG test result on day 1 of screening visit or ovarian stimulation.

Sponsors & Collaborators

• Jiangsu HengRui Medicine Co., Ltd.: lead

Study Sites (1)

Peking University Third Hospital

Beijing, Beijing Municipality, 100191, China

Location

Related Publications (1)

• Chi H, Song Y, Jin L, Song X, Wang X, Ma Q, Cao Y, Liang X, Tan J, Guan Y, Diao F, Li Y, Li Z, Sun Y, Shu C, Chen H, Shen K, Qiao J. SHR7280, an oral gonadotropin-releasing hormone antagonist, for the prevention of premature luteinizing hormone surge in controlled ovarian hyperstimulation: a dose-finding, phase 2 trial. Hum Reprod. 2025 Jul 1;40(7):1357-1365. doi: 10.1093/humrep/deaf082.

  PMID: 40373184 DERIVED

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 29, 2021
• First Posted: October 18, 2021
• Study Start: March 6, 2022
• Primary Completion: August 3, 2023
• Study Completion: August 3, 2023
• Last Updated: February 20, 2024

Record last verified: 2024-02

Locations

CN (1)