Efficacy of a GLP-1/FGF21 Dual Agonist for Treating PCOS

Официальное название

A Preliminary Study to Explore the Efficacy of a GLP-1/FGF21 Dual Agonist (HEC88473) in Patients With Polycystic Ovary Syndrome (PCOS)

Обзор

Polycystic ovary syndrome (PCOS) is the most common reproductive endocrine and metabolic disorder among women of reproductive age. It is characterized by oligo-ovulation or anovulation, clinical and/or biochemical hyperandrogenism, and polycystic ovarian morphology. In addition, PCOS is frequently accompanied by multiple metabolic abnormalities, including insulin resistance, obesity, impaired glucose tolerance, and dyslipidemia. Clinical studies have demonstrated that treatment with glucagon-like peptide-1 receptor agonists (GLP-1RAs) in women with PCOS results in significant weight reduction, decreased free testosterone levels, improvement in menstrual regularity, and increased clinical pregnancy rates. Fibroblast growth factor 21 (FGF21) has been shown to enhance insulin sensitivity, promote fatty acid oxidation, and improve lipid distribution. HEC88473 is a novel long-acting dual agonist targeting both the glucagon-like peptide-1 (GLP-1) receptor and the fibroblast growth factor 21 (FGF21) receptor. This study is initiated to evaluate the clinical efficacy of HEC88473 in women with PCOS and to explore its potential as a new therapeutic option for the management of PCOS.

Вмешательства

• Препарат GLP-1/FGF21 dual agonist (HEC88473)
  GLP-1/FGF21 dual agonist (HEC88473) will be administered by subcutaneous injection once weekly. The starting dose is 15 mg for 3 consecutive weeks. If well tolerated, the dose will be escalated to 30 mg for an additional 3 weeks, followed by further escalation to 45 mg for 18 weeks, provided tolerability is maintained.

Первичные конечные точки

• Change From Baseline in Free Androgen Index Over 24 Weeks of Treatment [Срок оценки: Baseline to Week 24 (assessed at scheduled follow-up visits).]

Вторичные конечные точки (12)

• Change in the Number of Spontaneous Menstrual Cycles During the 24-Week Treatment Period Compared With the 24-Week Pre-treatment Period [Срок оценки: 24 weeks before treatment initiation to 24 weeks after treatment initiation.]
• Change From Baseline in Bilateral Antral Follicle Count (Diameter <10 mm) at Week 24 [Срок оценки: Baseline to Week 24.]
• Change From Baseline in Bilateral Ovarian Volume at Week 24 [Срок оценки: Baseline to Week 24.]
• Change From Baseline in Serum AMH at Week 24 [Срок оценки: Baseline to Week 24.]
• Change From Baseline in Serum Total Testosterone at Week 24 [Срок оценки: Baseline to Week 24.]
• Change From Baseline in Serum DHEA-S at Week 24 [Срок оценки: Baseline to Week 24.]
• Change From Baseline in Serum SHBG at Week 24 [Срок оценки: Baseline to Week 24.]
• Change From Baseline in HOMA IR Index at Week 24 [Срок оценки: Baseline to Week 24.]
• Change From Baseline in Lipid Profile at Week 24 [Срок оценки: Baseline to Week 24.]
• Change From Baseline in Body Weight at Week 24 [Срок оценки: Baseline to Week 24.]
• Change From Baseline in Waist Circumference at Week 24 [Срок оценки: Baseline to Week 24.]
• Change From Baseline in Quality of Life Assessed by SF-36 at Week 24 [Срок оценки: Baseline to Week 24.]

Критерии участия

Критерии включения

• Age between 18 and 40 years.
• Female.
• No plan for pregnancy from the time of signing the informed consent until 2 months after the last dose of study drug, and willingness to use study-approved contraceptive methods during this period.
• Fulfillment of at least two of the diagnostic criteria for PCOS according to the 2023 International Guideline, including:

• Irregular menstrual cycles:

1-3 years after menarche: cycle length <21 days or >45 days; ≥3 years after menarche to perimenopause: cycle length <21 days or >35 days, or fewer than 8 menstrual cycles per year; ≥1 year after menarche: any cycle >90 days;

• Polycystic ovarian morphology: at least one ovary with ≥20 antral follicles (diameter <10 mm), confirmed by transvaginal or transrectal pelvic ultrasonography;
• Hyperandrogenism: biochemical hyperandrogenism (total testosterone >1.67 nmol/L) or clinical hyperandrogenism (modified Ferriman-Gallwey \[mFG\] score >4).

Критерии исключения

• Use of hormonal contraceptives within 2 months prior to screening.
• History of acute or chronic pancreatitis or pancreatic injury.
• Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2A or 2B.
• History of type 1 or type 2 diabetes mellitus.
• Presence of other endocrine disorders that may cause polycystic ovarian morphology, such as 21-hydroxylase deficiency, pituitary prolactinoma, hypothyroidism, or Cushing's syndrome.
• Current use of other medications known to affect reproductive function, with discontinuation less than 2 months prior to screening, including GnRH agonists or antagonists, anti-androgens, and gonadotropins.
• Current use of other medications that may affect metabolism, with discontinuation less than 1 month prior to screening, including metformin, thiazolidinediones, and SGLT2 inhibitors.
• History of bariatric surgery within the past 12 months.
• Treatment with GLP-1 receptor agonists within the past 12 months.
• Pregnancy or lactation.
• Presence of other serious diseases of major organs such as the heart, liver, or kidney, or any malignancy.
• Any other condition that, in the investigator's opinion, may interfere with the evaluation of efficacy or safety or render the participant unsuitable for this study.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Zhongshan Hospital, Fudan University — Шанхай

Идентификаторы

NCT: NCT07616037 · B2025-709R

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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