PCOS (Polycystic Ovary Syndrome)
Conditions
Keywords
PCOS, GLP-1/FGF21 dual agonist
Brief summary
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.
Interventions
DRUGGLP-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.
Sponsors
Shanghai Zhongshan Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
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.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 40 Years
Healthy volunteers
No
Inclusion criteria
* 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: 1. 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; 2. Polycystic ovarian morphology: at least one ovary with ≥20 antral follicles (diameter \<10 mm), confirmed by transvaginal or transrectal pelvic ultrasonography; 3. Hyperandrogenism: biochemical hyperandrogenism (total testosterone \>1.67 nmol/L) or clinical hyperandrogenism (modified Ferriman-Gallwey \[mFG\] score \>4).
Exclusion criteria
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Free Androgen Index Over 24 Weeks of Treatment | Baseline to Week 24 (assessed at scheduled follow-up visits). | Longitudinal changes in free androgen index from baseline at each scheduled follow-up visit during the 24-week treatment period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in the Number of Spontaneous Menstrual Cycles During the 24-Week Treatment Period Compared With the 24-Week Pre-treatment Period | 24 weeks before treatment initiation to 24 weeks after treatment initiation. | Comparison of the number of spontaneous menstrual cycles during the 24-week intervention period with those during the 24-week period prior to treatment initiation. |
| Change From Baseline in Bilateral Antral Follicle Count (Diameter <10 mm) at Week 24 | Baseline to Week 24. | Change from baseline in the total number of antral follicles with a diameter \<10 mm in both ovaries after 24 weeks of treatment. |
| Change From Baseline in Bilateral Ovarian Volume at Week 24 | Baseline to Week 24. | Change from baseline in the total ovarian volume of both ovaries after 24 weeks of treatment. |
| Change From Baseline in Serum AMH at Week 24 | Baseline to Week 24. | Change from baseline in serum levels of anti-Müllerian hormone (AMH) after 24 weeks of treatment. |
| Change From Baseline in Serum Total Testosterone at Week 24 | Baseline to Week 24. | Change from baseline in serum levels of total testosterone after 24 weeks of treatment. |
| Change From Baseline in Serum DHEA-S at Week 24 | Baseline to Week 24. | Change from baseline in serum levels of dehydroepiandrosterone sulfate (DHEA-S) after 24 weeks of treatment. |
| Change From Baseline in Serum SHBG at Week 24 | Baseline to Week 24. | Change from baseline in serum levels of sex hormone-binding globulin (SHBG) after 24 weeks of treatment. |
| Change From Baseline in HOMA IR Index at Week 24 | Baseline to Week 24. | Change from baseline in insulin resistance assessed by the HOMA Insulin Resistance index (calculated from fasting plasma glucose in mmol/L × fasting serum insulin in μU/mL/22.5) after 24 weeks of treatment. |
| Change From Baseline in Lipid Profile at Week 24 | Baseline to Week 24. | Change from baseline in serum lipid profile after 24 weeks of treatment. |
| Change From Baseline in Body Weight at Week 24 | Baseline to Week 24. | Change from baseline in body weight after 24 weeks of treatment. |
| Change From Baseline in Waist Circumference at Week 24 | Baseline to Week 24. | Change from baseline in waist circumference after 24 weeks of treatment. |
| Change From Baseline in Quality of Life Assessed by SF-36 at Week 24 | Baseline to Week 24. | Change from baseline in quality of life evaluated using the Short Form-36 (SF-36) after 24 weeks of treatment. |
| Change From Baseline in Quality of Life Assessed by PCOSQ at Week 24 | Baseline to Week 24. | Change from baseline in quality of life evaluated using the Polycystic Ovary Syndrome Questionnaire (PCOSQ) after 24 weeks of treatment. |
| Incidence and Severity of Adverse Events During the 24-Week Treatment Period | Baseline to Week 24. | Assessment of the incidence, type, and severity of adverse events occurring during the 24-week treatment period. |
Countries
China
Contacts
CONTACTJingjing JIANG, MD, PhD
Outcome results
None listed