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Trial · Interventional

Not yet recruitingPhase 2Registry data

Mazdutide Plus LNG-IUS for Fertility-Sparing Treatment of AEH or Early Endometrial Cancer

Short name MELIA

Overview

Status
Not yet recruiting
Phase
Phase 2
Enrollment
128 participants (estimated)
Sponsor
Tongji Hospital · Other
Design
Randomized · Quadruple masking
Countries
1 country

China

Start
1 Nov 2026 (estimated)
Primary completion
30 Jun 2029 (estimated)
Completion
30 Jun 2031 (estimated)
First posted
24 Aug 2026
Last update posted
24 Aug 2026
Conditions
Obesity · Overweight · Atypical Endometrial Hyperplasia · Endometrial Carcinoma Stage I · Endometrioid Endometrial Cancer

Timeline

1 trial · 1 not yet recruiting

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
2026202720282029203020312032
  1. Ph 2

    MELIA

    NCT07781150

    est. 1 Nov 2026 to est. 30 Jun 2031

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

This is a prospective, multicenter, randomized, double-blind, placebo-controlled, parallel-group clinical trial designed to evaluate the efficacy and safety of mazdutide combined with a levonorgestrel-releasing intrauterine system (LNG-IUS) for fertility-sparing treatment in overweight or obese patients with atypical endometrial hyperplasia (AEH) or early-stage endometrioid endometrial cancer. Eligible participants will be randomized in a 1:1 ratio to receive LNG-IUS plus mazdutide or LNG-IUS plus matching placebo. The primary outcome is the complete response rate of endometrial lesions at 24 weeks after randomization.

Interventions

  • Mazdutide(Dual GLP-1R/GCGR Agonist)Drug
  • PlaceboDrug
  • Levonorgestrel-releasing intrauterine systemDevice

Arms2

  • Experimental

    LNG-IUS plus Mazdutide

    Participants will receive LNG-IUS placed in the uterine cavity and mazdutide by subcutaneous injection once weekly using a dose-escalation regimen.

  • Placebo comparator

    LNG-IUS plus Placebo

    Participants will receive LNG-IUS placed in the uterine cavity and matching placebo by subcutaneous injection once weekly using the same dose-escalation schedule as the mazdutide group.

Primary outcomes1

Outcomes the sponsor listed as primary.

  1. Complete response rate of endometrial lesions at 24 week

    Time frame · At 24 weeks after randomization

    Registry description

    The proportion of participants who achieve complete response of endometrial lesions at the week 24 assessment. Complete response is defined as no residual AEH or endometrioid endometrial cancer on evaluable endometrial pathology obtained by hysteroscopic endometrial biopsy.

Secondary outcomes(20)
  1. Complete response rate at 12 weeks

    Time frame · At 12 weeks after randomization

    Registry description

    The proportion of participants who achieve complete response at the week 12 pathological assessment.

  2. Complete response rate at 36 weeks

    Time frame · At 36 weeks after randomization

    Registry description

    The proportion of participants who achieve complete response at the week 36 pathological assessment.

  3. Time to first complete response

    Time frame · From randomization to first documented complete response, up to 36 weeks

    Registry description

    Time from randomization to the date of the first pathological assessment confirming complete response.

  4. Pathological response status

    Time frame · At 12, 24, and 36 weeks after randomization

    Registry description

    Distribution of pathological response categories, including complete response, partial response, stable disease, progressive disease, and unevaluable specimens.

  5. Fertility-sparing treatment failure and radical surgery

    Time frame · From randomization through the end of study follow-up, up to 2 years after complete response

    Registry description

    Proportion of participants who discontinue fertility-sparing treatment due to disease progression, persistent non-response, intolerance, or other oncologic reasons, and the proportion undergoing radical surgery.

  6. Change in body weight

    Time frame · Baseline, 12 weeks, 24 weeks, and 36 weeks after randomization

    Registry description

    Change from baseline in body weight measured in kilograms.

  7. Percentage change in body weight

    Time frame · Baseline, 12 weeks, 24 weeks, 36 weeks, and at early discontinuation of study treatment if applicable

    Registry description

    Percentage change from baseline in body weight, calculated as: \[(body weight at visit - baseline body weight) / baseline body weight\] × 100%.

  8. Proportion of participants with at least 5% body weight reduction

    Time frame · At 12, 24, and 36 weeks after randomization

    Registry description

    The proportion of participants with body weight reduction of at least 5% from baseline. The outcome will be reported as a percentage of participants.

  9. Proportion of participants with at least 10% body weight reduction

    Time frame · At 12, 24, and 36 weeks after randomization

    Registry description

    The proportion of participants with body weight reduction of at least 10% from baseline. The outcome will be reported as a percentage of participants.

  10. Change in body mass index

    Time frame · Baseline, 12 weeks, 24 weeks, 36 weeks, and at early discontinuation of study treatment if applicable

    Registry description

    Change from baseline in body mass index, measured in kg/m\^2.

  11. Change in waist circumference

    Time frame · Baseline, 12 weeks, 24 weeks, 36 weeks, and at early discontinuation of study treatment if applicable

    Registry description

    Change from baseline in waist circumference, measured in centimeters.

  12. Change in fasting plasma glucose

    Time frame · Baseline, 12 weeks, 24 weeks, 36 weeks, and at early discontinuation of study treatment if applicable

    Registry description

    Change from baseline in fasting plasma glucose, measured in mmol/L.

  13. Change in HbA1c

    Time frame · Baseline, 12 weeks, 24 weeks, 36 weeks, and at early discontinuation of study treatment if applicable

    Registry description

    Change from baseline in glycated hemoglobin, measured as percentage.

  14. Change in fasting insulin

    Time frame · Baseline, 24 weeks, and at early discontinuation of study treatment if applicable

    Registry description

    Change from baseline in fasting insulin, measured in μIU/mL or mIU/L according to the local laboratory standard.

  15. Change in HOMA-IR

    Time frame · Baseline, 24 weeks, and at early discontinuation of study treatment if applicable

    Registry description

    Change from baseline in homeostatic model assessment of insulin resistance. HOMA-IR is calculated from fasting glucose and fasting insulin and is reported as a unitless index.

  16. Change in total cholesterol

    Time frame · Baseline, 12 weeks, 24 weeks, 36 weeks, and at early discontinuation of study treatment if applicable

    Registry description

    Change from baseline in total cholesterol, measured in mmol/L.

  17. Change in triglycerides

    Time frame · Baseline, 12 weeks, 24 weeks, 36 weeks, and at early discontinuation of study treatment if applicable

    Registry description

    Change from baseline in triglycerides, measured in mmol/L.

  18. Change in LDL cholesterol

    Time frame · Baseline, 12 weeks, 24 weeks, 36 weeks, and at early discontinuation of study treatment if applicable

    Registry description

    Change from baseline in low-density lipoprotein cholesterol, measured in mmol/L.

  19. Change in HDL cholesterol

    Time frame · Baseline, 12 weeks, 24 weeks, 36 weeks, and at early discontinuation of study treatment if applicable

    Registry description

    Change from baseline in high-density lipoprotein cholesterol, measured in mmol/L.

  20. Change in alanine aminotransferase

    Time frame · Baseline, 12 weeks, 24 weeks, 36 weeks, and at early discontinuation of study treatment if applicable

    Registry description

    Change from baseline in alanine aminotransferase, measured in U/L.

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

No results are posted for this trial.

A trial that is still running, or that stopped early, may post results later.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies0

Studies that cite this trial.

No study cites this trial.

Eligibility

Who could join, as posted.

Sex
Female
Age
from 18 Years up to 45 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
Inclusion Criteria: * Female participants aged 18 to 45 years. * Participants have a clear desire to preserve fertility, fully understand that fertility-sparing treatment is not the standard radical treatment for endometrial cancer, are willing to accept the potential risks of disease progression or recurrence associated with delayed radical surgery, and are able to comply with close follow-up as required by the protocol. * Histologically confirmed disease meeting one of the following criteria: atypical endometrial hyperplasia; or FIGO grade 1 endometrioid endometrial cancer meeting FIGO 2023 stage IA1, with disease confined to the endometrium or an endometrial polyp and no myometrial invasion. * Imaging confirms disease confined to the endometrium, with no evidence of myometrial invasion, adnexal involvement, extrauterine disease, or distant metastasis. * Estrogen receptor-positive disease. * Molecular pathology requirements are fulfilled for participants with endometrial cancer, including exclusion of the p53-abnormal molecular subtype. For participants with POLE-ultramutated or mismatch repair-deficient tumors, suitability for fertility-sparing treatment should be determined based on age, family history, genetic findings, and multidisciplinary assessment. Genetic counseling, germline testing, or additional molecular testing may be performed when clinically indicated. * No contraindication to progestin therapy. * Uterine cavity suitable for LNG-IUS placement. * Completed baseline fertility assessment; after complete response, a specific pregnancy plan should be developed after evaluation by reproductive specialists. * BMI ≥28 kg/m2, or BMI ≥24 kg/m2 with at least one weight-related comorbidity, such as hyperglycemia, hypertension, dyslipidemia, fatty liver disease, or obstructive sleep apnea. * No contraindication to mazdutide. * No contraindication to LNG-IUS. * Able to understand and sign informed consent and willing to comply with all study treatments, assessments, and follow-up procedures. Exclusion Criteria: * Pathological diagnosis not consistent with atypical endometrial hyperplasia or eligible early endometrioid endometrial cancer; endometrioid carcinoma grade 2 or higher; or p53-abnormal molecular subtype. * Imaging or pathological evidence of myometrial invasion, ovarian malignancy, extrauterine disease, or distant metastasis. * Prior fertility-sparing drug therapy or intrauterine progestin therapy for atypical endometrial hyperplasia or endometrial cancer. * Use of hormonal therapy or GLP-1 receptor agonists within 6 months before enrollment. * Pregnancy or breastfeeding at enrollment. * Request for hysterectomy or treatment other than conservative medical therapy. * Active pelvic inflammatory disease, recurrent pelvic inflammatory disease, or lower genital tract infection. * Cervical dysplasia or congenital or acquired uterine abnormalities, including fibroids that distort the uterine cavity. * Uterine cavity too large for adequate LNG-IUS coverage or history of LNG-IUS expulsion. * Known hypersensitivity to mazdutide, any of its excipients, or LNG-IUS materials. * History of malignancy at another site. * Uncontrolled clinically significant comorbidities or medical history that may increase study risk or interfere with study evaluation, including cardiovascular, cerebrovascular, thromboembolic, hepatic, renal, coagulation, endocrine, psychiatric, pancreatic, biliary, or severe gastrointestinal disorders. * Diabetes diagnosed by oral glucose tolerance test. * Secondary obesity or endocrine disorders that may affect body weight or metabolic assessment. * Contraindications or major risk factors related to GLP-1 receptor agonist therapy, including pancreatitis, clinically significant gallbladder disease, severe gastrointestinal motility disorder, medullary thyroid carcinoma, or multiple endocrine neoplasia type 2. * Participation in another interventional clinical trial. * Any condition that, in the investigator's opinion, may increase risk during study treatment, interfere with safety assessment, or affect interpretation of study results.

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