ObesityPhase 2MELIANCT07781150
Mazdutide Plus LNG-IUS for Fertility-Sparing Treatment of AEH or Early Endometrial Cancer
A Phase 2 study testing Mazdutide(Dual GLP-1R/GCGR Agonist) and Levonorgestrel-releasing intrauterine system in people with Obesity and Overweight, run by Tongji Hospital at 6 sites in China.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 to 45 years, women only
- Conditions the study is for
- Obesity, Overweight, Atypical Endometrial Hyperplasia
- What is being tested?
- Mazdutide(Dual GLP-1R/GCGR Agonist) and Levonorgestrel-releasing intrauterine system
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 128 participants
- Where
- 6 sitesChina
- Study dates
- 1 Nov 2026to 30 Jun 2031
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
6 sites in 1 country. Contact the study team or a site near you to ask about taking part.
6 sites in 1 country
China6 sites
The Second Hospital of Jilin University
Changchun, Jilin
Tianmin Xu, PhD, xutianmin@126.com
Zhejiang Cancer Hospital
Hangzhou, Zhejiang
Yingli Zhang, PhD
Shanghai Tenth People's Hospital
Shanghai
Xiaojun Chen, PhD, xiaojunchen2013@sina.com
Tianjin Medical University General Hospital
Tianjin
Yingmei Wang, PhD, wangyingmei@tmu.edu.cn
Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
Wuhan, Hubei
Gang Chen, PhD, tjchengang@hust.edu.cn
tjchengang@hust.edu.cn
The First Affiliated Hospital of Zhengzhou University
Zhengzhou, Henan
Lei Chang
About this study
Official title: Mazdutide Plus Levonorgestrel-Releasing Intrauterine System for Fertility-Sparing Treatment in Overweight or Obese Patients With Atypical Endometrial Hyperplasia or Early Endometrioid Endometrial Cancer
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.
Read the detailed description
Eligible participants are premenopausal women with a strong desire to preserve fertility, diagnosed with AEH or FIGO grade 1 early-stage endometrioid endometrial cancer confined to the endometrium, and with overweight or obesity. All participants will receive LNG-IUS. Participants will be randomized 1:1 to receive either mazdutide or matching placebo by subcutaneous injection once weekly, using a dose-escalation regimen. Endometrial response will be assessed by hysteroscopic endometrial biopsy and pathology evaluation at prespecified time points. The study will compare pathological response, time to complete response, safety, body weight and metabolic changes, reproductive endocrine parameters, subsequent pregnancy outcomes, recurrence, patient-reported outcomes, and exploratory biomarker changes between the two treatment groups.
- Conditions
- Obesity, Overweight, Atypical Endometrial Hyperplasia, Endometrial Carcinoma Stage I, Endometrioid Endometrial Cancer
- Being tested
- Mazdutide(Dual GLP-1R/GCGR Agonist), Placebo, Levonorgestrel-releasing intrauterine system
- Keywords
- Mazdutide, Levonorgestrel-releasing intrauterine system, LNG-IUS, Atypical endometrial hyperplasia, Early endometrial cancer, Endometrioid endometrial cancer, Obesity
- Medical subject headings
- Obesity, Overweight, Endometrial Hyperplasia, Endometrial Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Mazdutide(Dual GLP-1R/GCGR Agonist)Drug
Also called IBI362
Mazdutide will be administered by subcutaneous injection once weekly. The starting dose is 2 mg once weekly for weeks 1-4, followed by 4 mg once weekly for weeks 5-8, and 6 mg once weekly from week 9 onward. If 6 mg is not tolerated, the dose may be reduced to 4 mg once weekly according to the protocol.
PlaceboDrug
Matching placebo will be administered by subcutaneous injection once weekly using the same injection route, frequency, injection volume, appearance, packaging, labeling, injection device, and dose-escalation procedure as mazdutide.
Levonorgestrel-releasing intrauterine systemDevice
Also called LNG-IUS
The levonorgestrel-releasing intrauterine system will be placed in the uterine cavity according to standard clinical practice and will be used as the background fertility-sparing progestin therapy in both treatment groups.
| Study group | Role | What they receive |
|---|---|---|
| LNG-IUS plus Mazdutide | Experimental | Participants will receive LNG-IUS placed in the uterine cavity and mazdutide by subcutaneous injection once weekly using a dose-escalation regimen. Receives: Drug: Mazdutide(Dual GLP-1R/GCGR Agonist); Device: Levonorgestrel-releasing intrauterine system |
| LNG-IUS plus Placebo | Placebo comparator | 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. Receives: Drug: Placebo; Device: Levonorgestrel-releasing intrauterine system |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete response rate of endometrial lesions at 24 week
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.
Measured: At 24 weeks after randomization
Secondary outcomes (22)
Complete response rate at 12 weeks
The proportion of participants who achieve complete response at the week 12 pathological assessment.
Measured: At 12 weeks after randomization
Complete response rate at 36 weeks
The proportion of participants who achieve complete response at the week 36 pathological assessment.
Measured: At 36 weeks after randomization
Time to first complete response
Time from randomization to the date of the first pathological assessment confirming complete response.
Measured: From randomization to first documented complete response, up to 36 weeks
Pathological response status
Distribution of pathological response categories, including complete response, partial response, stable disease, progressive disease, and unevaluable specimens.
Measured: At 12, 24, and 36 weeks after randomization
Fertility-sparing treatment failure and radical surgery
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.
Measured: From randomization through the end of study follow-up, up to 2 years after complete response
Change in body weight
Change from baseline in body weight measured in kilograms.
Measured: Baseline, 12 weeks, 24 weeks, and 36 weeks after randomization
Percentage change in body weight
Percentage change from baseline in body weight, calculated as: [(body weight at visit - baseline body weight) / baseline body weight] × 100%.
Measured: Baseline, 12 weeks, 24 weeks, 36 weeks, and at early discontinuation of study treatment if applicable
Proportion of participants with at least 5% body weight reduction
The proportion of participants with body weight reduction of at least 5% from baseline. The outcome will be reported as a percentage of participants.
Measured: At 12, 24, and 36 weeks after randomization
Proportion of participants with at least 10% body weight reduction
The proportion of participants with body weight reduction of at least 10% from baseline. The outcome will be reported as a percentage of participants.
Measured: At 12, 24, and 36 weeks after randomization
Change in body mass index
Change from baseline in body mass index, measured in kg/m^2.
Measured: Baseline, 12 weeks, 24 weeks, 36 weeks, and at early discontinuation of study treatment if applicable
Change in waist circumference
Change from baseline in waist circumference, measured in centimeters.
Measured: Baseline, 12 weeks, 24 weeks, 36 weeks, and at early discontinuation of study treatment if applicable
Change in fasting plasma glucose
Change from baseline in fasting plasma glucose, measured in mmol/L.
Measured: Baseline, 12 weeks, 24 weeks, 36 weeks, and at early discontinuation of study treatment if applicable
Change in HbA1c
Change from baseline in glycated hemoglobin, measured as percentage.
Measured: Baseline, 12 weeks, 24 weeks, 36 weeks, and at early discontinuation of study treatment if applicable
Change in fasting insulin
Change from baseline in fasting insulin, measured in μIU/mL or mIU/L according to the local laboratory standard.
Measured: Baseline, 24 weeks, and at early discontinuation of study treatment if applicable
Change in HOMA-IR
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.
Measured: Baseline, 24 weeks, and at early discontinuation of study treatment if applicable
Change in total cholesterol
Change from baseline in total cholesterol, measured in mmol/L.
Measured: Baseline, 12 weeks, 24 weeks, 36 weeks, and at early discontinuation of study treatment if applicable
Change in triglycerides
Change from baseline in triglycerides, measured in mmol/L.
Measured: Baseline, 12 weeks, 24 weeks, 36 weeks, and at early discontinuation of study treatment if applicable
Change in LDL cholesterol
Change from baseline in low-density lipoprotein cholesterol, measured in mmol/L.
Measured: Baseline, 12 weeks, 24 weeks, 36 weeks, and at early discontinuation of study treatment if applicable
Change in HDL cholesterol
Change from baseline in high-density lipoprotein cholesterol, measured in mmol/L.
Measured: Baseline, 12 weeks, 24 weeks, 36 weeks, and at early discontinuation of study treatment if applicable
Change in alanine aminotransferase
Change from baseline in alanine aminotransferase, measured in U/L.
Measured: Baseline, 12 weeks, 24 weeks, 36 weeks, and at early discontinuation of study treatment if applicable
Change in aspartate aminotransferase
Change from baseline in aspartate aminotransferase, measured in U/L.
Measured: Baseline, 12 weeks, 24 weeks, 36 weeks, and at early discontinuation of study treatment if applicable
Change in serum uric acid
Change from baseline in serum uric acid, measured in μmol/L.
Measured: Baseline, 12 weeks, 24 weeks, 36 weeks, and at early discontinuation of study treatment if applicable
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Aug 2026
- Study start1 Nov 2026 (estimated)
- Primary completion30 Jun 2029 (estimated)
- Study completion30 Jun 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ObesityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants will be randomized in a 1:1 ratio to receive LNG-IUS plus mazdutide or LNG-IUS plus matching placebo. Randomization will be implemented through an interactive web response system, with stratification by study center, baseline disease type, and BMI category.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 128 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Tongji Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Innovent Biologics, Inc.
- Responsible party
- Principal investigator, Gang Chen (101199), Tongji Hospital
- Investigators
- Gang Chen, Principal Investigator, Principal investigator, Tongji Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07781150
- Sponsor's protocol ID
- MELIA-IIT-001
- Acronym
- MELIA
- Status last verified
- Aug 2026
- First submitted
- 18 Aug 2026
- Last updated
- 24 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Individual participant data will not be publicly shared because the study involves sensitive reproductive, oncologic, genetic, and biomarker-related clinical information. De-identified data may be made available from the principal investigator upon reasonable request and after approval by the study steering committee and ethics committee, where applicable.