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This is a 56-week randomized, open-label, controlled study evaluating the efficacy and safety of the HDM1005 compared to tirzepatide in adults with obesity but without diabetes. Eligible participants will be screened and randomized to different dose group of HDM1005 or the tirzepatide group at a ratio of 1:1:1 :1, HDM1005 or tirzepatide will be given once weekly for 52 weeks, following by a safety follow up of 4 weeks. All participants received a lifestyle intervention that involved counselling on diet and physical activity.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| HDM1005 injection dose group 1 | Experimental | Initiate at a once weekly dose of 0.5 mg and followed a dose escalation regimen, with dose increases every 4 weeks aiming at reaching the maintenance dose, the intervention will last for 52 weeks in total. |
|
| HDM1005 injection dose group 2 | Experimental | Initiate at a once weekly dose of 0.5 mg and followed a dose escalation regimen, with dose increases every 4 weeks aiming at reaching the maintenance dose, the intervention will last for 52 weeks in total. |
|
| HDM1005 injection dose group 3 | Experimental | Initiate at a once weekly dose of 0.5 mg and followed a dose escalation regimen, with dose increases every 4 weeks aiming at reaching the maintenance dose, the intervention will last for 52 weeks in total. |
|
| tirzepatide injection | Active Comparator | Initiate at a once weekly dose of 2.5 mg and followed a dose escalation regimen, with dose increases every 4 weeks aiming at reaching the maintenance dose, the intervention will last for 52 weeks in total. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| HDM1005 dose level 1 | Drug | Initiate at a once weekly dose of 0.5 mg and followed a dose escalation regimen, with dose increases every 4 weeks aiming at reaching the maintenance dose level 1, the intervention will last for 52 weeks in total. |
| Measure | Description | Time Frame |
|---|---|---|
| Primary Outcome | The percentage change in body weight from baseline to week 40 | week 40 |
| Measure | Description | Time Frame |
|---|---|---|
| Secondary Outcome | The proportion of participants reaching a body weight loss of at least 5%, 10% and 15% at week 40 | week 40 |
| Secondary Outcome | The percentage change in body weight from baseline to week 52 |
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Inclusion Criteria:
Exclusion Criteria:
Previous diagnosis of type 1, type 2, or any other type of diabetes.
History or family history of medullary thyroid carcinoma, C cell hyperplasia, or multiple endocrine neoplasia type
According to the investigator's judgment, the subjects have endocrine diseases or histories that affect gastric emptying, may significantly affect body weight, or diseases or conditions that affect the absorption of gastrointestinal nutrients, such as Cushing syndrome, hypothyroidism or hyperthyroidism, bariatric surgery or other gastrectomy, irritable bowel syndrome, dyspepsia, and chronic pancreatitis; Or a history of acute pancreatitis or acute gallbladder disease within 3 months before signing ICF.
Hypertension that was not stably controlled at screening: systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥100 mmHg (with stable treatment for at least 30 days if antihypertensive medications were used).
Have any malignant tumor within 5 years before signing ICF (except basal cell carcinoma which has received curative treatment and is regarded as cured).
Those who had severe infection, severe trauma, or large or medium-sized surgery within 3 months before signing ICF, or planned to undergo surgery during the study (except outpatient surgery).
Previous or combined presence or suspicion of depression or other psychiatric disorders or screening PHQ-9 score ≥15.
Known intolerance or allergy to any component of the study drug or glucagon-like peptide-1 receptor (GLP-1R) agonist, or a previous history of severe drug allergy.
Use of any of the following drugs, products, or treatments within 3 months prior to signing the ICF, including but not limited to:
A. a drug, product or treatment with weight loss effect b. Medications, products, or treatments that significantly increase body weight
Use of hypoglycemic drugs within 3 months before signing ICF.
Have participated in any clinical trial within 3 months before signing ICF or within 5 half-lives (whichever is longer) after the last dose of the investigational drug used in the clinical trial (except for those who signed ICF without drug or device intervention).
History of addictive drug abuse within 1 year before signing ICF.
Estimated glomerular filtration rate (eGFR) according to the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation <60 mL/min/1.73 m2;
Those who donated blood or lost ≥400 mL of total blood within 3 months before signing ICF, or received blood transfusion or used blood products, or planned to donate blood during the study period.
Pregnant or lactating women.
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Ling Tao | Contact | +86 021-64041990 | cxytaoling@eastchinapharm.com |
| Name | Affiliation | Role |
|---|---|---|
| Xiaoying Li, Medical doctor | Shanghai Zhongshan Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Zhongshan Hoapital | Recruiting | Shanghai | China |
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| ID | Term |
|---|---|
| D009765 | Obesity |
| ID | Term |
|---|---|
| D050177 | Overweight |
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| D000098860 | Tirzepatide |
| ID | Term |
|---|---|
| D000067757 | Glucagon-Like Peptide-1 Receptor |
| D000067756 | Glucagon-Like Peptide Receptors |
| D043562 | Receptors, G-Protein-Coupled |
| D011956 | Receptors, Cell Surface |
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| HDM1005 dose level 2 | Drug | Initiate at a once weekly dose of 0.5 mg and followed a dose escalation regimen, with dose increases every 4 weeks aiming at reaching the maintenance dose level 2, the intervention will last for 52 weeks in total. |
|
| HDM1005 dose level 3 | Drug | Initiate at a once weekly dose of 0.5 mg and followed a dose escalation regimen, with dose increases every 4 weeks aiming at reaching the maintenance dose level 3, the intervention will last for 52 weeks in total. |
|
| Tirzepatide | Drug | Initiate at a once weekly dose of 2.5 mg and followed a dose escalation regimen, with dose increases every 4 weeks aiming at reaching the maintenance dose, the intervention will last for 52 weeks in total. |
|
| week 52 |
| Secondary Outcome | Change in waist circumference at week 40 | week 40 |
| Secondary Outcome | Change in body weight at week 40 | week 40 |
| Secondary Outcome | Change in BMI at week 40 | week 40 |
| Secondary Outcome | Change in BMI at week 52 | week 52 |
| Secondary Outcome | Change in waist circumference at week 52 | week 52 |
| Secondary Outcome | Change in waist body weight at week 52 | week 52 |
| Secondary Outcome | Change in systolic blood pressure (SBP) at week 40 | week 40 |
| Secondary Outcome | Change in diastolic blood pressure (DBP) at week 40 | week 40 |
| Secondary Outcome | Change in lipids at week 40 | week 40 |
| Secondary Outcome | Change in SBP at week 52 | week 52 |
| Secondary Outcome | Change in DBP at week 52 | week 52 |
| Secondary Outcome | Change in lipids at week 52 | week 52 |
| Safety Outcome | the incidence of adverse events | week 52 |
| Immunogenicity Outcome | ADA and NAb | week 52 |
| D001835 |
| Body Weight |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D008565 | Membrane Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D011964 | Receptors, Gastrointestinal Hormone |
| D018000 | Receptors, Peptide |