Clinical Trials of IBI3040 in Healthy Participants and Overweight or Obese Participants

Inclusion criteria

All participants in Part A (SAD) and Part B (MAD) must meet inclusion criteria 1-3:

• 1.The age at the time of informed consent should be between 18 and 65 years old (including both values), and there is no gender restriction.
• 2.Female participants who are fertile and male participants whose partners are fertile must agree to use the contraceptive methods specified in the protocol during the study period and within 90 days after the last administration. The pregnancy test results of female participants with fertility before randomization must be negative. Female participants should not breastfeed. Male/female participants must be willing to avoid donating sperm/eggs during the study period and within 90 days after the last administration.
• 3. Be able to understand the procedures and methods of this research, be willing to strictly follow the clinical trial protocol to complete this trial, and voluntarily sign the informed consent form.

Participants of Part A (SAD) also need to meet inclusion criteria 4-6:

• 4. Participants who were determined by the researchers to be normal or abnormal based on the results of various examinations such as medical history, vital signs, physical examination, 12-lead electrocardiogram, laboratory tests, infectious disease screening, chest X-ray, and abdominal color Doppler ultrasound, but were determined by the researchers to have no clinical significance.
• 5. During screening, 20 kg/m ² ≤BMI <28 kg/m ²;
• 6. When screening, the standard weight should be ≥50 kg

Participants of Part B (MAD) also need to meet inclusion criteria 7-8:

• 7. During screening, 24 kg/m2 ≤BMI ≤40 kg/m2;
• 8. The standard weight change within 3 months prior to screening should be no more than 5kg (reported by the participants themselves).

Exclusion criteria

All participants in Part A (SAD) and Part B (MAD) who meet any one of the exclusion criteria 1-17 cannot be included in the corresponding stage of the study:

• 1.Participants may be allergic to any component of the investigational drug, GLP-1 or Amylin receptor agonists (see Appendix 3 for details), or have used GLP-1 or Amylin receptor agonists within 3 months prior to screening;
• 2. A history of diabetes, or a glycated hemoglobin level of ≥6.5% during the screening period, or a fasting blood glucose level of ≥7.0 mmol/L;
• 3. Previous history of thyroid C-cell carcinoma, multiple endocrine adenomatosis (MEN) 2A or 2B, or related family history, or calcitonin ≥20 ng/L at screening;
• 4. A history of acute or chronic pancreatitis in the past, or amylase or lipase >1.5× upper limit of the normal range (ULN) at the time of screening;
• 5. Alanine aminotransferase >1.5×ULN during the screening period; Or aspartate aminotransferase >1.5×ULN; Or total bilirubin >1.5×ULN;
• 6. During the screening period, the hepatitis B surface antigen is positive, or the hepatitis C antibody is positive, or the syphilis helix specific antibody is positive, or the HIV antibody is positive;
• 7. Abnormal 12-lead electrocardiogram (ECG) during the screening period and judged by the researcher as having clinical significance, or ECG QTcF >450 ms, or heart rate <60 beats per minute or >100 beats per minute;
• 8. Having a history of suicidal behavior, or being considered to have a significant suicide risk at present, or having a PHQ (Depression Screening Scale) score of ≥15 at the time of screening, or being classified as category 4 or 5 on the C-SSRS (Columbia Suicide Severity Scale) at the time of screening, or choosing "yes" in suicidal behavior or suicidal ideation;
• 9. Use of prescription and over-the-counter drugs within 2 weeks before screening or within 5 half-lives (excluding topical eye/nasal drops and creams without systemic exposure risk);
• 10. Have participated in any clinical trials of drugs (or within five half-lives) or medical devices within three months prior to screening, or plan to participate in clinical trials of other drugs or medical devices during the trial period;
• 11. Those who consumed an average of more than 2 units of alcohol per day in the three months prior to screening (1 unit of alcohol ≈360 mL of beer with an alcohol content of 5% or 45 mL of spirits with an alcohol content of 40% or 150 mL of wine with an alcohol content of 12%), or those who were unable to quit drinking during the trial period, or those with a positive breath test for alcohol;
• 12. Smoking more than 5 cigarettes per day within the 3 months prior to screening;
• 13. Those who have a history of drug abuse within the five years prior to screening, or have used drugs within the three months prior to screening, or have a positive urine drug screening result;
• 14. Blood donation and/or blood loss within 3 months prior to screening ≥450 mL, or having undergone bone marrow donation, blood transfusion or severe blood loss, or having hemoglobinopathy, hemolytic anemia, sickle cell anemia, or hemoglobin <120 g/L (for men) or <110 g/L (for women);
• 15. Inability to tolerate venipuncture for blood collection or fainting at the sight of needles and blood;
• 16. Those whose injection site assessment is considered abnormal by the researchers;
• 17. The researcher believes that there are other factors that are not suitable for participating in this trial.

Participants in Part A (SAD) cannot be included in the study if they meet the following exclusion criteria:

• 18. During the screening period, the systolic blood pressure is less than 90mmHg or ≥140mmHg, or the diastolic blood pressure is less than 50 mmHg or ≥90mmHg, or the pulse rate is less than 60 beats per minute or >100 beats per minute.

Participants in Part B (MAD) who meet any one of the exclusion criteria 19-25 cannot be included in the study:

• 19. The following diseases (including but not limited to gastrointestinal, kidney, liver, nervous, blood, endocrine, tumor, lung, immune, mental or cardiovascular and cerebrovascular diseases) with clinical findings indicating clinical significance within 12 months prior to screening;
• 20. A history of life-threatening diseases (excluding basal cell skin cancer or squamous cell skin cancer) within the five years prior to screening;
• 21. Previous researchers have considered clinically significant gastric emptying abnormalities (for example, severe gastroparesis or gastric outlet obstruction), who have undergone gastric bypass (bariatric) surgery or restrictive bariatric surgery, or have been taking drugs that directly affect gastrointestinal motility for a long time;
• 22. During the screening period, systolic blood pressure is less than 90 mmHg or ≥160mmHg, or diastolic blood pressure is less than 50 mmHg or ≥100mmHg, or pulse rate is less than 60 beats per minute or >100 beats per minute.
• 23. For drugs that have been used or are currently being used within the three months prior to screening and may cause significant standard weight gain, including but not limited to: tricyclic antidepressants, psychotropic drugs or sedatives (such as imipramine, amitriptyline, mirtazapine, paroxetine, phenylhydrazine, chlorpromazine, thiridazine, clozapine, olanzapine, valproic acid, valproic acid derivatives, lithium salts);
• 24. Having used weight-loss drugs or alternative therapies within the three months prior to screening, including but not limited to: GLP-1 or Amylin receptor agonists, orlistat, sibutramine hydrochloride, phenylpropanolamine, chlorphenimidole, butylamine, clocaserin hydrochloride, fentamine, fentamine/topiramate mixture, anferylene and naltrexone/bupropion mixture.
• 25. Thyroid tumors or thyroid nodules with a Thyroid Imaging Reporting and Data System (TI-RADS) grade of ≥4 were present during screening.