Study to Evaluate the Efficacy and Safety of IN-B00009 Injection in Adults With Obesity or Overweight Without Diabetes Mellitus

A Phase 3, Multi-center, Randomized, Double-Blind, Placebo-Controlled, Parallel Study to Evaluate the Efficacy and Safety of IN-B00009 Injection in Adults With Obesity or Overweight Without Diabetes Mellitus

This Phase 3 study is designed to evaluate the efficacy and safety of IN-B00009 injection in adults with obesity or overweight without diabetes mellitus

Inclusion Criteria:

1. Aged 19 to 75 years as of the date of written consent

2. Those who meet any of the following obesity criteria at the screening visit

   • BMI ≥ 30 kg/m2

   • 27 kg/m2 ≤ BMI < 30 kg/m2 with at least one risk factor or comorbidity

     • BMI (kg/m2) = weight (kg) / height (m)2

       • Hypertension: Taking antihypertensive medication or sitSBP ≥ 140 mmHg or sitDBP ≥ 90 mmHg
       • Dyslipidemia: Taking dyslipidemia medication or Total Cholesterol ≥ 240mg/dL or LDL-C ≥ 160 mg/dL or TG ≥ 200 mg/dL or HDL-C < 40 mg/dL
       • Obstructive sleep apnea
       • Cardiovascular and cerebrovascular diseases: Ischemic cardiovascular and cerebrovascular diseases not corresponding to exclusion criterion 17, heart failure of NYHA Class I to III, etc.
       • Prediabetes: 100 mg/dL ≤ FPG ≤ 125 mg/dL or 140 mg/dL ≤ PG ≤ 199 mg/dL at 2 hours after 75 g oral glucose load or 5.7% ≤ HbA1c ≤ 6.4%

3. Self-reported history of at least one failed attempt at weight control using diet and exercise therapy prior to the screening visit

4. Able to agree to and follow the reduced-calorie diet and exercise therapy recommended in this study during the study period

5. Agrees to use a medically appropriate method of contraception (including medically infertile conditions) during the study period

Exclusion Criteria:

1. Body weight change exceeding 5 kg within 3 months of the screening visit

2. Diabetes (Type 1, Type 2, etc.) or HbA1c ≥ 6.5% at the screening visit

3. Received any of the following medications or treatments within 3 months of the screening visit

   ① Obesity-related medications (such as GLP-1 receptor agonists) or medications including over-the-counter drugs, herbal medicines, or health functional foods for weight control

   ② Received hypoglycemic agent or requires continuous administration during the study period

   ③ Received systemic steroids for 30 consecutive days or more, or requires continuous administration during the study period

   ④ Received other medications that cause significant body weight changes or requires continuous administration during the study period (e.g.: antipsychotics, tricyclic antidepressants, selective serotonin reuptake inhibitors, noradrenergic and specific serotonergic antidepressant, mood stabilizers (lithium), anticonvulsants, serotonin antagonists, first-generation antihistamines, etc.)

4. Diagnosed with obesity due to endocrine disorders (hypothalamic obesity, Cushing's syndrome, insulinoma, adult growth hormone deficiency, hypothyroidism, etc.)

5. Diagnosed with obesity due to genetic variations and congenital disorders

   • Obesity-causing genes: ob, db, Proopiomelanocortin (POMC), Melanocortin 4 receptor (MC4R) genes, etc.
   • Congenital disorders: Prader-Willi syndrome, Laurence-Moon-Biedl syndrome, Alström syndrome, Cohen syndrome, Carpenter syndrome, etc.

6. History of bariatric surgery (e.g., adjustable gastric banding, sleeve gastrectomy, Roux-en-Y gastric bypass, biliopancreatic diversion/duodenal switch, etc.) or device procedures, or plans for such during the study period

   • However, those who have had devices (e.g., gastric band, intragastric balloon) removed for more than 1 year can participate
   • Those who have had liposuction or abdominoplasty for more than 1 year can participate

7. Clinically significant gastrointestinal disorders (e.g., gastroparesis, gastric outlet obstruction, peptic ulcer, severe gastroesophageal reflux disease)

8. History (including family history) of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia type 2 (MEN2), or results of clinical laboratory test at the screening visit meeting the following:

   • Calcitonin ≥ 100 ng/L
   • TSH < 0.6 mIU/L or TSH > 6.8 mIU/L (However, subjects being treated for hypothyroidism with 0.6 mIU/L ≤ TSH ≤ 6.8 mIU/L, taking stable doses of thyroid hormonal preparation for 3 months prior to the screening visit and unlikely to have dose changes during the study period can participate)

9. History of acute or chronic pancreatitis, or results of clinical laboratory test at the screening visit meeting the following:

   - Amylase or Lipase > 3 times the upper limit of normal

10. Severe hepatic impairment or results of clinical laboratory test at the screening visit meeting the following:

    - AST or ALT > 3 times the upper limit of normal or Total bilirubin > 2 times the upper limit of normal

11. Severe renal impairment (eGFR < 30mL/min/1.73m2)

12. Uncontrolled hypertension (sitSBP ≥ 160 mmHg or sitDBP ≥ 100 mmHg) at the screening visit

13. Answered "yes" to question 4 or 5 in the suicidal ideation section of the Columbia-Suicide Severity Rating Scale (C-SSRS) at the screening visit or history of suicide attempt

14. Score of 15 or higher on the Patient Health Questionnaire-9 (PHQ-9) at the screening visit, or history of major depressive disorder with unstable state, anxiety, or other severe psychiatric disorders (schizophrenia, bipolar disorder, etc.) within 2 years

15. History of alcohol addiction or drug abuse within 3 months of the screening visit

16. History of malignant tumor within the last 5 years

    • Those who have been determined as complete remission (CR, pCR) of the tumor and had no relapse for 5 years or more from the date of assessment can participate
    • Those with a history of thyroid cancer (excluding MTC), basal cell and squamous cell skin cancer within the last 5 years can participate

17. Any of the following medical histories confirmed within 3 months of the screening visit

    • Heart failure of NYHA class IV
    • Coronary artery bypass graft (CABG), percutaneous coronary intervention (PCI)
    • Ischemic heart disease (acute myocardial infarction, unstable angina, etc.). However, if the condition has been stable for 6 months or more from the screening visit, participation is possible at the investigator's discretion
    • Severe cerebrovascular disease (cerebral infarction, cerebral hemorrhage, etc.), transient ischemic attack (TIA). However, if the condition has been stable for 6 months or more from the screening visit, participation is possible at the investigator's discretion

18. History of non-arteritic anterior ischemic optic neuropathy (NAION)

19. History of resistance or hypersensitivity to investigational product class drugs (GLP analogues) or history of multi-drug allergies

20. Requires administration of contraindicated medications during the study period

21. Received other investigational products within 30 days or 5 times the half-life (whichever is longer) if the half-life is known, prior to the screening visit

22. Positive for HBsAg, HCV antibody, or HIV antibody at the screening visit

    - However, those who are HCV-Ab positive but confirmed negative in HCV-RNA test can participate

23. Hematological conditions that may interfere with HbA1c measurement (e.g.: hemolytic anemia, hemoglobinopathies)

24. Scheduled for surgery requiring hospitalization during the study period or requires surgical treatment

25. Positive pregnancy test, pregnant or lactating women

26. Considered inappropriate as a study subject by the investigator for other reasons