Bridge Study to Evaluate the Efficacy and Safety of IN-B00009 Injection in Patients With T2DM Inadequately Controlled by Diet and Exercise Alone

Official title

A Multi-center, Randomized, Double-Blind, Placebo Controlled, Parallel, Phase 3 Bridge Study to Evaluate the Efficacy and Safety of IN-B00009 Injection in Patients With T2DM Inadequately Controlled by Diet and Exercise Alone

Overview

This Phase 3 Bridge study is designed to evaluate the efficacy and safety of IN-B00009 Injection in Patients with T2DM Inadequately Controlled by Diet and Exercise Alone

Detailed description

This is a double-blind, randomized, placebo-controlled, Parallel, Phase 3 Bridge study. If the subjects are ultimately determined to meet all inclusion/exclusion criteria based on the results of the pre-randomization testing conducted at Visit 3, they are stratified based on HbA1c (≤ 8.5%, \> 8.5%) and randomly assigned to either the study group or the placebo group in a 1:1 ratio at Visit 4. Subjects will receive the investigational product once weekly for up to 24 weeks.

During the 24-week treatment period, the study group will begin with IN-B00009 injection at an initial dose of 0.3 mg and increase the dose at 4-week intervals to reach a target dose of 1.2 mg. After reaching the target dose, the dose will be maintained. The placebo group will receive the same volume of placebo as the study group at each time point.

\* Duration of Administration / Study Group / Placebo Group 4 weeks(week 0 \~ week 3) / IN-B00009 inj. 0.3 mg / Placebo 0.15 mL 4 weeks(week 4 \~ week 7) / IN-B00009 inj. 0.6 mg / Placebo 0.3 mL 16 weeks(week 8 \~ week 23) / IN-B00009 inj. 1.2 mg / Placebo 0.6 mL

Interventions

• Drug IN-B00009
  Test drug
• Drug Placebo
  Placebo drug

Primary outcome measures

• A change in HbA1c from baseline at Week 24 [Time frame: Baseline, 24 Weeks]

Secondary outcome measures (9)

• A change in HbA1c from baseline at each time point at Weeks 4, 8, 12, and 16 [Time frame: Baseline, 4 weeks, 8 weeks, 12 weeks, 16 weeks]
• Proportion of subjects with HbA1c <7% at week 24 [Time frame: 24 weeks]
• Proportion of subjects with HbA1c ≤6.5% at week 24 [Time frame: 24 weeks]
• A change in glucose metabolism indicators from baseline at week 24 [Time frame: Baseline, 24 weeks]
• A percent change in lipids from baseline at week 24 [Time frame: Baseline, 24 weeks]
• A change in blood pressure from baseline at week 24 [Time frame: Baseline, 24 weeks]
• A change in body weight from baseline at week 24 [Time frame: Baseline, 24 weeks]
• A percent change in body weight from baseline at week 24 [Time frame: Baseline, 24 weeks]
• A change in waist circumference from baseline at week 24 [Time frame: Baseline, 24 weeks]

Eligibility criteria

Inclusion criteria

• Subjects aged 19 to 75 years at the time of written consent
• Subjects with a BMI ≥ 20 kg/m² and ≤ 35 kg/m² at the screening visit

☞BMI (kg/m²) = Weight (kg) / Height (m)²

• Among subjects who have been diagnosed with T2DM at least 12 weeks ago and have followed a stable diet and exercise program for at least 8 weeks prior to the screening visit, those who meet any of the following criteria:

• Those who have not administered hypoglycemic agents within the past 12 weeks
• Those who have administered oral hypoglycemic agents within the past 12 weeks, but have not administered them within 5 weeks prior to the screening visit
• Subjects with HbA1c levels of 7.5% to 11.0% at the screening visit and 7.0% to 10.5% before randomization
• Subjects with fasting plasma glucose (FPG) levels ≤ 250 mg/dL (13.9 mmol/L) at the screening visit and pre-randomization testing
• Subjects who are able to self-monitor blood glucose levels and record subject diary cards during the study
• Subjects who agree to use medically acceptable contraceptive methods (including those medically incapable of pregnancy) during the study
• Subjects who are able to understand and follow instructions and participate throughout the study

Exclusion criteria

• Subjects who have been diagnosed with type 1 diabetes mellitus (T1DM) or diabetes due to a genetic defect or exocrine pancreatic dysfunction
• Subjects who have been administered GLP-1 analogues or DPP-4 inhibitors within 12 weeks prior to the screening visit
• Subjects who have used insulin within 24 weeks prior to the screening visit (excluding the short-term use for the treatment of hyperglycemia symptoms within a total of 14 days)
• Subjects with a history of diabetic ketoacidosis, hyperosmolar hyperglycemia, or diabetic lactic acidosis within 24 weeks prior to the screening visit
• Subjects with a history of severe chronic diabetic complications (proliferative diabetic retinopathy or diabetic maculopathy, diabetic peripheral neuropathy, etc.) within 24 weeks prior to the screening visit
• Subjects with a history of level 3 severe hypoglycemia within 24 weeks, or two or more events of level 2 hypoglycemia (blood glucose < 54 mg/dL) within 4 weeks prior to the screening visit
• Subjects with a history of severe trauma, infection, or surgery that may affect glycemic control within 4 weeks prior to the screening visit
• Subjects with a history of uncontrolled hyperthyroidism or hypothyroidism (However, those with 0.4 uIU/mL ≤ TSH ≤ 6.8 uIU/mL at the screening visit, who have been taking a stable dose of thyroid hormone medication for the past 12 weeks, and whose dose is unlikely to change during the study can participate.)
• Subjects with a history (including family history) of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia type 2 (MEN2)
• Subjects who have received medical or non-medical weight management, including weight management medications or products, within 12 weeks prior to the screening visit, or whose weight percent change confirmed by clinical interview exceeded 5%
• Subjects with at least one of the following medical histories confirmed within 24 weeks prior to the screening visit

• NYHA class III or IV heart failure
• Coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI)
• Ischemic heart disease (acute myocardial infarction, unstable angina, etc.)
• Severe cerebrovascular disease (cerebral infarction, cerebral hemorrhage, etc.), transient ischemic attack (TIA)
• Subjects with a history of uncontrolled respiratory disease (chronic obstructive pulmonary disease, bronchial asthma, active tuberculosis, etc.) within 24 weeks prior to the screening visit
• Subjects who have had severe gastrointestinal disease (active ulcer, etc.), gastrointestinal surgery, or clinically significant abnormal gastric emptying, or those who have chronically used medications that directly affect gastrointestinal motility within 24 weeks prior to the screening visit (However, those with a history of appendectomy or cholecystectomy are eligible to participate)
• Subjects with a history of acute or chronic pancreatitis (e.g., acute and chronic pancreatitis, symptomatic cholecystitis, pancreatic injury, etc.)
• Subjects with a history of malignant tumor within the past 5 years

• Those who have been assessed as having achieved complete remission (CR, pCR) of the tumor and have remained free of recurrence for ≥5 years from the date of assessment are eligible to participate
• Those with a history of thyroid cancer, excluding medullary thyroid carcinoma (MTC), carcinoma in situ of cervix, or basal cell or squamous cell carcinoma within the past 5 years are eligible to participate
• Subjects with a history of major depressive disorder, anxiety disorder, or other severe mental illness (e.g., schizophrenia, bipolar disorder, etc.) in an unstable state
• Subjects who tested positive for HBsAg, HCV antibody, or HIV antibody at the screening visit (However, those who tested positive for HCV-Ab but negative for HCV-RNA may participate.)
• Subjects whose test results meet the following at the screening visit and pre-randomization testing:

• Uncontrolled hypertension: siSBP≥160 mmHg or siDBP≥100 mmHg
• AST or ALT > 3 times the upper limit of normal , total bilirubin > 2 times the upper limit of normal
• Amylase or Lipase > 3 times the upper limit of normal
• eGFR ≤ 45mL/min/1.73m²
• TG > 500 mg/dL (or 5.65 mmol/L)
• Fasting C-peptide < 0.6 ng/mL (or 0.2 nmol/L)
• Hemoglobin <11.0 g/dL (male), <10.0 g/dL (female)
• Calcitonin ≥ 100 ng/L (or 100 pg/mL)
• Subjects with hematologic conditions (e.g., hemolytic anemia, hemoglobinopathies) that may interfere with HbA1c measurements at the screening visit and pre-randomization testing
• Subjects with a history of alcoholism or substance abuse
• Subjects who have taken systemic steroids or growth hormones for 7 days or more (including oral and intravenous administration) within 8 weeks prior to the screening visit
• Subjects with a history of resistance or hypersensitivity to the drugs in the same class as the investigational product
• Subjects who have received other investigational products or used investigational devices within 12 weeks prior to the screening visit
• Subjects who have donated blood, had significant bleeding (>400 mL), or received blood transfusion or blood products within 12 weeks prior to the screening visit
• Subjects with a history of nonarteritic anterior ischemic optic neuropathy (NAION)
• Subjects with a positive pregnancy test, pregnant women, or lactating women
• Subjects who deemed ineligible as subjects by the investigator for other reasons

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07308184 · IN_ECN_302

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗