A Phase 1 Study of DD01 in Overweight/Obese Subjects With T2DM and NAFLD

A Phase 1, Randomized, Double-blind, Placebo-controlled, Single and Multiple Dose Study to Assess Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of DD01 in Overweight/Obese Subjects With T2DM and NAFLD

This is a Phase 1, first in human (FiH), randomized, double-blind, placebo-controlled, single ascending dose (SAD) and multiple ascending dose (MAD) study to investigate the safety, tolerability, PK and PD of DD01 administered by subcutaneous (SC) injection in overweight/obese subjects with type 2 diabetes (T2DM) and nonalcoholic fatty liver disease (NAFLD).

The study will be conducted in 2 Parts (Part A and B), with up to 8 cohorts included in each part (Part A; Cohorts A1 to A8 and Part B; Cohorts B2 to B8).

Part A (SAD):

In Part A, subjects will receive a single dose of study drug, and the safety and efficacy of DD01 will be evaluated in overweight/obese subjects with T2DM.

Part B (MAD):

In Part B, subjects will receive once-weekly doses of the study drug for 4 weeks, and the safety and efficacy of DD01 will be evaluated in overweight/obese subjects with T2DM and NAFLD.

Part A Inclusion Criteria:

• Type 2 diabetes ≥ 12 months.
• Treatment with diet and exercise or metformin monotherapy on stable dose for 3 months prior to screening
• HbA1c ≤ 10%).
• Body Mass Index (BMI) ≥ 25 and ≤ 40.0 kg/m2

Part B Inclusion Criteria

• Type 2 diabetes ≥ 12 months.
• Treatment with diet and exercise or metformin monotherapy on stable dose for 3 months prior to screening
• HbA1c ≤ 10%
• BMI ≥ 30 kg/m2 and ≤ 40.0 kg/m2
• Waist circumference ≤ 57 inches
• Controlled attenuation parameter by FibroScan
• Liver fat fraction ≥ 10% by magnetic resonance imaging (MRI)

Part A Exclusion Criteria:

• History of type 1 diabetes mellitus (T1DM)
• History of acute proliferative retinopathy or maculopathy, severe gastroparesis, and/or severe neuropathy, in particular autonomic neuropathy, as judged by the Investigator.
• Uncontrolled hypertension
• Treatment with antihypertensive medication and statins not stable during the past 2 months prior to screening
• Treatment with thyroid hormones not stable during the past 3 months prior to screening
• History of any weight control treatment, including over-the-counter and herbal medication and supplements, or any medication with a labeled indication for weight loss or weight gain within 3 months prior to screening
• History of surgical treatment for obesity
• History of heart disease
• History of renal disease
• History or current diagnosis of acute or chronic pancreatitis or factors for pancreatitis, such as a history of cholelithiasis (without cholecystectomy) or alcohol abuse
• A history of or active chronic liver disease due to alcohol, auto-immune, HIV, HBV or active HCV-infection or NASH
• History of major depression, anxiety, suicidal behavior or attempts, or other psychiatric disorder requiring medical treatment
• Personal or family history of medullary thyroid carcinoma (MTC) or a genetic condition that predispose to MTC (i.e., multiple endocrine neoplasia type 2)
• Administration of Vaccines/Immunizations within 14 days prior to first dosing or if scheduled during the study. Vaccination for COVID-19 is allowed during the study if a washout period of 5 days after vaccine administration is followed before dosing.
• History of any major surgery within 6 months prior to screening
• Participation in any other clinical interventional study receiving active treatment within 30 days or 5 half-lives prior to screening, whichever is longer
• History of alcohol or illicit drug abuse including marijuana
• Existence of any surgical or medical condition that, in the judgment of the Investigator, might interfere with the investigational product

PART B Exclusion Criteria

• History of type 1 diabetes mellitus (T1DM)
• History of acute proliferative retinopathy or maculopathy, severe gastroparesis, and/or severe neuropathy, in particular autonomic neuropathy, as judged by the Investigator
• Uncontrolled hypertension (treatment with medications must be stable)
• History of any weight control treatment
• History of surgical treatment for obesity
• History of heart disease
• History of renal disease
• Subjects with a history or clinically significant active disease of the gastrointestinal, cardiovascular, hepatic, neurological, renal, pancreatic, immunological, dermatological, endocrine, genitourinary or hematological system.
• History or current diagnosis of acute or chronic pancreatitis
• History of major depression, anxiety, suicidal behavior or attempts, or other psychiatric disorder requiring medical treatment
• History of alcohol or illicit drug abuse including marijuana
• Existence of any surgical or medical condition that, in the judgment of the Investigator, might interfere with the investigational product
• Any history of clinically significant chronic liver disease