a phase 1 study of dd01 in overweight/obese subjects with t2dm and nafld

Conditions: Overweight and Obesity; Type2 Diabetes; NAFLD

Summary: 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.

Eligibility criteria:
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

Keywords: liver disease