NAFLD, Overweight and Obesity, Type2 Diabetes
Conditions
Keywords
Liver Disease
Brief 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).
Detailed description
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.
Interventions
DRUGDD01
The active of DD01 is a synthetic peptide, administered in a 1mL volume for injection.
DRUGPlacebo
Placebo drug of DD01, administered in a 1mL volume for injection
Sponsors
Neuraly, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Part A - Cohorts A1, A2, A3, A4, A5, A6, A7 & A8 Part B - Cohorts B2, B3, B4, B5, B6, B7 & B8
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of participants with treatment-related adverse events and serious adverse events | Part A - 43 days |
| Number of participants with treatment-related adverse events and serious adverse events (TEAEs) | Part B - 57 days |
| Number of participants with clinically significant abnormalities in clinical laboratory values | Part A - 43 days |
| Number of participants with clinically significant abnormalities in physical examinations | Part A - 43 days |
| Number of participants with clinically significant abnormalities in vital signs | Part A - 43 days |
| Blood Pressure assessed by 24-hour ambulatory blood pressure monitoring (ABPM) | Part A - 43 days |
| Heart Rate assessed by 24-hour ambulatory electrocardiography monitoring reader) | Part A - 43 days |
| Number of participants with clinically significant abnormalities in 12-lead ECGs | Part A - 43 days |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum observed blood/plasma concentration of DD01 | Part A - 43 days | Maximum observed blood/plasma concentration (Cmax) |
| Time of the maximum observed blood/plasma concentration of DD01 | Part A - 43 days | Time of the maximum observed blood/plasma concentration (Tmax) |
| Apparent blood/plasma terminal elimination half life of DD01 | Part A - 43 days | Apparent blood/plasma terminal elimination half life (t1/2) |
| Termination elimination rate constant of DD01 | Part A - 43 days | Termination elimination rate constant (kel) |
| Apparent total blood/plasma clearance of DD01 | Part A - 43 days | Apparent total blood/plasma clearance (CL/F) |
| Apparent volume of distribution of DD01 | Part A - 43 days | Apparent volume of distribution(Vz/F) |
| Area under the blood/plasma concentration time curve from time zero to the time of the last quantifiable concentration of DD01 | Part A - 43 days | Area under the blood/plasma concentration time curve from time zero to the time of the last quantifiable concentration (AUC0-t) |
| Area under the blood/plasma concentration time curve from time zero to 144 hours postdose of DD01 | Part A - 43 days | Area under the blood/plasma concentration time curve from time zero to 144 hours postdose (AUC0-144) |
| Area under the blood/plasma concentration time curve from time zero to 216 hours postdose of DD01 | Part A - 43 days | Area under the blood/plasma concentration time curve from time zero to 216 hours postdose (AUC0-216) |
| Area under the blood/plasma concentration time curve from time zero to 168 hours postdose of DD01 | Part B - 57 days | Part B only: Area under the blood/plasma concentration time curve from time zero to 168 hours postdose (AUC0-168) |
| Number of participants with antidrug antibodies (ADAs) | Part A - 43 days | — |
Countries
Puerto Rico, United States
Outcome results
None listed