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

Overweight and Obesity Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04812262
• Other study ID #: DD01-DN-1
• Status: Completed
• Phase: Phase 1
• Start date: February 24, 2021
• Est. completion date: February 14, 2023

Study information

• Verified date: April 2024
• Source: Neuraly, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 255
• Est. completion date: February 14, 2023
• Est. primary completion date: December 20, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• NAFLD
• Non-alcoholic Fatty Liver Disease
• Overweight
• Overweight and Obesity
• Type2 Diabetes

Intervention

Drug:
• DD01
The active of DD01 is a synthetic peptide, administered in a 1mL volume for injection.
• Placebo
Placebo drug of DD01, administered in a 1mL volume for injection

Locations

Country	Name	City	State
Puerto Rico	FDI Clinical Research	San Juan
United States	Prosciento	Chula Vista	California
United States	Southwest General Healthcare Center	Fort Myers	Florida
United States	Combined Research Orlando	Orlando	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Neuraly, Inc.

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with treatment-related adverse events and serious adverse events		Part A - 43 days
Primary	Number of participants with treatment-related adverse events and serious adverse events (TEAEs)		Part B - 57 days
Primary	Number of participants with clinically significant abnormalities in clinical laboratory values		Part A - 43 days
Primary	Number of participants with clinically significant abnormalities in clinical laboratory values		Part B - 57 days
Primary	Number of participants with clinically significant abnormalities in physical examinations		Part A - 43 days
Primary	Number of participants with clinically significant abnormalities in physical examinations		Part B - 57 days
Primary	Number of participants with clinically significant abnormalities in vital signs		Part A - 43 days
Primary	Number of participants with clinically significant abnormalities in vital signs		Part B - 57 days
Primary	Blood Pressure assessed by 24-hour ambulatory blood pressure monitoring (ABPM)		Part A - 43 days
Primary	Blood Pressure assessed by 24-hour ambulatory blood pressure monitoring (ABPM)		Part B - 57 days
Primary	Heart Rate assessed by 24-hour ambulatory electrocardiography monitoring reader)		Part A - 43 days
Primary	Heart Rate assessed by 24-hour ambulatory electrocardiography monitoring reader)		Part B - 57 days
Primary	Number of participants with clinically significant abnormalities in 12-lead ECGs		Part A - 43 days
Primary	Number of participants with clinically significant abnormalities in 12-lead ECGs		Part B - 57 days
Secondary	Maximum observed blood/plasma concentration of DD01	Maximum observed blood/plasma concentration (Cmax)	Part A - 43 days
Secondary	Maximum observed blood/plasma concentration of DD01	Maximum observed blood/plasma concentration (Cmax)	Part B - 57 days
Secondary	Time of the maximum observed blood/plasma concentration of DD01	Time of the maximum observed blood/plasma concentration (Tmax)	Part A - 43 days
Secondary	Time of the maximum observed blood/plasma concentration of DD01	Time of the maximum observed blood/plasma concentration (Tmax)	Part B - 57 days
Secondary	Apparent blood/plasma terminal elimination half life of DD01	Apparent blood/plasma terminal elimination half life (t1/2)	Part A - 43 days
Secondary	Apparent blood/plasma terminal elimination half life of DD01	Apparent blood/plasma terminal elimination half life (t1/2)	Part B - 57 days
Secondary	Termination elimination rate constant of DD01	Termination elimination rate constant (kel)	Part A - 43 days
Secondary	Termination elimination rate constant of DD01	Termination elimination rate constant (kel)	Part B - 57 days
Secondary	Apparent total blood/plasma clearance of DD01	Apparent total blood/plasma clearance (CL/F)	Part A - 43 days
Secondary	Apparent total blood/plasma clearance of DD01	Apparent total blood/plasma clearance (CL/F)	Part B - 57 days
Secondary	Apparent volume of distribution of DD01	Apparent volume of distribution(Vz/F)	Part A - 43 days
Secondary	Apparent volume of distribution of DD01	Apparent volume of distribution(Vz/F)	Part B - 57 days
Secondary	Area under the blood/plasma concentration time curve from time zero to the time of the last quantifiable concentration of DD01	Area under the blood/plasma concentration time curve from time zero to the time of the last quantifiable concentration (AUC0-t)	Part A - 43 days
Secondary	Area under the blood/plasma concentration time curve from time zero to the time of the last quantifiable concentration of DD01	Area under the blood/plasma concentration time curve from time zero to the time of the last quantifiable concentration (AUC0-t)	Part B - 57 days
Secondary	Area under the blood/plasma concentration time curve from time zero to 144 hours postdose of DD01	Area under the blood/plasma concentration time curve from time zero to 144 hours postdose (AUC0-144)	Part A - 43 days
Secondary	Area under the blood/plasma concentration time curve from time zero to 144 hours postdose of DD01	Area under the blood/plasma concentration time curve from time zero to 144 hours postdose (AUC0-144)	Part B - 57 days
Secondary	Area under the blood/plasma concentration time curve from time zero to 216 hours postdose of DD01	Area under the blood/plasma concentration time curve from time zero to 216 hours postdose (AUC0-216)	Part A - 43 days
Secondary	Area under the blood/plasma concentration time curve from time zero to 216 hours postdose of DD01	Area under the blood/plasma concentration time curve from time zero to 216 hours postdose (AUC0-216)	Part B - 57 days
Secondary	Area under the blood/plasma concentration time curve from time zero to 168 hours postdose of DD01	Part B only: Area under the blood/plasma concentration time curve from time zero to 168 hours postdose (AUC0-168)	Part B - 57 days
Secondary	Number of participants with antidrug antibodies (ADAs)		Part A - 43 days
Secondary	Number of participants with antidrug antibodies (ADAs)		Part B - 57 days