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).

Study Overview

• Status: Recruiting
• Conditions: NAFLD; Overweight and Obesity; Type2 Diabetes
• Intervention / Treatment: Drug: DD01; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Phase 1

Contacts and Locations

Study Locations

• Puerto Rico
  • San Juan, Puerto Rico, 00927
    • Recruiting
    • FDI Clinical Research
    • Contact: Digmarie Rivera; Phone Number: 787-722-1248; Email: drivera@fdipr.com
• United States
  • California
    • Chula Vista, California, United States, 91911
      • Recruiting
      • ProSciento
      • Contact: Robyn Rodriguez; Phone Number: 619-799-4818; Email: robyn.rodriguez@prosciento.com
  • Florida
    • Fort Myers, Florida, United States, 33907
      • Recruiting
      • Southwest General Healthcare Center
      • Contact: Brian Warnsky; Phone Number: 407-476-0514; Email: brian.swghcc@gmail.com
      • Principal Investigator: Jose E Rodriguez
    • Orlando, Florida, United States, 32807
      • Recruiting
      • Combined Research Orlando
      • Contact: Yenilady Estevez; Phone Number: 407-440-4493; Email: yenilady@clinicaltrialsorlando.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

15

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A1 - Single Ascending Dose; DD01 Dose 1 (N=6) Placebo (N=2) Subcutaneous injection	Drug: DD01; The active of DD01 is a synthetic peptide, administered in a 1mL volume for injection.; Drug: Placebo; Placebo drug of DD01, administered in a 1mL volume for injection
Experimental: Group A2, Single Ascending Dose; DD01 Dose 2 (N=6) Placebo (N=2) Subcutaneous injection	Drug: DD01; The active of DD01 is a synthetic peptide, administered in a 1mL volume for injection.; Drug: Placebo; Placebo drug of DD01, administered in a 1mL volume for injection
Experimental: Group A3, Single Ascending Dose; DD01 Dose 3 (N=6) Placebo (N=2) Subcutaneous injection	Drug: DD01; The active of DD01 is a synthetic peptide, administered in a 1mL volume for injection.; Drug: Placebo; Placebo drug of DD01, administered in a 1mL volume for injection
Experimental: Group A4, Single Ascending Dose; DD01 Dose 4 (N=6) Placebo (N=2) Subcutaneous injection	Drug: DD01; The active of DD01 is a synthetic peptide, administered in a 1mL volume for injection.; Drug: Placebo; Placebo drug of DD01, administered in a 1mL volume for injection
Experimental: Group B2 - Multiple Ascending Dose; DD01 Dose 2 (N=6) Placebo (N=2) Subcutaneous injection once weekly for 4 weeks	Drug: DD01; The active of DD01 is a synthetic peptide, administered in a 1mL volume for injection.; Drug: Placebo; Placebo drug of DD01, administered in a 1mL volume for injection
Experimental: Group B3 - Multiple Ascending Dose; DD01 Dose 3 (N=6) Placebo (N=2) Subcutaneous injection once weekly for 4 weeks	Drug: DD01; The active of DD01 is a synthetic peptide, administered in a 1mL volume for injection.; Drug: Placebo; Placebo drug of DD01, administered in a 1mL volume for injection
Experimental: Group B4 - Multiple Ascending Dose; DD01 Dose 4 (N=6) Placebo (N=2) Subcutaneous injection once weekly for 4 weeks	Drug: DD01; The active of DD01 is a synthetic peptide, administered in a 1mL volume for injection.; Drug: Placebo; Placebo drug of DD01, administered in a 1mL volume for injection
Experimental: Group B5 - Multiple Ascending Dose; DD01 Dose 4 (N=6) Placebo (N=2) Subcutaneous injection once weekly for 4 weeks	Drug: DD01; The active of DD01 is a synthetic peptide, administered in a 1mL volume for injection.; Drug: Placebo; Placebo drug of DD01, administered in a 1mL volume for injection
Experimental: Group B6 - Multiple Ascending Dose; DD01 Dose 4 (N=6) Placebo (N=2) Subcutaneous injection once weekly for 4 weeks	Drug: DD01; The active of DD01 is a synthetic peptide, administered in a 1mL volume for injection.; Drug: Placebo; Placebo drug of DD01, administered in a 1mL volume for injection
Experimental: Group A5, Single Ascending Dose; DD01 Dose 4 (N=6) Placebo (N=2) Subcutaneous injection	Drug: DD01; The active of DD01 is a synthetic peptide, administered in a 1mL volume for injection.; Drug: Placebo; Placebo drug of DD01, administered in a 1mL volume for injection
Experimental: Group A6, Single Ascending Dose; DD01 Dose 4 (N=6) Placebo (N=2) Subcutaneous injection	Drug: DD01; The active of DD01 is a synthetic peptide, administered in a 1mL volume for injection.; Drug: Placebo; Placebo drug of DD01, administered in a 1mL volume for injection
Experimental: Group A7, Single Ascending Dose; DD01 Dose 4 (N=6) Placebo (N=2) Subcutaneous injection	Drug: DD01; The active of DD01 is a synthetic peptide, administered in a 1mL volume for injection.; Drug: Placebo; Placebo drug of DD01, administered in a 1mL volume for injection
Experimental: Group A8, Single Ascending Dose; DD01 Dose 4 (N=6) Placebo (N=2) Subcutaneous injection	Drug: DD01; The active of DD01 is a synthetic peptide, administered in a 1mL volume for injection.; Drug: Placebo; Placebo drug of DD01, administered in a 1mL volume for injection
Experimental: Group B7 - Multiple Ascending Dose; DD01 Dose 4 (N=6) Placebo (N=2) Subcutaneous injection once weekly for 4 weeks	Drug: DD01; The active of DD01 is a synthetic peptide, administered in a 1mL volume for injection.; Drug: Placebo; Placebo drug of DD01, administered in a 1mL volume for injection
Experimental: Group B8 - Multiple Ascending Dose; DD01 Dose 4 (N=6) Placebo (N=2) Subcutaneous injection once weekly for 4 weeks	Drug: DD01; The active of DD01 is a synthetic peptide, administered in a 1mL volume for injection.; Drug: Placebo; Placebo drug of DD01, administered in a 1mL volume for injection

What is the study measuring?

Primary Outcome Measures

Outcome 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 clinical laboratory values	Part B - 57 days
Number of participants with clinically significant abnormalities in physical examinations	Part A - 43 days
Number of participants with clinically significant abnormalities in physical examinations	Part B - 57 days
Number of participants with clinically significant abnormalities in vital signs	Part A - 43 days
Number of participants with clinically significant abnormalities in vital signs	Part B - 57 days
Blood Pressure assessed by 24-hour ambulatory blood pressure monitoring (ABPM)	Part A - 43 days
Blood Pressure assessed by 24-hour ambulatory blood pressure monitoring (ABPM)	Part B - 57 days
Heart Rate assessed by 24-hour ambulatory electrocardiography monitoring reader)	Part A - 43 days
Heart Rate assessed by 24-hour ambulatory electrocardiography monitoring reader)	Part B - 57 days
Number of participants with clinically significant abnormalities in 12-lead ECGs	Part A - 43 days
Number of participants with clinically significant abnormalities in 12-lead ECGs	Part B - 57 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum observed blood/plasma concentration of DD01	Maximum observed blood/plasma concentration (Cmax)	Part A - 43 days
Maximum observed blood/plasma concentration of DD01	Maximum observed blood/plasma concentration (Cmax)	Part B - 57 days
Time of the maximum observed blood/plasma concentration of DD01	Time of the maximum observed blood/plasma concentration (Tmax)	Part A - 43 days
Time of the maximum observed blood/plasma concentration of DD01	Time of the maximum observed blood/plasma concentration (Tmax)	Part B - 57 days
Apparent blood/plasma terminal elimination half life of DD01	Apparent blood/plasma terminal elimination half life (t1/2)	Part A - 43 days
Apparent blood/plasma terminal elimination half life of DD01	Apparent blood/plasma terminal elimination half life (t1/2)	Part B - 57 days
Termination elimination rate constant of DD01	Termination elimination rate constant (kel)	Part A - 43 days
Termination elimination rate constant of DD01	Termination elimination rate constant (kel)	Part B - 57 days
Apparent total blood/plasma clearance of DD01	Apparent total blood/plasma clearance (CL/F)	Part A - 43 days
Apparent total blood/plasma clearance of DD01	Apparent total blood/plasma clearance (CL/F)	Part B - 57 days
Apparent volume of distribution of DD01	Apparent volume of distribution(Vz/F)	Part A - 43 days
Apparent volume of distribution of DD01	Apparent volume of distribution(Vz/F)	Part B - 57 days
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
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
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
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
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
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
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
Number of participants with antidrug antibodies (ADAs)		Part A - 43 days
Number of participants with antidrug antibodies (ADAs)		Part B - 57 days

Collaborators and Investigators

• Sponsor: Neuraly, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): February 24, 2021
• Primary Completion (Anticipated): December 1, 2022
• Study Completion (Anticipated): December 1, 2022

Study Registration Dates

• First Submitted: March 19, 2021
• First Submitted That Met QC Criteria: March 22, 2021
• First Posted (Actual): March 23, 2021

Study Record Updates

• Last Update Posted (Actual): May 9, 2022
• Last Update Submitted That Met QC Criteria: May 3, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: Liver Disease
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Body Weight; Fatty Liver; Overweight; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: DD01-DN-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No