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

NCT04812262 | Completed Phase 1 FDA Drug

• 1 other identifier: DD01-DN-1
• Study Type: interventional
• Target: 255
• Locations: 2 countries
• Sites: 4

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).

Conditions

Overweight and Obesity; Type2 Diabetes; NAFLD

Keywords

Liver Disease

Outcome Measures

Primary Outcomes (14)

• 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 Outcomes (21)

• Maximum observed blood/plasma concentration of DD01

  Part A - 43 days

• Maximum observed blood/plasma concentration of DD01

  Part B - 57 days

• Time of the maximum observed blood/plasma concentration of DD01

  Part A - 43 days

• Time of the maximum observed blood/plasma concentration of DD01

  Part B - 57 days

• Apparent blood/plasma terminal elimination half life of DD01

  Part A - 43 days

Study Arms (15)

Group A1 - Single Ascending Dose

EXPERIMENTAL

DD01 Dose 1 (N=6) Placebo (N=2) Subcutaneous injection

Drug: DD01; Drug: Placebo

Group A2, Single Ascending Dose

EXPERIMENTAL

DD01 Dose 2 (N=6) Placebo (N=2) Subcutaneous injection

Drug: DD01; Drug: Placebo

Group A3, Single Ascending Dose

EXPERIMENTAL

DD01 Dose 3 (N=6) Placebo (N=2) Subcutaneous injection

Drug: DD01; Drug: Placebo

Group A4, Single Ascending Dose

EXPERIMENTAL

DD01 Dose 4 (N=6) Placebo (N=2) Subcutaneous injection

Drug: DD01; Drug: Placebo

Group B2 - Multiple Ascending Dose

EXPERIMENTAL

DD01 Dose 2 (N=6) Placebo (N=2) Subcutaneous injection once weekly for 4 weeks

Drug: DD01; Drug: Placebo

Group B3 - Multiple Ascending Dose

EXPERIMENTAL

DD01 Dose 3 (N=6) Placebo (N=2) Subcutaneous injection once weekly for 4 weeks

Drug: DD01; Drug: Placebo

Group B4 - Multiple Ascending Dose

EXPERIMENTAL

DD01 Dose 4 (N=6) Placebo (N=2) Subcutaneous injection once weekly for 4 weeks

Drug: DD01; Drug: Placebo

Group B5 - Multiple Ascending Dose

EXPERIMENTAL

DD01 Dose 4 (N=6) Placebo (N=2) Subcutaneous injection once weekly for 4 weeks

Drug: DD01; Drug: Placebo

Group B6 - Multiple Ascending Dose

EXPERIMENTAL

DD01 Dose 4 (N=6) Placebo (N=2) Subcutaneous injection once weekly for 4 weeks

Drug: DD01; Drug: Placebo

Group A5, Single Ascending Dose

EXPERIMENTAL

DD01 Dose 4 (N=6) Placebo (N=2) Subcutaneous injection

Drug: DD01; Drug: Placebo

Group A6, Single Ascending Dose

EXPERIMENTAL

DD01 Dose 4 (N=6) Placebo (N=2) Subcutaneous injection

Drug: DD01; Drug: Placebo

Group A7, Single Ascending Dose

EXPERIMENTAL

DD01 Dose 4 (N=6) Placebo (N=2) Subcutaneous injection

Drug: DD01; Drug: Placebo

Group A8, Single Ascending Dose

EXPERIMENTAL

DD01 Dose 4 (N=6) Placebo (N=2) Subcutaneous injection

Drug: DD01; Drug: Placebo

Group B7 - Multiple Ascending Dose

EXPERIMENTAL

DD01 Dose 4 (N=6) Placebo (N=2) Subcutaneous injection once weekly for 4 weeks

Drug: DD01; Drug: Placebo

Group B8 - Multiple Ascending Dose

EXPERIMENTAL

DD01 Dose 4 (N=6) Placebo (N=2) Subcutaneous injection once weekly for 4 weeks

Drug: DD01; Drug: Placebo

Interventions

DD01 DRUG

The active of DD01 is a synthetic peptide, administered in a 1mL volume for injection.

Group A1 - Single Ascending Dose; Group A2, Single Ascending Dose; Group A3, Single Ascending Dose; Group A4, Single Ascending Dose; Group A5, Single Ascending Dose; Group A6, Single Ascending Dose; Group A7, Single Ascending Dose; Group A8, Single Ascending Dose; Group B2 - Multiple Ascending Dose; Group B3 - Multiple Ascending Dose; Group B4 - Multiple Ascending Dose; Group B5 - Multiple Ascending Dose; Group B6 - Multiple Ascending Dose; Group B7 - Multiple Ascending Dose; Group B8 - Multiple Ascending Dose

Placebo DRUG

Placebo drug of DD01, administered in a 1mL volume for injection

Group A1 - Single Ascending Dose; Group A2, Single Ascending Dose; Group A3, Single Ascending Dose; Group A4, Single Ascending Dose; Group A5, Single Ascending Dose; Group A6, Single Ascending Dose; Group A7, Single Ascending Dose; Group A8, Single Ascending Dose; Group B2 - Multiple Ascending Dose; Group B3 - Multiple Ascending Dose; Group B4 - Multiple Ascending Dose; Group B5 - Multiple Ascending Dose; Group B6 - Multiple Ascending Dose; Group B7 - Multiple Ascending Dose; Group B8 - Multiple Ascending Dose

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Neuraly, Inc.: lead

Study Sites (4)

Prosciento

Chula Vista, California, 91911, United States

Location

Southwest General Healthcare Center

Fort Myers, Florida, 33907, United States

Location

Combined Research Orlando

Orlando, Florida, 32807, United States

Location

FDI Clinical Research

San Juan, 00927, Puerto Rico

Location

MeSH Terms

Conditions

Overweight; Obesity; Non-alcoholic Fatty Liver Disease; Liver Diseases

Condition Hierarchy (Ancestors)

Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Fatty Liver; Digestive System Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Part A - Cohorts A1, A2, A3, A4, A5, A6, A7 \& A8 Part B - Cohorts B2, B3, B4, B5, B6, B7 \& B8

Study Record Dates

• First Submitted: March 19, 2021
• First Posted: March 23, 2021
• Study Start: February 24, 2021
• Primary Completion: December 20, 2022
• Study Completion: February 14, 2023
• Last Updated: April 29, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (3); PR (1)