A Study to Evaluate DD01 in Overweight/Obese Subjects With MASLD/MASH

A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Evaluate the Efficacy, Safety, and Tolerability of Treatment With DD01 for 48 Weeks in Overweight/Obese Subjects With MASLD/MASH

This is a Phase 2 Study to evaluate the effect of DD01 treatment in overweight/obese patients with metabolic dysfunction-associated steatotic liver disease (MASLD)/metabolic dysfunction-associated steatohepatitis (MASH).

Study Overview

• Status: Not yet recruiting
• Conditions: NAFLD; NASH
• Intervention / Treatment: Drug: DD01; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 68
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Study Director; Phone Number: 240-937-5880; Email: info@neuralymed.com

Study Locations

• United States
  • Florida
    • Maitland, Florida, United States, 92751
      • Summit Research Site
  • Louisiana
    • West Monroe, Louisiana, United States, 71291
      • Summit Research Site
  • Texas
    • Austin, Texas, United States, 78757
      • Summit Research Site
    • Brownsville, Texas, United States, 78520
      • Summit Research Site
    • Corpus Christi, Texas, United States, 78404
      • Summit Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or Female, 18 to 70 years of age

• With MASLD or confirmed diagnosis of MASH based on MRI PDFF ≥10% AND 1 of the following:

  1. Biopsy proven MASH obtained during Screening which confirms the presence of MASH characterized by a NAS ≥4 with at least 1 in each component (steatosis, ballooning, and lobular inflammation) and fibrosis stage F1 to F3. A historical biopsy obtained within 6 months may be acceptable OR
  2. Meets at least 2 additional metabolic syndrome factors
• Participants with a BMI ≥25 kg/m2, with stable body weight by history for 3 months
• Participants must have a waist circumference ≥35 inches (females), or ≥40 inches (males), and must have a waist circumference ≤57 inches (both males and females)
• Female participants must be non-pregnant, non-lactating or post-menopausal
• Participants must have the ability and willingness to comply with all Protocol procedures, provide written informed consent and meet all inclusion criteria as outlined in the study protocol

Exclusion Criteria: Participants who have:

• A history of active or chronic liver disease
• Liver cirrhosis (fibrosis stage F4), any prior history of hepatic decompensation, including low platelet counts, esophageal varices, ascites, hepatic encephalopathy, splenomegaly, any hospitalization for treatment of chronic liver disease, or a Model for End Stage Liver Disease score of ≥12
• Recent (within 3 months of Screening) use of therapies associated with development of MASLD/MASH (eg, systemic corticosteroids, methotrexate, tamoxifen, aromatase inhibitors, amiodarone, or long-term use of tetracyclines)
• Previous surgical treatment for obesity as well as clinically significant GI disorders
• Type 1 diabetes mellitus, or T2DM on insulin and/or GLP-1 receptor agonist therapy, dipeptidyl peptidase-4 inhibitors, or other therapies
• Uncontrolled hypertension or uncontrolled dyslipidemia
• Participated in an investigational study within 30 days prior to dosing or who have participated in another MASLD/MASH interventional study within 60 days prior to Screening
• With a history or current diagnosis of acute or chronic pancreatitis or factors for pancreatitis, symptomatic cholelithiasis and/or choledocholithiasis, or alcohol abuse
• With a history of any major surgery within 3 months prior to Screening
• With heart failure (New York Heart Association Class III or IV) or any cardiovascular event or evidence of active cardiovascular disease
• With a presence of clinically significant 12-lead ECG findings at Screening, or cardiac arrhythmia requiring medical or surgical treatment within 6 months prior to Screening
• With personal or family history of medullary thyroid carcinoma (MTC)
• With a history of renal disease
• With a history of alcohol or illicit drug abuse
• A positive test for hepatitis B surface antigen, hepatitis C RNA, or HIV type 1 or type 2 antibody
• A clinically significant physical examination, ECG, or laboratory finding, as judged by the Investigator, may interfere with any aspect of study conduct or interpretation of results
• Not met any other exclusion criteria as outlined in the study protocol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Matching Placebo	Drug: Placebo; Placebo matching DD01
Experimental: DD01; Study Drug	Drug: DD01; Dual GLP-1 and glucagon receptor agonist

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Proportion of subjects who achieve at least 30% liver fat reduction measured by MRI-PDFF	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute change in percent liver fat content as assessed by MRI-PDFF		12 weeks and 48 weeks
Change in liver stiffness as assessed by Magnetic Resonance Elastography (MRE)		12 weeks and 48 weeks
Change in liver stiffness measurements as assessed by FibroScan		12 weeks and 48 weeks
Change in liver steatosis as assessed by FibroScan		12 weeks and 48 weeks
Number of participants with Adverse Events		12 and 48 weeks
Change in liver biochemistry	To determine the effect in liver biochemistry parameters including ALT, AST, AST/ALT ration, Gamma-glutamyl transferase, bilirubin	12 and 48 weeks
Change in glucose metabolism parameters	To determine the effect on glucose metabolism parameters including glucose, insulin, C-peptide and HbA1c	12 and 48 weeks
Effect on pharmacokinetics as assessed by serum concentration-time profiles		Day 1 to 48 weeks

Other Outcome Measures

Outcome Measure	Time Frame
Histologic evidence for improvements in MASH	48 weeks

Collaborators and Investigators

• Sponsor: Neuraly, Inc.
• Investigators: Study Director: Dennis To, Neuraly, Inc.

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2024
• Primary Completion (Estimated): March 1, 2025
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: May 8, 2024
• First Submitted That Met QC Criteria: May 8, 2024
• First Posted (Actual): May 13, 2024

Study Record Updates

• Last Update Posted (Actual): May 16, 2024
• Last Update Submitted That Met QC Criteria: May 13, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Non-alcoholic fatty liver disease; Liver Disease; Fatty Liver; Non-alcoholic steatohepatitis; MASLD; MASH
• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Body Weight; Overweight
• Other Study ID Numbers: DD01-DN-02

Drug and device information, study documents

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