NAFLD, NASH
Conditions
Keywords
Liver Disease, Fatty Liver, Non-alcoholic fatty liver disease, Non-alcoholic steatohepatitis, MASH, MASLD
Brief summary
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).
Interventions
DRUGDD01
Dual GLP-1 and glucagon receptor agonist
DRUGPlacebo
Placebo matching DD01
Sponsors
Neuraly, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Proportion of subjects who achieve at least 30% liver fat reduction measured by MRI-PDFF | 12 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 12 and 48 weeks | To determine the effect in liver biochemistry parameters including ALT, AST, AST/ALT ration, Gamma-glutamyl transferase, bilirubin |
| Change in glucose metabolism parameters | 12 and 48 weeks | To determine the effect on glucose metabolism parameters including glucose, insulin, C-peptide and HbA1c |
| Effect on pharmacokinetics as assessed by serum concentration-time profiles | Day 1 to 48 weeks | — |
Countries
United States
Contacts
STUDY_DIRECTORDennis To
Neuraly, Inc.
Outcome results
None listed