Metabolic Dysfunction-Associated Steatohepatitis (MASH)
Conditions
Brief summary
Phase 3, multicenter, multinational, 2-cohort, randomized, double-blind, placebo controlled, parallel-group pivotal study to evaluate the efficacy, safety, and clinical outcomes of pemvidutide treatment in subjects with noncirrhotic (F2 or F3) metabolic dysfunction-associated steatohepatitis (MASH). Participants will be assigned either to Cohort 1 based on screening histologic (liver biopsy) criteria or to Cohort 2 based on non-invasive test criteria.
Interventions
DRUGPemvidutide
Pemvidutide SC Injection
OTHERPlacebo
Placebo SC Injection
Sponsors
Altimmune, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
All subjects: * No significant changes in body weight (±5%) and not participating in a structured weight loss program for the 3 months prior to screening (or since the historical biopsy, if applicable) * Body mass index (BMI) ≥ 25.0 kg/m2; if Asian, BMI ≥ 23.0 kg/m2 * Type 2 diabetes (T2D) or at least 2 components of metabolic syndrome * Subject agrees to have liver biopsy(ies) as required per protocol Cohort 1 - Histologic diagnosis of F2/F3 MASH based on liver biopsy during screening or historical biopsy within 6 months before screening Cohort 2 - Presumed F2/F3 MASH based on noninvasive testing
Exclusion criteria
* Cirrhosis (F4); portal hypertension or hepatic decompensation; acute or chronic liver disease other than MASH; liver function tests (ALT, AST; alkaline phosphatase; total bilirubin; INR; and platelet count) outside of acceptable ranges; positive HBsAg; active hepatitis C * Uncontrolled T2D or clinically significant persistent hyperglycemia
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Outcome Event | Baseline through end of study (approximately Month 60) | Time to first occurrence of any of the following events through the end of the study: Histologic progression to cirrhosis (F4) on liver biopsy; Liver related events; Liver transplantation; or Death due to any cause |
| Histological Response: MASH resolution | Baseline through Week 52 | Proportion of subjects achieving MASH resolution (according to NASH Clinical Research Network \[CRN\] classification) without worsening of fibrosis |
| Histological Response: Fibrosis improvement | Baseline through Week 52 | Proportion of subjects achieving ≥ 1 stage improvement in liver fibrosis according to the NASH CRN fibrosis staging system without worsening of MASH |
Secondary
| Measure | Time frame |
|---|---|
| Histologic Response: Proportion of subjects achieving both MASH resolution (according to NASH CRN classification) without worsening of fibrosis and ≥ 1 stage improvement in liver fibrosis without worsening of MASH | Baseline through Week 52 |
| HistoIndex qFibrosis: Proportion of subjects with at least a 1 stage improvement in qFibrosis | Baseline through Week 52 |
| Anthropometric parameters: Relative (%) change from baseline in body weight (kg) | Baseline through End of Study (approximately Month 60) |
| Anthropometric parameters: Relative (%) change from baseline in body mass index (BMI; kg/m2) | Baseline through End of Study (approximately Month 60) |
| Anthropometric parameters: Relative (%) change from baseline in waist circumference (cm) | Baseline through End of Study (approximately Month 60) |
| Noninvasive Tests of MASH Inflammatory and Fibrotic Activity: Absolute change from baseline in alanine aminotransferase (ALT; U/L) | Baseline through End of Study (approximately Month 60) |
| Noninvasive Tests of MASH Inflammatory and Fibrotic Activity: Absolute change from baseline in enhanced liver fibrosis (ELF) score | Baseline through End of Study (approximately Month 60) |
| Noninvasive Tests of MASH Inflammatory and Fibrotic Activity: Relative (%) change from baseline in vibration controlled transient elastography (VCTE; kPa) by Fibroscan | Baseline through End of Study (approximately Month 60) |
| HRQoL: Change from baseline in core symptoms of MASH on the NASH-CHECK questionnaire. | Baseline through End of Study (approximately Month 60) |
| HRQoL: Change from baseline in Short-form 36 (SF-36) summary scores. | Baseline through End of Study (approximately Month 60) |
| HRQoL: Change from baseline in Chronic Liver Disease Questionnaire for Nonalcoholic Steatohepatitis (CLDQ-NASH) domain scores. | Baseline through End of Study (approximately Month 60) |
Countries
United States
Contacts
CONTACTShaheen Tomah, MD
Outcome results
None listed