Clinical trial NCT05989711: IMPACT TRIAL: Efficacy and Safety of Pemvidutide in Subjects With Nonalcoholic Steatohepatitis (NASH)
Official title: A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled Study Evaluating the Efficacy and Safety of Pemvidutide in Non-Cirrhotic Subjects With Nonalcoholic Steatohepatitis (NASH)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Non-Alcoholic Steatohepatitis (NASH)
Lead sponsor: Altimmune, Inc.
Sponsor class: INDUSTRY
First posted: 2023-08-14
Enrollment: 190
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, Double-blind, Placebo-controlled
Primary purpose: TREATMENT

Brief summary: Purpose of this study is to assess the effects of pemvidutide on NASH resolution and NASH fibrosis.

Detailed description: A Phase 2, multi-center, double-blind, placebo-controlled study to evaluate the efficacy and safety of pemvidutide in NASH.

Eligibility criteria: Inclusion Criteria:

1. Written informed consent
2. Male or female 18-75 years
3. Histologic diagnosis of NASH and/or histologic confirmation of NASH based on central pathology evaluation of a liver biopsy during screening

   1. A histologic NAFLD Activity Score (NAS) ≥ 4 with a score of at least 1 on each subcomponent score based on central pathology evaluation (steatosis \[0-3\], lobular inflammation \[0-3\], and hepatocyte ballooning \[0-2\])
   2. NASH fibrosis stages 2 through 3 according to the NASH CRN fibrosis staging system based on central pathology evaluation
4. Subject agrees to have a liver biopsy performed during the screening period (if no biopsy within the preceding 6 months is available) and at 24 weeks of treatment
5. BMI ≥ 27.0 kg/m2
6. Subjects with Type 2 diabetes mellitus (T2D) should be on a stable treatment regimen for their T2D for at least 90 days prior to screening
7. Subject meets at least 3 of the 5 criteria of Metabolic Syndrome (American Heart Association 2005)
8. Liver fat content by MRI-PDFF ≥ 8%

Exclusion Criteria:

1. Weight gain or loss \> 5% in the 3 months prior to randomization or \> 10% in the 6 months prior to screening
2. History or clinical evidence of Type 1 diabetes mellitus
3. Hemoglobin A1c (HbA1c) \> 9.5% or clinically significant persistent hyperglycemia
4. Liver conditions:

   1. History of cirrhosis or complications of cirrhosis, including but not limited to variceal bleeding, encephalopathy, or ascites
   2. Documented causes of chronic liver disease other than NASH
   3. ALT or AST laboratory values \> 5 × ULN

Primary outcomes:
measure: Proportion of subjects achieving NASH resolution (NAFLD activity score [NAS], ballooning = 0; lobular inflammation = 0, 1) with at least a 2-point reduction in NAS without worsening of fibrosis
timeFrame: 24 weeks
measure: Proportion of subjects achieving at least 1 stage improvement in liver fibrosis without worsening of NASH (defined as no change in the NAS, ie, the sum score for ballooning, inflammation, and steatosis)
timeFrame: 24 weeks
Secondary outcomes:
measure: Proportion of subjects achieving the composite of both NASH resolution and at least 1 stage improvement of liver fibrosis at 24 weeks
timeFrame: 24 weeks
measure: Relative change (%) in liver fat content by MRI-PDFF
timeFrame: 24 weeks and 48 weeks
measure: Absolute change in MRI-based corrected T1 (cT1) imaging
timeFrame: 24 weeks and 48 weeks
measure: Absolute change in alanine aminotransferase (ALT)
timeFrame: 24 weeks and 48 weeks
measure: Absolute change in Enhanced Liver Fibrosis (ELF) score
timeFrame: 24 weeks and 48 weeks
measure: Absolute change in Fibroscan-AST (FAST) score
timeFrame: 24 weeks and 48 weeks
measure: Relative (%) change in body weight
timeFrame: 24 weeks and 48 weeks
measure: Absolute changes in fasting lipids (total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides)
timeFrame: 24 weeks and 48 weeks
measure: Change in HbA1c (%)
timeFrame: 24 weeks and 48 weeks
measure: Change in glucose (mg/dL)
timeFrame: 24 weeks and 48 weeks
measure: Change in systolic and diastolic blood pressure (mmHg)
timeFrame: 24 weeks and 48 weeks
measure: Change in heart rate (beats per minute)
timeFrame: 24 weeks and 48 weeks
measure: The number of subjects with treatment emergent adverse events
timeFrame: 48 weeks
Other outcomes:
Locations:
city: Chandler
country: United States
facility: Altimmune Clinical Study Site
state: Arizona
city: Peoria
country: United States
facility: Altimmune Clinical Study Site
state: Arizona
city: Tucson
country: United States
facility: Altimmune Clinical Study Site
state: Arizona
city: Tucson
country: United States
facility: Altimmune Clinial Study Site
state: Arizona
city: North Hollywood
country: United States
facility: Altimmune Clinical Study Site
state: California
city: Panorama City
country: United States
facility: Altimmune Clinical Study Site
state: California
city: Englewood
country: United States
facility: Altimmune Clinical Study Site
state: Colorado
city: Bradenton
country: United States
facility: Altimmune Clinical Study Site
state: Florida
city: Fort Myers
country: United States
facility: Altimmune Clinical Study Site
state: Florida
city: Hialeah Gardens
country: United States
facility: Altimmune Clinical Study Site
state: Florida
city: Miami Lakes
country: United States
facility: Altimmune Clinical Study Site
state: Florida
city: Port Orange
country: United States
facility: Altimmune Clinical Study Site
state: Florida
city: Sarasota
country: United States
facility: Altimmune Clinical Study Site
state: Florida
city: West Palm Beach
country: United States
facility: Altimmune Clinical Study Site
state: Florida
city: Dalton
country: United States
facility: Altimmune Clinical Study Site
state: Georgia
city: Marietta
country: United States
facility: Altimmune Clinical Study Site
state: Georgia
city: Bastrop
country: United States
facility: Altimmune Clinical Study Site
state: Louisiana
city: Shreveport
country: United States
facility: Altimmune Clinical Study Site
state: Louisiana
city: Clarksville
country: United States
facility: Altimmune Clinical Study Site
state: Tennessee
city: Germantown
country: United States
facility: Altimmune Clinical Study Site
state: Tennessee
city: Austin
country: United States
facility: Altimmune Clinical Study Site
state: Texas
city: Bellaire
country: United States
facility: Altimmune Clinical Study Site
state: Texas
city: Edinburg
country: United States
facility: Altimmune Clinical Study Site
state: Texas
city: Edinburg
country: United States
facility: Altimmune Clinical Study Site
state: Texas
city: Georgetown
country: United States
facility: Altimmune Clinical Study Site
state: Texas
city: Houston
country: United States
facility: Altimmune Clinical Study Site
state: Texas
city: San Antonio
country: United States
facility: Altimmune Clinical Study Site
state: Texas
city: San Antonio
country: United States
facility: Altimmune Clinical Study Site
state: Texas
city: West Jordan
country: United States
facility: Altimmune Clinical Study Site
state: Utah
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: Liverpool
country: Australia
facility: Liverpool Hospital
state: New South Wales
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital/ Translational Research Institute
state: Queensland
city: Bedford Park
country: Australia
facility: Flinders Medical Centre
state: South Australia
city: Fitzroy
country: Australia
facility: St. Vincent's Hospital Melbourne
state: Victoria
city: Heidelberg
country: Australia
facility: Austin Health
state: Victoria
city: Box Hill
country: Australia
facility: Box Hill Hospital
state: Victory
city: Clayton
country: Australia
facility: Monash Hospital
state: Victory
city: Murdoch
country: Australia
facility: Fiona Stanley Hospital
state: Western Australia
city: Nedlands
country: Australia
facility: Sir Charles Gairdner Hospital
state: Western Australia
city: San Juan
country: Puerto Rico
facility: Altimmune Clinical Study Site
Study officials:
References: