Efficacy and Safety of Pemvidutide in Subjects With Nonalcoholic Steatohepatitis (NASH) (IMPACT Trial)

Phase 2

Active, not recruiting

• Conditions: Non-Alcoholic Steatohepatitis (NASH)
• Interventions: Drug: Placebo; Drug: Pemvidutide

• Registration Number: NCT05989711
• Lead Sponsor: Altimmune, Inc.

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.

Study Timeline

• Study First Submitted: 2023-07-24
• Study Start: 2023-07-27
• Study First Submitted QC: 2023-08-10
• Study First Posted: 2023-08-14
• Status Verified: 2024-09
• Last Update Submitted: 2024-09-27
• Last Update Posted: 2024-09-30
• Primary Completion: 2025-02-28
• Study Completion: 2025-09-30

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 190

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo (n=76)	Placebo	-
Pemvidutide 1.2 mg (n=38)	Pemvidutide	-
Pemvidutide 1.8 mg (n=76)	Pemvidutide	-

Primary Outcome Measures

Name	Time	Method
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	24 weeks
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)	24 weeks

Secondary Outcome Measures

Name	Time	Method
Change in HbA1c (%)	24 weeks and 48 weeks
Change in glucose (mg/dL)	24 weeks and 48 weeks
Relative change (%) in liver fat content by MRI-PDFF	24 weeks and 48 weeks
Relative (%) change in body weight	24 weeks and 48 weeks
Proportion of subjects achieving the composite of both NASH resolution and at least 1 stage improvement of liver fibrosis at 24 weeks	24 weeks
Absolute change in Fibroscan-AST (FAST) score	24 weeks and 48 weeks
Change in systolic and diastolic blood pressure (mmHg)	24 weeks and 48 weeks
The number of subjects with treatment emergent adverse events	48 weeks
Absolute change in MRI-based corrected T1 (cT1) imaging	24 weeks and 48 weeks
Absolute change in alanine aminotransferase (ALT)	24 weeks and 48 weeks
Absolute change in Enhanced Liver Fibrosis (ELF) score	24 weeks and 48 weeks
Absolute changes in fasting lipids (total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides)	24 weeks and 48 weeks
Change in heart rate (beats per minute)	24 weeks and 48 weeks

Trial Locations

Locations (12)

Altimmune Clinical Study Site; 🇵🇷 San Juan, Puerto Rico

Altimmune Clinial Study Site; 🇺🇸 Tucson, Arizona, United States

Royal Prince Alfred Hospital; 🇦🇺 Camperdown, New South Wales, Australia

Liverpool Hospital; 🇦🇺 Liverpool, New South Wales, Australia

Princess Alexandra Hospital/ Translational Research Institute; 🇦🇺 Woolloongabba, Queensland, Australia

Flinders Medical Centre; 🇦🇺 Bedford Park, South Australia, Australia

St. Vincent's Hospital Melbourne; 🇦🇺 Fitzroy, Victoria, Australia

Austin Health; 🇦🇺 Heidelberg, Victoria, Australia

Box Hill Hospital; 🇦🇺 Box Hill, Victory, Australia

Monash Hospital; 🇦🇺 Clayton, Victory, Australia

Fiona Stanley Hospital; 🇦🇺 Murdoch, Western Australia, Australia

Sir Charles Gairdner Hospital; 🇦🇺 Nedlands, Western Australia, Australia