ALG-055009 in Non-cirrhotic Adults With MASH (HERALD) (HERALD)

A Randomized, Double-Blind, Placebo-Controlled Phase 2a Study Evaluating the Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics of ALG-055009 in Non-Cirrhotic Adults With Metabolic Dysfunction-Associated Steatohepatitis

This is a Phase 2a study to evaluate the safety, tolerability, efficacy, pharmacokinetics, and pharmacodynamics of oral (PO) daily (QD) doses of ALG-055009 (soft gelatin [softgel] capsule) for 12 weeks.

Study Overview

• Status: Completed
• Conditions: Nonalcoholic Steatohepatitis; NASH; MASH; Metabolic Dysfunction-Associated Steatohepatitis
• Intervention / Treatment: Drug: ALG-055009; Drug: Placebo

Detailed Description

This is a double-blind, randomized, placebo-controlled Phase 2a study to evaluate the safety, tolerability, efficacy, pharmacokinetics, and pharmacodynamics of oral (PO) daily (QD) doses of ALG-055009 (soft gelatin [softgel] capsule) for 12 weeks. The study will be conducted in approximately 100 adult non-cirrhotic subjects with presumed MASH and liver fibrosis (F1-F3). The study will be conducted at up to approximately 45 sites throughout the United States of America.

• Study Type: Interventional
• Enrollment (Actual): 102
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Aligos Clinical Study Site 18
    • Peoria, Arizona, United States, 85301
      • Aligos Clinical Study Site 15
    • Tucson, Arizona, United States, 85641
      • Aligos Clinical Study Site 17
  • California
    • Chula Vista, California, United States, 91902
      • Aligos Clinical Study Site 35
    • Lincoln, California, United States, 95648
      • Aligos Clinical Study Site 1
    • Poway, California, United States, 92025
      • Aligos Clinical Study Site 37
    • Rialto, California, United States, 92316
      • Aligos Clinical Study Site 10
  • Florida
    • Bradenton, Florida, United States, 34205
      • Aligos Clinical Study Site 26
    • Clearwater, Florida, United States, 33755
      • Aligos Clinical Study Site 25
    • Fort Myers, Florida, United States, 33901
      • Aligos Clinical Study Site 39
    • Maitland, Florida, United States, 32751, 32794
      • Aligos Clinical Study Site 2
    • Ocoee, Florida, United States, 32703
      • Aligos Clinical Study Site 22
    • Port Orange, Florida, United States, 32119
      • Aligos Clinical Study Site 32
    • Sarasota, Florida, United States, 34230
      • Aligos Clinical Study Site 38
    • The Villages, Florida, United States, 32159
      • Aligos Clinical Study Site 31
    • Viera, Florida, United States, 32924
      • Aligos Clinical Study Site 3
    • Winter Park, Florida, United States, 32789
      • Aligos Clinical Study Site 30
  • Georgia
    • Athens, Georgia, United States, 30601
      • Aligos Clinical Study Site 23
  • Kansas
    • Topeka, Kansas, United States, 66546
      • Aligos Clinical Study Site 12
  • Kentucky
    • Louisville, Kentucky, United States, 40018
      • Aligos Clinical Study Site 29
  • Louisiana
    • Bastrop, Louisiana, United States, 71220
      • Aligos Clinical Study Site 24
    • Houma, Louisiana, United States, 70360
      • Aligos Clinical Study Site 5
    • Marrero, Louisiana, United States, 70072
      • Aligos Clinical Study Site 4
    • Metairie, Louisiana, United States, 70001
      • Aligos Clinical Study Site 6
  • Michigan
    • Chesterfield, Michigan, United States, 48047
      • Aligos Clinical Study Site 14
  • New York
    • New York, New York, United States, 10001
      • Aligos Clinical Study Site 7
  • North Carolina
    • Morehead City, North Carolina, United States, 28557
      • Aligos Clinical Study Site 8
  • Ohio
    • Columbus, Ohio, United States, 43004
      • Aligos Clinical Study Site 21
    • Westlake, Ohio, United States, 44145
      • Aligos Clinical Study Site 16
  • Rhode Island
    • East Greenwich, Rhode Island, United States, 02818
      • Aligos Clinical Study Site 36
  • Tennessee
    • Nashville, Tennessee, United States, 37011
      • Aligos Clinical Study Site 9
  • Texas
    • Austin, Texas, United States, 73301
      • Aligos Clinical Study Site 19
    • Bellaire, Texas, United States, 77401
      • Aligos Clinical Study Site 33
    • Brownsville, Texas, United States, 78520
      • Aligos Clinical Study Site 27
    • Edinburg, Texas, United States, 78504
      • Aligos Clinical Study Site 28
    • Farmers Branch, Texas, United States, 75006
      • Aligos Clinical Study Site 40
    • San Antonio, Texas, United States, 78015
      • Aligos Clinical Study Site 20
    • Waco, Texas, United States, 76633
      • Aligos Clinical Study Site 11
  • Virginia
    • Manassas, Virginia, United States, 20108
      • Aligos Clinical Study Site 13
  • Washington
    • Seattle, Washington, United States, 98039
      • Aligos Clinical Study Site 34

Participation Criteria

Eligibility Criteria

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

Description

Key Inclusion Criteria:

• Male or female, 18 to 75 years of age
• Body mass index (BMI) ≥ 25 kg/m2

• Diagnosis of presumed NASH/MASH with F1-F3 liver fibrosis based on one of the following:

  • Liver biopsy within 6 months prior to screening showing a NAFLD activity score (NAS) of ≥4 with at least a score of 1 in each of the NAS components; OR
  • Having ≥2 metabolic syndrome criteria and a screening FibroScan liver stiffness measurement between 7 - 20 kPa
• Screening FibroScan with CAP score of >300 dB/m
• Screening MRI-PDFF with ≥10% liver fat content

Key Exclusion Criteria:

• History or clinical evidence of chronic liver disease other than metabolic dysfunction-associated steatotic liver disease (MASLD)
• History or current evidence of cirrhosis
• History of liver transplantation or known planned liver transplantation
• History or current evidence of a pituitary disorder or hyperthyroidism
• Untreated clinical or subclinical hypothyroidism; or on thyroid replacement therapy at screening or within the last 6 months prior to screening.
• TSH, free T4, or Total T3 >1.1 x ULN or <0.9 x LLN
• Clinically concerning abnormal ECG or cardiac history
• HbA1c ≥9.5%
• Platelet count ≤135,000/mm3
• ALT or AST >5 x ULN
• INR >1.3
• Albumin <3.5 g/dL
• eGFR <45 mL/min/1.73 m2

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ALG-055009 softgel capsule 0.3mg; ALG-055009 softgel capsule 0.3mg Daily for 12 weeks	Drug: ALG-055009; Softgel Capsule
Experimental: ALG-055009 softgel capsule 0.5mg; ALG-055009 softgel capsule 0.5mg Daily for 12 weeks	Drug: ALG-055009; Softgel Capsule
Experimental: ALG-055009 softgel capsule 0.7mg; ALG-055009 softgel capsule 0.7mg Daily for 12 weeks	Drug: ALG-055009; Softgel Capsule
Experimental: ALG-055009 softgel capsule 0.9mg; ALG-055009 softgel capsule 0.9mg Daily for 12 weeks	Drug: ALG-055009; Softgel Capsule
Placebo Comparator: Placebo; Placebo softgel capsule Daily for 12 weeks	Drug: Placebo; Softgel Capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent relative change from baseline in liver fat content	Percent relative change from baseline in liver fat content by MRI-PDFF at Week 12	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute change from baseline in liver fat content	Absolute change from baseline in liver fat content by MRI-PDFF at Week 12	12 weeks
Proportion of subjects with ≥30% relative reduction in liver fat content	Proportion of subjects with ≥30% relative reduction in liver fat content by MRI-PDFF at Week 12	12 weeks
Proportion of subjects with ≥50% relative reduction in liver fat content	Proportion of subjects with ≥50% relative reduction in liver fat content by MRI-PDFF at Week 12	12 weeks
Proportion of subjects with ≥70% relative reduction in liver fat content	Proportion of subjects with ≥70% relative reduction in liver fat content by MRI-PDFF at Week 12	12 weeks
Proportion of subjects with normalization (<5%) in liver fat content	Proportion of subjects with normalization (<5%) in liver fat content by MRI-PDFF at Week 12	12 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline (absolute/percent) in lipid/lipoprotein levels	Change from baseline (absolute/percent) in lipid/lipoprotein levels at Week 12	12 weeks
Change from baseline (absolute/percent) in SHBG	Change from baseline (absolute/percent) in SHBG	up to 16 weeks
Change from baseline (absolute/percent) alanine aminotransferase (ALT)	Change from baseline (absolute/percent) in alanine aminotransferase (ALT) at Week 12	12 weeks
Change from baseline (absolute/percent) aspartate aminotransferase (AST)	Change from baseline (absolute/percent) in aspartate aminotransferase (AST) at Week 12	12 weeks
Safety and tolerability will be assessed by monitoring TEAEs	Safety and tolerability will be assessed by monitoring TEAEs	16 weeks
Safety and tolerability will be assessed by monitoring 12-lead electrocardiograms (ECGs)	Safety and tolerability will be assessed by monitoring 12-lead electrocardiograms (ECGs)	16 weeks
PK parameters of ALG-055009 in plasma, AUCs	PK parameters of ALG-055009 in plasma, AUCs	12 weeks
PK parameters of ALG-055009 in plasma, Tmax	PK parameters of ALG-055009 in plasma, Tmax	12 weeks
PK parameters of ALG-055009 in plasma, Cmax	PK parameters of ALG-055009 in plasma, Cmax	12 weeks
PK parameters of ALG-055009 in plasma, Cmin	PK parameters of ALG-055009 in plasma, Cmin	12 weeks

Collaborators and Investigators

• Sponsor: Aligos Therapeutics
• Investigators: Principal Investigator: Stephen Harrison, MD

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2024
• Primary Completion (Actual): August 19, 2024
• Study Completion (Actual): September 9, 2024

Study Registration Dates

• First Submitted: March 15, 2024
• First Submitted That Met QC Criteria: March 26, 2024
• First Posted (Actual): April 2, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 13, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Nonalcoholic Steatohepatitis; NASH; Liver Disease; Liver; Fatty Liver Disease; THR-β; Metabolic Dysfunction-Associated Steatohepatitis; MASH; THR-B; THR B; THR β
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: ALG-055009-303

Drug and device information, study documents

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