Clinical trial NCT06342947: ALG-055009 in Non-cirrhotic Adults With MASH (HERALD)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: NASH
MASH
Metabolic Dysfunction-Associated Steatohepatitis
Nonalcoholic Steatohepatitis
Keywords: NASH
MASH
Metabolic Dysfunction-Associated Steatohepatitis
Nonalcoholic Steatohepatitis
Liver
Fatty Liver Disease
Liver Disease
THR-B
THR B
THR-β
THR β
Lead sponsor: Aligos Therapeutics
Sponsor class: INDUSTRY
First posted: 2024-04-02
Enrollment: 102
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Percent relative change from baseline in liver fat content
timeFrame: 12 weeks
Secondary outcomes:
measure: Absolute change from baseline in liver fat content
timeFrame: 12 weeks
measure: Proportion of subjects with ≥30% relative reduction in liver fat content
timeFrame: 12 weeks
measure: Proportion of subjects with ≥50% relative reduction in liver fat content
timeFrame: 12 weeks
measure: Proportion of subjects with ≥70% relative reduction in liver fat content
timeFrame: 12 weeks
measure: Proportion of subjects with normalization (<5%) in liver fat content
timeFrame: 12 weeks
Other outcomes:
measure: Change from baseline (absolute/percent) in lipid/lipoprotein levels
timeFrame: 12 weeks
measure: Change from baseline (absolute/percent) in SHBG
timeFrame: up to 16 weeks
measure: Change from baseline (absolute/percent) alanine aminotransferase (ALT)
timeFrame: 12 weeks
measure: Change from baseline (absolute/percent) aspartate aminotransferase (AST)
timeFrame: 12 weeks
measure: Safety and tolerability will be assessed by monitoring TEAEs
timeFrame: 16 weeks
measure: Safety and tolerability will be assessed by monitoring 12-lead electrocardiograms (ECGs)
timeFrame: 16 weeks
measure: PK parameters of ALG-055009 in plasma, AUCs
timeFrame: 12 weeks
measure: PK parameters of ALG-055009 in plasma, Tmax
timeFrame: 12 weeks
measure: PK parameters of ALG-055009 in plasma, Cmax
timeFrame: 12 weeks
measure: PK parameters of ALG-055009 in plasma, Cmin
timeFrame: 12 weeks
Locations:
city: Chandler
country: United States
facility: Aligos Clinical Study Site 18
state: Arizona
city: Peoria
country: United States
facility: Aligos Clinical Study Site 15
state: Arizona
city: Tucson
country: United States
facility: Aligos Clinical Study Site 17
state: Arizona
city: Chula Vista
country: United States
facility: Aligos Clinical Study Site 35
state: California
city: Lincoln
country: United States
facility: Aligos Clinical Study Site 1
state: California
city: Poway
country: United States
facility: Aligos Clinical Study Site 37
state: California
city: Rialto
country: United States
facility: Aligos Clinical Study Site 10
state: California
city: Bradenton
country: United States
facility: Aligos Clinical Study Site 26
state: Florida
city: Clearwater
country: United States
facility: Aligos Clinical Study Site 25
state: Florida
city: Fort Myers
country: United States
facility: Aligos Clinical Study Site 39
state: Florida
city: Maitland
country: United States
facility: Aligos Clinical Study Site 2
state: Florida
city: Ocoee
country: United States
facility: Aligos Clinical Study Site 22
state: Florida
city: Port Orange
country: United States
facility: Aligos Clinical Study Site 32
state: Florida
city: Sarasota
country: United States
facility: Aligos Clinical Study Site 38
state: Florida
city: The Villages
country: United States
facility: Aligos Clinical Study Site 31
state: Florida
city: Viera
country: United States
facility: Aligos Clinical Study Site 3
state: Florida
city: Winter Park
country: United States
facility: Aligos Clinical Study Site 30
state: Florida
city: Athens
country: United States
facility: Aligos Clinical Study Site 23
state: Georgia
city: Topeka
country: United States
facility: Aligos Clinical Study Site 12
state: Kansas
city: Louisville
country: United States
facility: Aligos Clinical Study Site 29
state: Kentucky
city: Bastrop
country: United States
facility: Aligos Clinical Study Site 24
state: Louisiana
city: Houma
country: United States
facility: Aligos Clinical Study Site 5
state: Louisiana
city: Marrero
country: United States
facility: Aligos Clinical Study Site 4
state: Louisiana
city: Metairie
country: United States
facility: Aligos Clinical Study Site 6
state: Louisiana
city: Chesterfield
country: United States
facility: Aligos Clinical Study Site 14
state: Michigan
city: New York
country: United States
facility: Aligos Clinical Study Site 7
state: New York
city: Morehead City
country: United States
facility: Aligos Clinical Study Site 8
state: North Carolina
city: Columbus
country: United States
facility: Aligos Clinical Study Site 21
state: Ohio
city: Westlake
country: United States
facility: Aligos Clinical Study Site 16
state: Ohio
city: East Greenwich
country: United States
facility: Aligos Clinical Study Site 36
state: Rhode Island
city: Nashville
country: United States
facility: Aligos Clinical Study Site 9
state: Tennessee
city: Austin
country: United States
facility: Aligos Clinical Study Site 19
state: Texas
city: Bellaire
country: United States
facility: Aligos Clinical Study Site 33
state: Texas
city: Brownsville
country: United States
facility: Aligos Clinical Study Site 27
state: Texas
city: Edinburg
country: United States
facility: Aligos Clinical Study Site 28
state: Texas
city: Farmers Branch
country: United States
facility: Aligos Clinical Study Site 40
state: Texas
city: San Antonio
country: United States
facility: Aligos Clinical Study Site 20
state: Texas
city: Waco
country: United States
facility: Aligos Clinical Study Site 11
state: Texas
city: Manassas
country: United States
facility: Aligos Clinical Study Site 13
state: Virginia
city: Seattle
country: United States
facility: Aligos Clinical Study Site 34
state: Washington
Study officials:
name: Stephen Harrison, MD
role: PRINCIPAL_INVESTIGATOR
References: