MASH, Metabolic Dysfunction-Associated Steatohepatitis, NASH, Nonalcoholic Steatohepatitis
Conditions
Keywords
NASH, MASH, Metabolic Dysfunction-Associated Steatohepatitis, Nonalcoholic Steatohepatitis, Liver, Fatty Liver Disease, Liver Disease, THR-B, THR B, THR-β, THR β
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.
Interventions
DRUGALG-055009
Softgel Capsule
DRUGPlacebo
Softgel Capsule
Sponsors
Aligos Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent relative change from baseline in liver fat content | 12 weeks | Percent relative change from baseline in liver fat content by MRI-PDFF at Week 12 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Absolute change from baseline in liver fat content | 12 weeks | Absolute change from baseline in liver fat content by MRI-PDFF at Week 12 |
| Proportion of subjects with ≥30% relative reduction in liver fat content | 12 weeks | Proportion of subjects with ≥30% relative reduction in liver fat content by MRI-PDFF at Week 12 |
| Proportion of subjects with ≥50% relative reduction in liver fat content | 12 weeks | Proportion of subjects with ≥50% relative reduction in liver fat content by MRI-PDFF at Week 12 |
| Proportion of subjects with ≥70% relative reduction in liver fat content | 12 weeks | Proportion of subjects with ≥70% relative reduction in liver fat content by MRI-PDFF at Week 12 |
| Proportion of subjects with normalization (<5%) in liver fat content | 12 weeks | Proportion of subjects with normalization (\<5%) in liver fat content by MRI-PDFF at Week 12 |
Other
| Measure | Time frame | Description |
|---|---|---|
| PK parameters of ALG-055009 in plasma, AUCs | 12 weeks | PK parameters of ALG-055009 in plasma, AUCs |
| PK parameters of ALG-055009 in plasma, Tmax | 12 weeks | PK parameters of ALG-055009 in plasma, Tmax |
| Change from baseline (absolute/percent) in lipid/lipoprotein levels | 12 weeks | Change from baseline (absolute/percent) in lipid/lipoprotein levels at Week 12 |
| PK parameters of ALG-055009 in plasma, Cmin | 12 weeks | PK parameters of ALG-055009 in plasma, Cmin |
| PK parameters of ALG-055009 in plasma, Cmax | 12 weeks | PK parameters of ALG-055009 in plasma, Cmax |
| Change from baseline (absolute/percent) in SHBG | up to 16 weeks | Change from baseline (absolute/percent) in SHBG |
| Change from baseline (absolute/percent) alanine aminotransferase (ALT) | 12 weeks | Change from baseline (absolute/percent) in alanine aminotransferase (ALT) at Week 12 |
| Change from baseline (absolute/percent) aspartate aminotransferase (AST) | 12 weeks | Change from baseline (absolute/percent) in aspartate aminotransferase (AST) at Week 12 |
| Safety and tolerability will be assessed by monitoring TEAEs | 16 weeks | Safety and tolerability will be assessed by monitoring TEAEs |
| Safety and tolerability will be assessed by monitoring 12-lead electrocardiograms (ECGs) | 16 weeks | Safety and tolerability will be assessed by monitoring 12-lead electrocardiograms (ECGs) |
Countries
United States
Outcome results
None listed