ALG-055009 in Non-cirrhotic Adults With MASH (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.

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.

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