Safety, Tolerability, and Biologic Activity of AXA1125 and AXA1957 in Subjects With Nonalcoholic Fatty Liver Disease.
Am J Gastroenterol
; 116(12): 2399-2409, 2021 12 01.
Article
en En
| MEDLINE
| ID: mdl-34382947
ABSTRACT
INTRODUCTION:
AXA1125 and AXA1957 are novel, orally administered endogenous metabolic modulator compositions, specifically designed to simultaneously support multiple metabolic and fibroinflammatory pathways associated with nonalcoholic fatty liver disease (NAFLD). This study assessed safety, tolerability, and biologic activity of AXA1125 and AXA1957 in NAFLD.METHODS:
In this multicenter, 16-week, placebo-controlled, single-blind, randomized clinical study in subjects with NAFLD stratified by type 2 diabetes, AXA1125 24 g, AXA1957 13.5 g or 20.3 g, or placebo was administered twice daily. Key metabolism (MRI-proton density fat fraction [MRI-PDFF] and homeostasis model assessment of insulin resistance [HOMA-IR]) and fibroinflammation markers (alanine aminotransferase [ALT], corrected T1 [cT1], keratin-18 [K-18] M65, and N-terminal type III collagen propeptide [Pro-C3]) were evaluated. Safety outcomes included adverse events and standard laboratory assessments.RESULTS:
Baseline characteristics of the 102 enrolled subjects, including 40 with type 2 diabetes, were consistent with presumed nonalcoholic steatohepatitis. AXA1125 showed consistently greater biologic activity than AXA1957 or placebo. Week 16 changes from baseline with AXA1125 vs placebo MRI-PDFF -22.9% vs -5.7%, HOMA-IR -4.4 vs +0.7, ALT -21.9% vs -7.2%, K-18 M65 -13.6% vs +20.1%, cT1 -69.6 vs +18.3 ms (P < 0.05), and Pro-C3 -13.6% vs -3.6%. Week 16 changes from baseline with AXA1957 20.3 g MRI-PDFF -8.1%, HOMA-IR +8.4, ALT -20.7%, K-18 M65 6.6%, cT1 -34.7 ms, and Pro-C3 -15.6%. A greater proportion of subjects treated with AXA1125 achieved clinically relevant thresholds ≥30% MRI-PDFF, ≥17-IU/L ALT, and ≥80-ms cT1 reductions at week 16. Study products were safe and well tolerated with stable lipid and weight profiles.DISCUSSION:
Both compositions showed multitargeted activity on relevant NAFLD pathways. AXA1125 demonstrated the greatest activity over 16 weeks, warranting continued clinical investigation in nonalcoholic steatohepatitis subjects.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Arginina
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Acetilcisteína
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Valina
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Diabetes Mellitus Tipo 2
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Tolerancia a Medicamentos
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Enfermedad del Hígado Graso no Alcohólico
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Glutamina
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Isoleucina
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Leucina
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Hígado
Tipo de estudio:
Clinical_trials
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Diagnostic_studies
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Prognostic_studies
Límite:
Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Am J Gastroenterol
Año:
2021
Tipo del documento:
Article
País de afiliación:
Estados Unidos