ALG-055009 em adultos não cirróticos com esteato-hepatite associada à disfunção metabólica (HERALD): um ensaio de fase 2a, randomizado, em dupla ocultação, controlado com placebo

Resumo original em inglês

O que aconteceu

Thyroid hormone receptor β (THR-β) agonists reduce atherogenic lipids, hepatic fat, and improve histology in metabolic dysfunction-associated steatohepatitis (MASH). The phase 2a HERALD study evaluated the efficacy, safety, pharmacokinetics, and pharmacodynamics of the selective and potent THR-β agonist ALG-055009 in non-cirrhotic adult patients with presumed MASH.

In this double-blind, placebo-controlled, phase 2a trial, participants aged 18-75 years with a BMI of at least 25 kg/m2 and a diagnosis of presumed non-alcoholic steatohepatitis (NASH) or MASH with F1-F3 liver fibrosis were randomly assigned to receive oral ALG-055009 (0·3 mg, 0·5 mg, 0·7 mg, or 0·9 mg) or placebo once daily for 12 weeks. Enrolment in the 0·9 mg group was limited to participants with bodyweight of more than 85 kg. The primary endpoint was percentage relative change from baseline in liver fat by MRI-proton density fat fraction (MRI-PDFF) at week 12 in the MRI-PDFF analysis population. The trial is registered at ClinicalTrials.gov, NCT06342947, and is now completed.

Aligos Therapeutics.

O que encontraram

102 participants (39 [38%] males and 63 [62%] females) were randomly assigned to receive ALG-055009 0·3 mg (n=20), ALG-055009 0·5 mg (n=22), ALG-055009 0·7 mg (n=20), ALG-055009 0·9 mg (n=18), or placebo (n=22); five participants (two in the 0·3 mg group, one in the 0·5 mg group, one in the 0·9 mg group, and one in the placebo group) did not have baseline and week 12 MRI-PDFF data and were thus not included in the analysis of the primary endpoint. Least-squares mean relative change in liver fat at week 12 was -6·9% (95% CI -19·2 to 5·3) with 0·3 mg ALG-055009, -11·2% (-22·9 to 0·4) with 0·5 mg ALG-055009, -25·9% (-37·7 to -14·1) with 0·7 mg ALG-055009, -24·3% (-37·9 to -10·6) with 0·9 mg ALG-055009, and 7·3% (-4·0 to 18·6) with placebo. Placebo-adjusted least-squares mean relative changes in liver fat at week 12 were therefore -14·3% (95% CI -29·6 to 1·0; p=0·067) for 0·3 mg ALG-055009, -18·5% (-33·3 to -3·8; p=0·014) for 0·5 mg ALG-055009, -33·2% (-48·1 to -18·3; p<0·0001) for 0·7 mg ALG-055009, and -31·6% (-47·4 to -15·8; p=0·0001) for 0·9 mg ALG-055009. Treatment-emergent adverse events occurred in 13 (65%) participants receiving 0·3 mg ALG-055009, ten (45%) receiving 0·5 mg ALG-055009, 13 (65%) receiving 0·7 mg ALG-055009, 11 (61%) receiving 0·9 mg ALG-055009, and in 16 (73%) receiving placebo. Most treatment-emergent adverse events were mild or moderate, with the most common being diarrhoea (ten [10%]), fatigue (six [6%]), and constipation (five [5%]). One serious adverse event occurred in the placebo group, and no deaths occurred. Gastrointestinal treatment-emergent adverse event rates for ALG-055009 were similar to placebo, and no clinically meaningful changes in laboratory tests, electrocardiogram, vital signs, physical exams, or thyroid function were observed.

Por que isso importa

Statistically significant reductions in liver fat with ALG-055009 and no relevant safety issues suggest that ALG-055009 could offer a promising treatment approach for patients with MASH. Results support evaluating extended ALG-055009 dosing on liver histology in participants with MASH.

Resumo publicado sob licença CC BY. A tradução para o português ainda não chegou a este estudo.