A Phase 3, Randomized, Controlled Trial of Resmetirom in NASH with Liver Fibrosis (MAESTRO-NASH)
Harrison SA et al. NEJM (February 2024)
Bottom Line: This is an ongoing phase 3 clinical trial studying the effectiveness of resmetirom, an oral, liver-directed, thyroid hormone receptor beta-selective agonist, in treating nonalcoholic steatohepatitis (NASH) with liver fibrosis. The study includes 966 adults with confirmed NASH and fibrosis stage F1B, F2, or F3, who were randomly assigned to receive either 80 mg or 100 mg of resmetirom once daily or placebo. The primary outcomes at week 52 were NASH resolution, as measured by a reduction in the nonalcoholic fatty liver disease (NAFLD) activity score by ≥2 points (scores range from 0 to 8, with higher scores indicating more severe disease) with no worsening of fibrosis, and improvement in fibrosis by at least one stage with no worsening of the NAFLD activity score. 25.9% of the patients in the 80 mg resmetirom group and 29.9% of those in the 100 mg resmetirom group had NASH resolution with no worsening of fibrosis, as compared with 9.7% in the placebo group (P<0.001 for both comparisons with placebo). Fibrosis improvement was achieved in 24.2% of the patients in the 80 mg group, 25.9% in the 100 mg group, and 14.2% in the placebo group (P<0.001 for both comparisons with placebo). Safety outcomes showed a decrease in low-density lipoprotein cholesterol levels, but also a higher incidence of diarrhea and nausea with resmetirom. In conclusion, both doses of resmetirom were effective in treating NASH with liver fibrosis.
Twice-Yearly Lenacapavir for HIV Prevention in Men and Gender-Diverse Persons (PURPOSE 2)
Kelley CF et al. NEJM (November 2024)
Bottom line: This phase 3, double-blind, randomized, active-controlled trial evaluated the efficacy of subcutaneous lenacapavir every 26 weeks compared to daily oral emtricitabine-tenofovir disoproxil fumarate (F/TDF) in preventing HIV infection among 3265 cisgender men, transgender women, transgender men, and gender-nonbinary persons. The primary efficacy analysis compared the incidence of HIV infection in the lenacapavir group with the background HIV incidence in the screened population, which was 2.37 per 100 person-years amongst 4634 participants (95% CI, 0.43 to 1.77). The secondary efficacy analysis compared the incidence of HIV infection in the lenacapavir group with that in the F/TDF group. There were 2 infections in the lenacapavir group (0.10 per 100 person-years) and 9 in the F/TDF group (0.93 per 100 person-years). Thus, the incidence of HIV infection in the lenacapavir group was significantly lower than both the background incidence (incidence rate ratio, 0.04; 95% CI, 0.01 to 0.18; P<0.001) and the incidence in the F/TDF group (incidence rate ratio, 0.11; 95% CI, 0.02 to 0.51; P=0.002). No safety concerns were identified, supporting the efficacy of lenacapavir for HIV prevention.
High-Dose Vitamin D in Clinically Isolated Syndrome Typical of Multiple Sclerosis: The D-Lay MS Randomized Clinical Trial
Thouvenot E et al. JAMA (March 2025)
Bottom Line: The D-Lay MS trial was a parallel, double-blind, randomized placebo-controlled clinical trial conducted across 36 multiple sclerosis (MS) centers in France. 316 patients aged 18 to 55 years with 1) untreated clinically isolated syndrome (CIS) typical for MS with duration < 90 days, 2) diagnostic MRI, and 3) serum vitamin D concentration < 100 nmol/L were randomized 1:1 to receive either oral cholecalciferol 100,000 IU or placebo every 2 weeks for 24 months. The primary outcome of disease activity, defined as occurrence of relapse and/or MRI activity (new and/or contrast-enhancing lesions) over 24 months of follow up, was observed in 60.3% of the vitamin D group compared to 74.1% in the placebo group (HR 0.66 [95% CI, 0.50-0.87]; P = 0.004). Severe adverse events were reported in 17 patients in the vitamin D group and 13 in the placebo group, with none related to cholecalciferol treatment. The study concluded that high-dose vitamin D significantly reduces disease activity in CIS and early relapsing-remitting MS.
Trial Files Issue #2025-08