Abstract Background Current pharmacological treatments have demonstrated limited effectiveness in reversing atherosclerotic plaques. YN001, an innovative active-target liposomal drug, has been designed to promote significant plaque regression by enhancing cholesterol efflux and exerting anti-inflammatory effects. Aim This study aimed to explore the preliminary efficacy and safety of YN001 in Chinese patients with coronary atherosclerosis through a multicenter, randomized, controlled, open-label, multiple-dose ascending, proof-of-concept Phase 1b/2a clinical trial. Methods Patients with 25-75% coronary artery stenosis determined by angiography were enrolled at 6 sites. They were randomly assigned (3:1) to YN001 or standard of care control group. YN001 was administered intravenously at 6 dosage groups: 10mg once a week (QW), 10mg twice a week (BIW), 20mg QW, 20mg BIW, 40mg QW and 40mg BIW. Each cohort underwent 12 weeks of treatment followed by a 2-week safety follow-up. Efficacy endpoints included coronary plaque volume changes measured by intravascular ultrasound (IVUS) and coronary CTA, plaque composition changes measured by optical coherence tomography (OCT) and peripheral artery atherosclerosis measured by ultrasound. Results A total of 62 patients were enrolled and 16 patients of two cohorts (10mg BIW and 20mg QW) have completed the trial. Analysis of these patients’ efficacy endpoints was performed. Compared with the control group, IVUS measured coronary total atheroma volume (TAV) reduced significantly in treatment groups: -13.8% ± 9.4% vs 0.6% ± 4.7% (P=0.023), along with percent atheroma volume (PAV) (-11.53% ± 9.38% vs. 1.58% ± 2.09%, P=0.027); Coronary CTA measured TAV also reduced significantly in the treatment groups, with a mean reduction percentage of 27.8%. OCT data revealed that YN001 enhanced plaque stability. Compared to the control group, the treatment group showed significant differences in changes from baseline for minimal fibrous cap thickness (minFCT) (90.4 ± 55.4 µm vs. 7.5 ± 25 µm, P=0.013), lipid arc (-66.3 ± 86.4° vs. 16 ± 22.5°, P=0.013), and macrophage arc (-40.5 ± 33.3° vs. 10.8 ± 27.3°, P=0.006). Ultrasound measurements also demonstrated significant reductions in carotid intima-media thickness (cIMT), plaque area, and maximal plaque thickness in peripheral arteries in the YN001 treatment group. Conclusion YN001 showed promising effectiveness in atherosclerotic plaque regression and stabilization in this proof-of-concept Phase 1b/2a clinical trial. Further results from the full study are awaited.Plaque regression effects of YN001 Representative illustration
Zhou et al. (Sat,) studied this question.