Primary data analyses of MAESTRO-NAFLD-1 a 52 week double-blind placebo-controlled phase 3 clinical trial of resmetirom in patients with NAFLD
Journal of Hepatology
; 77:S14, 2022.
Article
in English
| EMBASE | ID: covidwho-1967492
ABSTRACT
Background and aims:
Approval of a drug therapy for NASH requires a very good safety/tolerability profile and acceptable therapeutic index. MAESTRO-NAFLD-1 (NCT04197479) is a randomized doubleblind (DB) Phase 3 clinical trial of placebo (PBO) versus resmetirom (RES), a once-a-day oral selective thyroid hormone receptor β agonist, in >1100 patients with NAFLD with safety as the primary end point.Method:
Enrollment was Dec 2019 to Oct 2020 at 79 US sites. Requirements included 3 metabolic risk factors, fibroscan (FS) ≥5.5 kPa/CAP≥280 dBm, MRI-PDFF≥8%. Randomization was 1111 to 3 DB arms, PBO, 80 or 100 mg RES (n = 972) or an 100 mg open label (OL) arm (n = 171). The primary objective was to evaluate the safety and tolerability of 80 or 100 mg RES versus PBO measured by the incidence of adverse events (AEs).Results:
At baseline the DB safety population (n = 969) was age 55.9 (11.8);female, 54.4%, white 88.6%;hispanic 34.7%;BMI 35.3 (6.0) type 2 diabetes 49%, hypertension 76.1%, dyslipidemia 87.9%;FS 7.4 (4.7) kPa. Discontinuations (22.5%) did not differ by treatment, most patient decision (pandemic related). DB compliancewas impacted by COVID drug kit delays. AE withdrawals were 80 mg, 2.4%;100 mg, 2.8%;PBO, 1.3%. The primary objective was met. TEAEs were 80 mg, 88.4%;100 mg, 86.1%;PBO, 81.8%. TEAEs ≥grade 3 severity were 80 mg, 7.6%;100 mg, 9.0%;PBO, 9.1%. AEs in excess of PBOwere grade 1–2 AEs of diarrhea (80 mg, 23.5%;100 mg, 31.2%;PBO, 13.8%) and nausea (80 mg, 11.9%;100 mg, 18.2%;PBO, 7.9%), in the first few weeks. ALT increases ≥3XULN were 80 mg, 0.61%;100 mg, 0.31%;PBO,1.6%. Therewere no changes in bodyweight or HR. BP decreased by 2–3 mmHg in the RES arms. Key 2o end points were met (Table). Comparative mean reduction in FS VCTE was not significant;a responder analysis of FS and MRE showed significant reductions with RES treatment.Conclusion:
RES achieved the primary safety end point in this 52- week Phase 3 NAFLD clinical trial that identified patients by metabolic risk and non-invasive imaging. Key 2o end points were met including LDL-C, ApoB, triglycerides, MRI-PDFF, FS (CAP).(Table Presented) 1MRE combined RES groups.
apolipoprotein B; endogenous compound; low density lipoprotein cholesterol; placebo; resmetirom; thyroid hormone receptor beta; triacylglycerol; adult; adverse drug reaction; body mass; body weight; clinical trial; conference abstract; controlled study; coronavirus disease 2019; data analysis; diarrhea; double blind procedure; drug safety; drug therapy; drug tolerability; drug withdrawal; dyslipidemia; elastograph; female; Hispanic; human; hypertension; incidence; major clinical study; nausea; non insulin dependent diabetes mellitus; nonalcoholic fatty liver; nuclear magnetic resonance imaging; pandemic; phase 3 clinical trial; randomization; randomized controlled trial; risk assessment; risk factor; side effect
Full text:
Available
Collection:
Databases of international organizations
Database:
EMBASE
Type of study:
Experimental Studies
/
Prognostic study
/
Randomized controlled trials
Language:
English
Journal:
Journal of Hepatology
Year:
2022
Document Type:
Article
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