Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults with Symptomatic Non-Obstructive Hypertrophic Cardiomyopathy (ACACIA)

Phase 3 trial of aficamten in participants with nHCM is designed to further evaluate the effect of aficamten on quality of life, exercise capacity, heart failure symptoms, cardiac biomarkers, cardiac remodeling, and clinical outcomes. Additionally, the safety and tolerability will be assessed in participants with nHCM.

Study Duration:

• 6-week screening period (< 42 prior to Day 1)
• 72 weeks treatment
• Week 76 EOS visit
• Afic vs Placebo; Echo & CPET; Opt genetic & future sample testing
• Optional CMR sub-study (excluded if ICD or pacemaker)

Inclusion

• BMI <40 kg/m2

• nHCM dx by Echo w/ LV WT > 15 mm or > 13 mm & gene mut or + FHx of HCM

• NYHA II or III; KCCQ-CSS score of >30 and < 85

• Hemoglobin >10

• O2 Sat % 90 @ RA; Resp exch > 1.00 & pVO2 <90% by scr CPET

• Echo: Rest gradient <30 & Valsalva <50 & EF >60

• NT-ProBNP > 300, or in afib/aflut > 900 (Blacks > 225 & > 675)

• Stable doses of BB, CCB > 2 wks p/t scr CPET

• Off Mavacamten >12 weeks prior to screening (Must discuss w/MM)

Exclusion

• Hx of MI; CAS >70%

• SRT < 6 mo

• DBP >100; Hx resistant HTN

• Mod-Sev Aortic stenosis or MR (Invest dec)

• Inability to exercise

• Parx or Pers Afib or A-flutter; (A-flutter tx w/ ablation w/out recurrence < 3 mo)

• Hx of Syncope, vent arrhythmia, or sustained VT w/ exercise w/in 3 mo

• Hepatic impairment

• Any hx of significant disorder, malignancy, inf, or condition that could pose a risk during study