Table 4.

Overview of reported clinical trials on cardiac myosin inhibitors.

Drug Name	Trial, (Phase) and Year(s)	Study Design	(n) Targeted Population	Dose and (Trial Duration)	Primary Endpoint/or Aim	Key Findings	Ref.
Mavacamten (formerly known as MYK-461)	NCT02329184 (I) 2014–2016	Open-label, First-in-human study	(15) Patients with HCM	No available data (28 days)	To assess safety, tolerability, preliminary pharmacokinetics and pharmacodynamics of single ascending oral doses	-No available data	[126]
	NCT02842242 PIONEER-HCM (II) 2016–2017	Open-label, Nonrandomised, Pilot Study	(21) Patients with HOCM with resting LVOT gradients of ≥30 or ≥50 mm Hg of provoked gradient	Cohort A Mava 10–20 mg/day w/o background medications Cohort B Mava 2–5 mg/day with b-blockers allowed (12 weeks)	Change in post-exercise peak LVOT gradient from baseline to week 12	-In cohort A, Mava reduced mean post-exercise LVOT gradient from 103 to 19 mmHg at week 12 (p = 0.008), reduced resting LVEF and increased Peak VO2 -In cohort B, Mava decreased post-exercise LVOT gradient from 86 to 64 mm Hg (p = 0.020), 6% mean change in resting LVEF and elevated peak VO2 -Most serious AEs are reduced LVEF at higher plasma concentrations and atrial fibrillation	[118,127,128]
	NCT03496168 PIONEER-OLE (II) 2018–2020	Open-label extension study	(13) Patients with HOCM from PIONEER-HCM	After 6-18 months of PIONEER-HCM, Mava was administered in doses of 5,10 or 15 mg (48 weeks)	Frequency and severity of adverse events and serious adverse events	-Interventricular septal thickness was reduced without changes in posterior wall thickness -AEs were mostly mild and transient in nature, no serious adverse events were reported -Mava reduced resting and post-exercise LVOT	[119]
	NCT 03442764 MAVERICK-HCM (II) 2018–2020	Randomised, double-blind, exploratory, placebo-controlled, multicentre, dose-ranging study	(59) Patients with nHCM	Initial dose 5 mg 1 dose titration at week 6 (2.5, 5, 10 or 15 mg) (16 weeks followed by 8 weeks washout)	To assess the safety and tolerability of Mava in patients with systemic nHCM	-SAEs occurred in 10% of participants on Mava and in 21% participants on placebo, indicating significant no difference. -Reversible reduction in LVEF ≤ 45% -NT-proBNP decreased by 53% in the pooled Mava group versus 1% in the placebo group (p = 0.0005), 34% reduction in cardiac troponin I in Mava group (p = 0.009)	[120,129,130]
	NCT03470545 EXPLORER-HCM (III) 2018–2020	Multicentre, randomised, double-blind, placebo-controlled parallel-group study	(250) Patients with HOCM	Starting dose 5 mg (30 weeks)	1.5 mL/kg per min or greater increase in pVO2 and at least one NYHA class reduction OR 3 mL/kg per min or greater pVO2 increase without NYHA class worsening	-37% of patients on Mava vs. 17% on placebo met the composite primary endpoint (p = 0·0005) -A post-exercise LVOT gradient 50 mmHg was achieved in 74% of patients in Mava group and increased pVO2 -complete ablation of all LVOT was achieved in 57%	[121,122]
	NCT03723655 MAVA-LTE (III) 2018–2025	Randomised, long-term safety extension study	(310) Patients who completed MAVERICK-HCM or EXPLORER-HCM	No available data (252 weeks)	Frequency and severity of treatment-emergent adverse events and serious AEs	Ongoing phase III trial	[131]
	NCT04349072 VALOR-HCM (III) 2020–2024	Randomised, double-blind, placebo-controlled study	(100) Patients with HOCM who are eligible for septal reduction therapy	No available data (32 weeks)	Septal Reduction Therapy (SRT) Status	Ongoing phase III trial	[132]
CK-274	NCT03767855 (I) 2018–2020	Double-Blind, randomised, placebo-controlled, multi-part, single and multiple ascending dose study	(115) healthy volunteers	No available data (Up to 29 days)	To assess safety, PK and PD of CK-274	- CK-274 was safe and well tolerated in healthy participants. -No serious AEs and clinically meaningful changes in vital signs, ECGs or laboratory tests were observed -Dose-dependent reduction in LVEF	[133,134,135]
	NCT04219826 REDWOOD-HCM (II) 2020–2021	Multicentre, randomised, double-blind, placebo-controlled, dose-finding study	Patients with HOCM	Cohort A 5–10 mg [ECG guided] Cohort 3 10–30 mg of oral CK-274 (10 weeks of treatment and 4 weeks of washout)	To determine the safety and tolerability of CK-274	Ongoing phase II trial	[136]

OM, Omecamtiv Mecarbil; IV, intravenous; SET, systolic ejection time; SEF, systolic ejection fraction; SV, stroke volume; HR, heart rate; CPK-MB, cardiac creatinine kinase myocardial band; LVESD, left ventricular end-systolic dimension; AHF, acute heart failure; LVEF, left ventricular ejection fraction; PK, pharmacokinetic; PD, pharmacodynamic; HF, heart failure; HFrEF, heart failure with reduced ejection fraction; BID, twice daily; LVSV, left ventricular stroke volume; pVO₂, peak oxygen uptake; ECG, electrocardiogram; OLE, open-label extension.