Safety, pharmacokinetics, and exploratory efficacy of the oral ghrelin receptor agonist AC01 in heart failure with reduced ejection fraction (GOAL-HF1): a randomised, double-blind, placebo-controlled, phase 1b/2a study.
Summary
In 58 HFrEF patients randomized to AC01 or placebo, AC01 over 7–28 days was safe and well tolerated without excess tachyarrhythmias, ischemic ECG changes, biomarker rises, or symptomatic hypotension. Treatment-emergent events were mostly mild/moderate; no AC01-related serious adverse events occurred, supporting further efficacy trials of this first-in-class oral inotrope.
Key Findings
- Across phase 1b/2a (n=58), AC01 had no treatment-related serious adverse events; most TEAEs were mild or moderate.
- Continuous rhythm and ECG monitoring revealed no excess tachyarrhythmias, ischemia, or conduction abnormalities with AC01.
- No apparent effects on high-sensitivity cardiac troponin I or NT-proBNP; no symptomatic hypotension was observed.
Clinical Implications
No immediate change in practice, but supports advancing AC01 into larger efficacy trials as a potential safer inotrope option for symptomatic HFrEF.
Why It Matters
Demonstrates early-phase safety of a novel, mechanistically distinct oral inotrope in HFrEF, addressing a long-standing therapeutic gap where prior inotropes increased risk.
Limitations
- Small sample size and early-phase duration (7–28 days)
- Highly selected population with transvenous ICDs and backup pacing
Future Directions
Conduct larger phase 2/3 trials assessing clinical efficacy (symptoms, quality of life, exercise capacity) and safety over longer durations, with mechanistic biomarkers and arrhythmic risk profiling.
Study Information
- Study Type
- RCT
- Research Domain
- Treatment
- Evidence Level
- II - Randomized controlled early-phase clinical trial focused on safety/tolerability
- Study Design
- OTHER