Testing AC01 for heart failure with reduced ejection fraction

Randomized, Double-blind, Multiple Ascending Dose, Placebo-controlled, Safety, Tolerability, Efficacy, Pharmacokinetic (PK) and Pharmacodynamic (PD) Phase Ib/IIa Clinical Trial With AC01 in Patients With HFrEF

This study is testing a new medication called AC01 to see if it can safely help people with heart failure and improve their condition.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 80 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: AnaCardio AB (Industry-sponsored)
• Locations: 13 sites (Brescia and 12 other locations)
• Trial ID: NCT05642507 on ClinicalTrials.gov

What this trial studies

This is a randomized, double-blind, placebo-controlled clinical trial designed to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of AC01 in patients with heart failure with reduced ejection fraction (HFrEF). The study consists of two parts: a dose escalation phase where patients will receive AC01 orally twice daily for seven days, followed by a cohort expansion phase where the same treatment will continue for 28 days at doses determined from the first phase. The trial aims to gather comprehensive data on how AC01 affects patients with stable HFrEF.

Who should consider this trial

Good fit: Ideal candidates include male and female outpatients aged 18-80 with stable HFrEF and specific cardiac health criteria.

Not a fit: Patients with cardiac rhythms that interfere with ECG or echocardiography interpretation, such as permanent atrial fibrillation, may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients suffering from heart failure with reduced ejection fraction.

How similar studies have performed: Other studies have explored treatments for HFrEF, but the specific approach with AC01 is novel and has not been extensively tested.

Eligibility criteria

Key Inclusion Criteria:

* Male and female out-patients of any ethnicity, between 18-80 years (inclusive), with stable HFrEF.
* Chronic HF for at least 6 months duration defined by history with current NYHA class II-III severity.
* LVEF ≤40% by TTE more than 6 months before screening and again at screening (screening measurement confirmed by echocardiography core lab).
* Sinus rhythm with mean resting heart rate 55-90 bpm.
* Cardiac Index 0.5-2.4 measured by Innocor at screening and Day -1. Screening measurement confirmed by core lab.
* Transvenous ICD for primary prevention in place and active (as long as it is not subcutaneous).
* Optimal guideline-based medical therapy for HFrEF as judged by the Investigator, at stable doses for ≥2 weeks with no intention to change dosing during trial duration.

Key Exclusion Criteria:

* Any cardiac rhythm that does or could interfere with ECG or TTE interpretation, including but not limited to permanent or persistent atrial fibrillation or flutter or paroxysmal atrial fibrillation or flutter with an episode in the last 3 months, frequent premature ventricular contractions, or atrial or ventricular pacing
* Ongoing or planned mechanical circulatory support, treatment with any IV vasoactive drugs (vasodilators, inotropes, or vasopressors) or diuretics, and/or dialysis or hemofiltration or ultrafiltration.
* Probable alternative explanations for symptoms or signs (e.g., but not limited to, known primary cardiomyopathy \[hypertrophic, constrictive, restrictive, infiltrative, congenital\]). Primary uncorrected hemodynamically significant valve disease, right-sided HF not due to left-sided HF.
* History of aborted cardiac arrest and/or ICD for secondary prevention.
* Hospitalized for HF or received IV diuretics, vasodilators, or inotropes for HF ≤30 days.
* Clinical diagnosis of acute coronary syndrome or stroke ≤30 days.
* PCI or percutaneous valve intervention ≤30 days or planned.
* Angina pectoris ≤30 days.
* Any cardiovascular procedure planned during study duration.
* Hospitalized or unplanned visit to the emergency department for any reason in last 30 days; patient is eligible 30 days from discharge from hospital.
* Use of any drugs or substances known to be strong inducers of CYP3A4 enzyme within 28 days prior to the dosing day and/or planned to be used during the overall study period.
* eGFR by CKD-EPI \<30 mL/min/1.73 m2 at screening or at Day -1.
* Serum or plasma potassium \<3.5 or \>5.2 mEq/L at screening or at Day -1. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>3 times upper limit of normal (ULN) or total bilirubin \>2 times ULN at screening or at Day -1. Or known cirrhosis or severe liver or pancreatic disease, or Gilbert's syndrome.
* Any condition that in the opinion of the Investigator may interfere with adherence to the protocol.
* Systolic blood pressure \<90 mmHg or \>140 mmHg at screening or at Day-1.
* Any of the following ECG findings: atrial or ventricular pacing, QTcF \>450 ms, AV block I with PQ \> 240 ms, AV block II or III at screening and at Day -1. In the case of non-paced QRS prolongation \>120 ms, or if CRT is determined to be required and is actively pacing the ventricles, the QTcF is allowed to be up to but not greater than 470 ms.

Where this trial is running

Brescia and 12 other locations

• Spedali Civilia di Brescia — Brescia, Italy (Not_yet_recruiting)
• Azienda Sanitaria Universitaria Integrata — Trieste, Italy (Not_yet_recruiting)
• Amsterdam University Medical Centre — Amsterdam, Netherlands (Recruiting)
• University Medical Centre Groningen/ICON — Groningen, Netherlands (Recruiting)
• Maastricht Heart and Vascular Center — Maastricht, Netherlands (Recruiting)
• Erasmus Medical Centre — Rotterdam, Netherlands (Recruiting)
• Sahlgrenska University Hospital — Gothenburg, Sweden (Recruiting)
• Skånes Universitetssjukhus Lund — Lund, Sweden (Recruiting)
• Karolinska University Hospital — Stockholm, Sweden (Recruiting)
• Ninewells Hospital and Medical School — Dundee, United Kingdom (Recruiting)
• University of Glasgow, Institute of Cardiovascular & Medical Sciences — Glasgow, United Kingdom (Recruiting)
• Golden Jubilee National Hospital — Glasgow, United Kingdom (Recruiting)
• King's College Hospital — London, United Kingdom (Recruiting)

Study contacts

• Study coordinator: Goran Westerberg, PhD

Conditions Heart Failure With Reduced Ejection Fraction