Phase Ib/IIa Trial With AC01 in Patients With HFrEF

Heart Failure With Reduced Ejection Fraction Clinical Trial

— GOAL-HF1  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05642507
• Other study ID #: AC01-01
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: February 23, 2023
• Est. completion date: June 30, 2025

Study information

• Verified date: April 2024
• Source: AnaCardio AB
• Contact: Goran Westerberg, PhD
• Phone: +39 0577 803065
• Email: Goran.Westerberg[@]anacardio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a randomized, double-blind, placebo-controlled two-part study with a multiple escalating dose phase followed by a cohort expansion phase to assess safety, tolerability, pharmacokinetics and pharmacodynamics of AC01 in patients with heart failure with reduced ejection fraction (HFrEF).

Description:

During the dose escalation phase, patients will be given AC01 orally twice daily for seven days. In the cohort expansion phase, patients will be given AC01 orally twice daily for 28 days at dose levels selected on the basis of results of the dose escalation phase.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: June 30, 2025
• Est. primary completion date: June 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Heart Failure
• Heart Failure With Reduced Ejection Fraction

Intervention

Drug:
• AC01
AC01 microtablets

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
AnaCardio AB

Countries where clinical trial is conducted

Italy,  Netherlands,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and tolerability: Adverse Events (AEs)	Type and frequency of AEs.	Up to 12 days during dose escalation phase and up to 35 days during cohort expansion phase.
Primary	Safety and tolerability: Vital signs.	Pulse rate.	Up to 12 days during dose escalation phase and up to 35 days during cohort expansion phase.
Primary	Safety and tolerability: Vital signs.	Systolic and diastolic blood pressure.	Up to 12 days during dose escalation phase and up to 35 days during cohort expansion phase.
Primary	Safety and tolerability: Electrocardiogram (ECG).	Number of clinically significant abnormal findings values of RR-, PR-, QRS- QTc intervals.	Up to 12 days during dose escalation phase and up to 35 days during cohort expansion phase.
Primary	Safety and tolerability: Clinical laboratory evaluations.	Number of clinically significant laboratory abnormalities	Up to 12 days during dose escalation phase and up to 35 days during cohort expansion phase.
Secondary	Pharmacokinetics of AC01 and its major metabolite: Cmax.	Maximal observed concentration (Cmax).	Up to Day 8 during dose escalation phase and up to Day 32 during cohort expansion phase.
Secondary	Pharmacokinetics of AC01 and its major metabolite: AUC	Area under the concentration-time curve.	Up to Day 8 during dose escalation phase and up to Day 32 during cohort expansion phase.
Secondary	Pharmacodynamics: Cardiac Function.	Cardiac output.	Up to 12 days during dose escalation phase and up to 35 days during cohort expansion phase.
Secondary	Pharmacodynamics: Cardiac Function.	Stroke volume.	Up to 12 days during dose escalation phase and up to 35 days during cohort expansion phase.
Secondary	Pharmacodynamics: Cardiac Function.	Ejection fraction.	Up to 12 days during dose escalation phase and up to 35 days during cohort expansion phase.
Secondary	Pharmacodynamics: Mechanistic markers.	Growth hormone (GH), insulin-like growth factor 1 (IGF1), aldosterone, ACTH.	Up to 12 days during dose escalation phase and up to 35 days during cohort expansion phase.