Phase Ib/IIa Trial With AC01 in Patients With HFrEF

NCT05642507 | Completed Phase 1

• 1 other identifier: AC01-01
• Study Type: interventional
• Target: 58
• Locations: 4 countries
• Sites: 14

Brief 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).

Conditions

Heart Failure With Reduced Ejection Fraction

Outcome Measures

Primary Outcomes (9)

• Safety and tolerability: Adverse Events (AEs)

  Number of participants with Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Adverse Events of Special Interest (AESIs).

  From first dose of study drug up to end of follow up (up to 12 days during dose escalation phase and up to 35 days during cohort expansion phase).

• Safety and tolerability: Vital signs.

  Change from baseline in pulse rate.

  Baseline and end-of-treatment (Day 7 during the dose escalation and Day 28 during cohort expansion)

• Safety and tolerability: Vital signs.

  Change from baseline in systolic blood pressure.

  Baseline and end-of-treatment (Day 7 during the dose escalation and Day 28 during cohort expansion).

• Safety and tolerability: Vital signs.

  Change from baseline in body weight.

  Baseline and end-of-treatment (Day 7 during the dose escalation and Day 28 during cohort expansion).

• Safety and tolerability: Electrocardiogram (ECG).

  Number of participants with brady- or tachyarrhythmia.

  From first dose of study drug up to end of follow up (up to 12 days during dose escalation phase and up to 35 days during cohort expansion phase).

• Safety and tolerability: Electrocardiogram (ECG).

  Change from baseline in RR-, PR-, QRS- QTc intervals.

  Baseline and end-of-treatment (Day 7 during the dose escalation and Day 28 during cohort expansion).

• Safety and tolerability: Clinical laboratory evaluations.

  Change from baseline in N-terminal prohormone of Brain Natriuretic Peptide (NT-proBNP).

  Baseline and end-of-treatment (Day 7 during the dose escalation and Day 28 during cohort expansion).

• Safety and tolerability: Clinical laboratory evaluations.

  Change from baseline in hs-Troponin-I

  Baseline and end-of-treatment (Day 7 during the dose escalation and Day 28 during cohort expansion).

• Safety and tolerability: Clinical laboratory evaluations.

  Change from baseline in eGFR

  Baseline and end-of-treatment (Day 7 during the dose escalation and Day 28 during cohort expansion).

Secondary Outcomes (3)

• Pharmacokinetics of AC01 and its major metabolite: Cmax.

  Up to Day 8 during dose escalation phase and up to Day 32 during cohort expansion phase.

• Pharmacokinetics of AC01 and its major metabolite: AUC

  Up to Day 8 during dose escalation phase and up to Day 32 during cohort expansion phase.

• Pharmacodynamics: Mechanistic circulating biomarkers.

  Up to 12 days during dose escalation phase and up to 35 days during cohort expansion phase.

Other Outcomes (3)

• Exploratory efficacy: Non-invasive hemodynamics

  Baseline, Day 1 and end-of-treatment (Day 7 during the dose escalation and Day 28 during cohort expansion).

• Exploratory efficacy: Cardiac Function

  Baseline and end-of-treatment (Day 7 during the dose escalation and Day 28 during cohort expansion).

• Exploratory efficacy: Appetite

  Baseline and end-of-treatment (Day 7 during the dose escalation and Day 28 during cohort expansion).

Study Arms (8)

Cohort A1: Active (AC01) Minitablets 0.1 mg

EXPERIMENTAL

Participants will receive AC01 orally twice daily (BID) for 7 days.

Drug: AC01

Cohort A2: Active (AC01) Minitablets 0.3 mg

EXPERIMENTAL

Participants will receive AC01 orally twice daily (BID) for 7 days.

Drug: AC01

Cohort A3: Active (AC01) Minitablets 1 mg

EXPERIMENTAL

Participants will receive AC01 orally twice daily (BID) for 7 days.

Drug: AC01

Cohort A4: Active (AC01) Minitablets 3 mg

EXPERIMENTAL

Participants will receive AC01 orally twice daily (BID) for 7 days.

Drug: AC01

Placebo Minitablets

PLACEBO COMPARATOR

Participants will receive matching placebo orally BID for 7 days.

Drug: Placebo Minitablets

Cohort B1: Active (AC01) Minitablets 1 mg

EXPERIMENTAL

Participants will receive AC01 orally twice daily (BID) for 28 days.

Drug: AC01

Cohort B2: Active (AC01) Minitablets 3 mg

EXPERIMENTAL

Participants will receive AC01 orally twice daily (BID) for 28 days.

Drug: AC01

Cohort B3: Placebo Minitablets

PLACEBO COMPARATOR

Participants will receive matching placebo orally BID for 28 days.

Drug: Placebo Minitablets

Interventions

Placebo Minitablets DRUG

Placebo Minitablets are indistinguishable from active AC01 Minitablets.

Cohort B3: Placebo Minitablets; Placebo Minitablets

AC01 DRUG

AC01 Minitablets

Cohort A1: Active (AC01) Minitablets 0.1 mg; Cohort A2: Active (AC01) Minitablets 0.3 mg; Cohort A3: Active (AC01) Minitablets 1 mg; Cohort A4: Active (AC01) Minitablets 3 mg; Cohort B1: Active (AC01) Minitablets 1 mg; Cohort B2: Active (AC01) Minitablets 3 mg

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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 (cardiac arrest in the setting of myocardial infarction is allowed).
• 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 first dose of study drug and/or planned to be used during the overall study period until the day after the final dose of study drug (e.g., rifampin, phenytoin).
• 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, or makes patient not suitable for, entry into the study.
• Mean systolic blood pressure \<90 mmHg or \>140 mmHg, sitting after at least 5 minutes rest at screening or at Day -1.

Sponsors & Collaborators

• AnaCardio AB: lead

Study Sites (14)

Spedali Civilia di Brescia

Brescia, 25123, Italy

Location

Azienda Sanitaria Universitaria Integrata

Trieste, 34149, Italy

Location

Amsterdam University Medical Centre

Amsterdam, 1081 HV, Netherlands

Location

University Medical Centre Groningen/ICON

Groningen, 9718 GZ, Netherlands

Location

Maastricht Heart and Vascular Center

Maastricht, 6229 HX, Netherlands

Location

Erasmus Medical Centre

Rotterdam, 3015 GD, Netherlands

Location

University Medical Center

Utrecht, Netherlands

Location

Sahlgrenska University Hospital

Gothenburg, 413045, Sweden

Location

Skånes Universitetssjukhus Lund

Lund, 222 42, Sweden

Location

Karolinska University Hospital

Stockholm, 171 76, Sweden

Location

Ninewells Hospital and Medical School

Dundee, DD1 9SY, United Kingdom

Location

University of Glasgow, Institute of Cardiovascular & Medical Sciences

Glasgow, G12 8QQ, United Kingdom

Location

Golden Jubilee National Hospital

Glasgow, G81 4DY, United Kingdom

Location

King's College Hospital

London, SE5 9RS, United Kingdom

Location

Study Officials

• Lars H Lund, MD PhD

  Karolinska University Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Sequential, escalating, multiple doses

Study Record Dates

• First Submitted: November 18, 2022
• First Posted: December 8, 2022
• Study Start: February 23, 2023
• Primary Completion: October 27, 2025
• Study Completion: October 27, 2025
• Last Updated: May 7, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, CSR
• Time Frame: As per Clinical Trial Regulation principles.
• Access Criteria: Public disclosure.

Locations

IT (2); SE (3); GB (4); NL (5)