A Study to Evaluate the Safety and Efficacy of AC01 Compared to Placebo in Participants With Chronic Heart Failure (GOAL-HF2)

Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter Study to Evaluate the Safety and Efficacy of 2 Dose Levels of the Oral Ghrelin Receptor Agonist AC01 Over 12 Weeks in Patients With Chronic Advanced Heart Failure With Reduced Ejection Fraction (HFrEF)

The primary purpose of the study is to evaluate the safety and efficacy of 2 doses of AC01 compared to placebo over 12 weeks in participants with chronic advanced HFrEF.

Study Overview

• Status: Not yet recruiting
• Conditions: Heart Failure With Reduced Ejection Fraction (HFrEF)
• Intervention / Treatment: Drug: AC01; Other: Placebo

Detailed Description

This is a randomized, double-blind, placebo-controlled, parallel-group, multicenter study designed to evaluate the safety and efficacy of the ghrelin-receptor agonist AC01 compared to placebo in participants with chronic advanced HFrEF. Approximately 400 participants will be randomized to 1 of 3 treatment arms: 3 milligram (mg) AC01, 1 milligram (mg) AC01, or placebo twice daily for 12 weeks. The primary objective is to evaluate the effect of AC01 compared to placebo on cardiac structure and function assessed by echocardiography.

• Study Type: Interventional
• Enrollment (Estimated): 400
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Robert Edfors, MD, PhD; Phone Number: +46 760 542 609; Email: studyinfo@anacardio.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• History of Chronic Heart Failure (CHF) diagnosed greater than or equal to (>=6) months before screening, and in NYHA Class II to IV at screening.

• Chronic advanced HFrEF defined as:

  • LVEF less than or equal to (<=) 35 percentage (%) by local reading >=6 months before screening or a record of LVEF qualitatively described as severely reduced or moderately-severely reduced >=6 months before screening, and
  • LVEF <=35% at the screening echocardiography (confirmed by core lab), and
  • no known LVEF greater than (>) 35% (or qualitatively described as less than moderately-severely reduced) between the 2 readings.
• Sinus rhythm or permanent, persistent, or paroxysmal atrial fibrillation flutter (AFF) (AFF at screening is capped at maximum 15% of participants enrolled) with mean resting heart rate of >=55 and <=90 beats per minute (bpm) at screening, and >=50 and <=95 bpm at randomization, regardless of rhythm.
• NT-proBNP >=400 picograms per milliliter (pg/mL) in sinus rhythm and >=800 pg/mL in AFF at screening (confirmed by central laboratory).
• Transvenous implantable cardioverter-defibrillator (ICD) for primary prevention with back-up pacing set at 40 bpm.
• Treated with optimal, stable, medical therapy for HF consistent with prevailing local and international guidelines unless contraindicated or not tolerated, as judged and documented by the investigator.

Key Exclusion Criteria:

• Any acute or serious co-morbid condition that could lead to premature termination of study participation or interfere with the measurement or interpretation of the efficacy and safety assessments in the study.
• Admitted to hospital with the primary reason of HF within 24 hours before randomization or currently hospitalized with the primary reason of HF for more than 10 days. Current hospitalization (>24 hours and <=10 days) is capped at a maximum of 15% of participants enrolled.
• Acute coronary syndrome, stroke or transient ischemic attack, severe ventricular arrhythmia, or major cardiac intervention, percutaneous coronary intervention, valvuloplasty/other cardiac valve repair or implantation, or cardiac surgery within 60 days before randomization.
• Systolic blood pressure >130 or ˂90 millimeters of mercury (mmHg) at screening, or >140 or ˂85 mmHg at randomization.
• Uncontrolled diabetes mellitus, defined as Hemoglobin A1c (HbA1c) >=9.0% (>=75 millimoles per mole [mmol/mol]) at screening, or severe complications of diabetes.
• Body weight <50 kilogram (kg) or body mass index (BMI) <18 kilograms per square meter (kg/m^2) or >45 kg/m^2 at screening.
• Any of the following electrocardiogram (ECG) findings at screening: Corrected QT interval using Fridericia's formula (QTcF) >450 milliseconds (ms), 1st degree atrioventricular (AV) block with PQ >240 ms, or AV block 2nd or 3rd degree.
• History of aborted cardiac arrest, sustained ventricular tachycardia, or Torsades-de Pointes, or congenital long QT syndrome. Family history of sudden cardiac death, unexplained death, long QT syndrome, or death from a primary dysrhythmia.
• Cardiac resynchronization therapy, Cardiac Contractility Modulation, or pacemaker device other than the back-up pacing function of the ICD.
• Mechanical hemodynamic support, kidney support, or ventilation within 7 days before randomization.
• Treatment with i.v. inotropes, i.v. vasodilators, or i.v. vasopressors within 3 days before randomization.
• Treatment with any i.v. diuretics or supplemental oxygen within 6 hours before randomization.
• Use of any drugs or substances known to be strong inducers of Cytochrome P450 3A4 (CYP3A4) enzyme within 28 days before randomization or planned to be used during the study period or strong inhibitors of CYP3A4 within 7 days before randomization or planned to be used during the study period.
• Use of any drug that is known to prolong the QT interval (for example, sotalol, dofetilide, macrolides, some antidepressants, and some antipsychotics) within 28 days before randomization or planned to be used during the study period.
• Treatment changes in glucose lowering therapy within 28 days before randomization.
• Estimated glomerular filtration rate (eGFR) <20 milliliters per minute per 1.73 square meters (mL/min/1.73 m2) according to the Chronic Kidney Disease Epidemiology Collaboration formula, planned renal replacement therapy within the next 6 months, or receiving dialysis at screening.
• Serum potassium <3.5 or >5.2 milliequivalents per liter (mEq/L) at screening.
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3 *upper limit of normal (ULN) or total bilirubin >2 * ULN, or known cirrhosis, severe liver, or pancreatic disease at screening.
• Use of any anti-arrhythmic drugs within 28 days before randomization or planned to be used during the study period, except for amiodarone, ivabradine, digoxin, and beta blockers.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AC01 3 mg; Participants will receive AC01 orally twice daily (BID) for 12 weeks.	Drug: AC01; AC01 tablets for oral administration.
Experimental: AC01 1 mg; Participants will receive AC01 orally BID for 12 weeks.	Drug: AC01; AC01 tablets for oral administration.
Placebo Comparator: Placebo; Participants will receive matching placebo orally BID for 12 weeks.	Other: Placebo; AC01 matching placebo tablets for oral administration.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute Change from Baseline in Composite Echocardiography Z-Score at Week 12	The composite echocardiography Z-score integrates left ventricular stroke volume (LVSV), left ventricular end systolic volume (LVESV), left ventricular ejection fraction (LVEF), and left atrial minimal volume index (LAVImin).	Baseline and Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute Change from Baseline in LVSV at Week 12		Baseline and Week 12
Absolute Change from Baseline in LVEF at Week 12		Baseline and Week 12
Absolute Change from Baseline in LVESV at Week 12		Baseline and Week 12
Absolute Change From Baseline in LAVImin at Week 12		Baseline and Week 12
Absolute Change from Baseline in N-terminal prohormone of Brain Natriuretic Peptide (NT-proBNP)		Baseline and Week 12
Absolute Change From Baseline in Kansas City Cardiomyopathy Questionnaire Total Symptom Score (KCCQ-TSS) at Week 12	The KCCQ is a validated, 23-item, self-administered questionnaire designed to assess health status in participants with congestive heart failure. It evaluates six domains: symptoms, physical function, quality of life, social limitation, self-efficacy, and symptom stability. Each domain score is transformed to a scale of 0 to 100, with higher scores indicating better health status. The KCCQ-TSS is derived from the domain scores.	Baseline and Week 12
Absolute Change From Baseline in Patient Global Impression of Severity (PGIS) at Week 12	PGIS is 1-item questionnaire used to rate the severity of a specific condition. Participants record their perceived severity of heart failure (HF) symptoms, specifically shortness of breath, fatigue, and swelling, and choose 1 response that best described the extent of their symptoms based on a 5-point scale. Response options include none, mild, moderate, severe, and very severe. Higher PGIS scores indicate more severe HF symptoms; lower scores indicate less severe symptoms.	Baseline and Week 12
Patient Global Impression of Change (PGIC) at Week 12	The PGIC questionnaire is administered to assess the participant's impression of change in HF symptoms since the initiation of study treatment, specifically changes in shortness of breath, fatigue, and swelling. Participants select one response to describe the overall change (if any) in HF symptoms on a 7-category scale: 7=very much improved, 6 =much improved, 5 =minimally improved, 4 =no change, 3 =minimally worse, 2 =much worse, and 1 =very much worse. Higher PGIC scores indicate greater improvement in HF symptoms, while lower scores indicate worsening or no change.	At Week 12
Number of Participants With Death, Cardiovascular Death, Hospitalization, Cardiovascular Hospitalization, Heart Failure Hospitalization, Heart Failure Events, Other Adjudicated Events, and Listed for Heart Transplantation		At Week 12
Change From Baseline in Guideline-directed Medical Therapy (GDMT) Use for HFrEF at Week 12		Baseline and Week 12
Absolute Change from Baseline in Estimated Glomerular Filtration Rate (eGFR)		Baseline and Week 12
Number of Participants With Dialysis		At Week 12
Absolute Change from Baseline in Council on Nutrition Appetite Questionnaire (CNAQ) Total Score	The CNAQ is an 8-item, self-administered questionnaire used to assess appetite over time. Each item is scored on a scale of 1 to 5, and the total score is calculated as the sum of all item scores. The instrument has demonstrated acceptable psychometric properties, including internal consistency, construct validity, and predictive validity, for assessing appetite in participants with heart failure. Higher CNAQ scores indicate better appetite.	Baseline and Week 12
Absolute Change From Baseline in New York Heart Association (NYHA) Class		Baseline and Week 12
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 Week 16)
AUC,ss: Area Under the Concentration-Time Curve at Steady State of AC01 and its Metabolite M6	Population pharmacokinetic parameters	At Week 4 and Week 12
Cmax,ss: Maximum Observed Concentration at Steady State of AC01 and its Metabolite M6	Population pharmacokinetic parameters	At Week 4 and Week 12
Tmax,ss: Time to Reach Maximum Concentration at Steady State	Population pharmacokinetic parameters	At Week 4 and Week 12
Ctrough: Trough concentration at steady state of AC01 and its Metabolite M6	Population pharmacokinetic parameters	At Week 4 and Week 12
Rac (Cmax): Accumulation Ratio of Cmax for AC01 and its Metabolite M6	Population pharmacokinetic parameters. Accumulation ratio of Cmax calculated as Cmax at Week 12/Cmax at Week 4.	At Week 4 and Week 12
Rac (AUC): Accumulation Ratio of AUC for AC01 and its Metabolite M6	Population pharmacokinetic parameters. Accumulation ratio of AUC calculated as AUC at Week 12/AUC at Week 4.	At Week 4 and Week 12

Collaborators and Investigators

• Sponsor: AnaCardio AB

Study record dates

Study Major Dates

• Study Start (Estimated): November 15, 2026
• Primary Completion (Estimated): July 30, 2028
• Study Completion (Estimated): August 30, 2028

Study Registration Dates

• First Submitted: May 4, 2026
• First Submitted That Met QC Criteria: May 8, 2026
• First Posted (Actual): May 13, 2026

Study Record Updates

• Last Update Posted (Actual): September 14, 2026
• Last Update Submitted That Met QC Criteria: September 11, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Keywords: Heart Failure; Cardiovascular Diseases; Heart Diseases
• Additional Relevant MeSH Terms: Heart Failure; Cardiovascular Diseases; Heart Diseases
• Other Study ID Numbers: AC01-02; 2025 (U.S. NIH Grant/Contract: Faculty of Social Sciences Scientific Grant at the University of Gdańsk); 2025-524469-25-00 (Ctis); PIP number (Other Identifier: EMA/PE/0000267875)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual de-identified participant data will be shared with qualified scientific and medical researchers whose proposed use of data has been approved by the study executive committee, beginning 9 months and ending 36 months following article publication. Proposals should be directed to the Central Contact Person.
• IPD Sharing Time Frame: Links to the Study Protocol and Statistical Analysis Plan will be made available on ClinicalTrials.gov
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No