A Phase IIb Study of AZD5462 in Patients With Chronic Heart Failure

Chronic Heart Failure Clinical Trial

— LUMINARA  

Official title:

A Phase IIb Two-Cohort, Randomised, Placebo-controlled, Double-blind, Multi-centre, Dose-ranging Study of AZD5462 in Stable Patients With Chronic Heart Failure

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06299826
• Other study ID #: D9090C00008
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: June 10, 2024
• Est. completion date: November 24, 2025

Study information

• Verified date: February 2024
• Source: AstraZeneca
• Contact: AstraZeneca Clinical Study Information Center
• Phone: 1-877-240-9479
• Email: information.center[@]astrazeneca.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The main purpose of this study is to evaluate the effect of AZD5462 on cardiac function in participants with chronic heart failure (HF).

Description:

This is a Phase IIb randomized, double-blind, placebo-controlled, multi-center, dose-ranging study to evaluate the efficacy, safety, and pharmacokinetic (PK) of AZD5462 on top of standard of care in 2 cohorts of participants with HF: Cohort A, and Cohort B.

The study will include 3 periods and approximately 12 study visits:

• Screening period of up to 4 weeks (at least 1 study visit)

• Treatment period of 24 weeks (8 study visits)

• Follow-up period of 4 weeks (3 study visits)

Eligible participants in each cohort will be randomized equally 1:1:1:1 to receive a once daily (OD) oral dose of AZD5462 tablets or placebo.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 360
• Est. completion date: November 24, 2025
• Est. primary completion date: November 24, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

• Participants must have a pre-existing diagnosis of HF NYHA FC II to IV.

• Participants must be on stable HF standard of care medication for at least 4 weeks prior to Screening.

• Minimum body mass index (BMI) of 18 kilograms per meter square (kg/m^2) at Screening.

• For female participants, the participant must not be pregnant or lactating and must be of non-childbearing potential.

• All male participants should refrain from fathering a child or donating sperm until 3 months after the final study Follow-up Visit. Non-sterilised male participants should avoid fathering a child either by true abstinence or use of a condom for all sexual intercourse with a female partner of childbearing potential from the first dose until 3 months after the final Follow-up Visit.

Exclusion Criteria:

• Historical or current evidence of a clinically significant disease or disorder including, but not limited to:

1. Myocardial infarction, stroke, transient ischaemic attack, coronary artery bypass grafting, or percutaneous coronary intervention within 12 weeks prior to Screening or transcatheter structural heart interventions or cardiac valve surgery within 6 months prior to Screening.

2. Sarcoidosis, restrictive cardiomyopathy, active myocarditis, constrictive pericarditis, or hypertrophic (obstructive) cardiomyopathy.

3. History of untreated clinically significant valve disease or a Screening confirmation of severe aortic stenosis, severe mitral stenosis, moderate or severe aortic insufficiency or severe mitral insufficiency.

4. Amyloidosis, Fabry disease, or haemochromatosis.

5. Pericardial disease (i.e., visually significant white pericardium on echocardiogram).

6. Known coagulation disorders.

7. Current diagnosis of active hepatitis.

8. Severe pulmonary disease that is not expected to improve over time, as assessed by the investigator.

9. Decompensated HF or any cardiopulmonary hospitalisation within 4 weeks prior to Screening.

10. History of active malignancy within 2 years, except for fully excised or treated basal cell carcinoma, or = 2 squamous cell carcinomas of the skin and participants who are under investigation for breast or cervical cancer, including participants with a pap smear of grade = 3.

• History of hypersensitivity to drugs with a similar chemical structure or class to AZD5462 or any component of AZD5462 drug product.

• Known history of drug or alcohol abuse within 24 months of Screening.

• Congenital long QT syndrome or history of QT prolongation associated with other medications that required discontinuation of that medication.

• Cardiac ventricular arrhythmia that requires treatment.

• History of or anticipated heart transplant.

• Current or planned bi-ventricular assist device implantation.

• Any planned highly invasive cardiovascular procedure (eg, coronary revascularisation, ablation of atrial fibrillation/flutter etc).

• Positive hepatitis C antibody, hepatitis B virus surface antigen or hepatitis B virus core antibody at Screening.

• Known to have historically tested positive for Human immunodeficiency virus.

Related Conditions & MeSH terms

• Chronic Heart Failure
• Heart Failure

Intervention

Drug:
• AZD5462
Participants will receive low, medium & high doses of film-coated tablets of AZD5462 OD orally.
• Placebo
Participants will receive matching doses of film-coated tablets of Placebo OD orally.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cohort A and B: Change from Baseline in Ejection Fraction	To evaluate the effect of AZD5462 after treatment in participants with HF.	From Baseline to Week 25
Secondary	Cohort A and B: Change from Baseline in Ejection Fraction	To evaluate the effect and dose response of AZD5462 and effect on echocardiographic markers related to structural, systolic and diastolic function after treatment in participants with HF.	From Baseline to Week 13 and Week 25
Secondary	Cohorts A and B: Change from Baseline in Kansas City Cardiomyopathy Questionnaire overall summary score (KCCQ-OSS)	To evaluate the effect of AZD5462 on HF health status in participants with HF.; The KCCQ is a validated questionnaire developed for patients with congestive HF. It is a 23-item, self-administered health status measure that quantifies physical limitations, symptoms, social interference, self-efficacy, and quality of life. Results for each domain are summarized and transformed to a score of 0 to 100 with higher scores indicating better health status.	From Baseline to Weeks 3, 5, 13, and 25
Secondary	Cohorts A and B: Change from Baseline in New York Heart Association Functional Class (NYHA FC)	To evaluate the effect of AZD5462 on HF health status in participants with HF.; The NYHA Functional Classification is a system to measure the severity of symptoms of heart failure. It places patients in four categories based on limitations of physical activity, from Class I with no limitation, progressing to Class IV with severe limitations.	Baseline and Week 25
Secondary	Cohorts A and B: Percentage Change from Baseline in cardiac biomarkers	To evaluate the effect of AZD5462 on biomarkers of cardiac function in treatment participants with HF.	From Baseline to Weeks 5, 13, and 25
Secondary	Cohorts A and B : Plasma Concentration of AZD5462	To evaluate the PK of AZD5462 after repeat OD oral dosing in participants with HF.	Day 15 (Week 3), Day 29 (Week 5) and 85 (Week 13)
Secondary	Cohorts A and B: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)	To evaluate the safety and tolerability of AZD5462 as compared to placebo in participants with HF.	From Baseline to Week 29 (Day 197)