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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

AstraZeneca AB

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

3 Jul 2024 → 10 Feb 2026

Decision date (initial)

2024-07-05

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

AstraZeneca AB

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Dose response, Safety, Pharmacogenomic, Pharmacokinetic, Efficacy, Pharmacodynamic

To evaluate the effect and dose response of AZD5462 after 24 weeks of treatment in participants with HF.

Secondary objectives 5

1. To evaluate the effect of AZD5462 on echocardiographic markers related to structural, systolic and diastolic function after 12 and 24 weeks of treatment in participants with HF.
2. To evaluate the effect of AZD5462 on HF health status in participants with HF.
3. To evaluate the effect of AZD5462 on biomarkers of cardiac function in treatment participants with HF.
4. To evaluate the PK of AZD5462 after repeat OD oral dosing in participants with HF.
5. To evaluate the safety and tolerability of AZD5462 as compared to placebo in participants with HF.

Conditions and MedDRA coding

Chronic Heart Failure

Study design 3 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Participant must be 18 years (or the legal age of consent in the jurisdiction in which the study is taking place) to 85 years of age, inclusive, at the time of signing the ICF.
2. Participants must have a pre-existing diagnosis of HF NYHA FC II to IV
3. Participants must be on stable HF standard of care medications for at least 4 weeks prior to consent and during the Screening period. If the participant is currently taking diuretics, then diuretics must also be stable for at least 1 week prior to consent (minor dose adjustments in diuretics are allowed based on the investigator’s judgment).
4. Minimum BMI of 18 kg/m2 at Screening.
5. Participants LVEF must be centrally confirmed at Screening
6. Participants NT-pro-BNP must be centrally confirmed at screening
7. For female participants, the participant must not be pregnant or lactating and must be of non-childbearing potential.
8. Capable of giving and willing to give signed informed consent

Exclusion criteria 7

1. Historical or current evidence of a clinically significant disease or disorder.
2. History of hypersensitivity to AZD5462 or any component of AZD5462 drug product.
3. Poor acoustic window on 2-chamber and 4-chamber views, as determined by the sonographer.
4. Any planned highly invasive cardiovascular procedure
5. Participants requiring iron infusion during the study.
6. Any laboratory values outside of the defined range at Screening
7. Vital signs outside of the defined range at Screening

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change in echocardiographic measurements from Baseline to Week 25

Secondary endpoints 5

1. Change in echocardiographic measurements from Baseline to Week 13 and Week 25
2. • Change in Health Status from Baseline to Week 3, Week 5, Week 13, and Week 25 • Change in NYHA FC from Baseline to Week 25
3. Change echocardiographic measurements from baseline to week 25
4. Change in cardiac biomarkers from Baseline to Week 5, Week 13, and Week 25
5. AZD5462 plasma PK concentrations

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AstraZeneca AB

Sponsor organisation

AstraZeneca AB

Address

-

City

Sodertalje

Postcode

151 85

Country

Sweden

Scientific contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Centre

Public contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Centre

Third parties 8

Locations

7 EU/EEA countries · 29 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 88 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

11 submissions — initial application plus substantial / non-substantial modifications