Clinical trial NCT06299826: A Phase IIb Study of AZD5462 in Patients With Chronic Heart Failure
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Chronic Heart Failure
Keywords: Relaxin Family Peptide Receptor 1 (RXFP1) agonist
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2024-03-08
Enrollment: 360
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Detailed 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 dose (OD) of 3 dose levels (low, medium, or high) oral dose of AZD5462 tablets or placebo.

Eligibility criteria: 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 consent and during the Screening period.
* 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 consent or transcatheter structural heart interventions or cardiac valve surgery within 6 months prior to consent.
  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, except planned hospitalisation without worsening of cardiac or pulmonary functions, within 4 weeks prior to consent or during the Screening period.
  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 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 cardiac resynchronization therapy/bi-ventricular pacemaker or mechanical assist device implantation.
* Any planned highly invasive cardiovascular procedure (eg, coronary revascularisation, ablation of atrial fibrillation/flutter etc).
* Positive hepatitis C antibody, or hepatitis B virus surface antigen at Screening. Participants with positive hepatitis B virus core antibody can be included in the study as long as hepatitis B virus surface antigen is negative, and there are no other signs of an active hepatitis B.
* Known to have historically tested positive for Human Immunodeficiency Virus.

Primary outcomes:
measure: Cohort A and B: Change from Baseline in Echocardiography Parameters
timeFrame: From Baseline to Week 25
Secondary outcomes:
measure: Cohort A and B: Change from Baseline in Echocardiography Parameters
timeFrame: From Baseline to Week 13 and Week 25
measure: Cohorts A and B: Change from Baseline in Kansas City Cardiomyopathy Questionnaire overall summary score (KCCQ-OSS)
timeFrame: From Baseline to Weeks 3, 5, 13, and 25
measure: Cohorts A and B: Change from Baseline in New York Heart Association Functional Class (NYHA FC)
timeFrame: Baseline and Week 25
measure: Cohorts A and B: Change from Baseline in cardiac biomarkers
timeFrame: From Baseline to Weeks 5, 13, and 25
measure: Cohorts A and B : Plasma Concentration of AZD5462
timeFrame: Day 15 (Week 3), Day 29 (Week 5) and 85 (Week 13)
measure: Cohorts A and B: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: From Baseline to Week 29 (Day 197)
Other outcomes:
Locations:
city: Alexander City
country: United States
facility: Research Site
state: Alabama
city: Northridge
country: United States
facility: Research Site
state: California
city: Torrance
country: United States
facility: Research Site
state: California
city: Vista
country: United States
facility: Research Site
state: California
city: Miami Beach
country: United States
facility: Research Site
state: Florida
city: Miami
country: United States
facility: Research Site
state: Florida
city: Richmond
country: United States
facility: Research Site
state: Indiana
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Buffalo
country: United States
facility: Research Site
state: New York
city: Rosedale
country: United States
facility: Research Site
state: New York
city: Chapel Hill
country: United States
facility: Research Site
state: North Carolina
city: Philadelphia
country: United States
facility: Research Site
state: Pennsylvania
city: Knoxville
country: United States
facility: Research Site
state: Tennessee
city: Manassas
country: United States
facility: Research Site
state: Virginia
city: Pleven
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Brno
country: Czechia
facility: Research Site
city: Jaromer
country: Czechia
facility: Research Site
city: Liberec 2
country: Czechia
facility: Research Site
city: Louny
country: Czechia
facility: Research Site
city: Ostrava-Dubina
country: Czechia
facility: Research Site
city: Plzeň
country: Czechia
facility: Research Site
city: Aalborg
country: Denmark
facility: Research Site
city: Herning
country: Denmark
facility: Research Site
city: Balatonfüred
country: Hungary
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Kistarcsa
country: Hungary
facility: Research Site
city: Nyíregyháza
country: Hungary
facility: Research Site
city: Székesfehérvár
country: Hungary
facility: Research Site
city: Cuttack Sadar
country: India
facility: Research Site
city: Kochi
country: India
facility: Research Site
city: Kolkata
country: India
facility: Research Site
city: Surat
country: India
facility: Research Site
city: Vadodara
country: India
facility: Research Site
city: Fukui-shi
country: Japan
facility: Research Site
city: Higashiibaraki-gun
country: Japan
facility: Research Site
city: Higashiohmi-shi
country: Japan
facility: Research Site
city: Kitakyushu
country: Japan
facility: Research Site
city: Kobe
country: Japan
facility: Research Site
city: Kumamoto
country: Japan
facility: Research Site
city: Miyazaki-shi
country: Japan
facility: Research Site
city: Morioka-shi
country: Japan
facility: Research Site
city: Naha
country: Japan
facility: Research Site
city: Omihachiman-shi
country: Japan
facility: Research Site
city: Shunan
country: Japan
facility: Research Site
city: Breda
country: Netherlands
facility: Research Site
city: Deventer
country: Netherlands
facility: Research Site
city: Enschede
country: Netherlands
facility: Research Site
city: Kraków
country: Poland
facility: Research Site
city: Kraków
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Wrocław
country: Poland
facility: Research Site
city: Wrocław
country: Poland
facility: Research Site
city: Łódź
country: Poland
facility: Research Site
city: Bratislava
country: Slovakia
facility: Research Site
city: Bratislava
country: Slovakia
facility: Research Site
city: Kosice
country: Slovakia
facility: Research Site
Study officials:
References: