Heart Failure Clinical Trial
Study to Evaluate the Efficacy and Safety of AZD4831 in Participants With Heart Failure With Left Ventricular Ejection Fraction > 40%
This is a randomised, double-blind, placebo-controlled, multi-center sequential phase 2b and Phase 3 study to evaluate the efficacy and safety of AZD4831 administered for up to 48 Weeks in participants with heart failure with left ventricular ejection fraction > 40%. The study will consist of 2 separate parts, Part A and Part B, approximately 660 participants will be randomised in Part A, 820 in Part B.
≥ 40 to ≤ 85 years of age, at the time of signing the informed consent.
Documented stable symptomatic HF (New York Heart Association Class II-IV) for at least 1 month at Screening (Visit 1) (transient HF in the setting of an MI does not qualify), with a medical history of typical symptoms of HF and receiving optimal therapy for HF as determined by the health-care physician.
LVEF > 40% at Screening (Visit 1). All participants will undergo a local echocardiogram at the Screening (Visit 1) with central reading to confirm the LVEF > 40% eligibility criteria before randomisation.
6MWD ≥ 30 meters and ≤ 400 meters at Screening (Visit 1) and Randomisation (Visit 3). Difference in 6MWD between Screening and Randomisation must be < 50 meters.
KCCQ-TSS ≤ 90 points at Screening (Visit 1) and Randomisation (Visit 3)
NT-proBNP ≥ 250 pg/mL (sinus rhythm) or ≥ 500 pg/mL (atrial fibrillation/flutter) at Screening (Visit 1) for patients with BMI ≤30 kg/m2.
NT-proBNP ≥ 200 pg/mL (sinus rhythm) or ≥ 400 pg/mL (atrial fibrillation/flutter) at Screening (Visit 1) for patients with BMI > 30 kg/m2.
The ECG performed at Screening should be used for heart rhythm evaluation.
7.At least one of the following:
Structural heart disease, ie, LA enlargement and/or left ventricular hypertrophy at the echocardiogram performed at Screening (Visit 1). Left atrial enlargement is defined by at least 1 of the following: LA width (diameter) ≥ 3.8 cm or LA length ≥ 5.0 cm, or LA area ≥ 20 cm2 or LA volume ≥ 55 mL or LAVI > 34 mL/m2. Left ventricular hypertrophy is defined by septal thickness or posterior wall thickness ≥ 1.1 cm or LVMI > 95 g/m2 in women and > 115 g/m2 in men.
Spectral tissue Doppler echocardiography - E/e' ratio (average of septal and lateral) ≥ 13 at rest at the echocardiogram performed at Screening (Visit 1).
Indirectly estimated elevation of PASP by TRmax velocity > 2.8 m/s (280 cm/s) (PASP > 35 mmHg) at the echocardiogram performed at Screening (Visit 1) OR directly measured pulmonary capillary wedge pressure > 15 mmHg at rest within the past 12 months or > 25 mmHg at exercise documented by right heart catheterisation within 12 months prior to Screening (Visit 1).
HF decompensation within 6 months before Randomisation (Visit 3), defined as hospitalisation for HF or IV diuretic treatment for HF during an urgent, unscheduled visit without hospitalisation.
8.Body mass index ≥ 18.0 kg/m2 and ≤ 45.0 kg/m2
9.Male or female of non-childbearing potential.
Participant must be ≥ 40 to ≤ 85 years of age, at the time of signing the informed consent.
Documented diagnosis of symptomatic HF (NYHA class II-IV) at Screening (Visit 1), and a medical history of typical symptoms/signs of heart failure ≥ 6 weeks before Screening (Visit 1), and receiving optimal therapy for HF as determined by the health-care physician, with at least intermittent need for diuretic treatment.
LVEF >40% and evidence of structural heart disease (ie, left ventricular hypertrophy or
left atrial enlargement [defined by at least one of the following:LA enlargement and/or left ventricular hypertrophy at the echocardiogram
performed at Screening (Visit 1). Left atrial enlargement is defined by at least 1 of the following: LA width
(diameter) ≥ 3.8 cm or LA length ≥ 5.0 cm, or LA area ≥ 20 cm2 or LA volume ≥ 55 mL or LAVI > 34
mL/m2. Left ventricular hypertrophy is defined by septal thickness or posterior wall thickness ≥ 1.1 cm or
LVMI > 95 g/m2 in women and > 115 g/m2 in men.]) documented by the most recent echocardiogram, or cardiac
magnetic resonance imaging within the last 12 months prior to Screening (Visit 1). If no
echocardiogram is available, it can be performed at Screening (Visit 1).
6MWD ≥ 30 meters and ≤ 400 meters at Screening (Visit 1) and Randomisation (Visit 2). Difference in 6MWD between Screening and Randomisation must be < 50 meters
KCCQ-TSS ≤ 90 points at Screening (Visit 1) and Randomisation (Visit 2).
NT-proBNP ≥ 250 pg/mL (sinus rhythm) or ≥ 500 pg/mL (atrial fibrillation/flutter) at Screening (Visit 1) for patients with BMI ≤ 30 kg/m2. NT-proBNP ≥ 200 pg/mL (sinus rhythm) or ≥ 400 pg/mL (atrial fibrillation/flutter) at Screening (Visit 1) for patients with BMI > 30 kg/m2. The ECG performed at Screening should be used for heart rhythm evaluation
Body mass index ≥ 18.0 kg/m2 and ≤ 45.0 kg/m2
Male or female of non-childbearing potential.
1 eGFR < 30 mL/min/1.73m2 (Chronic Kidney Disease-Epidemiology Collaboration formula) at Screening (Visit 1).
2. Systolic blood pressure < 90 mmHg or ≥ 160 mmHg if not on treatment with ≥ 3 blood pressure lowering medications or ≥ 180 mmHg irrespective of treatments at Randomisation
3. Heart rate > 110 bpm or < 50 bpm at Randomisation
4. Life expectancy < 3 years due to other reasons than cardiovascular disease.
5. History or ongoing allergy/hypersensitivity reactions to drugs (including but not limited to rash, angioedema, acute urticaria).
6. Presence of any disease or condition rather than HF constituting the main reason for limiting the ability to exercise/reduced exercise capacity.
7. Current decompensated HF and/or NT-proBNP > 5000 pg/mL at Screening (Visit 1)
8. Documented history of ejection fraction ≤ 40%.i.e. HF with recovered ejection fraction. Transient ejection fraction decrease e.g. in the setting of an MI does not apply
9. Any planned cardiovascular procedure (eg, coronary revascularisation, ablation of atrial fibrillation/flutter, valve repair/replacement, aortic aneurysm surgery, etc).
10. Any cardiac event (eg, myocardial infarction, unstable angina), coronary revascularisation (percutaneous coronary intervention or coronary artery bypass grafting), ablation of atrial fibrillation/flutter, valve repair/replacement, implantation of a cardiac resynchronisation therapy device within 12 weeks prior to Screening (Visit 1) or between Screening and Randomisation. Patients who underwent a successful atrial fibrillation/flutter cardioversion, can be enrolled in the study after 4 weeks.
14. Hb < 110 g/L (male) and < 100 g/L (female) or iron-deficiency with/without anaemia requiring ongoing or planned IV iron treatment.
15. Participants with hyperthyroidism, uncontrolled hypothyroidism (including but not limited to TSH ≥10 mIU/mL), or any clinically significant thyroid disease as judged by the investigator.
18. ALT or AST ≥ 2 × ULN at Screening (Visit 1).
19. Pulmonary arterial hypertension, chronic pulmonary embolism, severe pulmonary disease including COPD (ie, requiring home oxygen, chronic nebulizer therapy or chronic oral steroid therapy, or hospitalization for exacerbation of COPD requiring ventilatory support within 12 months prior to Screening (Visit 1).
20. Any active infection requiring oral, intravenous or intramuscular treatment at Screening (Visit 1) and/or at Randomisation.
23 Any signs or confirmation of COVID-19 infection:
Suspected (as judged by PI) or confirmed COVID-19 within the last 2 weeks prior to Screening (Visit 1) or at Randomisation.
Hospitalisation for COVID-19 within the last 12 weeks prior to Screening (Visit 1).
24. Any concomitant medications known to be a potent CYP3A4 inducers or inhibitors, eg, itraconazole, rifampicin, clarithromycin, or propylthiouracil
29. Previous enrolment and randomisation in the present study. (Participants who where screened and screen failed and not randomised in Part A can be screened for possible entry to Part B).
All exclusion criteria in Part A are applicable to Part B with the following exceptions:
Exclusion criteria 4; 19
Exclusion Criteria specific for Part B only [criteria numeration for Part B]
4. Life expectancy < 2 years due to other reasons than cardiovascular disease.
11. HF due to any of the following: known infiltrative cardiomyopathy (eg, amyloid, sarcoid, lymphoma, endomyocardial fibrosis), active myocarditis, constrictive pericarditis, cardiac tamponade, known genetic hypertrophic cardiomyopathy or obstructive hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D), or uncorrected primary valvular disease.
18. Primary pulmonary hypertension, chronic pulmonary embolism, severe pulmonary disease including COPD (ie, requiring home oxygen, chronic nebulizer therapy or chronic oral steroid therapy, or hospitalization for exacerbation of COPD requiring ventilatory support within 12 months prior to Screening [Visit 1]).
Check Your Eligibility
Let’s see if you might be eligible for this study.
What is your age and gender ?
There are 169 Locations for this study
Alexander City Alabama, 35010, United States
Little Rock Arkansas, 72205, United States
Sacramento California, 95821, United States
Miami Beach Florida, 33140, United States
Miami Florida, 33144, United States
Ocala Florida, 34471, United States
Evanston Illinois, 60208, United States
Hazel Crest Illinois, 60429, United States
Shreveport Louisiana, 71105, United States
Baltimore Maryland, 21229, United States
Saint Louis Missouri, 63136, United States
Buffalo New York, 14215, United States
New York New York, 10019, United States
Rosedale New York, 11422, United States
Chapel Hill North Carolina, 27599, United States
Pinehurst North Carolina, 28374, United States
Cleveland Ohio, 44195, United States
Philadelphia Pennsylvania, 19107, United States
Knoxville Tennessee, 37916, United States
Tullahoma Tennessee, 37388, United States
Norfolk Virginia, 23510, United States
Bedford Park , 5042, Australia
Chermside , 4032, Australia
Concord , 2139, Australia
Frankston , 3199, Australia
Aalst , 9300, Belgium
Dendermonde , 9200, Belgium
Hasselt , 3500, Belgium
Huy , 4500, Belgium
Kortrijk , 8500, Belgium
Leuven , 3000, Belgium
Roeselare , 8800, Belgium
Brasilia , 72145, Brazil
Campina Grande do Sul , 83430, Brazil
Campinas , 13060, Brazil
Campinas , 13092, Brazil
Canoas , 92425, Brazil
Curitiba , 80730, Brazil
Porto Alegre , 90035, Brazil
Ribeirão Preto , 14026, Brazil
Ribeirão Preto , 14051, Brazil
Rio de Janeiro , 22061, Brazil
São Paulo , 01228, Brazil
Blagoevgrad , 2700, Bulgaria
Pleven , 5804, Bulgaria
Plovdiv , 4003, Bulgaria
Sofia , 1202, Bulgaria
Sofia , 1309, Bulgaria
Sofia , 1407, Bulgaria
Sofia , 1431, Bulgaria
Sofia , 1527, Bulgaria
Sofia , 1606, Bulgaria
Sofia , 1784, Bulgaria
Varna , 9000, Bulgaria
Guelph Ontario, N1H 1, Canada
Newmarket Ontario, L3Y 2, Canada
Ottawa Ontario, K1Y 4, Canada
Toronto Ontario, M6G 1, Canada
Waterloo Ontario, N2T 0, Canada
York Ontario, M9N 1, Canada
Chicoutimi Quebec, G7H 7, Canada
Trois-Rivières Quebec, G9A 4, Canada
Brno , 625 0, Czechia
Broumov , 55001, Czechia
Jaromer , 551 0, Czechia
Kolin , 280 0, Czechia
Louny , 440 0, Czechia
Plzen , 320 0, Czechia
Praha 2 , 121 1, Czechia
Praha , 110 0, Czechia
Pribram , 261 0, Czechia
Zlin , 760 0, Czechia
Copenhagen O , 2100, Denmark
Hvidovre , 2650, Denmark
København NV , 2400, Denmark
København , 2300, Denmark
Roskilde , 4000, Denmark
Viborg , 8800, Denmark
Århus N , 8200, Denmark
Bayonne , 64100, France
Dijon Cedex , 21079, France
La Tronche , 38043, France
Le Coudray Cedex , 28630, France
Montauban , 82017, France
Montpellier Cedex , 34295, France
Paris , 75010, France
Paris , 75015, France
Pierre Benite , 69495, France
Rennes Cedex 9 , 35033, France
Saint Brieuc , 22027, France
Toulon , 83100, France
Toulouse Cedex 9 , 31059, France
TOURCOING cedex , 59208, France
Balatonfüred , 8230, Hungary
Budapest , 1096, Hungary
Budapest , 1122, Hungary
Nyíregyháza , 4400, Hungary
Fukui-shi , 910-8, Japan
Higashiohmi-shi , 527-8, Japan
Iwakuni-shi , 740-8, Japan
Kanazawa-shi , 920-8, Japan
Kasugai-shi , 487-0, Japan
Kishiwada-shi , 596-0, Japan
Kure-shi , 737-0, Japan
Kyoto-shi , 612-8, Japan
Matsumoto-shi , 390-8, Japan
Minami-ku , 861-4, Japan
Nagano , 399-8, Japan
Naha , 902-8, Japan
Oita-shi , 870-8, Japan
Omihachiman-shi , 523-0, Japan
Otaru-shi , 047-8, Japan
Sagamihara-shi , 252-5, Japan
Toshima-ku , 171-0, Japan
Ueda-shi , 386-8, Japan
Uwajima-shi , 798-8, Japan
Yokohama-shi , 245-8, Japan
Amsterdam , 1081 , Netherlands
Den Bosch , 5223 , Netherlands
Den Haag , 2545 , Netherlands
Deventer , 7416 , Netherlands
Heerlen , 6419 , Netherlands
Bydgoszcz , 85-07, Poland
Lublin , 20-04, Poland
Rzeszow , 35-05, Poland
Skierniewice , 96-10, Poland
Tarnów , 33-10, Poland
Tczew , 83-11, Poland
Tychy , 43-10, Poland
Warszawa , 02-75, Poland
Warszawa , 02-79, Poland
Warszawa , 04-74, Poland
Wołomin , 05-20, Poland
Aramil , 62400, Russian Federation
Kemerovo , 65000, Russian Federation
Moscow , 11999, Russian Federation
Moscow , 12120, Russian Federation
Moscow , 12155, Russian Federation
Novosibirsk , 63005, Russian Federation
Perm , 61400, Russian Federation
St Petersburg , 19506, Russian Federation
Tver , 17003, Russian Federation
Banska Bystrica , 974 0, Slovakia
Bratislava , 821 0, Slovakia
Brezno , 977 0, Slovakia
Kosice , 04022, Slovakia
Kosice , 044 2, Slovakia
Nitra , 949 0, Slovakia
Presov , 080 0, Slovakia
Göteborg , 413 4, Sweden
Jönköping , 551 8, Sweden
Lund , 222 2, Sweden
Norrköping , 603 7, Sweden
Stockholm , 118 8, Sweden
Stockholm , 171 7, Sweden
Stockholm , 18288, Sweden
Örebro , 701 8, Sweden
Kaohsiung , 807, Taiwan
Kaohsiung , 81362, Taiwan
Kaohsiung , 833, Taiwan
Taichung , 40201, Taiwan
Taichung , 40447, Taiwan
Taichung , 40705, Taiwan
Tainan , 70403, Taiwan
Tainan , 710, Taiwan
Taipei 112 , , Taiwan
Taipei City , 110, Taiwan
Taipei , 100, Taiwan
Taoyuan , 333, Taiwan
Eskisehir , 26480, Turkey
Izmir , 35340, Turkey
How clear is this clinincal trial information?
Introducing, the Journey Bar
Use this bar to access information about the steps in your cancer journey.