Ischemic or non-ischemic cardiomyopathy and heart failure with reduced ejection fraction. Danke MedDRA version: 20.0 Level: PT Classification code 10007554 Term: Cardiac failure System Organ Class: 10007541 - Cardiac disorders MedDRA version: 27.0 Level: PT Classification code 10078289 Term: Heart failure with reduced ejection fraction System Organ Class: 10007541 - Cardiac disorders MedDRA version: 20.0 Level: LLT Classification code 10055222 Term: Non-ischemic cardiomyopathy System Organ Cl
Conditions
Interventions
Product Name: Mitiperstat (AZD4831)
Pharmaceutical Form: Tablet
INN or Proposed INN: Mitiperstat
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-
Pharmaceutical
Sponsors
Philipps University Marburg
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Adult patients aged =18 years (male and female). 2. Confirmed diagnosis of chronic HFrEF present for at least 6 months. HFrEF may be of any etiology, i.e. ischemic as well as non-ischemic cardiomyopathy. 3. Documented LVEF = 40% at screening (assessed by echocardiography). 4. In stable condition (NYHA class II or III). 5. On optimized, guideline-directed medical heart failure therapy; stable medication and dose for = 4 weeks, diuretics = 1 week). 6. NT-proBNP > 300 pg/ml (sinus rhythm), >1000 pg/ml (atrial fibrillation). If available the average of NTproBNP values within the last 12 months should not be =25% than NTproBNP at time of inclusion to exclude decompensation 7. 6MWD =100m at screening. 8. Signed written informed consent. 9. Capability and willingness to comply with study procedures. 10. Females must have a negative pregnancy test at the screening visit and on admission to the clinical unit, must not be lactating and must be of non-child-bearing potential, confirmed at the screening visit by fulfilling one of the following criteria: a) Postmenopausal defined as amenorrhea for at least 12 months or more following cessation of all exogenous hormonal treatments or alternatively FSH levels in the postmenopausal range. b) Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation. 11. Male patients must be surgically sterile or using an acceptable method of contraception (defined as barrier methods in conjunction with spermicides) for the duration of the study (from the time they sign consent) and for 3 months after the last dose of mitiperstat/matching placebo to prevent pregnancy in a partner. Male patients must not donate or bank sperm during this same time period. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 63 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 63
Exclusion criteria
Exclusion criteria: 1. Cardiomyopathy based on infiltrative diseases (e.g. amyloidosis), accumulation diseases (e.g. haemochromatosis, Fabry disease), muscular dystrophies, cardiomyopathy with reversible causes (e.g. stress cardiomyopathy), hypertrophic obstructive cardiomyopathy or known pericardial constriction. 2. Any high-grade valvular defect which, in judgement of the investigator, has an impact on LVEF (e.g. high-grade aortic valve stenosis or mitral valve regurgitation), expected to lead to surgery during the trial. High-grade tricuspid regurgitation in isolation is not an exclusion criterion. 3. Diagnosis of cardiomyopathy induced by chemotherapy or peripartum within the 12 months prior to Visit 1. 4. Acutely decompensated heart failure. 5. Recent device implant for heart failure (i.e. potential influence on LVEF such as cardiac resynchronization therapy, TAVR, MitraClip, LVAD, etc.) within 60 days prior to randomization. Recent ICD without CRT implantation is not an exclusion criterion. 6. Inadequately controlled atrial or ventricular arrhythmia (e.g. Atrial fibrillation with average resting ventricular rate >110bpm). 7. Current indication for percutaneous coronary intervention (PCI) or CABG (at the time of randomization). 8. Significant cardiac ischemia in a stress test within 12 months of enrollment without revascularization since. 9. Uncontrolled hypotension ( 2x ULN. 13. Haemoglobin (HgB) <9 g/dl at Visit 1. 14. Hypersensitivity to the active substance or one of the ingredients (see current IB). 15. Participation in another interventional clinical study within 30 days before baseline. 16. Any clinically significant disease or disorder (e.g. cardiovascular, gastrointestinal, liver, renal, neurological, musculoskeletal, endocrine, metabolic, psychiatric, infectious disease or major physical impairment) which, as judged by the Investigator, might put the patient at risk because of participation in the study, or probable alternative primary reason for patient’s symptoms in judgment of Investigator. 17. Any active infection requiring oral, intravenous, or intramuscular treatment at Screening and/or Randomization. 18. 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. 19. History or ongoing severe allergy / hypersensitivity reactions to drugs (including but not limited to rash, angioedema, acute urticaria), that might put the patient at risk because of participation in the study, as judged by the Investigator. 20. Drug or alcohol abuse, either current or within previous 12 months. 21. Judgement by the Investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements. 22. Pregnant or breastfeeding women. 23. Presence of any other disease than heart failure with a life expectancy of <1 years in the opin
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy of 12 weeks treatment of mitiperstat (AZD4831) in patients by measuring the change in NTproBNP levels;Secondary Objective: To assess the efficacy of 12 weeks of mitiperstat administration in patients with with ischemic or nonischemic cardiomyopathy and heart failure with reduced ejection fraction ;Primary end point(s): Change in log NTproBNP levels from baseline to week 12 (mitiperstat vs. placebo);Timepoint(s) of evaluation of this end point: week 12 of treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Change in 6MWD from baseline to week 12 • Change in KCCQ-TSS from baseline to week 12 • Change in LVEF as assessed via transthoracic echocardiography (TTE) from baseline to week 12 • Change in NYHA class from baseline to week 12 • Change in HR, systolic and diastolic BP, mean arterial pressure • Incidence of major adverse cardiovascular events (MACE, i.e. cardiovascular death, hospitalization for heart failure, non-fatal acute myocardial infarction, non-fatal cerebrovascular accident (transient ischemic attack or stroke) • Change in use/dose of HF medication including diuretics Substudy: The patients from primary site Cologne will enter a substudy that will assess the following additional endpoints (from baseline to week 12): • Change in flow-mediated brachial dilation and retinal vessel analysis ;Timepoint(s) of evaluation of this end point: week 12 of treatment | — |
Countries
Germany
Contacts
Public ContactNelli Ens-Jäger
Koordinierungszentrum für Klinische Studien (KKS) Marburg
Outcome results
None listed