E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Heart Failure, Dilated Cardiomyopathy |
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E.1.1.1 | Medical condition in easily understood language |
Heart failure |
Herzschwäche |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10056419 |
E.1.2 | Term | Dilated cardiomyopathy |
E.1.2 | System Organ Class | 100000004849 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective is to investigate whether intravenous COR-1 administration every 4 weeks in addition to standard therapy enhances cardiac function at rest in patients with heart failure due to DCM, compared to standard therapy alone after 6 months. |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives aim to determine the efficacy and safety of COR-1 in DCM patients and characterise patient-specific factors that may predict COR-1 treatment success. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Sub-study #1: Effect of COR-1 on Cardiac Autonomic Function in Patients with Heart Failure (Tübingen)
Objective: To evaluate the effect of study drug on cardiac autonomic function. The exploratory hypotheses for this sub-study are that the presence of anti-ß1-receptor autoantibodies is associated with cardiac autonomic dysfunction by means of severe cardiac autonomic failure in patients with dilated cardiomyopathy and that neutralizing ß1-receptor autoantibodies in patients with dilated cardiomyopathy leads to a recovery of cardiac autonomic dysfunction (i.e. proportion of patients with severe cardiac autonomic failure).
Sub-study #2: Monitoring left ventricular sympathetic nerve function with I-123 MIBG SPECT and myocardial perfusion and function with ECG-gated Tc-99m Tetrofosmin SPECT (Würzburg)
Objective: To describe the myocardial changes induced by treatment with COR-1 in heart failure patients using myocardial SPECT techniques. This sub-study will use nuclear imaging to assess the effect of COR-1 on the cardiac sympathetic nervous system which may contribute to the understanding of the pathophysiology of non-ischemic heart failure.
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E.3 | Principal inclusion criteria |
- Diagnosed heart failure due to dilated cardiomyopathy
- presence of anti-β1-adrenoreceptor autoantibodies in patients` blood samples
- LVEF < 45%, as determined by biplane echocardiography
- New York Heart Association (NYHA) class II – III
- disease duration: symptomatic heart failure for >1 year and <8 years
- Treatment with ACE inhibitors or angiotensin II receptor blockers (ARB), beta-blockers and aldosterone antagonists (the latter at the discretion of the attending physician) according to 2012 European Society of Cardiology guidelines for at least 6 months (with the exception of lack of tolerability of any of these drugs) and at stable doses for at least 2 months prior to screening (Note: “standard therapy” can include, but does not have to include, any of the following: ACE inhibitor, angiotensin II receptor blockers (ARB) or beta-blocker.) |
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E.4 | Principal exclusion criteria |
- Ischemic heart disease characterised by ≥ 50% coronary artery stenosis and/or history of myocardial infarction as determined by coronary angiography
- Third or higher degree valvular defect
- Clinically relevant disorder of the immune system (as determined by anamnesis)
- History of severe allergies, increased risk for anaphylactic shock (as determined by anamnesis e.g. bronchial asthma)
- Any disease requiring immunosuppressive drugs, except ≤ 5 mg/day prednisone equivalent dose
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy measure of COR-1 treatment is to assess the change in left ventricular ejection fraction (LVEF) from baseline to 6 months by biplane echocardiography. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Secondary / Exploratory Efficacy Endpoints
-Change in LVEF from baseline to 9 months by biplane echocardiography
-Change in transmitral flow velocity time integral and tissue Doppler mitral annular velocity from baseline to 6 months by echocardiography
-Change in NT-Pro-BNP values from baseline to 6 months
-Investigating whether COR-1 treatment attenuates cardiac morbidity by measuring the extent of heart failure by New York Heart Association (NYHA) classification throughout the study
-Occurrence of major adverse cardiac events (MACE)
-Monitoring any change in exercise capacity (six-minute walk test) from baseline to 6 and 9 months
-Monitoring quality of life at baseline and 6 months
-Monitoring Holter ECG parameters from baseline to 6 months
-Monitoring disease progression and survival by assessing all-cause death, cardiac resuscitation, emergency hospitalisation for heart failure, clinical deterioration and need for cardiac surgery to improve myocardial pump function (e.g. transplantation, mechanical assist, myoplasty, bi-ventricular pacing)
-Comparison of COR-1 treatment success from baseline to 6 and 9 months
obetween patients receiving beta-blockers and those who do not
o based on patients’ age
o based on patients’ disease duration and symptom duration |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
summarised at 6 and 9 months |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |