Clinical Trial: Pilot Study of COR-1 in Heart Failure

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: COR-1, an Anti-Beta1 Receptor Antibody Cyclopeptide in Heart Failure: a Phase II, Multicentre, Randomised, Double-Blind and Placebo-Controlled Study With Parallel Groups

Brief Summary: The purpose of this study is to investigate the effect of COR-1 in combination with standard therapy in patients with heart failure. The safety and tolerability of COR-1 will also be assessed.

Detailed Summary: In patients with dilated cardiomyopathy (heart is weakened and enlarged), the presence of anti-beta1-receptor autoantibodies has been shown to predict more depressed left ventricular function, increased prevalence of serious ventricular arrhythmias, sudden cardiac death, and cardiovascular mortality. In animal models, COR-1 cyclopeptide has been shown to bind to, and therefore decrease, the anti-beta1-receptor autoantibody titre. This study will investigate the safety and effectiveness of COR-1 treatment in patients with dilated cardiomyopathy. This study will be a randomized (the study treatment is assigned by chance), double-blind, (neither investigator nor patient knows the treatment that the volunteer receives), multicenter (study is conducted in more than one center) placebo-controlled (one of the treatments is inactive), parallel group study (patients in different treatment groups receive medication at the same time) in men and women who have heart failure due to dilated cardiomyopathy. Eligible patients should also have a left ventricular ejection fraction of less than or equal to 45% (measurement of the percentage of blood leaving the heart each time it contracts) and should be positive for anti-beta1-receptor autoantibodies. The study will consist of 3 phases: a screening phase, a double-blind treatment period, and a follow-up phase. Patients will be randomly assigned to 1 of 4 treatment groups: 20 mg COR-1, 80 mg COR-1, 160 mg COR-1, or placebo (inactive medication). Each patient will receive 1 intravenous dose (medication is injected into a vein) every 4 weeks for a total of 6 months. Patients will come to the study center each time they receive study medication and will remain at the center for 2 to 3 hours following the injection. Blood samples will be drawn at time points during the screening, treatment, and follow-up periods. Patients will return to the study center for follow-up visits at 3 months following completion of the 6-month treatment period.
Sponsor: Corimmun GmbH

Current Primary Outcome: Change From Baseline in Left Ventricular Ejection Fraction (LVEF) at Month 6 [ Time Frame: Baseline and Month 6 ]

Original Primary Outcome: 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. [ Time Frame: Baseline and 6 months ]

Current Secondary Outcome:

• Change From Baseline in Local Left Ventricular Ejection Fraction (LVEF) at Month 9 [ Time Frame: Baseline and Month 9 ]
  The LVEF is a measure of how much blood is pumped out of the left ventricle of the heart (the main pumping chamber). Ejection fraction percentages greater than (>) 55% are considered normal. It was measured by biplane echocardiography (local assessment).
• Change From Baseline in N-Terminal Pro B-Type Natriuretic Peptide (NT-ProBNP) Level at Month 6 [ Time Frame: Baseline and Month 6 ]
  The NT-ProBNP is a biomarker (a biologic molecule) that has been shown to predict cardiac events.
• Change From Baseline in Central Transmitral Flow Velocity Time Integral (VTI) at Month 6 [ Time Frame: Baseline and Month 6 ]
  Transmitral flow VTI measures how blood flows through the heart. This was measured by echocardiogram. Most of the values for transmitral flow VTI were not provided in the reports from central core echocardiographic laboratory due to technical reasons.
• Change From Baseline in Central Tissue E-Wave Doppler Mitral Annular Velocity at Month 6 [ Time Frame: Baseline and Month 6 ]
  Tissue doppler mitral annular velocity is a measure of how well the heart fills with blood. This was measured by echocardiogram. Most of the values for E-wave were not provided in the reports from central core echocardiographic laboratory due to technical reasons.
• Change From Baseline in Distance Walked During Six-minute Walk Test at Month 6 [ Time Frame: Baseline and Month 6 ]
  A standardized 6-minute walk test was performed and the distance covered in 6 minutes was measured.
• Number of Participants With New York Heart Association (NYHA) Classification of Disease Progression [ Time Frame: Baseline and Month 6 ]
  Disease progression (morbidity) was measured by the NYHA classification. The NYHA classification assesses the severity of symptoms of heart failure as judged by the investigator and is comprised of 4 stages. Stage I- No symptoms/limitation in ordinary physical activity (for example, shortness of breath when walking, climbing stairs); Stage II-Mild symptoms (mild shortness of breath and/or angina) and slight limitation during ordinary activity; Stage III- Marked limitation in activity due to symptoms, even during less-than-ordinary activity, (for example, walking short distances [20-100 m]), comfortable only at rest; and Stage IV- Severe limitations in activity/experiences symptoms while at rest (mostly bedbound participants).
• Change From Baseline in Minnesota Living With Heart Failure Questionnaire Score at Month 6 [ Time Frame: Baseline and Month 6 ]
  Minnesota living with heart failure questionnaire is a self-administered, disease-specific measure of health related quality of life (QOL) that assesses participant's perceptions of the influence of heart failure on physical, socioeconomic and psychological aspects of life. Participants responded to 21 items using a six-point response scale (0-5). The total summary score can range from 0-105 with a lower score reflecting better heart failure related QOL.
• Change From Baseline in Holter Electrocardiography (ECG) Parameters (Heart Rate) at Month 6 [ Time Frame: Baseline and Month 6 ]
  A Holter monitor is a portable device which monitors the electrical activity (electrocardiography) of the heart. Mean heart rate, maximum heart rate and minimum heart rate were evaluated.
• Number of Participants With Holter Electrocardiography (ECG) Parameters [ Time Frame: Baseline and Month 6 ]
  A Holter monitor is a portable device which monitors the electrical activity (electrocardiography) of the heart. Block, Heart rhythm, AV junctional, Ventricular, Lown classification, Results were evaluated.

Original Secondary Outcome:

• Change in LVEF by biplane echocardiography [ Time Frame: baseline to 9 and 18 months ]
• Change in transmitral flow velocity time integral and tissue Doppler mitral annular velocity [ Time Frame: from baseline to 6 months ]
• Change in NT-Pro-BNP values [ Time Frame: 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 [ Time Frame: 18 months ]
• Occurrence of major adverse cardiac events (MACE) [ Time Frame: 18 months ]
• Monitoring any change in exercise capacity (six-minute walk test) [ Time Frame: from baseline to 6, 9 and 18 months ]
• Monitoring quality of life [ Time Frame: from baseline to 6 months ]
• Changes in cardiac autonomic function (deceleration capacity, heart rate turbulence, standard measures of heart rate variability in time and frequency domain) and repolarisation dynamics by Holter ECG [ Time Frame: from baseline to six months ]
• Disease progression and survival [ Time Frame: 18 months ]
  Assessment of 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)
• Incidence of adverse events [ Time Frame: 18 months ]

  Vital signs will be assessed at each visit. Regular assessment of ECG parameters. Regular determination of echocardiography parameters. Regular measurement of autoantibody titres (anti-ß1 receptor autoantibodies). Reporting AEs, laboratory abnormalities, treatment discontinuation for toxicity and use of concomitant medication.

  SAEs are to be accounted for during the treatment period (6 months).

Dates:
Date Received: July 4, 2011
Date Started: October 2011
Date Completion:
Last Updated: October 8, 2014
Last Verified: October 2014