Pilot Study of COR-1 in Heart Failure

Cardiomyopathy, Dilated Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01391507
• Other study ID #: CR100913
• Secondary ID: 2010-022579-68CO
• Status: Completed
• Phase: Phase 2
• First received: July 4, 2011
• Last updated: October 8, 2014
• Start date: October 2011
• Est. completion date: August 2013

Study information

• Verified date: October 2014
• Source: Corimmun GmbH
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Ethics CommissionGermany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial 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.

Description:

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. Patients will participate in the study for approximately 9 months. Patient safety will be monitored. The study drug (COR-1) is being investigated for the treatment of heart failure.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: August 2013
• Est. primary completion date: August 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Diagnosed heart failure due to dilated cardiomyopathy with left ventricular ejection fraction < 45%

• Presence of anti-beta1-receptor autoantibodies

• New York Heart Association (NYHA) class II to III heart failure

• Symptomatic heart failure for >1 year and < 8 years

• Treatment with adequate doses of angiotensin converting enzyme inhibitors or angiotensin II receptor blockers, beta-blockers, and optional aldosterone antagonists according to guidelines for at least six months (with the exception of lack of tolerability of any of these drugs) and at stable doses for 2 months prior to screening

Exclusion Criteria:

• Ischemic heart disease characterized by >= 50% coronary artery stenosis and/or history of myocardial infarction

• Third or higher degree valvular defect

• Any disease requiring immunosuppressive drugs (except for <= 5 mg/day prednisone-equivalent dose) or any clinically relevant disorder of the immune system

• History of severe allergies and increased risk for anaphylactic shock (e.g., bronchial asthma)

• History of, or currently active illness, considered to be clinically significant by the Investigator or any other illness that the Investigator considers should exclude the patient from the study or that could interfere with the interpretation of the study results

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cardiomyopathies
• Cardiomyopathy, Dilated
• Heart Failure

Intervention

Drug:
• 0.9 % sodium chloride
Monthly intravenous injection for 6 months
• COR-1
Monthly intravenous injection for 6 months
• Standard therapy for heart failure
All patients will continue to receive standard therapy for heart failure (ie, in accordance with guidelines) throughout the study.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Corimmun GmbH

Country where clinical trial is conducted

Germany, 

References & Publications (4)

Iwata M, Yoshikawa T, Baba A, Anzai T, Mitamura H, Ogawa S. Autoantibodies against the second extracellular loop of beta1-adrenergic receptors predict ventricular tachycardia and sudden death in patients with idiopathic dilated cardiomyopathy. J Am Coll Cardiol. 2001 Feb;37(2):418-24. — View Citation

Jahns R, Boivin V, Siegmund C, Inselmann G, Lohse MJ, Boege F. Autoantibodies activating human beta1-adrenergic receptors are associated with reduced cardiac function in chronic heart failure. Circulation. 1999 Feb 9;99(5):649-54. — View Citation

Lloyd-Jones D, Adams R, Carnethon M, De Simone G, Ferguson TB, Flegal K, Ford E, Furie K, Go A, Greenlund K, Haase N, Hailpern S, Ho M, Howard V, Kissela B, Kittner S, Lackland D, Lisabeth L, Marelli A, McDermott M, Meigs J, Mozaffarian D, Nichol G, O'Donnell C, Roger V, Rosamond W, Sacco R, Sorlie P, Stafford R, Steinberger J, Thom T, Wasserthiel-Smoller S, Wong N, Wylie-Rosett J, Hong Y; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics--2009 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation. 2009 Jan 27;119(3):480-6. doi: 10.1161/CIRCULATIONAHA.108.191259. Erratum in: Circulation. 2009 Jan 27;119(3):e182. — View Citation

Störk S, Boivin V, Horf R, Hein L, Lohse MJ, Angermann CE, Jahns R. Stimulating autoantibodies directed against the cardiac beta1-adrenergic receptor predict increased mortality in idiopathic cardiomyopathy. Am Heart J. 2006 Oct;152(4):697-704. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Left Ventricular Ejection Fraction (LVEF) at Month 6	The LVEF is a fraction of blood (in percent) 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 (central assessment).	Baseline and Month 6	Yes
Secondary	Change From Baseline in Local Left Ventricular Ejection Fraction (LVEF) at 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).	Baseline and Month 9	Yes
Secondary	Change From Baseline in N-Terminal Pro B-Type Natriuretic Peptide (NT-ProBNP) Level at Month 6	The NT-ProBNP is a biomarker (a biologic molecule) that has been shown to predict cardiac events.	Baseline and Month 6	No
Secondary	Change From Baseline in Central Transmitral Flow Velocity Time Integral (VTI) at 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.	Baseline and Month 6	No
Secondary	Change From Baseline in Central Tissue E-Wave Doppler Mitral Annular Velocity at 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.	Baseline and Month 6	No
Secondary	Change From Baseline in Distance Walked During Six-minute Walk Test at Month 6	A standardized 6-minute walk test was performed and the distance covered in 6 minutes was measured.	Baseline and Month 6	No
Secondary	Number of Participants With New York Heart Association (NYHA) Classification of Disease Progression	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).	Baseline and Month 6	No
Secondary	Change From Baseline in Minnesota Living With Heart Failure Questionnaire Score at 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.	Baseline and Month 6	No
Secondary	Change From Baseline in Holter Electrocardiography (ECG) Parameters (Heart Rate) at 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.	Baseline and Month 6	Yes
Secondary	Number of Participants With Holter Electrocardiography (ECG) Parameters	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.	Baseline and Month 6	Yes