Pilot Study of COR-1 in Heart Failure

• ClinicalTrials.gov Identifier: NCT01391507
• Recruitment Status: Completed
• First Posted: July 12, 2011
• Results First Posted: August 26, 2014
• Last Update Posted: October 17, 2014
• Sponsor: Corimmun GmbH
• Information provided by (Responsible Party): Corimmun GmbH

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Cardiomyopathy, Dilated	Drug: 0.9 % sodium chloride; Drug: COR-1; Drug: Standard therapy for heart failure	Phase 2

Detailed 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 36 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Study Start Date: October 2011
• Actual Primary Completion Date: August 2013
• Actual Study Completion Date: August 2013

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Placebo	Drug: 0.9 % sodium chloride; Monthly intravenous injection for 6 months; Drug: Standard therapy for heart failure; All patients will continue to receive standard therapy for heart failure (ie, in accordance with guidelines) throughout the study.
Experimental: 20 mg COR-1	Drug: COR-1; Monthly intravenous injection for 6 months; Drug: Standard therapy for heart failure; All patients will continue to receive standard therapy for heart failure (ie, in accordance with guidelines) throughout the study.
Experimental: 80 mg COR-1	Drug: COR-1; Monthly intravenous injection for 6 months; Drug: Standard therapy for heart failure; All patients will continue to receive standard therapy for heart failure (ie, in accordance with guidelines) throughout the study.
Experimental: 160 mg COR-1	Drug: COR-1; Monthly intravenous injection for 6 months; Drug: Standard therapy for heart failure; All patients will continue to receive standard therapy for heart failure (ie, in accordance with guidelines) throughout the study.

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline in Left Ventricular Ejection Fraction (LVEF) at Month 6 [ Time Frame: Baseline and 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).

Secondary Outcome Measures :

1. 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).
2. 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.
3. 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.
4. 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.
5. 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.
6. 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).
7. 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.
8. 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.
9. 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

Germany

München, Germany

Regensburg, Germany

Tübingen, Germany

Würzburg, Germany

Sponsors and Collaborators

Corimmun GmbH

Investigators

• Study Director: Corimmun GmbH Clinical Trial; Corimmun GmbH

More Information

Publications:

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. doi: 10.1161/01.cir.99.5.649.

Stork 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. doi: 10.1016/j.ahj.2006.05.004.

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. doi: 10.1016/s0735-1097(00)01109-8.

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. No abstract available. Erratum In: Circulation. 2009 Jan 27;119(3):e182.

• Responsible Party: Corimmun GmbH
• ClinicalTrials.gov Identifier: NCT01391507
• Other Study ID Numbers: CR100913; 2010-022579-68 ( EudraCT Number ); COR-1/02
• First Posted: July 12, 2011
• Results First Posted: August 26, 2014
• Last Update Posted: October 17, 2014
• Last Verified: October 2014

Keywords provided by Corimmun GmbH:

Anti-beta1-receptor autoantibodies; COR-1; Heart failure

Additional relevant MeSH terms:

Heart Failure; Cardiomyopathies; Cardiomyopathy, Dilated; Heart Diseases; Cardiovascular Diseases; Cardiomegaly; Laminopathies; Genetic Diseases, Inborn