Clinical trial NCT01391507: Pilot Study of COR-1 in Heart Failure
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cardiomyopathy, Dilated
Keywords: Anti-beta1-receptor autoantibodies
COR-1
Heart failure
Lead sponsor: Corimmun GmbH
Sponsor class: INDUSTRY
First posted: 2011-07-12
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 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.

Eligibility 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

Primary outcomes:
measure: Change From Baseline in Left Ventricular Ejection Fraction (LVEF) at Month 6
timeFrame: Baseline and Month 6
Secondary outcomes:
measure: Change From Baseline in Local Left Ventricular Ejection Fraction (LVEF) at Month 9
timeFrame: Baseline and Month 9
measure: Change From Baseline in N-Terminal Pro B-Type Natriuretic Peptide (NT-ProBNP) Level at Month 6
timeFrame: Baseline and Month 6
measure: Change From Baseline in Central Transmitral Flow Velocity Time Integral (VTI) at Month 6
timeFrame: Baseline and Month 6
measure: Change From Baseline in Central Tissue E-Wave Doppler Mitral Annular Velocity at Month 6
timeFrame: Baseline and Month 6
measure: Change From Baseline in Distance Walked During Six-minute Walk Test at Month 6
timeFrame: Baseline and Month 6
measure: Number of Participants With New York Heart Association (NYHA) Classification of Disease Progression
timeFrame: Baseline and Month 6
measure: Change From Baseline in Minnesota Living With Heart Failure Questionnaire Score at Month 6
timeFrame: Baseline and Month 6
measure: Change From Baseline in Holter Electrocardiography (ECG) Parameters (Heart Rate) at Month 6
timeFrame: Baseline and Month 6
measure: Number of Participants With Holter Electrocardiography (ECG) Parameters
timeFrame: Baseline and Month 6
Other outcomes:
Locations:
city: München
country: Germany
city: Regensburg
country: Germany
city: Tübingen
country: Germany
city: Würzburg
country: Germany
Study officials:
affiliation: Corimmun GmbH
name: Corimmun GmbH Clinical Trial
role: STUDY_DIRECTOR
References:
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. doi: 10.1161/01.cir.99.5.649.
citation: 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.
citation: 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.
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. No abstract available.