Pilot Study of COR-1 in Heart Failure

NCT ID: NCT01391507

Last Updated: 2014-10-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-10-31
• Study Completion Date: 2013-08-31

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.

Conditions

Cardiomyopathy, Dilated

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo

Group Type: PLACEBO_COMPARATOR

0.9 % sodium chloride

Intervention Type: DRUG

Monthly intravenous injection for 6 months

Standard therapy for heart failure

Intervention Type: DRUG

All patients will continue to receive standard therapy for heart failure (ie, in accordance with guidelines) throughout the study.

20 mg COR-1

Group Type: EXPERIMENTAL

COR-1

Intervention Type: DRUG

Monthly intravenous injection for 6 months

Standard therapy for heart failure

Intervention Type: DRUG

All patients will continue to receive standard therapy for heart failure (ie, in accordance with guidelines) throughout the study.

80 mg COR-1

Group Type: EXPERIMENTAL

COR-1

Intervention Type: DRUG

Monthly intravenous injection for 6 months

Standard therapy for heart failure

Intervention Type: DRUG

All patients will continue to receive standard therapy for heart failure (ie, in accordance with guidelines) throughout the study.

160 mg COR-1

Group Type: EXPERIMENTAL

COR-1

Intervention Type: DRUG

Monthly intravenous injection for 6 months

Standard therapy for heart failure

Intervention Type: DRUG

All patients will continue to receive standard therapy for heart failure (ie, in accordance with guidelines) throughout the study.

Interventions

0.9 % sodium chloride

Monthly intravenous injection for 6 months

Intervention Type: DRUG

COR-1

Monthly intravenous injection for 6 months

Intervention Type: 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.

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Corimmun GmbH

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Corimmun GmbH Clinical Trial

Role: STUDY_DIRECTOR

Corimmun GmbH

Locations

München, , Germany

Regensburg, , Germany

Tübingen, , Germany

Würzburg, , Germany

Countries

Germany

References

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.

Reference Type: BACKGROUND

PMID: 9950662 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 16996841 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 11216956 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 19171871 (View on PubMed)

Other Identifiers

2010-022579-68

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

COR-1/02

Identifier Type: -

Identifier Source: secondary_id

CR100913

Identifier Type: -

Identifier Source: org_study_id