Pilot Study of COR-1 in Heart Failure

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Corimmun GmbH
ClinicalTrials.gov Identifier:
NCT01391507
First received: July 4, 2011
Last updated: September 11, 2013
Last verified: September 2013

July 4, 2011
September 11, 2013
October 2011
August 2013   (final data collection date for primary outcome measure)
Change in left ventricular ejection fraction from baseline to 6 months [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: Yes ]
Left ventricular ejection fraction is a measure of how much blood is pumped out of the left ventricle of the heart (the main pumping chamber). It will be measured by biplane echocardiography.
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 ] [ Designated as safety issue: Yes ]
The primary objective is to investigate whether intravenous COR-1 administration every 4 weeks in addition to standard therapy enhances cardiac function at rest in patients with heart failure due to DCM, compared to standard therapy alone after 6 months.
Complete list of historical versions of study NCT01391507 on ClinicalTrials.gov Archive Site
  • Change in left ventricular ejection fraction [ Time Frame: Baseline and up to 9 months ] [ Designated as safety issue: Yes ]
    Left ventricular ejection fraction is a measure of how much blood is pumped out of the left ventricle of the heart (the main pumping chamber). It will be measured by biplane echocardiography.
  • Change in N-terminal pro B-type natriuretic peptide values [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: Yes ]
    N-terminal pro B-type natriuretic peptide is a biomarker (a biologic molecule) that has been shown to predict cardiac events.
  • Morbidity as measured by the New York Heart Association classification [ Time Frame: Up to 9 months ] [ Designated as safety issue: Yes ]
  • Occurrence of major adverse cardiac events [ Time Frame: Up to 9 months ] [ Designated as safety issue: Yes ]
  • Change in exercise capacity (six-minute walk test) [ Time Frame: Baseline and up to 9 months ] [ Designated as safety issue: Yes ]
  • Quality of life [ Time Frame: Baseline and up to 6 months ] [ Designated as safety issue: Yes ]
    Quality of life will be assessed by administering the Minnesota Living with Heart Failure Questionnaire
  • Holter electrocardiography parameters [ Time Frame: Baseline and up to 6 months ] [ Designated as safety issue: Yes ]
    A Holter monitor is a portable device which monitors the electrical activity (electrocardiography) of the heart.
  • Disease progression and survival [ Time Frame: Up to 9 months ] [ Designated as safety issue: Yes ]
    Assessment of all-cause death, cardiac resuscitation, emergency hospitalisation for heart failure, clinical deterioration, and need for cardiac surgery to improve myocardial pump function (eg, transplantation, mechanical assist, myoplasty, bi-ventricular pacing)
  • Number of patients with adverse events as a measure of safety and tolerability [ Time Frame: Up to 9 months ] [ Designated as safety issue: Yes ]
  • Change in transmitral flow velocity time integral [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: Yes ]
    Transmitral flow velocity time integral measures how blood flows through the heart and has been shown to predict outcomes in heart failure. This will be measured by echocardiogram.
  • Change in tissue doppler mitral annular velocity [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: Yes ]
    Tissue doppler mitral annular velocity is a measure of how well the heart fills with blood and has been shown to predict outcomes in heart failure. This will be measured by echocardiogram.
  • Change in LVEF by biplane echocardiography [ Time Frame: baseline to 9 and 18 months ] [ Designated as safety issue: Yes ]
  • Change in transmitral flow velocity time integral and tissue Doppler mitral annular velocity [ Time Frame: from baseline to 6 months ] [ Designated as safety issue: Yes ]
  • Change in NT-Pro-BNP values [ Time Frame: from baseline to 6 months ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]
  • Occurrence of major adverse cardiac events (MACE) [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]
  • Monitoring any change in exercise capacity (six-minute walk test) [ Time Frame: from baseline to 6, 9 and 18 months ] [ Designated as safety issue: Yes ]
  • Monitoring quality of life [ Time Frame: from baseline to 6 months ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]
  • Disease progression and survival [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]

    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).

Not Provided
Not Provided
 
Pilot Study of COR-1 in Heart Failure
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

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.

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Cardiomyopathy, Dilated
  • Drug: 0.9 % sodium chloride
    Monthly intravenous injection for 6 months
  • 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.
  • Placebo Comparator: Placebo
    Interventions:
    • Drug: 0.9 % sodium chloride
    • Drug: Standard therapy for heart failure
  • Experimental: 20 mg COR-1
    Interventions:
    • Drug: COR-1
    • Drug: Standard therapy for heart failure
  • Experimental: 80 mg COR-1
    Interventions:
    • Drug: COR-1
    • Drug: Standard therapy for heart failure
  • Experimental: 160 mg COR-1
    Interventions:
    • Drug: COR-1
    • Drug: Standard therapy for heart failure

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
36
August 2013
August 2013   (final data collection date for primary outcome measure)

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
Both
18 Years to 75 Years
No
Contact information is only displayed when the study is recruiting subjects
Germany
 
NCT01391507
CR100913, 2010-022579-68, COR-1/02
Yes
Corimmun GmbH
Corimmun GmbH
Not Provided
Study Director: Corimmun GmbH Clinical Trial Corimmun GmbH
Corimmun GmbH
September 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP