A Randomized, Double-blind, Multi-centre Study to Assess Safety and Efficacy of Incremental Doses of QGC001 in Patients With NYHA Class II/III Chronic Heart Failure (HF) With Left Ventricular Systolic Dysfunction Versus Placebo.
Overview
- Phase
- Phase 2
- Intervention
- QGC001
- Conditions
- Heart Failure
- Sponsor
- Quantum Genomics SA
- Enrollment
- 23
- Locations
- 23
- Primary Endpoint
- Relative decrease in NT-proBNP
- Status
- Terminated
- Last Updated
- 7 years ago
Overview
Brief Summary
Heart Failure (HF) a common clinical condition characterized by either by a heart that does not pump sufficiently or becomes stiff. A variety of mechanisms contribute to progressive cardiac remodeling and dysfunction.
A new therapeutic approaches by preventing activation of the brain neuromodulatory pathway, may lead to improve HF.
QCG001 is a prodrug of EC33, a aminopeptidase A (APA) inhibitor. QCG001 has been shown to be an antihypertensive agent in animal models.
This study investigates the safety and efficacy of QGC001 in HF patients.
Detailed Description
Despite advances in care, prognosis remains poor once overt Heart Failure (HF) has developed. HF is a common clinical condition characterized by either by a heart that does not pump sufficiently or becomes stiff and it is associates with higher incidences of patient illness and death in both case. A variety of mechanisms contribute to progressive cardiac remodeling and dysfunction. A new therapeutic approaches by preventing activation of the brain neuromodulatory pathway, may lead to improve HF. QCG001 is a prodrug of EC33, a specific and selective of the aminopeptidase A (APA) inhibitor. QCG001 has been shown to be an antihypertensive agent in animal models. This study investigates the safety and efficacy of QGC001 up-titrated form 50mg twice daily to a maximum of 500 mg twice daily, on patients with worsening chronic HF during 28 days and 7 days after discontinuation (day 35). 6 European countries are involved in this study (France, Netherlands, Germany, Norway, Poland and United Kingdom) including 20 investigational hospitals. Patients would be followed during 35 days and inclusion period lasts until December 2017.
Investigators
Eligibility Criteria
Inclusion Criteria
- •A signed and dated informed consent form prior to any study procedure
- •Adult male subjects and female subjects without childbearing potential.
- •Clinical diagnosis of CHF with history of NYHA class II-III for at least 3 months before randomisation.
- •Documented left ventricular ejection fraction (LVEF) \< 40% measured by any modality within the previous 12 months in the subject's medical history.
- •Subjects must also have at least one local measurement of BNP level ≥ 300 pg/mL or NT-proBNP level ≥ 1200 pg/mL (preferred assay, local laboratory) at the screening visit (maximum 7 days before randomisation).
- •eGFR \> 30 mL/min/1.73 m2 (MDRD) at screening.
- •Serum potassium \< 5.0 mmol/L at screening.
- •Systolic blood pressure \< 110 mmHg (average of 3 consecutive measurements) at screening.
- •Prescribed to optimal pharmacologic therapy per "ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2016", or based on the updated current clinical practice, unless contra-indicated or not-tolerated, and on a stable dose for at least 30 days prior to enrolment (the dosage of the drugs cannot be increased or decreased respectively by more than double or half of initial dosage).
- •Taking oral loop diuretics at doses \< 250 mg furosemide daily (or equivalent).
Exclusion Criteria
- •BMI \> 45 kg.m-
- •Patients who require the use of HF IV therapy or oral furosemide \> 250 mg (or equivalent) at any time during the 48 hours immediately before randomisation.
- •Patients with unstable angina, myocardial infarction, PTCA, coronary artery bypass graft, cerebral vascular accident, or transient ischemic attack within previous 3 months (90 days) before enrolment.
- •Patients whose primary cause of heart failure is mitral or aortic valve disease or congenital heart disease or hypertrophic obstructive cardiomyopathy or infiltrative cardiomyopathy (e.g. amyloidosis, sarcoidosis) or myocarditis.
- •Patients with "new" permanent atrial fibrillation (AF), discovered within 3 months prior to randomization.
- •Heart rate \> 110 beats/min at screening.
- •Patients scheduled for Pacemaker (including ICD, CRT), Angioplasty, CABG or LVAD within the next 3 months.
- •Patients with severe documented chronic obstructive lung disease (COPD), defined as chronic need for oxygen therapy
- •eGFR \< 30 mL/min/1.73 m2 (MDRD) at screening.
- •Decrease in eGFR greater than 20% within 3 weeks prior to the screening visit.
Arms & Interventions
QGC001
QGC001 from 50mg to 500mg capsule twice daily, for 28 days, oral use
Intervention: QGC001
Placebo
Placebo, capsule twice daily, for 28 days, oral use
Intervention: Placebo
Outcomes
Primary Outcomes
Relative decrease in NT-proBNP
Time Frame: 28 days
Percentage of subjects with a relative decrease in NT-proBNP of more than 30% from Baseline to day 28.
Blood pressure change
Time Frame: 28 days
Blood pressure changes at each visit (D7, D14, D21, D28), compared to the Baseline measure
Secondary Outcomes
- Blood biochemistry(35 days)
- Urinary biochemistry(35 days)
- Change of NT-proBNP(35 days)
- Change of BNP(35 days)
- Change of selected biomarker levels(28 days)
- Quality of life Minnesota Living with Heart Failure Score(28 days)