Patient with worsening chronic heart failure with left ventricular systolic dysfunction MedDRA version: 19.1 Level: LLT Classification code 10019279 Term: Heart failure System Organ Class: 100000004849
Conditions
Interventions
Product Name: AMINO BUTANE SULFONATE DISULFURE
Product Code: QGC001
Pharmaceutical Form: Capsule
INN or Proposed INN: QGC001
CAS Number:
Sponsors
QUANTUM GENOMICS
Eligibility
Sex/Gender
All
Inclusion 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. * Clinical diagnosis of WHF, as defined by a history of hospitalization for worsening symptoms of HF within the previous year. HF hospitalization is defined as an overnight stay in a hospital. Eligible subjects may be enrolled at any time before discharge from an episode of decompensated HF or during a post-discharge ambulatory state within one year of admission for WHF, if they fulfil all inclusion/exclusion criteria. *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 > 45 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 2012”, 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 =65 years) yes F.1.3.1 Number of subjects for this age range 30
Exclusion criteria
Exclusion criteria: *BMI > 35 kg.m-2 . *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 > 90 beats/min at screening. *Patients scheduled for Pacemaker (including ICD, CRT), Angioplasty, CABG or LVAD within the next 3 months. *Patients with documented chronic obstructive lung disease, defined as chronic need for oxygen therapy and/or daily-inhaled corticosteroid and/or daily bronchodilator treatment. *eGFR 5.0 mmol/L at screening. *Systolic blood pressure 450 ms). * A history of additional risk factors for Torsade de Pointes (TdP) (e.g. hypokalemia, family history of long QT Syndrome). *The use of concomitant medications that prolong the QT/QTc interval. *Insulin-requiring diabetic patients (including type 1 Diabetes). *HbA1c = 9% at screening visit. *History of angioneurotic edema. *Severe liver failure at screening defined by a value of ALAT and/or ASAT= 5 from the normal value. *Patients involved in any clinical study. *Patients who take an investigational or non-approved treatment. *Women of childbearing potential. *Patients with a prior cardiac transplant or patients currently on the list for cardiac transplantation. * Patient with hypersensitivity to the active substance or to one of the other components of the trial preparation. * Patients in whom an allergy requiring treatment is known or exists. *Patients with a history of previous illnesses of neurological or psychiatric nature that affect the Central Nervous System. *Patients with a life expectancy of less than 12 months per physician judgment. *Frail patient who, in the opinion of the investigator will not be able to follow the protocol.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to investigate the safety (blood pressure changes until Day 28) and efficacy (rate of decrease in N terminal pro-hormone B-type natriuretic peptide (NT-proBNP) of more than 30% from baseline to Day 28) of QGC001 up-titrated from 50 mg twice daily to a maximum of 500 mg twice daily.; Secondary Objective: Further exploratory objectives of the study are •To assess the effects of these doses on a composite endpoint of death from any cause and hospitalization for worsening heart failure (WHF) at Day 28 and after drug discontinuation up to Day 35. •To assess the effects of the respective dose levels, and of all doses combined, on changes in NT-proBNP and BNP, from baseline to Day 7, Day 14, Day 21, Day 28, and after drug discontinuation from day 28 to day 35 •To assess the changes in quality of life Minnesota Living with Heart Failure questionnaire score from randomisation to day 28. ; Primary end point(s): The Efficacy Primary endpoint will be the percentage of subjects with a relative decrease in NT proBNP (Central Lab) of more than 30% from baseline to Day 28. The Safety Primary endpoint will be the blood pressure changes at each visit, compared to the baseline measure ; Timepoint(s) of evaluation of this end point: for efficacy endpoint : at day 28 compared to Baseline for safety endpoint : at each visit, compared to the baseline | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The Efficacy Secondary endpoints will be •Blood biochemistry, electrolytes, urinary osmolarity at Day 7, Day 14, Day 21, Day 28, Day 35 •Change in central lab values of NT-proBNP and BNP, at Day 7, Day 14, Day 21, Day 28, Day 35 •Changes in central lab values from baseline in selected biomarker levels at Day 7, Day 14, Day 21, Day 28 •Death from any cause or readmission for worsening heart failure at Day 28 and Day 35 •Quality of life Minnesota Living with Heart Failure Score and D0 and Day 28. ;Timepoint(s) of evaluation of this end point: at each visit, compared to the baseline | — |
Countries
Czech Republic, Hungary, Netherlands, Norway, Poland, United Kingdom
Contacts
Public ContactStéphanie Grojean
EDDH - Fondation Transplantation
Outcome results
None listed