Patient with worsening chronic heart failure with left ventricular systolic dysfunction MedDRA version: 19.0 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: 648927-86-0
Current Sponsor code: QGC001
Other descriptive nam
Sponsors
QUANTUM GENOMICS
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: •Written informed consent will be obtained prior to any study procedure •Adult male subjects and female subjects without childbearing potential = 80 years •Clinical diagnosis of WHF who were New York Heart Association (NYHA) class II III at least 3 months prior to emergency presentation to hospital. •Eligible subjects must be enrolled short before discharge or within 8 days after discharge from an episode of decompensated HF (index event) defined as o(a) an overnight stay in a hospital, emergency department, or medical observation facility with the capability of treating with intravenous medications and observing HF patients, or o(b) an unscheduled outpatient visit to a HF management centre, where parenteral therapy is required for HF stabilization. •Documented left ventricular ejection fraction (LVEF) = 40% measured by any modality within the previous 6 months in the subject’s medical history •Subjects must also have at least one local measurement of BNP level = 400 pg/mL or NT-proBNP level =1600 pg/mL (preferred assay, local lab) at any time during the index hospitalization or before randomization. •eGFR = 60 mL/min/1.73 m2 (MDRD) at screening •No decrease in eGFR greater than 20% from admission to the index hospitalisation and up to the randomisation day. •Serum potassium = 5.0 mmol/L at screening •Systolic blood pressure = 120 mmHg (average of 3 consecutive measurements) •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 (e.g., recommended not more than double or decrease in dosage) for at least 30 days prior to enrolment. •Taking oral loop diuretics at doses = 250 mg furosemide daily (or equivalent) Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 45 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 30
Exclusion criteria
Exclusion criteria: • Age > 80 • BMI > 35kg.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 persistent or permanent atrial fibrillation (AF) (per “ACC/AHA/ESC 2006 guidelines for the management of patients with AF”) within 3 months (90days) prior to enrolment • Patients scheduled for Pacemaker (including ICD, CRT), Angioplasty, CABG or LVAD within the next 3 months • Patients with documented chronic obstructive lung disease. • eGFR 5.0 mmol/L at screening •Systolic blood pressure < 120 mmHg or with signs or symptoms of hypotension •symptomatic hypotension or orthostatic hypotension defined by a decrease of more than 30 mm Hg in the standing vs. sitting position at screening and at T0 of the D0 (before having taken the study medication) •Insulin-requiring diabetic patients (including type 1 Diabetes) •HbA1c = 10% at screening visit •History of angioneurotic edema •Patients with a life expectancy of less than 12 months per physician judgment •Patients involved in any concurrent clinical investigation •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
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 (copeptin, apelin, PRA and others TBD) 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, France, Germany, Hungary, Netherlands, Norway, Poland, United Kingdom
Contacts
Public ContactStéphanie Grojean
EDDH - Fondation Transplantation
Outcome results
None listed