This study is to evaluate whether 16 weeks of treatment with IMR-687 is a safe and effective treatment for patients with Heart Failure with Preserved Ejection Fraction (HFpEF). The primary objective is to evaluate whether IMR-687 reduces NT-proBNP compared to placebo in these patients.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
150 mg and 200 mg tablets
Matching placebo to IMR-687
Change in NT-proBNP
Calculated as the percent change from Baseline to Week 16 in NT-proBNP
Time frame: Baseline to Week 16
To evaluate the safety and tolerability in IMR-687 versus placebo (TEAEs: Treatment-emergent adverse events
An adverse event (AE) is an untoward medical occurrence in a subject who received study drug without regard to the possibility of a causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; and any other medically important serious event as judged by the investigator. AEs are considered treatment-emergent if they have started or worsened after the first application of study drug up to 30 days after end of treatment with study drug.
Time frame: Baseline to Week 16
Change in Baseline to Week 16 in the Kansas City Cardiomyopathy Questionnaire overall summary score
The Kansas City Cardiomyopathy Questionnaire is a self-administered questionnaire. It contains 23 items, covering physical function, clinical symptoms, social function, self-efficacy and knowledge, and quality of life, each with different Likert scale wording, including limitations, frequency, bother, change in condition, understanding, levels of enjoyment, and satisfaction. Scores are transformed to a range of 0-100, in which higher scores reflect better health status. A positive change from baseline indicates improvement.
Time frame: Baseline to Week 16
NYHA Classification
Change from Baseline to Week 16 in NYHA classification
Time frame: Baseline to Week 16
Change in Baseline to Week 16 in Clinical Composite Score
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
The clinical composite score is defined as follows: Improved = participant improved in KCCQ score questionnaire with no major adverse cardiovascular event. Worsened = participant worsened (markedly or moderately) in KCCQ score or experienced a major adverse cardiovascular event. Unchanged = participant had no worsening in KCCQ score with no major adverse cardiovascular event.
Time frame: Baseline to Week 16
Change From Baseline in Echocardiography (ECHO) Parameters: Left Ventricular End (LVE) Diastolic Diameter, LVE Systolic Diameter, Septal End Diastolic Thickness, Posterior LV Wall End Diastolic Thickness, Relative Wall Thickness, Left Atrial Dimension
A limited two-dimensional and Doppler ECHO examination will be done to assess ECHO parameters. A negative change from baseline indicates improvement.
Time frame: Baseline to Week 16
Change From Baseline in Echocardiography Parameters: LVE Diastolic Volume, LVE Systolic Volume, Left Ventricular Stroke Volume, Left Atrial Volume
A limited two-dimensional and Doppler ECHO examination will be done to assess ECHO parameters. A negative change from baseline indicates improvement.
Time frame: Baseline to Week 16
Change From Baseline in Echocardiography Parameters: Left Ventricular Ejection Fraction
A limited two-dimensional and Doppler ECHO examination will be done to assess ECHO parameters. A negative change from baseline indicates improvement.
Time frame: Baseline to Week 16
Change From Baseline in Echocardiography Parameters: Left Ventricular Mass
A limited two-dimensional and Doppler ECHO examination will be done to assess ECHO parameters. A negative change from baseline indicates improvement.
Time frame: Baseline to Week 16
Change From Baseline in Echocardiography Parameters: Left Ventricular Mass Index
A limited two-dimensional and Doppler ECHO examination will be done to assess ECHO parameters. A negative change from baseline indicates improvement.
Time frame: Baseline to Week 16
Change From Baseline in Echocardiography Parameters: Left Atrial Volume Index
A limited two-dimensional and Doppler ECHO examination will be done to assess ECHO parameters. A negative change from baseline indicates improvement.
Time frame: Baseline to Week 16
Change From Baseline in Echocardiography Parameters: Ewave Velocity, A Wave Velocity, e' at Septal Mitral Annulus, e' at Lateral Mitral Annulus
A limited two-dimensional and Doppler ECHO examination will be done to assess ECHO parameters. A negative change from baseline indicates improvement.
Time frame: Baseline to Week 16
Change From Baseline in Echocardiography Parameters: Ratio of E to A Velocity, E/e' Ratio
A limited two-dimensional and Doppler ECHO examination will be done to assess ECHO parameters. A ratio \< 1 indicates improvement.
Time frame: Baseline to Week 16
Change in Echocardiography Parameters: Isovolumic Relaxation Time
A limited two-dimensional and Doppler ECHO examination will be done to assess ECHO parameters. A negative change from baseline indicates improvement.
Time frame: Baseline to Week 16
Change From Baseline in Echocardiography Parameters: Tricuspid Regurgitation Velocity
A limited two-dimensional and Doppler ECHO examination will be done to assess ECHO parameters. A negative change from baseline indicates improvement.
Time frame: Baseline to Week 16
Exercise Capacity
Change from Baseline to Week 16 in 6MWT
Time frame: Baseline to Week 16
Body Composition and Biomarker Measures
Change from Baseline to Week 16 for body composition by waist-to-hip ratio, BMI, and Tissue Inhibitor of Metalloproteinases (TIMP) Evaluation of TIMP will be performed by central laboratory assessment. A negative change from baseline indicates improvement.
Time frame: Baseline to Week 16
Body Composition and Biomarker Measures
Change from Baseline to Week 16 for Procollagen III N-terminal Peptide (PIIINP) Evaluation of PIIINP will be performed by central laboratory assessment. A negative change from baseline indicates improvement.
Time frame: Baseline to Week 16
Body Composition and Biomarker Measures
Change from Baseline to Week 16 for Matrix Metalloproteinase-2 (MMP-2) Evaluation of serum MMP-2 will be performed by central laboratory assessment. A negative change from baseline indicates improvement.
Time frame: Baseline to Week 16
Body Composition and Biomarker Measures
Change from Baseline to Week 16 for C-peptide Evaluation of serum C-peptide will be performed by central laboratory assessment. A negative change from baseline indicates improvement.
Time frame: Baseline to Week 16
Body Composition and Biomarker Measures
Change from Baseline to Week 16 for Interleukin-6 (IL-6) Evaluation of serum IL-6 will be performed by central laboratory assessment. A negative change from baseline indicates improvement.
Time frame: Baseline to Week 16
Change from Baseline to Week 16 for Estimated Glomerular Filtration Rate (eGFR)
eGFR will be calculated from the serum creatinine concentration determined by central laboratory assessment. A positive change from baseline indicates improvement.
Time frame: Baseline to Week 16
Change from Baseline to Week 16 for Interferon-gamma (Ifn-gamma)
Evaluation of serum Ifn-gamma will be performed by central laboratory. A negative change from baseline indicates improvement.
Time frame: Baseline to Week 16
Change from Baseline to Week 16 in body composition quantification by dual-energy X-ray absorptiometry scan (at selected sites)
A dual-energy X-ray absorptiometry scan will be done to assess body composition parameters. A negative change indicates improvement
Time frame: Baseline to Week 16