Clinical trial NCT05312021: Selective PDE9 Inhibition With IMR-687 in Adults With Heart Failure With Preserved Ejection Fraction
Official title: Selective PDE9 Inhibition With IMR-687 in Adults With Heart Failure With Preserved Ejection Fraction: a Safety and Efficacy Phase 2 Randomized Clinical Study (SP9In-HFpEF)
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Heart Failure With Preserved Ejection Fraction
Keywords: heart failure
HFpEF
preserved ejection fraction
IMR-687
PDE9
Lead sponsor: Cardurion Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Imara, Inc.
First posted: 2022-04-05
Enrollment: 0
Sex: ALL
Minimum age (years): 45
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* Males or females ≥45 years
* Weight 60 to 160 kg, inclusive
* LVEF ≥45% by echo within 6 months prior to Screening Visit
* Symptoms of HFpEF requiring treatment with a diuretic(s) for at least 30 days prior to Screening
* NYHA class II to IV at the time of Screening
* LV hypertrophy, by echo within 6 months of screening, defined by either LV mass/BSA \>95 g/m² for females and 115 g/m² for males or LV mass/m² for males \>44 g/m2.7 for females and 48 g/m2.7 for males
* NT-proBNP criteria either ≥300 pg/mL if in sinus rhythm or ≥700 pg/mL if in atrial fibrillation at screening
* Elevated LV filling pressure criteria are defined as ONE OR MORE of the following:

  1. HF hospitalization within 12 months prior to screening
  2. LA enlargement (LA width (diameter) ≥3.8 cm, LA length ≥5.0 cm, LA area ≥20 cm² , LA volume ≥55 mL, or LA volume index \>29 mL/m²) within 6 months of screening for a participant in sinus rhythm
  3. Cardiac catheterization with at least one of the following in the 12 months prior to screening: rest LVEDP or PCWP ≥15 mm Hg, exercise PCWP ≥25 mm Hg, or fluid challenge PCWP ≥18 mm Hg
  4. Echocardiogram criteria of one or more within 6 months of screening for a participant in sinus rhythm: E/e' (mean of lateral and septal) \>13, E/e' lateral \>12, or E/e' septal \>14; or for a participant in atrial fibrillation: E/e' septal \>11
* For WOCBP: Two negative pregnancy tests and the use of highly effective contraception up to 3 months following end of study

Exclusion Criteria:

* Any prior echocardiographic imaging measurement of LVEF \<40%
* Six-minute walk test (6MWT) distance \<100 m or \>450 m at Screening Visit
* Kansas City Cardiomyopathy Questionnaire (KCCQ) overall summary score of \>80
* Major cardiovascular surgery, or urgent percutaneous coronary intervention (PCI) within the 3 months prior to Screening Visit, or an elective PCI within 30 days prior to Screening Visit
* Any clinical event within 6 months prior to Screening Visit that could have reduced the LVEF (eg, myocardial infarction, coronary artery bypass graft) unless an echocardiographic measurement was performed at least 1 month after the event confirming the LVEF to be ≥45%

Primary outcomes:
measure: Change in NT-proBNP
timeFrame: Baseline to Week 16
Secondary outcomes:
measure: To evaluate the safety and tolerability in IMR-687 versus placebo (TEAEs: Treatment-emergent adverse events
timeFrame: Baseline to Week 16
measure: Change in Baseline to Week 16 in the Kansas City Cardiomyopathy Questionnaire overall summary score
timeFrame: Baseline to Week 16
measure: NYHA Classification
timeFrame: Baseline to Week 16
measure: Change in Baseline to Week 16 in Clinical Composite Score
timeFrame: Baseline to Week 16
measure: 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
timeFrame: Baseline to Week 16
measure: Change From Baseline in Echocardiography Parameters: LVE Diastolic Volume, LVE Systolic Volume, Left Ventricular Stroke Volume, Left Atrial Volume
timeFrame: Baseline to Week 16
measure: Change From Baseline in Echocardiography Parameters: Left Ventricular Ejection Fraction
timeFrame: Baseline to Week 16
measure: Change From Baseline in Echocardiography Parameters: Left Ventricular Mass
timeFrame: Baseline to Week 16
measure: Change From Baseline in Echocardiography Parameters: Left Ventricular Mass Index
timeFrame: Baseline to Week 16
measure: Change From Baseline in Echocardiography Parameters: Left Atrial Volume Index
timeFrame: Baseline to Week 16
measure: Change From Baseline in Echocardiography Parameters: Ewave Velocity, A Wave Velocity, e' at Septal Mitral Annulus, e' at Lateral Mitral Annulus
timeFrame: Baseline to Week 16
measure: Change From Baseline in Echocardiography Parameters: Ratio of E to A Velocity, E/e' Ratio
timeFrame: Baseline to Week 16
measure: Change in Echocardiography Parameters: Isovolumic Relaxation Time
timeFrame: Baseline to Week 16
measure: Change From Baseline in Echocardiography Parameters: Tricuspid Regurgitation Velocity
timeFrame: Baseline to Week 16
measure: Exercise Capacity
timeFrame: Baseline to Week 16
measure: Body Composition and Biomarker Measures
timeFrame: Baseline to Week 16
measure: Body Composition and Biomarker Measures
timeFrame: Baseline to Week 16
measure: Body Composition and Biomarker Measures
timeFrame: Baseline to Week 16
measure: Body Composition and Biomarker Measures
timeFrame: Baseline to Week 16
measure: Body Composition and Biomarker Measures
timeFrame: Baseline to Week 16
measure: Change from Baseline to Week 16 for Estimated Glomerular Filtration Rate (eGFR)
timeFrame: Baseline to Week 16
measure: Change from Baseline to Week 16 for Interferon-gamma (Ifn-gamma)
timeFrame: Baseline to Week 16
measure: Change from Baseline to Week 16 in body composition quantification by dual-energy X-ray absorptiometry scan (at selected sites)
timeFrame: Baseline to Week 16
Other outcomes:
Locations:
Study officials:
affiliation: Cardurion Pharmaceuticals
name: Steve Luperchio
role: STUDY_DIRECTOR
References: