Selective PDE9 Inhibition With IMR-687 in Adults With Heart Failure With Preserved Ejection Fraction

NCT05312021 | Withdrawn Phase 2 DMC FDA Drug

• 2 other identifiers: IMR687-HFP-2012021-006535-25
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Heart Failure With Preserved Ejection Fraction

Keywords

heart failure; HFpEF; preserved ejection fraction; IMR-687; PDE9

Outcome Measures

Primary Outcomes (1)

• Change in NT-proBNP

  Calculated as the percent change from Baseline to Week 16 in NT-proBNP

  Baseline to Week 16

Secondary Outcomes (23)

• To evaluate the safety and tolerability in IMR-687 versus placebo (TEAEs: Treatment-emergent adverse events

  Baseline to Week 16

• Change in Baseline to Week 16 in the Kansas City Cardiomyopathy Questionnaire overall summary score

  Baseline to Week 16

• NYHA Classification

  Baseline to Week 16

• Change in Baseline to Week 16 in Clinical Composite Score

  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

  Baseline to Week 16

Study Arms (2)

IMR-687

EXPERIMENTAL

Participants randomly assigned to this arm will take IMR-687 orally with food BID for 16 weeks. IMR-687 dosing will be 300 mg BID for participants weighing less than 100 kg and 400 mg BID for participants weighing 100 kg or more.

Drug: IMR-687

Placebo

PLACEBO COMPARATOR

Participants randomly assigned to this arm will take placebo orally with food BID for 16 weeks.

Other: IMR-687 Placebo

Interventions

IMR-687 DRUG

150 mg and 200 mg tablets

IMR-687

IMR-687 Placebo OTHER

Matching placebo to IMR-687

Placebo

Eligibility Criteria

• Age: 45 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• HF hospitalization within 12 months prior to screening
• 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
• 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
• 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

You may not qualify if:

• 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%

Sponsors & Collaborators

• Cardurion Pharmaceuticals, Inc.: lead
• Imara, Inc.: collaborator

MeSH Terms

Conditions

Heart Failure

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Study Officials

• Steve Luperchio

  Cardurion Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 8, 2022
• First Posted: April 5, 2022
• Study Start: April 1, 2022
• Primary Completion: September 1, 2023
• Study Completion: November 1, 2023
• Last Updated: May 15, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share