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

NCT ID: NCT05312021

Last Updated: 2025-05-15

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-04-30
• Study Completion Date: 2023-11-30

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

IMR-687

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.

Group Type: EXPERIMENTAL

IMR-687

Intervention Type: DRUG

150 mg and 200 mg tablets

Placebo

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

Group Type: PLACEBO_COMPARATOR

IMR-687 Placebo

Intervention Type: OTHER

Matching placebo to IMR-687

Interventions

IMR-687

150 mg and 200 mg tablets

Intervention Type: DRUG

IMR-687 Placebo

Matching placebo to IMR-687

Intervention Type: OTHER

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%

• Minimum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Imara, Inc.

INDUSTRY

Sponsor Role: collaborator

Cardurion Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Steve Luperchio

Role: STUDY_DIRECTOR

Cardurion Pharmaceuticals

Other Identifiers

2021-006535-25

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

IMR687-HFP-201

Identifier Type: -

Identifier Source: org_study_id