Heart Failure With Preserved Ejection FractionPhase 2SP9In-HFpEFNCT05312021
Selective PDE9 Inhibition With IMR-687 in Adults With Heart Failure With Preserved Ejection Fraction
A Phase 2 study testing IMR-687 in people with Heart Failure With Preserved Ejection Fraction, run by Cardurion Pharmaceuticals, Inc..
Trial 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. Read more about this study
- Who is it for?
- Ages 45 years and older
- Conditions the study is for
- Heart Failure With Preserved Ejection Fraction
- What is being tested?
- IMR-687
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Apr 2022to Nov 2023
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 45 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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%
About this study
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)
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.
- Being tested
- IMR-687, IMR-687 Placebo
- Keywords
- heart failure, HFpEF, preserved ejection fraction, IMR-687, PDE9
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IMR-687Drug
150 mg and 200 mg tablets
IMR-687 PlaceboOther
Matching placebo to IMR-687
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: IMR-687 |
| Placebo | Placebo comparator | Participants randomly assigned to this arm will take placebo orally with food BID for 16 weeks. Receives: Other: IMR-687 Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in NT-proBNP
Calculated as the percent change from Baseline to Week 16 in NT-proBNP
Measured: Baseline to Week 16
Secondary outcomes (23)
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.
Measured: 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.
Measured: Baseline to Week 16
NYHA Classification
Change from Baseline to Week 16 in NYHA classification
Measured: Baseline to Week 16
Change in Baseline to Week 16 in Clinical Composite Score
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline to Week 16
Exercise Capacity
Change from Baseline to Week 16 in 6MWT
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: Baseline to Week 16
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Apr 2022
- Study startApr 2022 (estimated)
- Primary completionSep 2023 (estimated)
- Study completionNov 2023 (estimated)
Why it stopped: Study Termination
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Heart Failure With Preserved Ejection FractionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cardurion Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Imara, Inc.
- Responsible party
- Sponsor
- Investigators
- Steve Luperchio, Study director, Cardurion Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05312021
- Sponsor's protocol ID
- IMR687-HFP-201
- Other IDs
- 2021-006535-25
- Acronym
- SP9In-HFpEF
- Status last verified
- May 2025
- First submitted
- 8 Mar 2022
- Last updated
- 15 May 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT05312021
- Acronym / sponsor ID
- SP9In-HFpEF / IMR687-HFP-201
- Keywords
- heart failure, HFpEF, preserved ejection fraction, IMR-687, PDE9
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Study Termination
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Cardurion Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Imara, Inc.
- Study start
- Apr 2022 (estimated)
- Primary completion
- Sep 2023 (estimated)
- Study completion
- Nov 2023 (estimated)
- First posted
- 5 Apr 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| IMR-687 | Experimental | Drug: IMR-687Participants 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. |
| Placebo | Placebo comparator | Other: IMR-687 PlaceboParticipants randomly assigned to this arm will take placebo orally with food BID for 16 weeks. |
Who may qualify
- Ages
- 45 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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
Key exclusion criteria (5 listed)
- 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%
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IMR-687150 mg and 200 mg tablets | Drug | IMR-687 |
| IMR-687 PlaceboMatching placebo to IMR-687 | Other | Placebo |
Primary outcome
Change in NT-proBNP
Time frame: Baseline to Week 16
Calculated as the percent change from Baseline to Week 16 in NT-proBNP
23 secondary outcomes
To evaluate the safety and tolerability in IMR-687 versus placebo (TEAEs: Treatment-emergent adverse events
Time frame: Baseline to Week 16
Change in Baseline to Week 16 in the Kansas City Cardiomyopathy Questionnaire overall summary score
Time frame: Baseline to Week 16
NYHA Classification
Time frame: Baseline to Week 16
Change in Baseline to Week 16 in Clinical Composite Score
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
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
Time frame: Baseline to Week 16
Change From Baseline in Echocardiography Parameters: Left Ventricular Ejection Fraction
Time frame: Baseline to Week 16
Change From Baseline in Echocardiography Parameters: Left Ventricular Mass
Time frame: Baseline to Week 16
Change From Baseline in Echocardiography Parameters: Left Ventricular Mass Index
Time frame: Baseline to Week 16
Change From Baseline in Echocardiography Parameters: Left Atrial Volume Index
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
Time frame: Baseline to Week 16
Change From Baseline in Echocardiography Parameters: Ratio of E to A Velocity, E/e' Ratio
Time frame: Baseline to Week 16
Change in Echocardiography Parameters: Isovolumic Relaxation Time
Time frame: Baseline to Week 16
Change From Baseline in Echocardiography Parameters: Tricuspid Regurgitation Velocity
Time frame: Baseline to Week 16
Exercise Capacity
Time frame: Baseline to Week 16
Body Composition and Biomarker Measures
Time frame: Baseline to Week 16
Body Composition and Biomarker Measures
Time frame: Baseline to Week 16
Body Composition and Biomarker Measures
Time frame: Baseline to Week 16
Body Composition and Biomarker Measures
Time frame: Baseline to Week 16
Body Composition and Biomarker Measures
Time frame: Baseline to Week 16
Change from Baseline to Week 16 for Estimated Glomerular Filtration Rate (eGFR)
Time frame: Baseline to Week 16
Change from Baseline to Week 16 for Interferon-gamma (Ifn-gamma)
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)
Time frame: Baseline to Week 16
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 May 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Steve Luperchio study director
Cardurion Pharmaceuticals
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing IMR-687 in people with Heart Failure With Preserved Ejection Fraction, run by Cardurion Pharmaceuticals, Inc..
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 15 May 2025. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in NT-proBNP (time frame: Baseline to Week 16). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 May 2025.