Heart Failure with Reduced Ejection Fraction (HFrEF) MedDRA version: 20.0 Level: LLT Classification code 10078289 Term: Heart failure with reduced ejection fraction System Organ Class: 100000004849
Conditions
Sponsors
Akros Pharma Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: To qualify for the study, the participant must satisfy the following criteria: 1. Male or female, age 18 to 85 years (inclusive), at the Screening Visit; 2. Participants with a clinical diagnosis of symptomatic HF =3 months prior to the Screening Visit; 3. Participants with NYHA functional class II or III at the Screening Visit; 4. Participants must be on stable, guideline-directed medical therapy for HF, consistent with AHA, ACC, HFSA or ESC guidelines for at least 30 days prior to the Screening Visit. These therapies include an ACEI or ARB with/without a neprilysin inhibitor, in combination with an evidence-based ß-blocker and a MRA, in appropriate participants 5. Participants must have a documented history of LVEF =35% within 6 months prior to the Screening Visit using any of the following modalities: echocardiography, single-photon emission computed tomography (SPECT), multigated acquisition (MUGA), computed tomography (CT) scanning, magnetic resonance imaging (MRI) or ventricular angiography; if more than one measurement was performed, then the most recent one should be used for eligibility; Note: If LVEF measurement was obtained >6 months prior to the Screening Visit, a local echocardiography measurement and interpretation will be used to determine eligibility (i.e., LVEF =35%). 6. Participants with a plasma NT-pro-BNP level =900 pg/mL at the Screening Visit; 7. Females may participate if they meet one of the following criteria: • surgically sterile (e.g., hysterectomy, bilateral salpingectomy, bilateral oophorectomy), or • post-menopausal, as defined by permanent cessation of menstruation for =12 months without an alternative medical cause at Screening Visit. a. practice abstinence, or b. have same-sex partner, and not planning a pregnancy, or c. use one highly effective contraceptive method of birth control, which includes intrauterine devices, male partner sterilization (at least six months prior to screening with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate, and the vasectomized male partner should be the sole partner for that participant), tubal ligation, intrauterine hormone-releasing systems, or d. use a double-barrier method of birth control, which includes a combination of male condom with either diaphragm, cervical cap or vaginal sponge, all with spermicide. Note: Periodic abstinence (calendar, symptothermal, post ovulation methods), withdrawal (coitus interruptus), spermicides only, and concomitant use of a female condom and a male condom are not acceptable methods of contraception. 8. Males must either practice sexual abstinence, have same-sex partner, use a barrier contraceptive method with spermicide (for the duration of the treatment period and until 28 days after the last dose of study drug), or be sterilized at least six months prior to screening (with appropriate post-vasectomy documentation of the absence of sperm in the ejaculate). Notes: Males who are sterile or who have sterile or post-menopausal female partners are not required to use contraception if said female partner is the sole partner for that participant. Males must not donate sperm for the dur
Exclusion criteria
Exclusion criteria: The following criteria will exclude a participant from participating in the study: 1. Participants with confirmed acute MI (i.e., Type 1) within 30 days prior to the Screening Visit or unstable angina, a history of coronary revascularization (percutaneous coronary intervention and/or coronary artery bypass grafting) or other cardiovascular surgery within 90 days prior to the Screening Visit; 2. Participants whose HF is due to congenital heart disease, active myocarditis or constrictive pericarditis; 3. Participants who have received a heart transplant or are on a transplant list or who have a history of LV assist device implantation; 4. Participants with severe stenotic valvular disease or severe outflow tract obstruction; 5. Participants with a history of stroke or cerebral transient ischemic attack within 30 days prior to the Screening Visit; 6. Participants who started cardiac resynchronization therapy within 90 days prior to the Screening Visit; Note: Implantable cardioverter defibrillator (ICD) placement alone or generator change is acceptable. 7. Participants with planned cardiovascular surgery and/or cardiac resynchronization therapy during the double-blind treatment period; 8. Participants who were admitted to hospital for HF within 30 days prior to Visit 2; 9. Participants with known active liver disease or with aminotransferases (alanine aminotransferase [ALT] or aspartate aminotransferase [AST]) >3.0x upper limit of normal (ULN) or total bilirubin >1.5x ULN at the time of screening; Note: Participants with documented benign liver condition that can result in elevated bilirubin levels (e.g., Gilbert’s Syndrome) are eligible to participate in the study. 10. Participants unable to perform a six minute walk distance (6MWD) test at Visit 2; 11. Participants with resting symptomatic hypotension or uncontrolled hypertension (i.e., systolic blood pressure >160 mmHg and/or diastolic blood pressure >100 mmHg) at the Screening Visit; 12. Participants with clinically significant chronic renal insufficiency (i.e., estimated glomerular filtration rate [eGFR] 10% measured at the Screening Visit; 14. Participants with hemoglobin <8 g/dL at the Screening Visit; 15. Participants currently receiving or have received an investigational product (including an investigational drug or other investigational therapeutic intervention) within 28 days, five half-lives or twice the duration of the biological effect of the investigational product, if known (whichever is longer) prior to the Screening Visit; 16. Participants with a history of recreational drug abuse within six months of the Screening Visit; Note: Medical marijuana prescribed by a physician is acceptable. 17. Participants with a history of alcohol abu
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: Not Applicable ; Main Objective: - To evaluate the efficacy of JTT-251 in participants with Heart Failure with Reduced Ejection Fraction (HFrEF) - To evaluate the safety and tolerability of JTT-251 following administration for 24 weeks in participants with HFrEF - To evaluate the exposure-response of the efficacy and safety of JTT-251 in participants with HFrEF - To evaluate the PK of JTT-251 in participants with HFrEF ; Primary end point(s): • Change from baseline to end of treatment (EOT) in: - Left ventricular ejection fraction (LVEF), Left ventricular end systolic volume (LVESV) index and Left ventricular end diastolic volume (LVEDV) index as assessed by two-dimensional echocardiography (2D-echo) - NT-pro-BNP - 6MWD test - NYHA functional class • JTT-251 trough plasma levels at Weeks 4, 12 and 24 and JTT-251 plasma concentrations (post-dose) at Week 4 • Relationship between JTT-251 exposure and efficacy, and safety parameters • Safety - Number of participants with adverse events (AEs), type and severity of AEs - Change from baseline in safety laboratory, vital sign and electrocardiogram (ECG) parameters - AEs leading to permanent discontinuation of study drug. ;Timepoint(s) of evaluation of this end point: Week 0, 1, 2, 4, 8, 12, 16, 20, 24, 28 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Change from baseline to EOT in: - Supplementary cardiac function estimates as determined by echocardiography - Health-related quality of life (QoL) assessment as determined by the Kansas City Cardiomyopathy Questionnaire (KCCQ) - HbA1c and fasting plasma glucose - Branched-chain amino acids (BCAAs), alanine, pyruvic and lactic acid - Cardiac troponin I, suppression of tumorigenicity 2 (ST2) and galectin 3 - eGFR and cystatin C - Albumin-to-creatinine ratio (ACR) - Serum myostatin and brain-derived neurotrophic factor (BDNF) • All deaths (cardiovascular or non-cardiovascular) and cardiovascular hospitalizations up to Week 28 as defined in the Clinical Events Committee (CEC) charter ;Timepoint(s) of evaluation of this end point: Week 0, 1, 2, 4, 8, 12, 16, 20, 24, 28 | — |
Countries
Argentina, Chile, Denmark, Germany, Hungary, Israel, Netherlands, Poland, Romania, Russian Federation, Serbia, Ukraine, United Kingdom
Contacts
Public ContactKala Patel
Akros Pharma Inc.
Outcome results
None listed