Study of Dapansutrile Capsules in Heart Failure

Inclusion criteria

• Male and female subjects 18 years old or older
• Symptomatic stable HF (NYHA class II-III) with reduced left ventricular ejection fraction (LVEF≤40%, measured within 6 months of enrollment - no changes in cardiac medications or new device implantation within past 2 months)
• Peak exercise limited by shortness of breath and/or fatigue associated with a respiratory exchange ratio (RER) > 1.00 (reflecting maximal aerobic effort)
• Reduced peak aerobic exercise capacity (peak VO2) to less than 80% of predicted value by age/gender at Baseline
• Plasma CRP or hsCRP levels > 2 mg/L at Screening
• Acceptable overall medical condition to be safely enrolled in and to complete the study (with specific regard to cardiovascular, renal and hepatic conditions) in the opinion of the Principal Investigator
• Ability to provide written, informed consent prior to initiation of any study-related procedures, and ability, in the opinion of the Principal Investigator, to understand and comply with all the requirements of the study

Exclusion criteria

• Women of childbearing potential, or men whose sexual partner(s) is a woman of childbearing potential who:

• Are or intend to become pregnant (including use of fertility drugs) during the study
• Are nursing
• Are not using an acceptable, highly effective method of contraception until all follow-up procedures are complete. (Acceptable, highly effective forms of contraception are defined as: oral contraception, intrauterine device, systemic [injectable or patch] contraception, double barrier methods, naturally or surgically sterile, strict abstinence or partner has been sterilized. If hormonal-based birth control is being used, subject or subject's sexual partner(s) must be on a stable-dose for ≥ 3 months prior to the Baseline visit and maintained at the same dosing level throughout the study.)
• Abnormal blood pressure or heart rate response, angina or ECG changes (ischemia or arrhythmias) occurring during CPX
• Presence or known history of autoimmune conditions (e.g., systemic lupus erythematosus, hypophysitis, etc.)
• History or evidence of active tuberculosis (TB) infection at Baseline visit or one of the risk factors for tuberculosis such as but not limited or exclusive to:

• History of any of the following: residence in a congregate setting (e.g., jail or prison, homeless shelter, or chronic care facility), substance abuse (e.g., injection or non-injection), health-care workers with unprotected exposure to subjects who are at high risk of TB or subjects with TB disease before the identification and correct airborne precautions of the subject or
• Close contact (i.e., share the same air space in a household or other enclosed environment for a prolonged period (days or weeks, not minutes or hours)) with a person with active pulmonary TB disease within the last 12 months.
• Use of any prohibited concomitant medications/therapies over the periods defined in Section 5.6.3 or planned use of any prohibited concomitant medications/therapies during the Treatment Period
• Any other concomitant medical or psychiatric condition(s), disease(s) or prior surgery(ies) that, in the opinion of the Principal Investigator, would impair the subject from safely participating in the trial and/or completing protocol requirements, including but not limited to:

• physical inability to walk on a treadmill
• decompensated HF (edema, NYHA IV)
• significant ischemic heart disease, angina
• arterial hypotension (blood pressure [BP] systolic < 90 mmHg)
• arterial hypertension (resting BP systolic > 160 mmHg)
• atrial fibrillation with rapid ventricular response
• severe valvular disease
• severe chronic obstructive or restrictive pulmonary disease
• moderate-severe anemia (Hgb < 10 g/dL)
• severe diabetic neuropathy or myopathy
• Active or recent (within 2 weeks) infection prior to the Baseline visit
• History of or known positive for HIV, Hepatitis B surface antigen or antibodies to Hepatitis C Virus
• Known history of renal impairment and/or creatinine clearance less than 50 mL/min calculated by Cockcroft-Gault method
• Active malignancy or recent malignancy with chemotherapy treatment within the past 6 months
• Enrollment in any trial and/or use of any investigational product or device within the immediate 30-day period prior to the Baseline visit
• Previous exposure to the investigational product