A Randomized, Double-Blind, Placebo-controlled, Single-ascending Dose Study to Assess the Safety, Tolerability, and Pharmacokinetics of JK07 in Subjects With Heart Failure With Reduced Ejection Fraction (HFrEF)
This is a Phase 1, randomized, double-blind, placebo-controlled, single-ascending dose study to assess the safety, tolerability, immunogenicity, PK, and exploratory efficacy of JK07 in subjects 18 to 80 years of age with HFrEF ≤40%. Initially 5 cohorts are planned with the option to expand the study to a total of 7 cohorts. The size of the cohorts will range from 5 to 9 subjects. Each cohort will include one single active unblinded sentinel subject receiving a single IV dose of JK07 prior to randomized single dose administration of JK07 or placebo \[3:1\] in the remainder of the cohort.
• Adults 18 and 80 years with stable NYHA Class II or III HF diagnosis (ischemic or non-ischemic confirmed by medical history) at least 6 months prior to enrollment as confirmed by medical history.
• Stable HF defined as no hospitalizations for cardiac-related issues within the previous 2 months prior to the screening visit or between screening and randomization, other than for routine percutaneous procedures such as device, battery, generator changes or pacemaker lead insertion/ replacement.
• Subjects with clearly interpretable echocardiographic images and with a screening LVEF ≤ 40% in the absence of ≥ Grade 3 valvular disease on 2D-TTE.
• Subjects must be taking clinician-directed appropriate pharmacological therapy for HF as per the 2017 ACC/AHA/HFSA treatment guidelines at stable doses and at investigator determined discretion (except for diuretics) for at least 2 months prior to informed consent.
• Subjects with implantable cardioverter-defibrillators (ICDs) are allowed at the discretion of the investigator, but only if both the following criteria are met: (a) paced beats cannot exceed 15% of beats as quantified by screening e-Patch, and (b) if a non-paced baseline ECG can be obtained on day 1 prior to study drug administration.
• Body mass index ≥18 kg/m2 and ≤45 kg/m2. 6. Screening hemoglobin ≥9.0 g/dL, platelets ≥100 K/mL, ANC ≥1500/mL. 7. Able and willing to use adequate contraception until the end of the study.
• Capable of providing informed consent and to comply with the protocol.