A Study to Assess the Pharmacokinetics and Pharmacodynamics of JNJ-54452840 in Participants With Heart Failure and Anti-beta1-adrenergic Receptor Autoantibodies

The purpose of this study is to assess the pharmacokinetics (ie, how the body affects the drug) and pharmacodynamics (ie, how the drug affects the body) of JNJ-54452840 in participants with heart failure and anti-beta1-adrenergic receptor autoantibodies. The safety and tolerability of JNJ-54452840 will also be assessed.

This study will be randomized (the study treatment is assigned by chance), double-blind (neither investigator nor participant knows the treatment received), and placebo-controlled (one of the study treatments is inactive). This study will be conducted in participants with reduced systolic function heart failure (a reduced amount of blood is pumped around the body compared with a normal heart) and elevated levels of anti-beta1-adrenergic receptor autoantibodies (antibodies that may be involved in development, progression, or worsening of heart failure). The study will be conducted in 2 parts; participants will receive single doses of JNJ-54452840 in Part 1 and multiple doses in Part 2. Each part of the study will consist of 3 phases; a screening phase, a double-blind treatment phase, and a follow-up phase. There will be 2 cohorts (groups) of participants in Part 1 of the study. In Part 1 (Cohort A), participants will be randomly assigned to 1 of 4 treatment groups: a single intravenous (medication is injected into a vein) dose of 20 mg JNJ-54452840; a single intravenous dose of 80 mg JNJ-54452840; a single intravenous dose of 160 mg JNJ-54452840; or matching placebo (inactive medication). In Part 1 (Cohort B), participants will be randomly assigned to 1 of 2 treatment groups; a single intravenous dose of less than or equal to 240 mg JNJ-54452840 (as determined by the Data Review Committee after review of Cohort A data) or matching placebo. There will be 4 cohorts of participants in Part 2 of the study; the dose of JNJ-54452840 used in each cohort, initiation of each cohort, and the sequence will be decided by the Data Review Committee. In Part 2 (Cohort C), participants will be randomly assigned to 1 of 2 treatment groups: JNJ-54452840 or matching placebo given intravenously once daily for 3 days. In Part 2 (Cohort D), participants will be randomly assigned to 1 of 2 treatment groups: JNJ-54452840 or matching placebo given intravenously once daily for 5 days. In Part 2 (Cohort E), participants will be randomly assigned to 1 of 2 treatment groups: JNJ-54452840 or matching placebo given intravenously once weekly on Days 1, 8, 15, and 22. In Part 2 (Cohort F), participants will be randomly assigned to 1 or more treatment groups involving regimen(s) as explored in Cohorts C, D, or E. Single doses of JNJ-54452840 will not be greater than 240 mg for any Cohort. The active to placebo randomization ratio for each cohort following Cohort A (ie, Cohorts B, C, D, E, and F) will be determined by the Data Review Committee. Participants will come to the study center each time they receive study medication and will remain at the center for at least two hours following each injection. Blood samples will be drawn at time points during the screening period and treatment period for participants in both Part 1 and Part 2 of the study. Participants will return to the study center after the double-blind treatment phase on Day 29 and then for follow-up visits on Days 57 and 85. Participants in Part 1 or Part 2 will be involved in the study for approximately 112 days. Participant safety will be monitored. The study drug, JNJ-54452480 is being investigated for the treatment of heart failure.

Eligibility Criteria:
Inclusion Criteria:

* Must have documented medical history of symptomatic (ie, showing symptoms) reduced ejection fraction (measurement of the percentage of blood leaving the heart each time it contracts) heart failure due to either ischemic etiology (decreased blood supply to heart) or non-ischemic dilated cardiomyopathy (heart is weakened and enlarged) for at least 4 months prior to the screening visit
* Must have heart failure classified by the New York Heart Association classification system as class I through IIIa
* Must have a left ventricular ejection fraction (measurement of the percentage of blood leaving the heart each time it contracts) of \< = 45%
* Must have blood levels of anti-beta1-adrenergic receptor autoantibodies (antibodies that are involved in developing heart failure) that are above the reference range
* Must have been receiving guideline-directed medical therapy for heart failure for at least 4 months prior to screening and, in addition, be receiving stable and individually optimized drug doses for at least 2 months prior to screening.

Exclusion Criteria:

* History of, or current active illness that, in the opinion of the investigator, would make participation not in the best interest (eg, compromise the well-being) of the patient or that could interfere with the study assessments
* Left ventricular end-diastolic diameter index (a measure of the heart's performance) of \<= 32 mm/m2
* N-terminal pro-brain natriuretic peptide level (a biologic molecule that has been shown to predict cardiac events) that is \<= 200 pg/mL in participants with normal sinus rhythm or \<= 800 pg/mL in participants with atrial fibrillation
* Chronic treatment with immunosuppressive drugs (except for \<= 5 mg/day prednisone-equivalent dose)
* Known allergies to peptides or proteins, such as albumin.