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Effects of JNJ-54452840, an Anti-β1 Receptor Antibody Cyclopeptide in Heart Failure Patients: A Randomized, Double-blind, Parallel-group, Phase-2 Pilot Study

Stefan Störk, Alexei N Plotnikov, Gary Peters, Brian E Davies, Ivo Nnane, David Rivas, Fisseha Tesfaye, Stefan Kääb, Axel Bauer, Andreas Luchner, Martin Ungerer, Roland Jahns, Martin Lohse, and Georg Ertl

Aim: JNJ-54452840 (COR-1) is a novel investigational cyclopeptide with proposed mechanism of action that decreases circulating anti-β1-adrenergic receptor antibodies (anti-β1-Abs) in heart failure patients. In a phase-2, double-blind, placebo-controlled pilot study, effects of JNJ-54452840 were investigated on cardiac function at rest in patients with Dilated Cardiomyopathy (DCM) when administered in addition to guideline-recommended heart failure therapy versus 6-months of guideline-recommended therapy alone.

Methods: Patients with DCM and circulating anti-β1-Abs received treatment with placebo or JNJ-54452840 (6 doses of 20, 80 or 160 mg administered intravenously every 4 weeks) in addition to guideline-recommended heart failure therapy.

Results: Thirty-six patients (Caucasian, mean age 59.6 years, mean LVEF 32%) were enrolled. An increase (+5.4%) in centrally-assessed Left Ventricular Ejection Fraction (LVEF) was observed in 80 mg JNJ-54452840 group compared to a decrease (-1.6%) in the placebo group (primary efficacy endpoint). Among secondary efficacy endpoints, locally-assessed LVEF values were similar to primary results, suggesting lack of treatment effect from baseline to month 9. NT-proBNP values varied considerably between patients but were not significantly improved in JNJ-54452840-treated groups versus placebo. Compared to baseline, both JNJ-54452840 and placebo groups demonstrated a numerical increase in 6-minute walk test from baseline to month 6. The most common adverse events reported among JNJ-54452840-treated patients were cardiac failure and nasopharyngitis (n=4 each), and cough, sinusitis, increased heart rate (n=3 each).

Conclusion: Considering that this phase 2 trial, originally planned to recruit 160 patients was amended to a pilot study for strategic reasons, no definitive statements on the efficacy of JNJ-5445280 in DCM patients with circulating anti-β1-Abs can be made, although centrally-assessed LVEF appeared to improve in the 80 mg dose group. No compound-related safety or tolerability signals were observed.