A Phase II, Randomized, Double-Blind, Multicenter, Based on Standard Therapy, Placebo-Controlled Study of the Efficacy and Safety of Recombinant Human Neuregulin-1 in Patients With Chronic Heart Failure

Objectives The purpose of this study was to assess the safety and efficacy of recombinant human neuregulin-1 (rhNRG-1) in chronic heart failure (CHF) patients. Background Neuregulin-1 plays important roles in maintaining cardiomyocyte structure and cardiac pumping functionality and physiology. Previously, rhNRG-1 was proven to be effective in treating heart failure in animals by reducing end-diastolic volume (EDV) and end-systolic volume (ESV) and increasing left ventricular ejection fraction (LVEF%). Methods A total of 44 CHF patients designated as New York Heart Association functional class II or III were enrolled in a double-blind, randomized manner and treated with a placebo or rhNRG-1 (0.3, 0.6, or 1.2 μg/kg/day) for 10 days, in addition to standard therapies. The follow-up period was 90 days; left ventricular function and structure measured by magnetic resonance imaging were the primary end points. Results Although not statistically different from placebo, the LVEF% was significantly increased by 27.11 ± 31.12% (p = 0.009) at day 30 after rhNRG-1 treatment in the 0.6-μg/kg group, whereas it was only increased 5.83 ± 25.75% in the placebo group (p = 0.49). In addition, there were decreases in ESV (−11.58 ± 12.74%, p = 0.002) and EDV (−5.64 ± 10.03%, p = 0.05) in the 0.6-μg/kg/day group at day 30; more importantly, both ESV and EDV levels continued to decrease at day 90 (−20.79 ± 17.03% and −14.03 ± 13.17%, respectively), accompanied by a sustained increase in LVEF%. This suggests that short-term treatment with rhNRG-1 results in a long-term reversal of remodeling. The effective dose was proven to be tolerable and safe for CHF patients. Conclusions rhNRG-1 improved the cardiac function of CHF patients by increasing the LVEF% and showed the capability of antiremodeling by decreasing ESV and EDV compared with pre-treatment. (A Randomized, Double-Blind, Multi-Center, Placebo Parallel controlled, Standard Therapy Based Phase II Clinical Trial to Evaluate the Efficacy and Safety of Recombinant Human Neuregulin-1 for Injection in Patients with Chronic Heart Failure; ChiCTR-TRC-00000414 )