A gene transfer therapy improved left ventricular function in patients with HF with reduced ejection fraction, according to the results of a phase 2 clinical trial.
The researchers randomly assigned 56 patients with HF and an ejection fraction of 40% or less (mean age, 63 years; mean EF, 30%) to one to five doses of inactivated adenovirus vector encoding human adenylyl cyclase type 6 (Ad5.hAC6; RT-100, Renova Therapeutics) or placebo.
Before randomization, patients underwent exercise testing, measurement of LVEF by echocardiography and recording of LV pressure development (+dP/dt) and decline (–dP/dt) via cardiac catheterization. At 4 weeks, they received exercise testing, LVEF measurement and measurement of +dP/dt and –dP/dt, and at 12 weeks, they received exercise testing and LVEF measurement again.
The primary endpoints were exercise duration and EF at 4 weeks and 12 weeks and +dP/dt and –dP/dt at 4 weeks.
The gene transfer therapy and placebo groups had no difference in exercise duration (P at 4 weeks = .27; P at 12 weeks = .47), H. Kirk Hammond, MD, from the VA San Diego Healthcare System, and colleagues reported in JAMA Cardiology.
At 4 weeks, compared with those assigned placebo, those assigned four or five doses of the gene transfer therapy had increased EF (+6 EF units; standard error, 1.7; P < .004), but the same was not true at 12 weeks (+3 EF units; standard error, 2.4; P = .16), according to the researchers, who noted that those assigned placebo had no increase in EF at either time point.
In participants with non-ischemic HF, the gene transfer therapy increased LVEF compared with placebo (P = .024), according to a press release from Renova.
However, they found that four or five doses of the gene transfer therapy was associated with an increase in basal LV peak –dP/dt at 4 weeks (placebo group, 93 mm Hg/second; standard error, 51; gene therapy group, –39 mm Hg/second; standard error, 33; P < .03), and that those assigned the gene transfer therapy had no increase in arrhythmias.
There was no significant difference in hospital admission rate for HF during the study period (gene therapy group, 9.5%; placebo group, 28.6%; RR = 0.33; 95% CI, 0.08-1.36), according to the researchers. One death occurred in each group (P = .10).
Larger trials of the therapy are warranted, Hammond and colleagues concluded. – by Erik Swain
Disclosure: The study was funded by the NHLBI and Renova Therapeutics. Hammond reports being a founder, board member and unpaid consultant for Renova. Please see the full study for a list of the other researchers’ relevant financial disclosures.