Effect of immunisation against angiotensin II with CYT006-AngQb on ambulatory blood pressure:: a double-blind, randomised, placebo-controlled phase IIa study

Background Hypertension can be controlled adequately with existing drugs such as angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers. Nevertheless, treatment success is often restricted by patients not adhering to treatment. Immunisation against angiotensin II could solve this problem. We investigated the safety and efficacy of CYT006-AngQb-a vaccine based on a virus-like particle-that targets angiotensin II to reduce ambulatory blood pressure. Methods In this multicentre, double-blind, randomised, placebo-controlled phase IIa trial, 72 patients with mild-to-moderate hypertension were randomly assigned with a computer-generated randomisation list to receive subcutaneous injections of either 100 mu g CYT006-AngQb (n=24), 300 mu g CYT006-AngQb (24), or placebo (24), at weeks 0, 4, and 12. 24-h ambulatory blood pressure was measured before treatment and at week 14. The primary outcomes were safety and tolerability. Analyses were done by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00500786. Findings Two patients in the 100 mu g group, three in the 300 mu g group, and none in the placebo group discontinued study treatment. All patients were included in safety analyses; efficacy analyses did not include the five dropouts, for whom no data were available at week 14. Five serious adverse events were reported (two in the 100 mu g group, two in the 300 mu g group, and one in the placebo group); none were deemed to be treatment related. Most side-effects were mild, transient reactions at the injection site. Mild, transient influenza-like symptoms were seen in three patients in the 100 mu g group, seven in the 300 mu g group, and none in the placebo group. In the 300 mu g group, there was a reduction from baseline in mean ambulatory daytime blood pressure at week 14 by -9.0/-4. 0 mm Hg compared with placebo (p=0 . 015 for systolic and 0.064 for diastolic). The 300 mu g dose reduced the early morning blood-pressure surge compared with placebo (change at 0800 h -25/-13 mm Hg; p<0 . 0001 for systolic, p=0 . 0035 for diastolic). Interpretation Immunisation with CYT006-AngQb was associated with no serious adverse events; most observed adverse events were consistent with local or systemic responses similar to those seen with other vaccines. The 300 mu g dose reduced blood pressure in patients with mild-to-moderate hypertension during the daytime, especially in the early morning.