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

• Published in: The Lancet (British edition) 2008-03, Vol.371 (9615), p.821-827
• Main Authors: Tissot, Alain C, PhD, Maurer, Patrik, PhD, Nussberger, Juerg, Prof, Sabat, Robert, MD, Pfister, Thomas, PhD, Ignatenko, Stanislav, MD, Volk, Hans-Dieter, Prof, Stocker, Hans, PhD, Müller, Philipp, MD, Jennings, Gary T, PhD, Wagner, Frank, MD, Bachmann, Martin F, PhD
• Format: Article
• Language: English
• Subjects: ACE inhibitors; Adult; Aged; Angiotensin II - antagonists & inhibitors; Angiotensin II - immunology; Antibody Formation - drug effects; Biotechnology; Blood pressure; Blood Pressure - drug effects; Clinical medicine; Clinical trials; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug therapy; Enzyme inhibitors; Female; Humans; Hypertension; Hypertension - drug therapy; Hypertension - immunology; Immunization; Immunotherapy; Injections; Internal Medicine; Middle Aged; Monitoring, Ambulatory; Oligopeptides - adverse effects; Oligopeptides - immunology; Oligopeptides - therapeutic use; Patients; Safety; Vaccines; Vaccines, Synthetic - adverse effects; Vaccines, Synthetic - immunology; Vaccines, Synthetic - therapeutic use
• ISSN: 0140-6736; 1474-547X
• DOI: 10.1016/S0140-6736(08)60381-5

Summary 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 μg CYT006-AngQb (n=24), 300 μg 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 μg group, three in the 300 μg 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 μg group, two in the 300 μg 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 μg group, seven in the 300 μg group, and none in the placebo group. In the 300 μg 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 μg dose reduced the early morning blood-pressure surge compared with placebo (change at 0800 h −25/−13 mm Hg; p