title: Effect of immunisation against angiotensin II with CYT006-AngQb on ambulatory blood pressure: a double-blind, randomised, placebo-controlled phase IIa study.
abstract: 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 mug CYT006-AngQb (n=24), 300 mug 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.
  
  
  RESULTS
  Two patients in the 100 mug group, three in the 300 mug 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 mug group, two in the 300 mug 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 mug group, seven in the 300 mug group, and none in the placebo group. In the 300 mug 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 mug 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).
  
  
  CONCLUSIONS
  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 mug dose reduced blood pressure in patients with mild-to-moderate hypertension during the daytime, especially in the early morning.
  
  
  BACKGROUND
  Cytos Biotechnology AG.
authors.affiliation: Cytos Biotechnology AG, Zurich-Schlieren, Switzerland.
authors.forename: Alain C
authors.initials: AC
authors.lastname: Tissot
authors.forename: Patrik
authors.initials: P
authors.lastname: Maurer
authors.forename: Juerg
authors.initials: J
authors.lastname: Nussberger
authors.forename: Robert
authors.initials: R
authors.lastname: Sabat
authors.forename: Thomas
authors.initials: T
authors.lastname: Pfister
authors.forename: Stanislav
authors.initials: S
authors.lastname: Ignatenko
authors.forename: Hans-Dieter
authors.initials: HD
authors.lastname: Volk
authors.forename: Hans
authors.initials: H
authors.lastname: Stocker
authors.forename: Philipp
authors.initials: P
authors.lastname: Müller
authors.forename: Gary T
authors.initials: GT
authors.lastname: Jennings
authors.forename: Frank
authors.initials: F
authors.lastname: Wagner
authors.forename: Martin F
authors.initials: MF
authors.lastname: Bachmann
mesh_terms: D000328:Adult; D000368:Aged; D000804:Angiotensin II / Q000037:antagonists & inhibitors* / Q000276:immunology; D000917:Antibody Formation / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000276:immunology; D008875:Middle Aged; D018670:Monitoring, Ambulatory; D009842:Oligopeptides / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D014614:Vaccines, Synthetic / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*
chemical_list: C525491:CYT006-AngQb; D009842:Oligopeptides; D014614:Vaccines, Synthetic; D000804:Angiotensin II