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

@article{citeulike:2517417, abstract = {SummaryBackground 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[middle dot]0/-4[middle dot]0 mm[punctuation space]Hg compared with placebo (p=0[middle dot]015 for systolic and 0[middle dot]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[punctuation space]Hg; p<0[middle dot]0001 for systolic, p=0[middle dot]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.Funding Cytos Biotechnology AG.}, author = {Tissot, Alain C. and Maurer, Patrik and Nussberger, Juerg and Sabat, Robert and Pfister, Thomas and Ignatenko, Stanislav and Volk, Hans-Dieter and Stocker, Hans and Muller, Philipp and Jennings, Gary T. and Wagner, Frank and Bachmann, Martin F. }, citeulike-article-id = {2517417}, doi = {10.1016/S0140-6736(08)60381-5}, journal = {The Lancet}, number = {9615}, pages = {821--827}, posted-at = {2008-03-12 02:18:32}, priority = {2}, title = {Effect of immunisation against angiotensin II with CYT006-AngQb on ambulatory blood pressure: a double-blind, randomised, placebo-controlled phase IIa study}, url = {http://dx.doi.org/10.1016/S0140-6736(08)60381-5}, volume = {371} }

TY - JOUR ID - citeulike:2517417 L3 - citeulike-article-id:2517417 TI - Effect of immunisation against angiotensin II with CYT006-AngQb on ambulatory blood pressure: a double-blind, randomised, placebo-controlled phase IIa study JF - The Lancet VL - 371 IS - 9615 SP - 821 EP - 827 N2 - SummaryBackground 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[middle dot]0/-4[middle dot]0 mm[punctuation space]Hg compared with placebo (p=0[middle dot]015 for systolic and 0[middle dot]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[punctuation space]Hg; p<0[middle dot]0001 for systolic, p=0[middle dot]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.Funding Cytos Biotechnology AG. AU - Tissot, Alain AU - Maurer, Patrik AU - Nussberger, Juerg AU - Sabat, Robert AU - Pfister, Thomas AU - Ignatenko, Stanislav AU - Volk, Hans-Dieter AU - Stocker, Hans AU - Muller, Philipp AU - Jennings, Gary AU - Wagner, Frank AU - Bachmann, Martin UR - http://dx.doi.org/10.1016/S0140-6736(08)60381-5 ER -