Safety, Tolerability and Efficacy of a Vaccine Against Essential Hypertension

A Double Blind, Randomized, Placebo Controlled, Parallel Group, Dose-Titration Phase II Study to Evaluate Safety and Tolerability, Pharmacodynamic Effects and Efficacy of an Anti-Angiotensin II Vaccine (CYT006-AngQb) in Patients With Mild to Moderate Essential Hypertension

The study medication CYT006-AngQb is a vaccine, consisting of angiotensin II (Ang II), the naturally occurring octapeptide coupled onto the surface of virus-like particles (VLP). This form of presenting Ang II to the immune system induces a B-cell mediated immune response characterized by the generation of specific antibodies (IgG and IgM) against Ang II. The CYT006-AngQb vaccine is administered by subcutaneous (s.c.) injection. Immunization against angiotensin II may offer a valuable alternative to conventional drugs for the treatment of hypertension.

Study Overview

• Status: Completed
• Conditions: Mild Essential Hypertension; Moderate Essential Hypertension
• Intervention / Treatment: Biological: CYT006-AngQb

• Study Type: Interventional
• Enrollment (Actual): 83
• Phase: Phase 2

Contacts and Locations

Study Locations

• Switzerland
  • Schlieren, Switzerland, CH-8952
    • Cytos Biotechnology (Sponsor's Headquarter)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 69 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with mild to moderate essential hypertension (Grade I and Grade II) with mean sitting office SBP =140-179 mmHg and/or mean sitting office DBP = 90 -109 mmHg on 2 consecutive visits (screening and V1).
• Daytime blood pressure above threshold for definition of hypertension in the baseline ABPM measurement (SBP >135 mmHg).
• Stable baseline blood pressure confirmed on 2 consecutive visits (screening and V1). (Changes <20mmHg for sitting office SBP and <10mmHg for mean sitting office DPB).
• Patients without current antihypertensive therapy. Patients on previous mono-antihypertensive therapy, who can safely stop their medication
• Patient is willing and able to comply with all trial requirements and procedures.

Exclusion Criteria:

• Patients with "very high added risk" according to 2007 Guidelines for the Management of Arterial Hypertension (Journal of Hypertension, 2007, 25:1105- 1187), i.e. those with:grade III hypertension (mean sitting office SBP

  • 180mmHg and/or meansitting DBP ≥110mmHg/history or presence of established cardiovascular or renal disease (Ischemic stroke, cerebral hemorrhage, transient ischemic attack)/ Myocardial infarction, angina pectoris, coronary re-vascularization/ clinically relevant heart failure (NYHA class II-IV)/ Peripheral artery disease/ Diabetic nephropathy
• Electrocardiographic confirmed left ventricular hypertrophy
• Increased plasma creatinine
• Diabetes mellitus type I, history, presence or new diagnosis of diabetes mellitus type II.
• Postural hypotension at screening
• Arrhythmias that would interfere with the oscilloscopic measurement of the blood pressure.
• Known autoimmune disease.
• Severe allergy.
• Pregnancy or breastfeeding.
• Women in childbearing age that are not surgically sterilized.
• Patients with a history or current positive test for HIV infection, AIDS, or other immunosuppressive disorders; hepatitis B or C.
• Current diagnosis or history of malignancy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 2	Biological: CYT006-AngQb; s.c. injection
Experimental: 1; CYT006-AngQb	Biological: CYT006-AngQb; s.c. injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Adverse events: quality, quantity, severity	throughout complete study until week 48

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in daytime, nighttime and 24h ambulatory blood pressure from baseline	24 hours
anti-Angio II IgG antibody titer	throughout complete study until week 48
Level of RAS Biomarkers (concentrations of plasma renin, angiotensinII and aldosterone)	24 h

Collaborators and Investigators

• Sponsor: Cytos Biotechnology AG

Study record dates

Study Major Dates

• Study Start: June 1, 2008
• Primary Completion (Actual): July 1, 2009
• Study Completion (Actual): November 1, 2010

Study Registration Dates

• First Submitted: July 3, 2008
• First Submitted That Met QC Criteria: July 3, 2008
• First Posted (Estimate): July 4, 2008

Study Record Updates

• Last Update Posted (Estimate): November 15, 2010
• Last Update Submitted That Met QC Criteria: November 11, 2010
• Last Verified: November 1, 2010

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Essential Hypertension
• Other Study ID Numbers: CYT006-AngQb 03; EudraCT No.: 2007-007516-28