Study to Evaluate Safety and Tolerability, Pharmacodynamic Effects and Exploratory Efficacy of a Vaccine Against Essential Hypertension

Study Overview
=================
Brief Summary
-----------------
CYT006-AngQb is a vaccine that induces a B-cell mediated immune response characterized by the generation of specific antibodies (IgG and IgM) against Angiotensin II. The vaccine is administered by subcutaneous injection. The objectives of the study are: To evaluate safety and tolerability of 5 s.c. injections of 300µg CYT006-AngQb with Alhydrogel™ in patients with mild to moderate essential hypertension (hypertension Grade I and II). To assess pharmacodynamic effects, i.e. anti-Ang II immune response and renin- angiotensin system (RAS) biomarkers. To explore the effect on blood pressure using ABPM.

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

Conditions
-----------------
Hypertension

Intervention / Treatment
-----------------
* Biological: CYT006-AngQb
* Biological: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
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 screening ABPM measurement (SBP >135 mmHg). Patients without current antihypertensive therapy. Patients on antihypertensive therapy, which can be stopped. 18 to 69 years of age. Male patients, or female patients without childbearing potential . 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 mean sitting 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, heart failure Peripheral artery disease Diabetic nephropathy 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. Presence of suspicious lymphadenopathy or splenomegaly on physical examination. Drug or alcohol abuse within the past 2 years. Presence or history of relevant cardiovascular, renal, hepatic, pulmonary, endocrine, autoimmune, neurological and psychiatric disease as judged by the investigator. Any current or past disease or conditions (physical or mental) that would, in the opinion of the investigator, interfere with the study procedures or interpretation of the study data (e.g. workers in the night shift). Previous participation in a clinical trial with a Qb based vaccine. Use of an investigational drug within 3 months before enrolment, or planned use during the whole study period. Possible dependency of the patient on sponsor and/or investigator. Planned active immunization 2 weeks before or 2 weeks after any study medication vaccination. Donation or loss >=400 mL of blood within 8 weeks prior to dosing or major surgery within past 2 months.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 69 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Biological: CYT006-AngQb<br>* s.c.<br>|
| Placebo Comparator: 2<br> | Biological: Placebo<br>* s.c.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events: quality, quantity, severity |  | Throughout the study until week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in daytime, nighttime and 24-hour ambulatory blood pressure from baseline |  | 24 hours | 
| Titer of IgG specific for angiotensin II |  | Throughout the study untill week 48 | 
| Amount of RAS-Biomarkers (plasma renin concentration, angiotensin II, aldosterone) |  | 24 hours | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
mild essential hypertension, moderate essential hypertension