Mild to moderate essential hypertension MedDRA version: 9.1 Level: LLT Classification code 10020772 Term: Hypertension
Conditions
Interventions
Product Name: CYT006-AngQb
Product Code: AngQb
Pharmaceutical Form: Suspension for injection
Current Sponsor code: CYT006-AngQb
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: eq
Sponsors
Cytos Biotechnology AG
Eligibility
Sex/Gender
All
Inclusion 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 baseline ABPM measurement (SBP >130 mmHg and/or DBP >85 mmHg). • Stable baseline blood pressure confirmed on 2 consecutive visits (screening and V1). (Changes 30 U/mL) or surgically sterilized, documented). • Written informed consent must be signed before any study related procedure is performed including start of a wash-out from previous antihypertensive treatment. • Patient is willing and able to comply with all trial requirements and procedures. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
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, clinically relevant heart failure (NYHA class II-IV) - Peripheral artery disease - Diabetic nephropathy • Electrocardiographic confirmed left ventricular hypertrophy (Sokolow-Lyon index — sum of SV1+RV5 or V6>38 mm [3.8mV]) • Increased plasma creatinine (M >115 µmol/l, W >107 µmol/l). • Albumin/creatinine ratio in spot urine (M ? 22 mg/g, W ? 31 mg/g). • Diabetes mellitus type I, history, presence or new diagnosis of diabetes mellitus type II. • Fasting plasma glucose > 6.7 mmol/l • Body mass index (BMI) > 32 • LDL cholesterol > 4.9 mmol/l • Triglycerides > 3.4 mmol/l • Postural hypotension at screening (fall of SBP from sitting to standing position >20 mmHg or DBP >10 mmHg) or clinical signs of orthostatic hypotension. • Patient requiring long-term usage of not allowed concomitant medication. For details, please refer to Section “Concomitant medication”. • 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. • 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 (CYT006-AngQb, CYT001-DerQb, CYT002-NicQb, CYT003-QbG10, CYT005-AllQbG10, CYT007-TNFQb and CYT009-GhrQb). • 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To evaluate safety and tolerability in a dose-titration study design of 5 s.c. injections of 300µg, 600µg and up to 900µg 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 and office blood pressure. ;Secondary Objective: Not Applicable;Primary end point(s): Clinical Endpoints •Ambulatory blood pressure monitoring (ABPM) For a primary analysis of ABPM, daytime will be defined as the time period from 06:00 a.m. to21:59 p.m. • Standard office sitting and standing blood pressure readings . Pharmacodynamic Endpoints • Immune response: IgG titers of antibodies specific for either angiotensin II or Qb VLP • RAS biomarkers: Immunoreactive renin, angiotensin II, andaldosterone • Excretion of aldosterone and electrolytes (Na+, K+), creatinine Pharmacogenetic Evaluation • Pharmacogenetic analyses Safety Evaluations • Adverse events • Body temperature • 12 lead ECG • Body weight • Standard clinical laboratory evaluations (hematology, blood chemistry and urinalysis) • Calculated glomerular filtration from serum creatinine, calculated microalbuminuria from a spot urine sample • Inspection of Injection sites • Immune complexes and ANA (antinuclear antibodies) | — |
Countries
Germany
Outcome results
None listed