E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Mild to moderate essential hypertension |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10020772 |
E.1.2 | Term | Hypertension |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
• 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.
|
|
E.2.2 | Secondary objectives of the trial |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 <20mmHg for sitting office SBP and <10mmHg for mean sitting office DPB). • Patients without current antihypertensive therapy. For patients on previous antihypertensive therapy, who can safely stop their medication, the screening period will be prolonged for a wash-out phase, not shorter than 2 weeks. The screening office blood pressure and ABPM should be assessed at the end of the wash-out period to confirm the inclusion criteria. • 18 to 69 years of age. • Male patients, or female patients without childbearing potential (postmenopausal - one year without menses, in case of doubts serum FSH should be determined and must be >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.
|
|
E.4 | Principal 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.
|
|
E.5 End points |
E.5.1 | 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)
|
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 10 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
Last visit of last subject |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |