Men and women, 35-70 years old with mild to moderate Hypertension as classified by the British Hypertension Society (BHS) Guidelines - BHS-IV based on the following crietia of sitting blood pressure measured by spygomanography for patienst without diabetes or renal dysfunction: Grade 1 (mild): Systolic BP 140-159 mmHG and Diastolic BP of 90-99 mmHg Grade 2 (moderate): Systolic BP 160-179 mmHg and Diastolic BP 100-109 mmHg MedDRA version: 9.1 Level: LLT Classification code 10020772 Term: Hyperte
Conditions
Interventions
Product Name: Angiotensin Therapeutic Vaccine (ATV) conjugate
Product Code: PMD3117
Pharmaceutical Form: Solution for injection
Current Sponsor code: PMD3117
Other descriptive name: Angiotensin Therap
Sponsors
Protherics Medicines Development Ltd, a BTG plc company
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subjects must be competent to provide written informed consent. Subjects must sign an Institutional Review Board/Independent Ethics Committee (IRB/IEC) approved informed consent form (ICF). Authorization must also be obtained prior to the initiation of any study procedures. 2. Subjects must be 35-70 years of age. 3. Subjects must have a Body Mass Index (BMI) of 19 to 35 kg/m2, inclusive. 4. At baseline (Day -1), subjects must have mild to moderate hypertension as classified by the British Hypertension Society (BHS) Guidelines – BHS-IV based on the following criteria of sitting blood pressure measured by sphygmomanometry for subjects without diabetes or renal dysfunction. Systolic BP (SBP) Diastolic BP (DBP) Grade 1 140 – 159 mmHg 90 – 99 mmHg Grade 2 160 – 179 mmHg 100 – 109 mmHg 5. At baseline (Day -1), all subjects must have an average sitting morning DBP 90 to 109 mmHg (inclusive) and SBP 140 to 179 mmHg (inclusive) as measured by sphygmomanometry and have responded positively to a quinapril challenge in order to enter the study. No subject will be eligible for the study if his/her SBP is >180 mmHg any time during the Screening Period. 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: 1. Subjects who have failed the quinapril challenge. 2. Women of childbearing potential will be excluded from study participation. Women who are surgically sterile or are documented to have been post-menopausal for at least 2 years will be considered for study participation. Post-menopausal female subjects who are 180 mmHg or DBP of >110 mmHg. 4. Subjects with a BP difference between left and right arm on screening greater than 20 mmHg for SBP and 10 mmHg for DBP which is present on 3 consecutive readings. 5. Subjects with left ventricular (LV) systolic dysfunction as evidenced by a known LV ejection fraction 7.0% at Screening or a history of Type 1 or Type 2 diabetes. 7. Subjects who have a haemoglobin 2X ULN at Screening. 10. Subjects with other identifiable secondary causes of hypertension (eg, parathyroid disease, pheochromocytoma, Cushing’s disease, hyperaldosteronism, aortic coarctation). On Screening, if the difference between BP measured on the right and left arm is greater than 20 mmHg for SBP and 10 mmHg for DBP and are present on 3 consecutive readings, the subject will be excluded from the study. 11. Subjects who have experienced a myocardial infarction, unstable angina pectoris, or a cerebrovascular accident within 6 months of Screening. 12. Bradycardia <50 beats per minute at rest in the supine position prior to randomisation. 13. Subjects with sick sinus syndrome or second or third degree atrioventricular (AV) block, chronic atrial fibrillation or recurrent atrial tachyarrhythmia (including paroxysmal atrial tachycardia), a history of recurrent ventricular tachycardia, or symptomatic bradycardia. 14. Subjects with implanted pacemakers or an implanted cardioverter defibrillator (ICD). 15. Subjects with hemodynamically significant valvular heart disease. 16. Subjects with a history of renal dysfunction and/or estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 at Screening.18 17. Subjects who have had a diagnosis or recurrence of malignancy within the past 3 years, with the exception of basal cell carcinoma of the skin or in situ carcinoma of the cervix. 18. Subjects with sleep apnea are excluded unless a recent (within 30 days of Screening) sleep study demonstrates no recordings of arterial oxygen saturation (SaO2) <90%, treated or untreated, at any time during the Screening Period. 19. Subjects who perform alternating shift or night work. 20. Subjects not on stable doses of all concomitant medications for a minimum of 4 weeks prior to Screening, and subjects treated with any of the following prohibited medications: a. Oral corticosteroids within 3 months of Screening. b. Acetylsalicylic acid in excess of 325 mg per day. c. Chronic stable or unstable use of non-ste
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The Primary efficaccy objective of this study is to determine if immunization with ATV is effective in reducing mean daytime DBP measured by ambulatory blood pressure monitoring (ABPM) in subjects with mild to moderate hypertension.;Primary end point(s): The primary efficacy endpoint will be the change from baseline to Week 8 in mean daytime DBP measured by ABPM. ;Secondary Objective: The secondary objectives of this study are to examine the effect of immunization with ATV on: • Mean 24-hour SBP measured by ABPM • Mean 24-hour DBP measured by ABPM • Mean sitting and standing morning DBP and SBP measured by sphygmomanometry • Mean morning DBP and SBP, daytime SBP, and night-time DBP and SBP measured by ABPM • Percent of subjects meeting DBP and SBP treatment target goals as measured by sphygmomanometry Safety Objectives To assess the local and systemic safety and tolerability of immunization with ATV in the study population. Immunological Objective To evaluate the immunogenicity of the ATV as measured by anti-angiotensin IgG titres. Additional Measures of Interest Aldosterone (serum) and active renin (plasma) concentrations, immune complex formation as well as other pharmacologic and/or immunologic measures. | — |
Countries
United Kingdom
Outcome results
None listed