Safety and Efficacy Study of Angiotensin Therapeutic Vaccine in Subjects With Mild to Moderate Hypertension

Hypertension Clinical Trial

Official title:

A Randomised, Double Blind, Placebo Controlled Study of the Efficacy and Safety of Angiotensin Therapeutic Vaccine (ATV) in Subjects With Mild to Moderate Hypertension

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00702221
• Other study ID #: PR002-CLN-pro008
• Status: Terminated
• Phase: Phase 2
• First received: June 19, 2008
• Last updated: October 12, 2010
• Start date: June 2008
• Est. completion date: September 2010

Study information

• Verified date: October 2010
• Source: BTG International Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

Angiotensin Therapeutic Vaccine (ATV), which contains the novel adjuvant, CoVaccine HT™ , is being developed for the treatment of high blood pressure (hypertension), a major risk factor for serious diseases such as heart attacks and strokes. Many patients with high blood pressure fail to take their medicines as prescribed because they generally feel well, which often results in poor control of the condition. As a result, it is estimated that about 70% patients with hypertension do not have their blood pressure adequately controlled despite advances in the treatment of high blood pressure.

The main aim of this study is to find out if an injection of ATV given in the arm once every 3 weeks on 3 occasions results in lowering overall blood pressure measurements throughout the day. The other aims are to find out if ATV is safe and to see how well it is tolerated

Description:

One of the causes of hypertension is overactivity of the renin angiotensin system, the main mechanism by which the human body regulates its sodium and water balance. An enzyme called renin cleaves a peptide from the protein angiotensinogen, releasing angiotensin I (AI), which is then converted to a peptide hormone called angiotensin II (AII) by the angiotensin converting enzyme (ACE). Angiotensin II is a hormone which is a powerful vasoconstrictor and increases blood flow to vital organs. Angiotensin Therapeutic Vaccine acts by inducing antibodies which bind to angiotensin, so suppressing its actions.

ATV may offer a way of improving control of blood pressure by increasing patient compliance with treatment. Infrequent vaccinations may provide a sustained reduction in blood pressure and afford a desirable, slow onset of action. Such a vaccine could provide an adjunct to and possibly a replacement for existing therapy in some patients, particularly where patient compliance is likely to be a problem.

This study will determine if three injections of ATV given over the period of six weeks will reduce daytime BP as measured by ambulatory blood pressure monitoring.

The study is split into 2 stages Stage A and Stage B.

The rationale behind Stage A is to closely evaluate the safety and tolerability of ATV in a small number of subjects prior to enroling the majority of subjects into the remaining portion of the study. Stage A will include a minimum of 12 subjects who will receive each of their three injections at a dedicated Phase 1 facility with access to critical care facilities.

Based on the safety profile of the stage A subjects, a recommendation will be made by an independent Data Safety Monitoring Committee on whether to proceed to Stage B.

Stage B will include approximately 112 subjects. As safety and tolerability will have been closely assessed in Stage A, Stage B subjects will be monitored less closely and will be recruited from a number of sites in the UK.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 124
• Est. completion date: September 2010
• Est. primary completion date: June 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 35 Years to 70 Years

Eligibility

Inclusion Criteria (at randomisation):

1. Competent to provide written informed consent

2. 35-70 years old

3. Body Mass Index (BMI) 19 to 33 kg/m2

4. Mild to moderate hypertension per British Hypertension Society (BHS) Guidelines BHS-IV based on the following criteria of sitting blood pressure for subjects without diabetes or renal dysfunction.

5. Average sitting morning DBP 90 to 109 mmHg and SBP 140 to 179 mmHg and have responded positively to a quinapril challenge.

Principal exclusion criteria:

1. Women of childbearing potential: defined to be not surgically sterile and <2 y post-menopausal

2. Average sitting SBP of >180 mmHg or DBP of >110 mmHg.

3. A BP difference between left and right arm greater than 20 mmHg for SBP and 10 mmHg for DBP which is present on 3 consecutive readings.

4. Left ventricular (LV) systolic dysfunction as evidenced by a known LV ejection fraction <40% or symptomatic congestive heart failure requiring treatment.

5. HbA1c >7.0% or a history of Type 1 or Type 2 diabetes.

6. Haemoglobin <12 g/dL at Screening.

7. Hypo- or hyperthyroidism

8. Serum alanine aminotransferase or aspartate aminotransferase >2X ULN.

9. Other identifiable secondary causes of hypertension

10. Myocardial infarction, unstable angina pectoris, or a cerebrovascular accident within 6 months of Screening.

11. Bradycardia <50 beats per minute at rest in the supine position prior to randomisation.

12. Have sick sinus syndrome or second or third degree atrioventricular block, chronic atrial fibrillation or recurrent atrial tachyarrhythmia (including paroxysmal atrial tachycardia), history of recurrent ventricular tachycardia, or symptomatic bradycardia.

13. Implanted pacemakers or cardioverter defibrillator.

14. Haemodynamically significant valvular heart disease.

15. History of renal dysfunction and/or estimated glomerular filtration rate <60 mL/min/1.73 m2.

16. 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.

17. Sleep apnea 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.

18. Perform alternating shift or night work.

19. 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:

• Oral corticosteroids within 3 months of Screening.

• Acetylsalicylic acid in excess of 325 mg per day.

• Chronic stable or unstable use of non-steroidal anti-inflammatory drugs (NSAIDs) other than acetylsalicylic acid is prohibited.

• Selective serotonin reuptake inhibitors or selective serotonin norepinephrine reuptake inhibitors, if a subject is not compliant with the medication and/or has not been receiving a stable dose for at least 3 months prior to Screening.

• Tricyclic antidepressants, if a subject is not compliant with the medication and/or has not been receiving a stable dose for at least 3 months prior to Screening.

• Any angiotensin vaccine, including prior exposure to ATV.

20. Have participated in a clinical study involving another investigational drug or device within 4 weeks of Screening.

21. Any concomitant condition that, in the opinion of the investigator, may adversely affect the safety and/or efficacy of the study drug or severely limit the subject's ability to complete the study (eg, disabling or terminal illness, mental disorders).

22. Any major contraindication to stopping antihypertension medications for a period of up to 14 weeks.

23. Previous exposure to CoVaccine HT adjuvant, or other keyhole limpet haemocyanin-containing vaccines.

24. Previous serious reaction to a vaccine, such as angioedema or anaphylaxis.

25. Known history of drug and/or alcohol abuse and those known to be hepatitis positive.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cardiovascular Disease
• Cardiovascular Diseases
• Hypertension

Intervention

Biological:
• Angiotensin Therapeutic Vaccine plus CoVaccine HT™ adjuvant
Given as three separate intramuscular injections into the arm, 21 days apart
• CoVaccine HT™ adjuvant
Given as three separate intramuscular injections into the arm, 21 days apart

Locations

Country	Name	City	State
United Kingdom	Layton Medical Centre	Blackpool	Lancashire
United Kingdom	Avondale Surgery	Chesterfield	Derbyshire
United Kingdom	Fowey River Practice	Fowey	Cornwall
United Kingdom	Grey Gable Surgery	Inkberrow	Worcestershire
United Kingdom	Sherbourne Medical Centre	Leamington Spa	Warwickshire
United Kingdom	The Acumen Pharmaceutical Services Ltd	Manchester
United Kingdom	Alverton Practice	Penzance	Cornwall
United Kingdom	Knowle House Surgery	Plymouth	Devon
United Kingdom	Saltash Health Centre	Saltash	Cornwall
United Kingdom	Cape Cornwall Surgery	St. Just	Cornwall
United Kingdom	Brannel Surgery	St. Stephen	Cornwall
United Kingdom	Abbey Meads Medical Practice	Swindon	Wiltshire

Sponsors (2)

Lead Sponsor	Collaborator
BTG International Inc.	Encorium

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline to Week 8 in mean daytime Diastolic Blood Pressure (DBP) measured by Ambulatory Blood Pressure Monitoring (ABPM)		8 weeks	Yes
Secondary	Change from baseline to Week 8 in mean 24-hour Systolic Blood Pressure (SBP) and DBP measured by ABPM		8 weeks	Yes