Safety and Efficacy Study of Angiotensin Therapeutic Vaccine in Subjects With Mild to Moderate Hypertension
Condition: Hypertension; Cardiovascular Disease
MeSH terms: Hypertension; Cardiovascular Diseases
Intervention: Angiotensin Therapeutic Vaccine plus CoVaccine HT™ adjuvant; CoVaccine HT™ adjuvant
Intervention description: Angiotensin Therapeutic Vaccine plus CoVaccine HT™ adjuvant given as 3 separate intramuscular injections into the arm, 21 days apart; Given as three separate intramuscular injections into the arm, 21 days apart
Intervention MeSH terms: Vaccines
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 20.0
Sex: All
Minimum age: 35 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: high blood pressure; vaccines

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
    

Eligibility criteria:

        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.