HypertensionPhase 2NCT00702221
Safety and Efficacy Study of Angiotensin Therapeutic Vaccine in Subjects With Mild to Moderate Hypertension
A Phase 2 study testing Angiotensin Therapeutic Vaccine plus CoVaccine HT™ adjuvant and CoVaccine HT™ adjuvant in people with Hypertension and Cardiovascular Disease, run by BTG International Inc. at 12 sites in United Kingdom.
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. Read more about this study
- Who is it for?
- Ages 35 to 70 years
- Conditions the study is for
- Hypertension, Cardiovascular Disease
- What is being tested?
- Angiotensin Therapeutic Vaccine plus CoVaccine HT™ adjuvant and CoVaccine HT™ adjuvant
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 12 sitesUnited Kingdom
- Study dates
- Jun 2008to Sep 2010
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 35 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Competent to provide written informed consent
- 35-70 years old
- Body Mass Index (BMI) 19 to 33 kg/m2
- 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.
- 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:
Show all 37Show fewer
- Women of childbearing potential: defined to be not surgically sterile and <2 y post-menopausal
- Average sitting SBP of >180 mmHg or DBP of >110 mmHg.
- 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.
- Left ventricular (LV) systolic dysfunction as evidenced by a known LV ejection fraction <40% or symptomatic congestive heart failure requiring treatment.
- HbA1c >7.0% or a history of Type 1 or Type 2 diabetes.
- Haemoglobin <12 g/dL at Screening.
- Hypo- or hyperthyroidism
- Serum alanine aminotransferase or aspartate aminotransferase >2X ULN.
- Other identifiable secondary causes of hypertension
- Myocardial infarction, unstable angina pectoris, or a cerebrovascular accident within 6 months of Screening.
- Bradycardia <50 beats per minute at rest in the supine position prior to randomisation.
- 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.
- Implanted pacemakers or cardioverter defibrillator.
- Haemodynamically significant valvular heart disease.
- History of renal dysfunction and/or estimated glomerular filtration rate <60 mL/min/1.73 m2.
- 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.
- 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.
- Perform alternating shift or night work.
- 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.
- Have participated in a clinical study involving another investigational drug or device within 4 weeks of Screening.
- 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).
- Any major contraindication to stopping antihypertension medications for a period of up to 14 weeks.
- Previous exposure to CoVaccine HT adjuvant, or other keyhole limpet haemocyanin-containing vaccines.
- Previous serious reaction to a vaccine, such as angioedema or anaphylaxis.
- Known history of drug and/or alcohol abuse and those known to be hepatitis positive.
Who cannot join
None listed.
Trial locations and contacts
12 sites in 1 country.
12 sites in 1 country
United Kingdom12 sites
Layton Medical Centre
Blackpool, Lancashire, FY3 7EN
Avondale Surgery
Chesterfield, Derbyshire, S40 4FT
Fowey River Practice
Fowey, Cornwall, PL23 1DT
Grey Gable Surgery
Inkberrow, Worcestershire, WR7 4BW
The Acumen Pharmaceutical Services Ltd
Manchester, M50 2GY
Alverton Practice
Penzance, Cornwall, TR18 4JH
Knowle House Surgery
Plymouth, Devon, PL5 3JB
Sherbourne Medical Centre
Royal Leamington Spa, Warwickshire, CV32 4RA
Brannel Surgery
Saint Stephen, Cornwall, PL26 7RL
Saltash Health Centre
Saltash, Cornwall, PL12 6DL
Cape Cornwall Surgery
St Just, Cornwall, TR19 7HX
Abbey Meads Medical Practice
Swindon, Wiltshire, SN25 4YZ
About this study
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
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
Read the detailed 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.
- Conditions
- Hypertension, Cardiovascular Disease
- Being tested
- Angiotensin Therapeutic Vaccine plus CoVaccine HT™ adjuvant, CoVaccine HT™ adjuvant
- Keywords
- high blood pressure, vaccines
- Medical subject headings
- Hypertension, Cardiovascular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Angiotensin Therapeutic Vaccine plus CoVaccine HT™ adjuvantBiological
Angiotensin Therapeutic Vaccine plus CoVaccine HT™ adjuvant given as 3 separate intramuscular injections into the arm, 21 days apart
CoVaccine HT™ adjuvantBiological
Given as three separate intramuscular injections into the arm, 21 days apart
| Study group | Role | What they receive |
|---|---|---|
| ATV with CoVaccine HT™ | Experimental | Angiotensin Therapeutic Vaccine with CoVaccine HT™ adjuvant (an ingredient that may improve the immune response of the vaccine) Receives: Biological: Angiotensin Therapeutic Vaccine plus CoVaccine HT™ adjuvant |
| CoVaccine HT™ adjuvant alone | Placebo comparator | CoVaccine HT™ adjuvant alone Receives: Biological: CoVaccine HT™ adjuvant |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline to Week 8 in Mean Daytime Diastolic Blood Pressure (DBP) Measured by Ambulatory Blood Pressure Monitoring (ABPM)
Measured: baseline to 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jun 2008 (estimated)
- Study startJun 2008
- Primary completionJun 2009
- Study completionSep 2010
Why it stopped: Dose limiting adverse effects
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for HypertensionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- BTG International Inc.
- Sponsor type
- University, hospital or other
- Collaborators
- Encorium
- Responsible party
- Sponsor
- Investigators
- Wajdi H Turkie, MD, Principal investigator, The Acumen Pharmaceuticals Services Ltd
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00702221
- Sponsor's protocol ID
- PR002-CLN-pro008
- Status last verified
- Apr 2016
- First submitted
- 19 Jun 2008
- Last updated
- 29 Jul 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: Investigators provide information to participants
Study at a glance
From the registry record, last updated by the sponsor on 29 Jul 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00702221
- Acronym / sponsor ID
- PR002-CLN-pro008
- Conditions
- Hypertension, Cardiovascular Disease
- Keywords
- high blood pressure, vaccines
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Dose limiting adverse effects
- Enrolment
- 20 participants (actual)
- Lead sponsor
- BTG International Inc.University, hospital or other
- Collaborators
- Encorium
- Study start
- Jun 2008
- Primary completion
- Jun 2009 (actual)
- Study completion
- Sep 2010 (actual)
- First posted
- 20 Jun 2008 (estimated)
- Results
- Posted 29 Jul 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ATV with CoVaccine HT™ | Experimental | Biological: Angiotensin Therapeutic Vaccine plus CoVaccine HT™ adjuvantAngiotensin Therapeutic Vaccine with CoVaccine HT™ adjuvant (an ingredient that may improve the immune response of the vaccine) |
| CoVaccine HT™ adjuvant alone | Placebo comparator | Biological: CoVaccine HT™ adjuvantCoVaccine HT™ adjuvant alone |
Who may qualify
- Ages
- 35 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (37 listed)
- Competent to provide written informed consent
- 35-70 years old
- Body Mass Index (BMI) 19 to 33 kg/m2
- 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.
- Average sitting morning DBP 90 to 109 mmHg and SBP 140 to 179 mmHg and have responded positively to a quinapril challenge.
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Angiotensin Therapeutic Vaccine plus CoVaccine HT™ adjuvantAngiotensin Therapeutic Vaccine plus CoVaccine HT™ adjuvant given as 3 separate intramuscular injections into the arm, 21 days apart | Biological | ATV with CoVaccine HT™ |
| CoVaccine HT™ adjuvantGiven as three separate intramuscular injections into the arm, 21 days apart | Biological | CoVaccine HT™ adjuvant alone |
Primary outcome
Change From Baseline to Week 8 in Mean Daytime Diastolic Blood Pressure (DBP) Measured by Ambulatory Blood Pressure Monitoring (ABPM)
Time frame: baseline to 8 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jul 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. Investigators provide information to participants
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Wajdi H Turkie, MD principal investigator
The Acumen Pharmaceuticals Services Ltd
12 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Angiotensin Therapeutic Vaccine plus CoVaccine HT™ adjuvant and CoVaccine HT™ adjuvant in people with Hypertension and Cardiovascular Disease, run by BTG International Inc. at 12 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 37 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 29 Jul 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Jul 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline to Week 8 in Mean Daytime Diastolic Blood Pressure (DBP) Measured by Ambulatory Blood Pressure Monitoring (ABPM) (time frame: baseline to 8 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jul 2016.