HypertensionPhase 1NCT04925050
First-in-Human Study of VB0004 in Healthy Subjects and to Patients With Mild to Moderate Hypertension With Low Cardiovascular Risk
A Phase 1 study testing VB0004 in people with Hypertension, run by Syneos Health at 3 sites in Australia.
Trial summary
This will be a single center, Phase I/IB, randomized, double-blind, placebo-controlled, sequential SAD/MAD/FE study, with a patients arm. The study will be divided into three parts: Part A: SAD cohorts, with FE evaluation Part B: MAD cohorts with healthy volunteers Part C: MAD cohorts including naïve patients with… Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Hypertension
- What is being tested?
- VB0004
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 88 participants
- Where
- 3 sitesAustralia
- Study dates
- 17 Jun 2021to 23 Jan 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Male or female, non-smoker (no use of tobacco or nicotine products within 1 month prior to screening), ≥18 and ≤55 years of age, with BMI >18.0 and <32.0 kg/m2.
- Male subjects who are not vasectomized for at least 6 months, and who are sexually active with a female partner of childbearing potential (childbearing potential females are defined as women that are neither post-menopausal nor surgically sterile) must be willing to use one of the following acceptable contraceptive methods from (the first) study drug administration and for 90 days after (the last) study drug administration:
- simultaneous use of a male condom and, for the female partner, oral contraceptives containing combined estrogen and progesterone beginning a least 4 weeks prior to screening, a vaginal ring, injectable and implantable hormonal contraceptives, intrauterine hormone-releasing system (e.g. Mirena), and progestogen-only hormonal contraception associated with inhibition of ovulation, placed at least 4 weeks prior to the first study drug administration.
- simultaneous use of a male condom and, for the female partner, nonhormonal intrauterine device (IUD) placed at least 4 weeks prior to the first study drug.
Who cannot join
- Any laboratory test results deemed clinically significant by the Investigator or positive test for HIV, HBsAg, or HCV.
- Clinically significant ECG abnormalities or vital sign abnormalities (systolic BP lower than 90 or over 140 mmHg (except for hypertensive patients), diastolic BP lower than 40 or over 90 mmHg, HR less than 40 or over 100 bpm, or RR less than 10 or over 22 bpm) at screening.
- Orthostatic hypotension at Screening or Day -1 (Systolic BP falls > 20 mm Hg or Diastolic BP falls > 10 mm Hg on standing)
- History of significant alcohol abuse within 1 year prior to screening or regular use of alcohol within 6 months prior to the screening visit (more than 14 units of alcohol per week [1 unit = 375 mL of beer 3.5%, 100 mL of wine 13.5%, or 30 mL of distilled alcohol 40%]).
- Donation of plasma within 7 days prior to dosing. Donation or loss of blood (excluding volume drawn at screening) of 50 mL to 499 mL of blood within 30 days, or more than 499 mL within 56 days prior to the first dosing.
Trial locations and contacts
3 sites in 1 country.
Australia3 sites, 3 recruiting
- Recruiting
Nucleus Network Pty Ltd Geelong Site
Geelong, Victoria, 3220
Cameron Johnson, 0390768906, c.johnson@nucleusnetwork.com.au
Jason Lickliter
- Not yet recruiting
Scientia Clinical Research
Randwick, New South Whales, 2031
- Recruiting
Nucleus Network Pty Ltd
Victor Harbor, Melbourne, 3004
Jason Lickliter, 0390768960, j.lickliter@nucleusnetwork.com.au
About this study
Official title: A Phase I/IB, First-Time-in-Human, Single Centre, Double-Blind, Randomized, Placebo-controlled, Dose Escalating Study of the Safety, Tolerability and Pharmacokinetics of Single and Repeat Doses of VB0004 Administered Orally to Healthy Volunteers; and to Patients With Mild to Moderate Hypertension With Low Cardiovascular Risk.
This will be a single center, Phase I/IB, randomized, double-blind, placebo-controlled, sequential SAD/MAD/FE study, with a patients arm.
The study will be divided into three parts:
Part A: SAD cohorts, with FE evaluation Part B: MAD cohorts with healthy volunteers Part C: MAD cohorts including naïve patients with mild to moderate hypertension and low cardiovascular risk The three parts will be completed sequentially or with partial overlapping.
Read the detailed description
Part A - SAD Cohorts 1 to 5:
Part 1 will consist of up to 5 cohorts (1 cohort per dose level). Each cohort will include 8 subjects (6 subjects receiving the active study drug and 2 subjects receiving matching placebo), for a total of 40 subjects. Efforts will be made to have gender-balanced cohorts. A staggered dosing schedule will be used for dosing of each cohort and will include 2 sentinel subjects (1 active and 1 placebo) dosed initially, and the remaining 6 subjects dosed at least 24 hours later. Following completion of each dose level, a Safety Monitoring Committee (SMC) will review the safety and tolerability data, as well as available PK data up to the Follow-Up Visit (Day 8), for at least 6 subjects in the respective cohort, in order to make decisions whether to escalate to the next dose level, decrease the next dose level, repeat a dose level, or to not evaluate any additional dose. The FE study will be conducted with 2 cohorts of 8 healthy participants from the SAD study. Subjects from FE Cohort 3 and, if needed, Cohort 4 will receive the study drug under both fasting (in a first period) and fed conditions (in a second period). There will be a washout period of at least 14 days between dosing of the fasting and the fed periods. Safety, tolerability, and PK data through at least to the Follow-Up Visit (Day 8), from a subsequent cohort will be reviewed by the SMC prior to dosing the fed period of FE Cohort. Therefore, the fed period of a FE Cohort could be dosed in parallel of the SAD Cohort receiving two doses higher. The planned SAD dose range is anticipated to be from 2 mg to 300 mg.
Part B - MAD Cohorts 6 to 8 (Healthy Volunteers):
Part B will consist of 3 cohorts (1 cohort per dose level). Each cohort will include 8 subjects (6 subjects receiving the study drug and 2 subjects receiving matching placebo daily for 14 consecutive days), for a total of 24 subjects. Efforts will be made to have gender-balanced cohorts. Part B can be initiated only following review of the safety, tolerability, and PK data following dosing of the SAD Cohort 3 or 4. A staggered dosing schedule might be used for the first dose level, including 2 sentinel subjects (1 active and 1 placebo) initiating dosing first and the remaining 6 subjects initiating dosing at least 24 hours later. Following completion of each dose level, a SMC will review the safety and tolerability data, as well as available PK data for at least 6 subjects in the respective cohort, in order to make decisions whether to escalate to the next dose level, decrease the next dose level, repeat a dose level, or to not evaluate any additional dose. The planned MAD dose range is anticipated to be from 10 mg to 100 mg administered q.d. for 14 consecutive days.
Part C - MAD Cohorts 9 and 10 (Patients with mild to moderate hypertension): Part C will consist of 2 cohorts (1 cohort per dose level). Each cohort will include a maximum of 8 patients with mild to moderate hypertension with low cardiovascular risk (6 subjects receiving the study drug and 2 subjects receiving matching placebo daily for 28 consecutive days), for a total of 16 patients. The doses of VB0004 administered will be determined by the SAD and MAD PK data. Following completion of Cohort 9, a SMC will review the safety and tolerability data, as well as available PK data for at least 6 subjects in the respective cohort, in order to make decisions whether to escalate to the next dose level, decrease the next dose level, repeat a dose level, or to not evaluate any additional dose.
- Conditions
- Hypertension
- Being tested
- VB0004, Matching Placebo for VB0004
- Medical subject headings
- Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VB0004Drug
Each study part (A,B and C) will be completed sequentially or with partial overlapping. Safety and PK data through at least day 8 from a subsequent cohort will be reviewed by the SMC prior to dosing the fed period of FE cohort. Safety data will be assessed by SMC after completing each cohorts in MAD healthy volunteers and MAD mild Hypertension patients.
Matching Placebo for VB0004Other
Matching Placebo
| Study group | Role | What they receive |
|---|---|---|
| Drug VB0004 | Active comparator | Experimental, Single Ascending dose , Multiple Ascending dose in healthy subjects and naive patients with mild or moderate hypertension with low cardiovascular risk Receives: Drug: VB0004 |
| Placebo | Placebo comparator | Matching Placebo for VB0004 Receives: Other: Matching Placebo for VB0004 |
What is being measured
The primary outcome is the main question the study is designed to answer.
The occurrence and severity of treatment related adverse events as defined in CTCAE v4.0 to evaluate the safety and tolerability of VB0004 in healthy volunteers.
Adverse events observed during single ascending dose (SAD) and multiple ascending dose (MAD) studies
Measured: Upto Day 21 after each study vaccination
The occurrence and severity of treatment related adverse events as defined in CTCAE v4.0 which are observed during treatment with repeated doses of VB0004
Patients with mild to moderate hypertension (Blood pressure [BP] 140-15/90-99) will be used to evaluate the safety and tolerability of VB0004.
Measured: Upto Day 35 after each study vaccination
Secondary outcomes (3)
Calculation of the area under the plasma concentration-time curve for VB0004 to define the pharmacokinetic profile of VB0004 in healthy volunteers.
Both single and multiple doses of VB0004 will be used to define the pharmacokinetic profile of VB0004 from zero time to last measurable concentration
Measured: Up to Day 28
Calculation of the area under the plasma concentration-time curve for VB0004 to define the pharmacokinetic profile of VB0004 in patients with mild to moderate hypertension and low cardiovascular risk.
Both single and multiple doses of VB0004 will be used to define the pharmacokinetic profile of VB0004 from zero time to last measurable concentration
Measured: Up to Day 30
Comparison of the area under the plasma concentration-time curve for VB0004 in both fed and fasted states.
Both the fed and fasted states will be used to define whether food intake affects absorption and/or metabolism VB0004 from zero time to last measurable concentration
Measured: Up to Day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jun 2021
- Study start17 Jun 2021
- Primary completion16 Dec 2023 (estimated)
- Study completion23 Jan 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 88 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Syneos Health
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04925050
- Sponsor's protocol ID
- VB004-001
- Status last verified
- Feb 2023
- First submitted
- 21 May 2021
- Last updated
- 27 Feb 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/IB, First-Time-in-Human, Single Centre, Double-Blind, Randomized, Placebo-controlled, Dose Escalating Study of the Safety, Tolerability and Pharmacokinetics of Single and Repeat Doses of VB0004 Administered Orally to Healthy Volunteers; and to Patients With Mild to Moderate Hypertension With Low Cardiovascular Risk.
- ClinicalTrials.gov ID
- NCT04925050
- Acronym / sponsor ID
- VB004-001
- Conditions
- Hypertension
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 88 participants (estimated)
- Lead sponsor
- Syneos HealthUniversity, hospital or other
- Study start
- 17 Jun 2021 (actual)
- Primary completion
- 16 Dec 2023 (estimated)
- Study completion
- 23 Jan 2024 (estimated)
- First posted
- 14 Jun 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This will be a single center, Phase I/IB, randomized, double-blind, placebo-controlled, sequential SAD/MAD/FE study, with a patients arm.
The study will be divided into three parts:
Part A: SAD cohorts, with FE evaluation Part B: MAD cohorts with healthy volunteers Part C: MAD cohorts including naïve patients with mild to moderate hypertension and low cardiovascular risk The three parts will be completed sequentially or with partial overlapping.
Detailed description
Part A - SAD Cohorts 1 to 5:
Part 1 will consist of up to 5 cohorts (1 cohort per dose level). Each cohort will include 8 subjects (6 subjects receiving the active study drug and 2 subjects receiving matching placebo), for a total of 40 subjects. Efforts will be made to have gender-balanced cohorts. A staggered dosing schedule will be used for dosing of each cohort and will include 2 sentinel subjects (1 active and 1 placebo) dosed initially, and the remaining 6 subjects dosed at least 24 hours later. Following completion of each dose level, a Safety Monitoring Committee (SMC) will review the safety and tolerability data, as well as available PK data up to the Follow-Up Visit (Day 8), for at least 6 subjects in the respective cohort, in order to make decisions whether to escalate to the next dose level, decrease the next dose level, repeat a dose level, or to not evaluate any additional dose. The FE study will be conducted with 2 cohorts of 8 healthy participants from the SAD study. Subjects from FE Cohort 3 and, if needed, Cohort 4 will receive the study drug under both fasting (in a first period) and fed conditions (in a second period). There will be a washout period of at least 14 days between dosing of the fasting and the fed periods. Safety, tolerability, and PK data through at least to the Follow-Up Visit (Day 8), from a subsequent cohort will be reviewed by the SMC prior to dosing the fed period of FE Cohort. Therefore, the fed period of a FE Cohort could be dosed in parallel of the SAD Cohort receiving two doses higher. The planned SAD dose range is anticipated to be from 2 mg to 300 mg.
Part B - MAD Cohorts 6 to 8 (Healthy Volunteers):
Part B will consist of 3 cohorts (1 cohort per dose level). Each cohort will include 8 subjects (6 subjects receiving the study drug and 2 subjects receiving matching placebo daily for 14 consecutive days), for a total of 24 subjects. Efforts will be made to have gender-balanced cohorts. Part B can be initiated only following review of the safety, tolerability, and PK data following dosing of the SAD Cohort 3 or 4. A staggered dosing schedule might be used for the first dose level, including 2 sentinel subjects (1 active and 1 placebo) initiating dosing first and the remaining 6 subjects initiating dosing at least 24 hours later. Following completion of each dose level, a SMC will review the safety and tolerability data, as well as available PK data for at least 6 subjects in the respective cohort, in order to make decisions whether to escalate to the next dose level, decrease the next dose level, repeat a dose level, or to not evaluate any additional dose. The planned MAD dose range is anticipated to be from 10 mg to 100 mg administered q.d. for 14 consecutive days.
Part C - MAD Cohorts 9 and 10 (Patients with mild to moderate hypertension): Part C will consist of 2 cohorts (1 cohort per dose level). Each cohort will include a maximum of 8 patients with mild to moderate hypertension with low cardiovascular risk (6 subjects receiving the study drug and 2 subjects receiving matching placebo daily for 28 consecutive days), for a total of 16 patients. The doses of VB0004 administered will be determined by the SAD and MAD PK data. Following completion of Cohort 9, a SMC will review the safety and tolerability data, as well as available PK data for at least 6 subjects in the respective cohort, in order to make decisions whether to escalate to the next dose level, decrease the next dose level, repeat a dose level, or to not evaluate any additional dose.
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 |
|---|---|---|
| Drug VB0004 | Active comparator | Drug: VB0004Experimental, Single Ascending dose , Multiple Ascending dose in healthy subjects and naive patients with mild or moderate hypertension with low cardiovascular risk |
| Placebo | Placebo comparator | Other: Matching Placebo for VB0004Matching Placebo for VB0004 |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Male or female, non-smoker (no use of tobacco or nicotine products within 1 month prior to screening), ≥18 and ≤55 years of age, with BMI >18.0 and <32.0 kg/m2.
- Male subjects who are not vasectomized for at least 6 months, and who are sexually active with a female partner of childbearing potential (childbearing potential females are defined as women that are neither post-menopausal nor surgically sterile) must be willing to use one of the following acceptable contraceptive methods from (the first) study drug administration and for 90 days after (the last) study drug administration:
Key exclusion criteria (5 listed)
- Any laboratory test results deemed clinically significant by the Investigator or positive test for HIV, HBsAg, or HCV.
- Clinically significant ECG abnormalities or vital sign abnormalities (systolic BP lower than 90 or over 140 mmHg (except for hypertensive patients), diastolic BP lower than 40 or over 90 mmHg, HR less than 40 or over 100 bpm, or RR less than 10 or over 22 bpm) at screening.
- Orthostatic hypotension at Screening or Day -1 (Systolic BP falls > 20 mm Hg or Diastolic BP falls > 10 mm Hg on standing)
- History of significant alcohol abuse within 1 year prior to screening or regular use of alcohol within 6 months prior to the screening visit (more than 14 units of alcohol per week [1 unit = 375 mL of beer 3.5%, 100 mL of wine 13.5%, or 30 mL of distilled alcohol 40%]).
- Donation of plasma within 7 days prior to dosing. Donation or loss of blood (excluding volume drawn at screening) of 50 mL to 499 mL of blood within 30 days, or more than 499 mL within 56 days prior to the first dosing.
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 |
|---|---|---|
| VB0004Each study part (A,B and C) will be completed sequentially or with partial overlapping. Safety and PK data through at least day 8 from a subsequent cohort will be reviewed by the SMC prior to dosing the fed period of FE cohort. Safety data will be assessed by SMC after completing each cohorts in MAD healthy volunteers and MAD mild Hypertension patients. | Drug | Drug VB0004 |
| Matching Placebo for VB0004Matching Placebo | Other | Placebo |
Primary outcome
The occurrence and severity of treatment related adverse events as defined in CTCAE v4.0 to evaluate the safety and tolerability of VB0004 in healthy volunteers.
Time frame: Upto Day 21 after each study vaccination
Adverse events observed during single ascending dose (SAD) and multiple ascending dose (MAD) studies
The occurrence and severity of treatment related adverse events as defined in CTCAE v4.0 which are observed during treatment with repeated doses of VB0004
Time frame: Upto Day 35 after each study vaccination
Patients with mild to moderate hypertension (Blood pressure [BP] 140-15/90-99) will be used to evaluate the safety and tolerability of VB0004.
3 secondary outcomes
Calculation of the area under the plasma concentration-time curve for VB0004 to define the pharmacokinetic profile of VB0004 in healthy volunteers.
Time frame: Up to Day 28
Calculation of the area under the plasma concentration-time curve for VB0004 to define the pharmacokinetic profile of VB0004 in patients with mild to moderate hypertension and low cardiovascular risk.
Time frame: Up to Day 30
Comparison of the area under the plasma concentration-time curve for VB0004 in both fed and fasted states.
Time frame: Up to Day 28
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Feb 2023.
- Individual participant dataSharing planned: No
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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.
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing VB0004 in people with Hypertension, run by Syneos Health at 3 sites in Australia.
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 4 inclusion and 5 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: status not confirmed, as of the sponsor's last update on 27 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Australia. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Recruitment Officer (1800 243 733, Recruitment@nucleusnetwork.com.au), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The occurrence and severity of treatment related adverse events as defined in CTCAE v4.0 to evaluate the safety and tolerability of VB0004 in healthy volunteers. (time frame: Upto Day 21 after each study vaccination). The study lists 2 primary outcomes in all. 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 27 Feb 2023.