Human Immunodeficiency VirusPhase 1Ad4HIVNCT03408262
Clinical Trial of HIV Vaccine Combinations in Healthy Men and Women
A Phase 1 study testing Ad4-EnvCN54, MVA-CN54 and CN54gp140/MPLA in people with Human Immunodeficiency Virus, run by Imperial College London at 1 site in United Kingdom.
Trial summary
A Phase I Single-Blind randomised trial investigating immunisation strategies using Ad4-EnvCN54, MVA-CN54 and CN54gp140/MPLA combinations in order to maximise antibody responses to Human Immunodeficiency Virus Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Human Immunodeficiency Virus
- What is being tested?
- Ad4-EnvCN54, MVA-CN54 and CN54gp140/MPLA
- Type of treatment
- Vaccines, Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 68 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 6 Oct 2017to 10 Feb 2020
- Phase
- Phase 1
- 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 18 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Men and women aged between 18 and 50 years on the day of screening
- BMI between 18-30
- Seronegative for Adenovirus 4 serum neutralising antibodies
- Available for follow-up for the duration of the study
- Willing and able to give written informed consent
- At low risk of HIV infection and willing to remain so for the duration of the study defined as:
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- no history of injecting drug use in the previous ten years
- no gonorrhoea or syphilis in the last six months
- no high risk partner (e.g. injecting drug use, HIV positive partner) either currently or within the past six months
- no unprotected anal or vaginal intercourse in the last six months, outside a relationship with a regular partner known to be HIV negative
- Willing to undergo HIV testing
- Willing to undergo a STI screen for chlamydia, gonorrhoea and syphilis
- Must agree to require male sexual partner to use condoms, from at least 14 days before the first vaccination until at least 4 months after the last
- If heterosexually active female capable of becoming pregnant, must (in addition to requiring male partner to use condoms) agree to use hormonal contraception, or to complete abstinence, from at least 30 days before the first vaccination until at least 4 months after the last. [Note: Acceptable hormonal contraception is combined (estrogen and progestogen containing) or progestogen-only hormonal contraception associated with inhibition of ovulation. Complete abstinence can be used, when in line with the preferred and usual lifestyle of the subject. Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, lactational amenorrhoea method, and IUD/IUS are not acceptable methods of contraception.]
- If sexually active male, must agree to use condoms from the day of first vaccination until at least 4 months after the last. [Note: Additional use of an effective method of contraception is recommended for any non-pregnant female partner over the same period.]
- Agree to abstain from donating blood, eggs or sperm from the day of first vaccination until at least 3 months after the end of their participation in the trial
- Registered with a GP for at least the past month
- Entered and clearance obtained from The Overvolunteering Prevention System (TOPS) database
Who cannot join
- Are pregnant or breast feeding, or living with anyone under the age of 5 years old or over 75 years old
- Have close contact with an immunocompromised individual thought to be at clinical risk from Adenovirus infection
- Clinically relevant abnormality on history or examination including:
- Liver disease with inadequate hepatic function
- Any skin condition which may interfere with the trial assessment of the injection sites
- Haematological, metabolic, gastrointestinal or cardio-pulmonary disorders
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- Uncontrolled infection; autoimmune disease, immunodeficiency
- Known hypersensitivity to any component of the vaccine formulations used in this trial, or have severe or multiple allergies to drugs or pharmaceutical agents
- History of severe local or general reaction to vaccination defined as
- Local: extensive, indurated redness and swelling involving most of the antero-lateral thigh or the arm, not resolving within 72 hours
- General: fever ≥39.5oC within 48 hours; anaphylaxis; bronchospasm; laryngeal oedema; collapse; convulsions or encephalopathy within 72 hours
- Receipt of live attenuated vaccine within 60 days or other vaccine within 30 days of enrolment
- Receipt of an experimental vaccines containing HIV antigens, Ad4 and MVA-C products at any time in the past
- Receipt of blood products or immunoglobin within 4 months of screening, or drugs that suppress the immune system, such as steroids (including inhaled steroids, excluding topical steroids unless applied to the upper arm), in the preceding 3 months
- Participating in another trial of a medicinal product, completed less than 30 days prior to enrolment
- HIV 1 or 2 positive or indeterminate on screening
- Positive for antibodies to hepatitis B surface antigen, hepatitis C antibody or serology indicating active syphilis requiring treatment
- Clinically significant positive reaction in antinuclear antibody screen or clinically significant immunoglobulin (IgA, IgG or IgM) values
- Grade 1 or above clinically significant routine laboratory parameters
- Unable to read and/or speak English to a fluency level adequate for the full comprehension of procedures required in participation and consent
- Women with a history of toxic shock syndrome
- Women using an intrauterine device for contraception (as incompatible with softcup sampling)
- Any other significant disease, disorder or finding which may significantly increase the risk to the volunteer because of participation in the study, affect the ability of the volunteer to participate in the study or impair interpretation of the study data
- Unlikely to comply with protocol
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
NIHR Imperial Clinical Research Facility
London, W12 0HS
About this study
Official title: A Phase I Single-Blind Randomised Trial Investigating Immunisation Strategies Using Ad4-EnvCN54, MVA-CN54 and CN54gp140/MPLA Combinations in Order to Maximise Antibody Responses to Human Immunodeficiency Virus
A Phase I Single-Blind randomised trial investigating immunisation strategies using Ad4-EnvCN54, MVA-CN54 and CN54gp140/MPLA combinations in order to maximise antibody responses to Human Immunodeficiency Virus
Read the detailed description
This is a randomised two-part Phase I study which will explore the impact of different boosting options (MVA-CN54 and recombinant CN54gp140 protein) for oral Adenovirus serotype 4 vector prime expressing HIV-1 CN54 envelope (Ad4-EnvCN54) designed to optimize systemic and mucosal antibody responses.
Part 1 is exploratory and designed to select conditions capable of promoting enhanced systemic and mucosal B cell responses in a limited number of participants.
Part 2 is dependent upon Part 1 and is designed to study groups selected on performance in part 1 in an expanded number of subjects. Data from both stages will be combined for safety and immunological analyses.
- Conditions
- Human Immunodeficiency Virus
- Being tested
- Ad4-EnvCN54, MVA-CN54, CN54gp140/MPLA
- Medical subject headings
- Acquired Immunodeficiency Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ad4-EnvCN54Biological
Live, replication-competent adenovirus 4 vector, engineered to express the envelope glycoprotein of HIV-1 isolate 97CN54
MVA-CN54Biological
Live, non-replicating modified vaccinia Ankara vector, engineered to express the envelope glycoprotein of HIV-1 isolate 97CN54
CN54gp140/MPLABiological
Also called CN54-M
Recombinant glycoprotein of HIV-1 isolate 97CN54, with liposomal monophosphoryl lipid A adjuvant
| Study group | Role | What they receive |
|---|---|---|
| Group A | Active comparator | Month 0: oral placebo Month 3: oral placebo + I.M. CN54gp140/MPLA + I.M. placebo Month 6: oral placebo + I.M. CN54gp140/MPLA + I.M. placebo Receives: Biological: CN54gp140/MPLA |
| Group B | Experimental | Month 0: Ad4-EnvCN54 Month 3: oral placebo + I.M. CN54gp140/MPLA + I.M. placebo Month 6: oral placebo + I.M. CN54gp140/MPLA + I.M. placebo Receives: Biological: Ad4-EnvCN54; Biological: CN54gp140/MPLA |
| Group C | Experimental | Month 0: Ad4-EnvCN54 Month 3: Ad4-EnvCN54 + I.M. CN54gp140/MPLA + I.M. placebo Month 6: oral placebo + I.M. CN54gp140/MPLA + I.M. placebo Receives: Biological: Ad4-EnvCN54; Biological: CN54gp140/MPLA |
| Group D | Experimental | Month 0: Ad4-EnvCN54 Month 3: Ad4-EnvCN54 + I.M. CN54gp140/MPLA + I.M. placebo Month 6: Ad4-EnvCN54 + I.M. CN54gp140/MPLA + I.M. placebo Receives: Biological: Ad4-EnvCN54; Biological: CN54gp140/MPLA |
| Group E | Active comparator | Month 0: oral placebo Month 3: oral placebo + I.M. CN54gp140/MPLA + I.M. MVA-CN54 Month 6: oral placebo + I.M. CN54gp140/MPLA + I.M. MVA-CN54 Receives: Biological: MVA-CN54; Biological: CN54gp140/MPLA |
| Group F | Experimental | Month 0: Ad4-EnvCN54 Month 3: oral placebo + I.M. CN54gp140/MPLA + I.M. MVA-CN54 Month 6: oral placebo + I.M. CN54gp140/MPLA + I.M. MVA-CN54 Receives: Biological: Ad4-EnvCN54; Biological: MVA-CN54; Biological: CN54gp140/MPLA |
| Group G | Experimental | Month 0: Ad4-EnvCN54 Month 3: Ad4-EnvCN54 + I.M. CN54gp140/MPLA + I.M. MVA-CN54 Month 6: oral placebo + I.M. CN54gp140/MPLA + I.M. MVA-CN54 Receives: Biological: Ad4-EnvCN54; Biological: MVA-CN54; Biological: CN54gp140/MPLA |
| Group H | Experimental | Month 0: Ad4-EnvCN54 Month 3: Ad4-EnvCN54 + I.M. CN54gp140/MPLA + I.M. MVA-CN54 Month 6: Ad4-EnvCN54 + I.M. CN54gp140/MPLA + I.M. MVA-CN54 Receives: Biological: Ad4-EnvCN54; Biological: MVA-CN54; Biological: CN54gp140/MPLA |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Mucosal Binding IgG Antibodies to HIV CN54gp140 Antigen
Number of participants with mucosal (semen, nasal, vaginal or rectal) binding IgG antibodies to HIV CN54gp140 antigen, as determined by ELISA
Measured: At two weeks after the final immunisation
Number of Participants With Severe or Greater (Grades 3-4) Adverse Reactions During the Study
Number of Participants With Severe or Greater (Grades 3-4) Adverse Reactions up to twenty-four weeks after the final immunisation
Measured: Up to twenty-four weeks after the final immunisation
Median Concentration of CN54-gp140 Specific IgG Binding Antibodies
Median concentration of CN54-gp140 specific IgG binding antibodies, as measured by ELISA. Concentration is in ng/mL
Measured: At two weeks after the final immunisation
Secondary outcomes (1)
Number of Participants With Detectable Serum Binding Antibodies to HIV CN54gp140 Antigen
Number of participants with detectable serum binding antibodies to HIV CN54gp140 antigen, as measured by IgG binding ELISA
Measured: At two weeks post-final immunisation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jan 2018
- Study start6 Oct 2017
- Primary completion10 Feb 2020
- Study completion10 Feb 2020
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 Human Immunodeficiency VirusStudies of the same condition, open and under way.
- More trials run by Imperial College LondonThe sponsor's other registered studies.
- 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 68 participants (actual)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- David Lewis, MD, Principal investigator, Imperial College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03408262
- Sponsor's protocol ID
- Ad4HIV
- Acronym
- Ad4HIV
- Status last verified
- Oct 2024
- First submitted
- 5 Jan 2018
- Last updated
- 16 Oct 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Single-Blind Randomised Trial Investigating Immunisation Strategies Using Ad4-EnvCN54, MVA-CN54 and CN54gp140/MPLA Combinations in Order to Maximise Antibody Responses to Human Immunodeficiency Virus
- ClinicalTrials.gov ID
- NCT03408262
- Acronym / sponsor ID
- Ad4HIV / Ad4HIV
- Conditions
- Human Immunodeficiency Virus
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 68 participants (actual)
- Lead sponsor
- Imperial College LondonUniversity, hospital or other
- Study start
- 6 Oct 2017 (actual)
- Primary completion
- 10 Feb 2020 (actual)
- Study completion
- 10 Feb 2020 (actual)
- First posted
- 23 Jan 2018 (actual)
- Results
- Posted 16 Oct 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A Phase I Single-Blind randomised trial investigating immunisation strategies using Ad4-EnvCN54, MVA-CN54 and CN54gp140/MPLA combinations in order to maximise antibody responses to Human Immunodeficiency Virus
Detailed description
This is a randomised two-part Phase I study which will explore the impact of different boosting options (MVA-CN54 and recombinant CN54gp140 protein) for oral Adenovirus serotype 4 vector prime expressing HIV-1 CN54 envelope (Ad4-EnvCN54) designed to optimize systemic and mucosal antibody responses.
Part 1 is exploratory and designed to select conditions capable of promoting enhanced systemic and mucosal B cell responses in a limited number of participants.
Part 2 is dependent upon Part 1 and is designed to study groups selected on performance in part 1 in an expanded number of subjects. Data from both stages will be combined for safety and immunological analyses.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 8
| Arm | Type | Receives |
|---|---|---|
| Group A | Active comparator | Biological: CN54gp140/MPLAMonth 0: oral placebo Month 3: oral placebo + I.M. CN54gp140/MPLA + I.M. placebo Month 6: oral placebo + I.M. CN54gp140/MPLA + I.M. placebo |
| Group B | Experimental | Biological: Ad4-EnvCN54, Biological: CN54gp140/MPLAMonth 0: Ad4-EnvCN54 Month 3: oral placebo + I.M. CN54gp140/MPLA + I.M. placebo Month 6: oral placebo + I.M. CN54gp140/MPLA + I.M. placebo |
| Group C | Experimental | Biological: Ad4-EnvCN54, Biological: CN54gp140/MPLAMonth 0: Ad4-EnvCN54 Month 3: Ad4-EnvCN54 + I.M. CN54gp140/MPLA + I.M. placebo Month 6: oral placebo + I.M. CN54gp140/MPLA + I.M. placebo |
| Group D | Experimental | Biological: Ad4-EnvCN54, Biological: CN54gp140/MPLAMonth 0: Ad4-EnvCN54 Month 3: Ad4-EnvCN54 + I.M. CN54gp140/MPLA + I.M. placebo Month 6: Ad4-EnvCN54 + I.M. CN54gp140/MPLA + I.M. placebo |
| Group E | Active comparator | Biological: MVA-CN54, Biological: CN54gp140/MPLAMonth 0: oral placebo Month 3: oral placebo + I.M. CN54gp140/MPLA + I.M. MVA-CN54 Month 6: oral placebo + I.M. CN54gp140/MPLA + I.M. MVA-CN54 |
| Group F | Experimental | Biological: Ad4-EnvCN54, Biological: MVA-CN54, Biological: CN54gp140/MPLAMonth 0: Ad4-EnvCN54 Month 3: oral placebo + I.M. CN54gp140/MPLA + I.M. MVA-CN54 Month 6: oral placebo + I.M. CN54gp140/MPLA + I.M. MVA-CN54 |
| Group G | Experimental | Biological: Ad4-EnvCN54, Biological: MVA-CN54, Biological: CN54gp140/MPLAMonth 0: Ad4-EnvCN54 Month 3: Ad4-EnvCN54 + I.M. CN54gp140/MPLA + I.M. MVA-CN54 Month 6: oral placebo + I.M. CN54gp140/MPLA + I.M. MVA-CN54 |
| Group H | Experimental | Biological: Ad4-EnvCN54, Biological: MVA-CN54, Biological: CN54gp140/MPLAMonth 0: Ad4-EnvCN54 Month 3: Ad4-EnvCN54 + I.M. CN54gp140/MPLA + I.M. MVA-CN54 Month 6: Ad4-EnvCN54 + I.M. CN54gp140/MPLA + I.M. MVA-CN54 |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (18 listed)
- Men and women aged between 18 and 50 years on the day of screening
- BMI between 18-30
- Seronegative for Adenovirus 4 serum neutralising antibodies
- Available for follow-up for the duration of the study
- Willing and able to give written informed consent
Key exclusion criteria (24 listed)
- Are pregnant or breast feeding, or living with anyone under the age of 5 years old or over 75 years old
- Have close contact with an immunocompromised individual thought to be at clinical risk from Adenovirus infection
- Clinically relevant abnormality on history or examination including:
- Known hypersensitivity to any component of the vaccine formulations used in this trial, or have severe or multiple allergies to drugs or pharmaceutical agents
- History of severe local or general reaction to vaccination defined as
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 |
|---|---|---|
| Ad4-EnvCN54Live, replication-competent adenovirus 4 vector, engineered to express the envelope glycoprotein of HIV-1 isolate 97CN54 | Biological | Group B, Group C, Group D, Group F, Group G, Group H |
| MVA-CN54Live, non-replicating modified vaccinia Ankara vector, engineered to express the envelope glycoprotein of HIV-1 isolate 97CN54 | Biological | Group E, Group F, Group G, Group H |
| CN54gp140/MPLAAlso: CN54-MRecombinant glycoprotein of HIV-1 isolate 97CN54, with liposomal monophosphoryl lipid A adjuvant | Biological | Group A, Group B, Group C, Group D, Group E, Group F, Group G, Group H |
Primary outcome
Number of Participants With Mucosal Binding IgG Antibodies to HIV CN54gp140 Antigen
Time frame: At two weeks after the final immunisation
Number of participants with mucosal (semen, nasal, vaginal or rectal) binding IgG antibodies to HIV CN54gp140 antigen, as determined by ELISA
Number of Participants With Severe or Greater (Grades 3-4) Adverse Reactions During the Study
Time frame: Up to twenty-four weeks after the final immunisation
Number of Participants With Severe or Greater (Grades 3-4) Adverse Reactions up to twenty-four weeks after the final immunisation
Median Concentration of CN54-gp140 Specific IgG Binding Antibodies
Time frame: At two weeks after the final immunisation
Median concentration of CN54-gp140 specific IgG binding antibodies, as measured by ELISA. Concentration is in ng/mL
1 secondary outcome
Number of Participants With Detectable Serum Binding Antibodies to HIV CN54gp140 Antigen
Time frame: At two weeks post-final immunisation
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Oct 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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.
David Lewis, MD principal investigator
Imperial College London
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Ad4-EnvCN54, MVA-CN54 and CN54gp140/MPLA in people with Human Immunodeficiency Virus, run by Imperial College London at 1 site 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 18 inclusion and 24 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: finished, as of the sponsor's last update on 16 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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. 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?
Yes. Results are posted in the registry (first posted 16 Oct 2024). 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?
Number of Participants With Mucosal Binding IgG Antibodies to HIV CN54gp140 Antigen (time frame: At two weeks after the final immunisation). The study lists 3 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 16 Oct 2024.