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HIVPhase 1UKHVCSpoke003NCT01922284

Investigating Immunisation Strategies of DNA, MVA and CN54rgp140 Adjuvanted With GLA-AF to Maximise Antibody Responses

A Phase 1 study testing DNA, MVA-C and CN54rgp140 in people with HIV, run by Imperial College London at 2 sites in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

UKHVC Spoke 003 is a randomised Phase I, two centre study which will explore the impact of shortening a vaccination regimen using deoxyribonucleic acid (DNA) (CN54ENV and ZM96GPN), Modified Vaccinia Ankara - C (MVA-C) and CN54rgp140 adjuvanted with glucopyranosyl lipid A adjuvant - aqueous form (GLA-AF). Read more about this study

Who is it for?
Ages 18 to 45 yearsHealthy volunteers can take part
Conditions the study is for
HIV
What is being tested?
DNA, MVA-C and CN54rgp140
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
2 sitesUnited Kingdom
Study dates
Jun 2013to Dec 2015
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 45 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • Man or woman aged between 18 and 45 years on the day of screening
  • Available for follow-up for the duration of the study (up to ~10 months from enrolment)
  • At low risk of HIV and willing to remain so for the duration of the study defined as:
  • 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
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  • no unprotected anal intercourse in the last six months, outside a relationship with a regular partner known to be HIV negative
  • no unprotected vaginal intercourse in the last six months outside a relationship with a regular known/presumed HIV negative partner
  • Willing to undergo an HIV test
  • Willing to undergo a genital infection screen if indicated by sexual history
  • If heterosexually active female, using an effective method of contraception with partner other than an IUCD/IUS (combined oral contraceptive pill; injectable or implanted contraceptive; consistent record with condoms if using these; physiological or anatomical sterility in self or partner) from 14 days prior to the first vaccination until 4 months after the last, and willing to undergo urine pregnancy tests prior to each vaccination
  • If heterosexually active male, using an effective method of contraception with their partner from the first day of vaccination until 4 months after the last vaccination
  • Agree to abstain from donating blood for three months after the end of their participation in the trial, or longer if necessary
  • Registered with a general practitioner (GP) for at least the past three months
  • Satisfactory response received from GP before randomisation
  • Willing and able to give written informed consent

Who cannot join

  • Pregnant or lactating
  • Presence of an IUCD (intrauterine contraceptive device)/IUS (intrauterine system)
  • Clinically relevant abnormality on history or examination including
  • history of grand-mal epilepsy, seizure disorder or any history of prior seizure
  • severe eczema
  • liver disease with inadequate hepatic function
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  • any skin condition which may interfere with the trial assessment on the injection site
  • haematological, metabolic, gastrointestinal or cardio-pulmonary disorders
  • uncontrolled infection; toxic shock syndrome; autoimmune disease, immunodeficiency or use of immunosuppressives in preceding 3 months
  • 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 the major circumference of the arm, not resolving within 72 hours
  • general: fever >= 39.5°C 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 14 days of enrolment
  • Receipt of an experimental vaccine containing HIV antigens at any time in the past
  • Receipt of blood products or immunoglobin within 4 months of screening
  • Participation 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 hepatitis B surface antigen, hepatitis C antibody or serology indicating active syphilis requiring treatment
  • Grade 1 or above routine laboratory parameters. Hyperbilirubinaemia to be considered an exclusion criterion only when confirmed to be conjugated bilirubinaemia
  • Unable to read and speak English to a fluency level adequate for the full comprehension of procedures required in participation and consent.
  • Unlikely to comply with protocol

Trial locations and contacts

2 sites in 1 country.

United Kingdom2 sites

  • Imperial College London

    Greater London, W2 1PG

  • Surrey Clinical Research Centre, University of Surrey

    Guildford, Surrey, GU2 7XP

Other trials in United Kingdom

About this study

Official title: A Phase I Clinical Trial Investigating Immunisation Strategies Using DNA, MVA and CN54rgp140 Adjuvanted With GLA-AF to Maximise Antibody Responses

UKHVC Spoke 003 is a randomised Phase I, two centre study which will explore the impact of shortening a vaccination regimen using deoxyribonucleic acid (DNA) (CN54ENV and ZM96GPN), Modified Vaccinia Ankara - C (MVA-C) and CN54rgp140 adjuvanted with glucopyranosyl lipid A adjuvant - aqueous form (GLA-AF). The study population will be 40 healthy male and female volunteers 18 to 45 years old who are at low risk of HIV infection are to be recruited.

Study participants will be immunised with trial immunogens:

Read more
  • 8mg DNA: one plasmid encoding a gag-pol-nef polypeptide derived from the 96ZM651-8 clone and one plasmid encoding gp140 env derived from clade C 97CN54
  • 1.108 TCID50 MVA-C (nominal titre) expressing the gag-pol-nef and gp120 env proteins derived from clade-C 97CN54
  • 100ug CN54rgp140, a trimeric recombinant envelope protein derived from clade C 97CN54
  • 5ug GLA-AF, an aqueous glucopyranosyl lipid A adjuvant

All immunisations will be administered by the intramuscular route (IM). CN54gp140 and GLA will be mixed together before administration, and immunogens will be delivered in combination regimens

Read the detailed description

This is a phase I study exploring the safety and potency of five HIV vaccines in healthy volunteers. The main aim is to see whether three of the five vaccines can be given together rather than one after the other, in five rather than seven sets of vaccinations and a course shortened by eight weeks. All volunteers will receive three injections of the first two vaccines (DNA plasmids) and half will be randomly assigned to receive two injections each of the second (MVA-C) and subsequent vaccines (CN54rgp140 mixed with GLA-AF) during the same visit or two injections of the MVA-C followed by two of CN54rgp140 mixed with GLA-AF.

The investigators are interested in ensuring that the vaccines are safe and also that the immune responses in the two groups of volunteers are similar. The three vaccines have all been shown to stimulate the immune response to specific parts of the HIV virus and none are infectious. The first vaccine consists of two DNA plasmids. When injected into muscle cells small parts of the HIV virus which are encoded by the DNA are produced and these are then recognised by the immune system. The second vaccine MVAC, is derived from vaccinia virus which has been modified so that it cannot divide. The virus (Modified Vaccinia Ankara (MVA)) actually expresses the same portions of HIV as the DNA and results in amplification of the responses seen. The third vaccine is a synthetically produced component of the HIV viral outer coat and it will be administered with an additive which has been shown to greatly enhance particular types of immune response which have recently been shown to play a role in protection against infection

Conditions
HIV
Being tested
DNA, MVA-C, CN54rgp140, GLA-AF
Keywords
HIV, Vaccine, Immunisation, DNA, Adverse events, MVA-C, GLA-AF, Antibody

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DNABiological

    8mg DNA: one plasmid encoding a gag-pol-nef polypeptide derived from the 96ZM651-8 clone and one plasmid encoding gp140 env derived from clade C 97CN54

  • MVA-CBiological

    1.108 TCID50 MVA-C (nominal titre) expressing the gag-pol-nef and gp120 env proteins derived from clade C 97CN54

  • CN54rgp140Biological

    100ug CN54rgp140, a trimeric recombinant envelope protein derived from clade C 97CN54

  • GLA-AFBiological

    5ug GLA-AF, an aqueous glucopyranosyl lipid A adjuvant

Study groups in NCT01922284
Study groupRoleWhat they receive
Group 1 - Combination armExperimentalAll participants will receive DNA vaccines at 0,4 and 8 weeks. These will be administered in 2 separate injections of 1ml (CN54ENV into the muscle of the upper right arm and ZM96GPN into the muscle of upper left arm). Participants in group 1 will receive 5 immunisations (DNA, MVA and CN54rgp140 in GLA-AF vaccines) at weeks 0, 4, 8 16 and 20. At weeks 16 and 20, individuals in group 1 will be given MVAC in a volume of 0.5mls into the upper left arm and also 100ug CN54rgp140 mixed with 5ug GLA-AF in a total volume of 0.4mls into the muscle of the upper right arm.
Receives: Biological: DNA; Biological: MVA-C; Biological: CN54rgp140; Biological: GLA-AF
Group 2 - Non-combination armActive comparatorAll participants will receive DNA vaccines at 0,4 and 8 weeks. These will be administered in 2 separate injections of 1ml (CN54ENV into the muscle of the upper right arm and ZM96GPN into the muscle of upper left arm). Participants in group 2 will receive 7 immunisations (DNA, MVA and CN54rgp140 in GLA-AF vaccines) at weeks 0, 4, 8, 16, 20, 24 and 28. At weeks 16 \& 20 group 2 will receive only 0.5mls of MVAC into the muscle of the upper left arm. At weeks 24 and 28 they will receive injections of 100ug CN54rgp140 mixed with 5ugGLAAF in a total volume of 0.4mls into the muscle of the upper right arm.
Receives: Biological: DNA; Biological: MVA-C; Biological: CN54rgp140; Biological: GLA-AF

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Magnitude of antibody response

    Magnitude (reciprocal mean endpoint titre and concentration) of systemic Immunoglobulin G (IgG) binding antibody responses to CN54rgp140 measured four weeks after the final immunisation.

    Measured: Four weeks after final immunisation

  2. Adverse Events

    Grade 3 or above local solicited adverse event Grade 3 or above systemic clinical and laboratory solicited adverse event Any grade of adverse event that results in a clinical decision to discontinue further immunisations

    Measured: Every four weeks up to 32 weeks

Secondary outcomes (5)

  1. Magnitude of neutralising antibody (Nab) responses

    Confirmation of specific investigations will be provided at a later date.

    Measured: Four weeks after the final immunisation

  2. Magnitude of T-cell and B-cell responses

    Confirmation of specific investigations will be provided at a later date.

    Measured: Four weeks after the final immunisation

  3. Magnitude of mucosal IgG and IgA antibody responses

    Confirmation of specific investigations will be provided at a later date.

    Measured: Four weeks after the final immunisation

  4. Magnitude of antibody-dependent cell-mediated cytotoxicity or Antibody-dependent cell-mediated viral inhibition

    Confirmation of specific investigations will be provided at a later date.

    Measured: From first immunisation

  5. Magnitude of systemic Immunoglobulin A (IgA) binding antibody responses

    Confirmation of specific investigations will be provided at a later date.

    Measured: Four weeks after the final immunisation

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Aug 2013 (estimated)
  2. Study startJun 2013
  3. Primary completionJan 2014
  4. Study completionDec 2015

Resources

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
None (open label)
Enrolment
40 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01922284
Sponsor's protocol ID
CRO2059
Other IDs
2012-003277-26
Acronym
UKHVCSpoke003
Status last verified
Aug 2013
First submitted
10 Jul 2013
Last updated
27 Sep 2016
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing DNA, MVA-C and CN54rgp140 in people with HIV, run by Imperial College London at 2 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 16 inclusion and 22 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 27 Sep 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 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. 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Magnitude of antibody response (time frame: Four weeks after final immunisation). 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?

On the ClinicalTrials.gov record for NCT01922284.

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 Sep 2016.

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