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Modelling the Interaction Between Rationally-designed Synthetic Model Viral Protein Immunogens (EAVI2020_01)

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ClinicalTrials.gov Identifier: NCT03816137
Recruitment Status : Recruiting
First Posted : January 25, 2019
Last Update Posted : August 1, 2019
Sponsor:
Information provided by (Responsible Party):
Imperial College London

Brief Summary:

EVAI2020_01 is a single blinded two part experimental medicine study to determine the extent to which different prime-boost combinations of model immunogens based on HIV-1 envelope proteins (ConM and ConS), influence the breadth of viruses neutralised by induced antibodies and the associated diversity of B and T cell responses.

Our research will investigate the effect of a second immunisation challenge with a combination of three model mosaic envelope proteins designed to increase the breadth of induced antibody neutralisation.

The primary outcome will be measurement of specific viral neutralisation activity of serum antibodies. Exploratory outcomes will include characterisation of blood B and T cell responses to these model immunogens.


Condition or disease Intervention/treatment Phase
HIV-1-infection Biological: ConM SOSIP Biological: EDC ConM SOSIP Biological: ConS UFO Biological: EDC ConS UFO Biological: Mosaic SOSIPs Phase 1

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: This is a single-blind study with volunteers being randomised into five groups of n=10 (Groups A-E) stratified by gender
Masking: Double (Participant, Investigator)
Masking Description: Volunteers will be blinded to their treatment regimes, and laboratory teams undertaking immunological analysis will be blinded to group and dosing regimen to prevent in-house analysis bias. The clinical team will remain un-blinded throughout.
Primary Purpose: Prevention
Official Title: An Experimental Medicine Study Modelling the Interaction Between Rationally-designed Synthetic Model Viral Protein Immunogens and the Breadth of the Induced B and T Cell Repertoires.
Actual Study Start Date : March 19, 2019
Estimated Primary Completion Date : August 15, 2019
Estimated Study Completion Date : March 30, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Active Comparator: ConM SOSIP and Mosaic SOSIPs

ConM SOSIP 100g Intramuscular injections into the left or right arm Administered at 0, 3 and 6 months

Mosaic SOSIPs 100ug (3x33ug) Intramuscular injections into the left or right arm Administered at 12 months only

Biological: ConM SOSIP
Recombinant HIV-1 trimeric gp140 Env protein: ConM SOSIP gp140. Model immunogens will be used at the dosage of 100 ug and will be admixed with 500 ug MPLA formulated in liposomes and administered by intramuscular injection into the left or right deltoid muscle.

Biological: Mosaic SOSIPs

Mosaic gp140 Env trimers designed to overcome the immunodominance of hypervariable regions of Env

The immunogen will be used at the dosage of 100 ug (3x33ug) and will be admixed with 500 ug MPLA formulated in liposomes and administered by intramuscular injection into the left or right deltoid muscle.


Active Comparator: EDC ConM SOSIP and Mosaic SOSIPs

EDC ConM SOSIP 100G Intramuscular injections into the left or right arm Administered at 0, 3 and 6 months

Mosaic SOSIPs 100ug (3x33ug) Intramuscular injections into the left or right arm Administered at 12 months only

Biological: EDC ConM SOSIP
Chemically fixed version of recombinant HIV-1 trimeric gp140 Env: EDC-ConM SOSIP. Model immunogens will be used at the dosage of 100 ug and will be admixed with 500 ug MPLA formulated in liposomes and administered by intramuscular injection into the left or right deltoid muscle.

Biological: Mosaic SOSIPs

Mosaic gp140 Env trimers designed to overcome the immunodominance of hypervariable regions of Env

The immunogen will be used at the dosage of 100 ug (3x33ug) and will be admixed with 500 ug MPLA formulated in liposomes and administered by intramuscular injection into the left or right deltoid muscle.


Active Comparator: ConS UFO and Mosaic SOSIPs

ConS UFO 100g Intramuscular injections into the left or right arm Administered at 0, 3 and 6 months

Mosaic SOSIPs 100ug (3x33ug) Intramuscular injections into the left or right arm Administered at 12 months only

Biological: ConS UFO
Recombinant HIV-1 trimeric gp140 Env protein: ConS UFO gp140. Model immunogens will be used at the dosage of 100 ug and will be admixed with 500 ug MPLA formulated in liposomes and administered by intramuscular injection into the left or right deltoid muscle

Biological: Mosaic SOSIPs

Mosaic gp140 Env trimers designed to overcome the immunodominance of hypervariable regions of Env

The immunogen will be used at the dosage of 100 ug (3x33ug) and will be admixed with 500 ug MPLA formulated in liposomes and administered by intramuscular injection into the left or right deltoid muscle.


Active Comparator: EDC ConS UFO and Mosaic SOSIPs

EDC ConS UFO 100g Intramuscular injections into the left or right arm Administered at 0, 3 and 6 months

Mosaic SOSIPs 100ug (3x33ug) Intramuscular injections into the left or right arm Administered at 12 months only

Biological: EDC ConS UFO
Chemically fixed version of recombinant HIV-1 trimeric gp140 Env : EDC-ConS UFO. Model immunogens will be used at the dosage of 100 ug and will be admixed with 500 ug MPLA formulated in liposomes and administered by intramuscular injection into the left or right deltoid muscle.

Biological: Mosaic SOSIPs

Mosaic gp140 Env trimers designed to overcome the immunodominance of hypervariable regions of Env

The immunogen will be used at the dosage of 100 ug (3x33ug) and will be admixed with 500 ug MPLA formulated in liposomes and administered by intramuscular injection into the left or right deltoid muscle.


Active Comparator: ConS UFO and ConM SOSIPs and Mosaic SOSIPs

ConS UFO 100g Intramuscular injections into the left or right arm Administered at 0 and 3 months

ConM SOSIP Administered at 12 months

Mosaic SOSIPs 100ug (3x33ug) Intramuscular injections into the left or right arm Administered at 12 months only

Biological: EDC ConM SOSIP
Chemically fixed version of recombinant HIV-1 trimeric gp140 Env: EDC-ConM SOSIP. Model immunogens will be used at the dosage of 100 ug and will be admixed with 500 ug MPLA formulated in liposomes and administered by intramuscular injection into the left or right deltoid muscle.

Biological: ConS UFO
Recombinant HIV-1 trimeric gp140 Env protein: ConS UFO gp140. Model immunogens will be used at the dosage of 100 ug and will be admixed with 500 ug MPLA formulated in liposomes and administered by intramuscular injection into the left or right deltoid muscle

Biological: Mosaic SOSIPs

Mosaic gp140 Env trimers designed to overcome the immunodominance of hypervariable regions of Env

The immunogen will be used at the dosage of 100 ug (3x33ug) and will be admixed with 500 ug MPLA formulated in liposomes and administered by intramuscular injection into the left or right deltoid muscle.





Primary Outcome Measures :
  1. Neutralising antibodies [ Time Frame: 6 Months ]
    Serum titres of neutralising antibodies to virus expressing ConM and ConS envelopes

  2. Viral expression of Mosaic envelopes (1-3) [ Time Frame: 12 Months ]
    Serum titres of neutralising antibodies to virus expressing Mosaic envelopes (1-3)


Secondary Outcome Measures :
  1. Binding antibodies in serum [ Time Frame: 18 Months ]
    Measurement of the magnitude and phenotype of B cell (plasmablast and memory B cells) and T cell responses (CD4 and CD8) in peripheral blood mononuclear cells (PBMC)

  2. Paxgene blood transcriptomics [ Time Frame: 18 Months ]
    Paxgene tubes for blood transcriptomics will be collected only from group A



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 1. Healthy male and female volunteers aged between 18 and 55 years. 2. Available for ALL follow-up visits for the duration of the study. 3. Entered and clearance obtained from The Over volunteering Prevention System (TOPS) database (to avoid impact of any co-administered investigational products or treatments on our outcomes).

    4. Women capable of becoming pregnant willing to take hormonal contraception for the duration of the study.

    5. Willing and able to give written informed consent.

Exclusion Criteria:

  • 1. History of any medical, psychological or other condition, clinically significant laboratory result at screening, or use of any medications which, in the opinion of the investigators, would interfere with the study objectives or volunteers safety.

    2. HIV-1 or HIV-2 antibody positive or indeterminate upon screening, or history of receipt of Env-based HIV immunogens (which would render the volunteers non-naive to the model immunogens).

    3. Unable to read and/or speak English to a fluency level adequate for the full comprehension of study procedures and consent.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03816137


Contacts
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Contact: Aleisha N Miller, PhD 0207 594 9717 aleisha.miller1@imperial.ac.uk
Contact: Tom Cole, PhD 0203 313 6198 tom.cole@nhs.net

Locations
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United Kingdom
NIHR Imperial Clinical Resarch Facility Recruiting
London, United Kingdom, W12 0HS
Contact: Aleisha Miller, PhD    0207 597 9717    aleisha.miller1@imperial.acuk   
Contact: Tom Cole, PhD    0203 313 6198    tom.cole@nhs.net   
Principal Investigator: Federica Borghese, MD         
Sponsors and Collaborators
Imperial College London
Investigators
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Principal Investigator: Federica Borghese Imperial College Healthcare NHS Trust

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Responsible Party: Imperial College London
ClinicalTrials.gov Identifier: NCT03816137     History of Changes
Other Study ID Numbers: 18HH4893
First Posted: January 25, 2019    Key Record Dates
Last Update Posted: August 1, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Results from this study will be disseminated locally and to the wider scientific community at conferences and in published open-access peer-reviewed journals, as appropriate. Any data used for publication will be fully anonymised. We plan to publish the data and hold onto the data for 10 years.
Supporting Materials: Clinical Study Report (CSR)
Time Frame: 12 months from when the experimental study officially closes
Access Criteria: Directly from Professor Robin Shattock (r.shattock@imperial.ac.uk)

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Imperial College London:
Antibody
Antibody-dependent cell-mediated cytotoxicity
Neuralizing antibody responses
Additional relevant MeSH terms:
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Antibodies
Immunologic Factors
Physiological Effects of Drugs