NCT01922284: UKHVCSpoke003

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

Completed Phase 1 Last updated 26 September 2016

What this trial tests

Phase 1 trial testing DNA in HIV in 40 participants. Completed in 1 December 2015.

Timeline

1 June 2013

Primary endpoint
1 January 2014

1 December 2015

Quick facts

Lead sponsor	Imperial College London
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	prevention
Enrollment	40
Start date	1 June 2013
Primary completion	1 January 2014
Estimated completion	1 December 2015
Sites	2 locations across United Kingdom

Drugs / interventions tested

• DNA — full drug profile →
• MVA-C — full drug profile →
• CN54rgp140 — full drug profile →
• GLA-AF — full drug profile →

Conditions studied

• HIV — all drugs for HIV →

Sponsor

Imperial College London

Who can join

Adults 18 to 45, any sex, with HIV. Healthy volunteers can join.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• Magnitude of antibody response
  Time frame: Four weeks after final immunisation
  Magnitude (reciprocal mean endpoint titre and concentration) of systemic Immunoglobulin G (IgG) binding antibody responses to CN54rgp140 measured four weeks after the final immunisation.
• Adverse Events
  Time frame: Every four weeks up to 32 weeks
  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

Sponsor's own description

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:

* 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

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Vaccine adjuvants: mechanisms and platforms.
   Zhao T, Cai Y, Jiang Y, He X, et al · · 2023 · cited 599× · PMID 37468460 · DOI 10.1038/s41392-023-01557-7
2. Recent Advances in the Development of Toll-like Receptor Agonist-Based Vaccine Adjuvants for Infectious Diseases.
   Yang JX, Tseng JC, Yu GY, Luo Y, et al · · 2022 · cited 81× · PMID 35214155 · DOI 10.3390/pharmaceutics14020423
3. Progress in HIV vaccine development.
   Hsu DC, O'Connell RJ. · · 2017 · cited 62× · PMID 28281871 · DOI 10.1080/21645515.2016.1276138
4. A Comparative Phase I Study of Combination, Homologous Subtype-C DNA, MVA, and Env gp140 Protein/Adjuvant HIV Vaccines in Two Immunization Regimes.
   Joseph S, Quinn K, Greenwood A, Cope AV, et al · · 2017 · cited 23× · PMID 28275375 · DOI 10.3389/fimmu.2017.00149
5. Improved Immune Responses in Young and Aged Mice with Adjuvanted Vaccines against H1N1 Influenza Infection.
   Baldwin SL, Hsu FC, Van Hoeven N, Gage E, et al · · 2018 · cited 22× · PMID 29515589 · DOI 10.3389/fimmu.2018.00295
6. HIV Envelope Trimer Specific Immune Response Is Influenced by Different Adjuvant Formulations and Heterologous Prime-Boost.
   Apostólico Jde S, Boscardin SB, Yamamoto MM, de Oliveira-Filho JN, et al · · 2016 · cited 19× · PMID 26727218 · DOI 10.1371/journal.pone.0145637
7. Envelope-Specific Recognition Patterns of HIV Vaccine-Induced IgG Antibodies Are Linked to Immunogen Structure and Sequence.
   Nadai Y, Held K, Joseph S, Ahmed MIM, et al · · 2019 · cited 7× · PMID 31105688 · DOI 10.3389/fimmu.2019.00717
8. Systematic comparison of HIV-1 Envelope-specific IgG responses induced by different vaccination regimens: Can we steer IgG recognition towards regions of viral vulnerability?
   Horvath A, Rogers L, Pollakis G, Baranov O, et al · · 2022 · cited 1× · PMID 36741409 · DOI 10.3389/fimmu.2022.1075606