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GTU-MultiHIV B

Other Names: DNA-GTU vaccine, FIT-06 vaccine, GTU MultiHIV multi-gene, GTU-MultiHIV, GTU-MultiHIV B Clade, GTU-MultiHIV B DNA, GTU-multi-HIVB, Gene Transport Unit (GTU)-MultiHIV DNA Vaccine Drug Class: Therapeutic Vaccines Organization: FIT Biotech Phase of Development: GTU-MultiHIV B is in Phase II development as a therapeutic HIV vaccine. (GTU-MultiHIV B has also been studied as a preventive HIV vaccine.)

(Compound details obtained from Treatment Action Group website,1 FIT Biotech website,2 and Treatment Action Group HIV TB HCV Pipeline Report 2018)3

Pharmacology


Mechanism of Action: Therapeutic vaccines. GTU-MultiHIV B is a DNA-based therapeutic HIV vaccine. Therapeutic vaccines are being investigated as an immunotherapeutic approach to correcting HIV-associated immune dysfunction, such as impaired dendritic cell (DC) responses to HIV and suboptimal adaptive immune responses (including HIV-specific T cell responses).4-7 A therapeutic vaccine may potentially increase the effectiveness of ART, simplify ART regimens, or allow for periodic structured treatment interruptions. A successful therapeutic vaccine would either completely eradicate the virus or improve an individual’s immune response sufficiently to suppress viral replication without ART. In either case, a therapeutic vaccine would help to circumvent a lifetime of ART.8

The GTU-MultiHIV B vaccine is designed to generate immune responses to six HIV proteins. The vaccine consists of a DNA plasmid encoding a synthetic fusion protein that contains complete sequences of HIV-1 Rev, Nef, Tat, and Gag (p17/p24) and a number of T cell epitopes from Pol and Env. The protein sequences are derived from an HIV-1 subtype B isolate.6,9-12

GTU-MultiHIV B is being developed as both a preventive and therapeutic HIV vaccine.1 In a Phase II trial (FIT-06) that evaluated the immunogenicity and clinical effects of GTU-MultiHIV B in ART-naive participants, the vaccine was found to increase HIV-specific CD4 cells (TNF-alpha secreting) and CD8 cells (TNF-alpha and IFN-gamma secreting), decrease plasma viral load, and increase CD4 counts.6,10,11 As a therapeutic vaccine, GTU-MultiHIV B is also being evaluated in a Phase II trial (NCT01492985) in combination with the LIPO-5 vaccine in a prime-boost strategy and in a Phase I/II trial (NCT02972450) in combination with MVA HIV-B with or without the monoclonal antibody vedolizumab.13-15


Select Clinical Trials


GTU-MultiHIV B therapeutic vaccine

Study Identifiers: CUT*HIVTHER 001; NCT02457689
Sponsor: Imperial College London
Phase: I/II
Status: This study has been completed.
Study Purpose: The purpose of this trial was to investigate the safety and immunogenicity of the GTU-MultiHIV B vaccine administered by two different delivery methods.
Study Population:
  • Participants were adults with subtype B HIV who were receiving ART.
  • Participants had been on ART for at least 6 months and had HIV RNA <50 copies/mL on at least two occasions prior to study enrollment while on ART.
  • Participants have had nadir CD4 counts >250 cells/mm3 and, at screening, had CD4 counts >200 cells/mm3.16

Study Identifiers: VRI02/ANRS 149 LIGHT; NCT01492985
Sponsor: French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
Phase: II
Status: This study is ongoing, but not recruiting participants.
Study Purpose: The purpose of this proof-of-concept trial is to evaluate whether GTU-MultiHIV B (prime) combined with LIPO-5 (boost) can induce HIV-specific immune responses to control viral replication after treatment interruption.
Study Population:
  • Participants are adults with chronic HIV infection who are asymptomatic and have been on ART for at least 18 months.
  • Participants have had HIV RNA <50 copies/mL and CD4 cell counts ≥600 cells/mm3 for the 6 months previous to and at screening (Week 3 visit). Participants have had nadir CD4 counts ≥300 cells/mm3 while on ART.14
Selected Study Results:
Study Identifiers: FIT-06; EudraCT 2005-003071-20
Sponsor: FIT Biotech Oyj Plc
Phase: II
Status: This study has been completed.
Study Purpose: The FIT-06 trial evaluated the safety, immunogenicity, and clinical effect of GTU-MultiHIV B administered by either intradermal (ID) or intramuscular (IM) injection and compared it to that of placebo.
Study Population:
  • Participants were treatment-naive adults with chronic subtype C HIV infection.
  • Participants had HIV RNA ≥50 copies/mL and CD4 counts ≥350 cells/mm3.10,11,17,18
Selected Study Results:
Study Identifiers: EHVA T01/ANRS VRI05; NCT02972450
Sponsor: French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
Phase: I/II
Status: This study is not yet open for participant recruitment.
Study Purpose: The purpose of this trial is to evaluate the efficacy of three different experimental strategies in controlling viral load after treatment interruption of ART. The three experimental strategies are GTU-MultiHIV B combined with MVA HIV-B, vedolizumab only, and GTU-MultiHIV B combined with MVA HIV-B plus vedolizumab.
Study Population:
  • Participants are adults with HIV who started ART after 2009 and who have been on ART for at least 1 year.
  • At screening, participants have HIV RNA <50 copies/mL and CD4 counts >600 cells/mm3. Participants have had nadir CD4 counts >300 cells/mm3.13

A Phase I immunotherapeutic study (NCT01130376) of GTU-MultiHIV B given in combination with cytokine and hormone therapy in participants on suppressive ART has also been completed.19,20


Adverse Events


VRI02/ANRS 149 LIGHT (NCT01492985):

In this Phase II study, 103 participants enrolled to receive GTU-MultiHIV B and LIPO-5 vaccines or placebo vaccines. A preliminary safety analysis of 98 participants who had received at least one vaccine injection (93 of whom had received all injections) found that 94 participants experienced at least one adverse event (AE), most of which were mild. One participant experienced a serious adverse event (SAE) – arthritis – which was possibly related to vaccination (study vaccine or placebo). Among 90 participants who underwent a treatment interruption of ART, all had viral rebound. Twenty-three percent of participants had symptoms resembling acute HIV infection after treatment interruption of ART, although symptoms were mostly mild. One participant transmitted HIV infection during the period of treatment interruption.14,21

FIT-06 (EudraCT 2005-003071-20):

Results reported for this Phase II trial showed that GTU-MultiHIV B administered by either IM or ID injection to 63 participants was safe. There were no SAEs related to the vaccine. Mild to moderate local reactogenicity events occurring immediately or 30 minutes after administration (such as bleeding at the injection site, local indurations, and persistent local edema) were attributed more to ID injection than to IM injection. Other adverse events that occurred in both the active treatment and placebo groups included lymphadenopathy, upper respiratory tract infection, and increased CPK.10,11,17


Drug Interactions


Drug-drug interactions associated with GTU-MultiHIV B are currently unknown.


References


  1. Treatment Action Group website. Research toward a cure trials. http://www.treatmentactiongroup.org/cure/trials. Accessed January 18, 2019.
  2. FIT Biotech website. Our technology. https://www.fitbiotech.com/our-tech. Accessed January 18, 2019.
  3. Jefferys R. The HIV vaccines, passive immunization, and antibody gene transfer pipeline. Treatment Action Group HIV TB HCV Pipeline Report 2018. http://www.pipelinereport.org/2018/hiv-vaccines-pipeline. Accessed January 18, 2019.
  4. Lederman M, Rodriguez B, Sieg S. Immunopathogenesis of HIV Infection. In: Coffey S, Volberding P, eds. HIV InSite Knowledge Base. University of California San Francisco; 2004. http://hivinsite.ucsf.edu/InSite?page=kb-00&doc=kb-02-01-04. Accessed January 18, 2019.
  5. Miller E, Bhardwaj N. Advances in dendritic cell immunotherapies for HIV-1 infection. Expert Opin Biol Ther. 2014;14(11):1545-1549.
  6. Smith PL, Tanner H, Dalgleish A. Developments in HIV-1 immunotherapy and therapeutic vaccination. F1000Prime Rep. 2014;6(43). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4047951/. Accessed January 18, 2019.
  7. Routy J-P, Boulassel M-R, Yassine-Diab B, et al. Immunologic activity and safety of autologous HIV RNA–electroporated dendritic cells in HIV-1 infected patients receiving antiretroviral therapy. Clin Immunol. 2010;134(2):140.
  8. Graziani GM, Angel JB. Evaluating the efficacy of therapeutic HIV vaccines through analytical treatment interruptions. J Int AIDS Soc. 2015;18(1):20497.
  9. Blazevic V, Männik A, Malm M, et al. Induction of human immunodeficiency virus type-1-specific immunity with a novel Gene Transport Unit (GTU)-MultiHIV DNA vaccine. AIDS Res Hum Retroviruses. 2006;22(7):667-677.
  10. Vardas E, Stanescu I, Valtavaara M, et al. Indicators of therapeutic vaccine effect using GTU-MultiHIV B clade DNA in treatment-naive subtype C HIV-1 infected subjects. Abstract presented at: International AIDS Conference (IAC); July 18-23, 2010; Vienna, Austria. Abstract MOPDB102. http://www.abstract-archive.org/Abstract/Share/1945. Accessed January 18, 2019.
  11. Vardas E, Stanescu I, Leinonen M, et al. Indicators of therapeutic effect in FIT-06, a Phase II trial of a DNA vaccine, GTU(®)-Multi-HIVB, in untreated HIV-1 infected subjects. Vaccine. 2012;30(27):4046-4054.
  12. The Joint Research Centre of the European Commission. GMO Register: Notification Number B/FR/13/GT03. FIT Biotech GTU®-MultiHIV B – Part 1: Summary notification information format for the release of genetically modified organisms other than higher plants; Version 2.0; 10/04/2013. http://gmoinfo.jrc.ec.europa.eu/bsnifs-gmo/B-FR-13-GT03.pdf. Accessed January 18, 2019.
  13. French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS). A Phase IIb randomised therapeutic HIV vaccine trial in individuals who started antiretrovirals during primary or chronic infection. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on November 10, 2016. NLM Identifier: NCT02972450. https://clinicaltrials.gov/ct2/show/NCT02972450. Accessed January 18, 2019.
  14. French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS). Evaluation of a therapeutic immunization strategy associating a DNA vaccine (GTU-MultiHIV B) followed by a lipopeptide vaccine (LIPO-5) in the control of viral replication following antiretroviral treatment interruption in HIV-1 infected patients with a CD4 cell count ≥ 600/mm3. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on November 24, 2011. NLM Identifier: NCT01492985. https://clinicaltrials.gov/ct2/show/NCT01492985. Accessed January 18, 2019.
  15. European HIV Vaccine Alliance (EHVA): Press Release, dated November 27, 2018. European HIV Vaccine Alliance (EHVA) initiates a clinical trial to test a novel therapeutic vaccine and immunotherapy drug. http://www.ehv-a.eu/news/46-ehva-initiates-a-clinical-trial-to-test-a-novel-therapeutic-vaccine-and-immunotherapy-drug. Accessed January 18, 2019.
  16. Imperial College London. A randomized Phase I/II study to assess the safety and immunogenicity of the DNA-GTU vaccine administered by two novel routes compared to placebo in HIV-infected patients on antiretroviral therapy. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on May 27, 2015. NLM Identifier: NCT02457689. https://clinicaltrials.gov/ct2/show/NCT02457689. Accessed January 18, 2019.
  17. Vardas E, Stanescu I, Leinonen M, et al. Indicators of therapeutic effect in FIT-06: A Phase II Trial of a DNA vaccine GTU®-MultiHIV, in untreated HIV-1 infected participants. Slides presented at: AIDS Vaccine 2010; September 28 – October 1, 2010; Atlanta, GA. http://www.webcitation.org/6vB5fvLol. Accessed January 18, 2019.
  18. FIT Biotech Oyj Plc. Immunogenicity and therapeutic effects of GTU-MultiHIV B clade DNA vaccine. A randomized, controlled, phase II clinical trial in treatment-naive HIV-positive subjects. In: EU Clinical Trials Register. Registered on July 08, 2005. EudraCT Number: 2005-003071-20. https://www.clinicaltrialsregister.eu/ctr-search/trial/2005-003071-20/FI. Accessed January 18, 2019.
  19. Imperial College London. A randomised, open labelled, Phase I, safety, toxicity, and exploratory immunogenicity evaluation of therapeutic immunisation +/- IL-2, GM-CSF and growth hormone in HIV-1 infected subjects receiving highly active anti-retroviral therapy. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on May 25, 2010. NLM Identifier: NCT01130376. https://clinicaltrials.gov/ct2/show/NCT01130376. Accessed January 18, 2019.
  20. Herasimtschuk A, Downey J, Nelson M, et al. Therapeutic immunisation plus cytokine and hormone therapy improves CD4 T-cell counts, restores anti-HIV-1 responses and reduces immune activation in treated chronic HIV-1 infection. Vaccine. 2014;32(51):7005-7013.
  21. Levy Y, Lelievre J-D, Perrier A, et al. Preliminary safety results from VRI02 ANRS 149 Light (lipopeptide and DNA GTU HIV therapeutic trial). Poster presented at: HIV Research for Prevention (HIVR4P); October 17-21, 2016; Chicago, IL. Poster P27.09. https://www.abstractstosubmit.com/hivr4p2016/eposter/main.php?do=YToyOntzOjU6Im1vZHVsIjtzOjY6ImRldGFpbCI7czo4OiJkb2N1bWVudCI7aTo3NTt9&. Accessed January 18, 2019.


Last Reviewed: January 18, 2019