Summary

Name:

AGS-004

Synonyms:

AGS004; AGS 004; Arcelis

Sponsor:

Argos Therapeutics (formerly Merix Bioscience; USA)

Type of product:

Vaccine

Viral family:

Retroviridae

Status:

Phase II
2 Phase II trials completed (2011 and 2015)

AGS-004 

Synonyms:AGS004; AGS 004; Arcelis       Sponsor:Argos Therapeutics (formerly Merix Bioscience; USA)       Type of product:Vaccine       Mode of action:Other       Viral family:Retroviridae       Virus:HIV (Human Immunodeficiency virus)      

Details

Characteristics:
Autologous RNA-loaded dendritic cells, carrying amplified RNA to express 4 viral antigens (gag, nef, rev and vpr) along with RNA encoding CD40L (CD40 ligand, a member of TNF gene family playing a major role in development and regulation of adaptive immune response in mammals);
 

Uses genes from pt’s own viral strains (obtained from plasma samples taken immediately prior to starting antiretroviral therapy, from which viral RNA can be amplified) in vaccine, making it a “personalized” vaccine;

Designed to enhance CD8-specific responses to HIV;

 

Mature dendritic cells from the pt are submitted to electroporation with antigen-encoding RNAs, with the whole immunotherapy process called Arcelis™ by the sponsor

 

Ref. Sponsor's website

In vivo and clinical data:

In Phase I trial, primary endpoints of safety and induction of T-cells response to pt-specific HIV antigens were reached;

Phase I results were presented at XVII International AIDS Conference (Mexico City, Aug. 2008; Routy et al., Abstract TUPDA101):

  • 10 HIV-infecred pts under successful HAART (viral load suppressed under 40 copies/mL) and with CD4+ T-cell counts over 350 cells/µL were included in the study and received their respective treated dendritic cells in the form of 4 intradermal injections of 0.6mL containing 1.2x10 7 cells with a follow-up of 12 months maximum (ARV treatment uninterrupted)
  • Adverse events were mild and included flu-like and gastrointestinal symptoms, fatigue, and injection site reactions
  • No increases were seen in HIV viral load ("blips") and no significant changes in either absolute CD4 or CD8 cell counts were seen
  • A significant increase in CD8 T-cell proliferative response (at least double the baseline value) was noted in 4 of the 10 pts, and a partial response (significant increase above untreated controls) in a further 3 pts, and these responses were specific for the 4 HIV antigens selected
  • Pts treated with HAART early in the course of their infection (within 6 months) showed a trend towards more robust antiviral immune responses compared to those in whom therapy was started 6 months or more post-infection

 

Results of Phase IIb NCT01069809 were published in Jacobson et al., J Acquir Immune Defic Syndr 2016 May 1;72(1):31-8:

  • Phase IIb trial was a randomized, double-blind, placebo-controlled study enrolling 54 HIV-1-infected pts on ART with viral loads <50 copies per milliliter, current CD4 T-cell counts >450 cells/mm3, and nadir counts >200 cells/mm3, who received intradermal injections of AGS-004 into the axillary lymph node region every 4 weeks; At week 16, a 12-week analytical treatment interruption (ATI) was undertaken
  • No difference in the end-of-ATI viral loads (average of values from weeks 11 and 12) between the 2 arms of the study [4.39 (4.17, 4.69) vs. 4.47 (3.76, 4.64) log10 HIV-1 RNA; P = 0.73]
  • No change was observed between pre-antiretroviral therapy viral loads and the end-of-ATI viral loads [-0.06 (0.24, -0.32) vs. -0.17 (0.17, -0.32) log10 HIV-1 RNA; P = 0.43] in study arms
  • When IFN-γ, IL-2, TNF-α, CD107a, and granzyme b expressions were measured by multicolor flow cytometry, a greater percentage of AGS-004 than of placebo recipients had multifunctional cytotoxic T-lymphocyte responses induced in the CD28+/CD45RA-CD8 effector/memory T-cell population to dendritic cells electroporated with autologous antigens
  • AEs consisted of transient, mild (grade 1) local injection site reactions
  • Authors concluded that despite induction of HIV-specific effector/memory CD8 T-cell responses, no antiviral effect was seen after the administration of AGS-004 when compared with placebo

Development status

Phase II
2 Phase II trials completed (2011 and 2015)

Remarks

Vaccine, therapeutic, developed as personalized treatment, potentially as an approach to control HIV viral load while interrupting ARV therapy;

 

Collaboration with McGill University (Canada) and Kyowa Hakko Kirin Co.