Drugs

AGS-004

AGS-004

Drug Class: Therapeutic Vaccines Registry Number: 1807497-10-4 (CAS) Organization: Argos Therapeutics Phase of Development: IIb

(Compound details obtained from ChemIDplus Advanced,1 Treatment Action Group 2017 Pipeline Report,2 Argos Therapeutics website,3 and ClinicalTrials.gov4)

What is an investigational vaccine?

What is an investigational vaccine?

An investigational vaccine is one that is under study and is not approved by the U.S. Food and Drug Administration (FDA) for sale in the United States. Medical research studies are conducted to evaluate the safety and effectiveness of an investigational vaccine. These research studies are also called clinical trials. Once an investigational vaccine has been proven safe and effective in clinical trials, FDA may approve the vaccine for sale in the United States.

To learn more about investigational vaccines and investigational drugs, read the AIDSinfo What is an Investigational HIV Drug? fact sheet.

What is AGS-004?

What is AGS-004?

AGS-004 is an investigational vaccine that is being studied as a therapeutic vaccine for HIV.2 A therapeutic HIV vaccine is a type of vaccine that is designed to improve the body’s immune response to HIV in a person who already has HIV.5

HIV researchers are developing and testing therapeutic vaccines for various goals:

  • To slow down the progression of HIV infection.
  • To control HIV without antiretroviral therapy (ART). (ART is the recommended treatment for HIV infection and involves using a combination of different HIV medicines to prevent HIV from replicating.)
  • As part of a combination strategy that includes HIV medicines and a therapeutic vaccine to eliminate all HIV from the body.

The AIDSinfo fact sheet What is a Therapeutic HIV Vaccine? has more information on therapeutic HIV vaccines.6,7

AGS-004 is a personalized therapeutic vaccine, which means that it is designed to produce an immune response targeted to a person’s specific strain of HIV. AGS-004 can do this because the vaccine is produced from HIV proteins and immune cells taken from the person’s own blood.8,9

How are clinical trials of investigational vaccines conducted?

How are clinical trials of investigational vaccines conducted?

Clinical trials are conducted in phases. Each phase has a different purpose and helps researchers answer different questions.10

  • Phase I trials: Researchers test an investigational vaccine in a small group of people (20–80) for the first time. The purpose is to evaluate its safety, identify side effects, and determine if the vaccine produces an immune response in the body.
  • Phase II trials: The investigational vaccine is administered to a larger group of people (100–300). Researchers further evaluate the vaccine’s safety and ability to produce an immune response in the body. Some effectiveness data on the health benefits of the vaccine may also be collected.
  • Phase III trials: The investigational vaccine is administered to large groups of people (1,000–3,000) to confirm its effectiveness, monitor side effects, compare it with standard or equivalent treatments, and collect information that will allow the investigational vaccine to be used safely.10,11

In most cases, an investigational vaccine must be proven effective and must show continued safety in a Phase III clinical trial to be considered for approval by FDA for sale in the United States. Some vaccines go through FDA’s accelerated approval process and are approved before a Phase III clinical trial is complete. After a vaccine is approved by FDA and made available to the public, researchers track its safety in Phase IV trials to seek more information about the vaccine’s risks, benefits, and optimal use.10

Some clinical trials are categorized as “a” or “b,” such as “Phase Ia” or “Phase IIb.” These different subphases typically mean that a study is researching certain types of information or using a certain type of participant population.

In what phase of testing is AGS-004?

In what phase of testing is AGS-004?

AGS-004 has been studied in a Phase IIb clinical trial.4

What are some studies on AGS-004?

What are some studies on AGS-004?

Study Names: IGHID 11424; VORVAX; NCT02707900  
Sponsor: Cynthia L Gay, MD 
Phase: I/IIa
Status: This study is currently recruiting participants.
Location: United States
Participants:

  • Participants are adults with HIV who have been on ART for at least 6 months. Participants have also been on an ART regimen made up of 3 HIV medicines during the 24 weeks leading up to the study.
  • Participants have viral load levels of less than 50 copies/mL at the start of the study. Participants have also had this viral load for the past 6 months. (Viral load is the amount of HIV in a blood sample.)
  • Participants have CD4 counts of at least 300 cells/mm3 at the start of the study. (A CD4 count is a laboratory test that measures the number of CD4 cells—a type of immune cell—in a sample of blood and is an important indicator of immune function.)
Purpose: The purpose of this study is to evaluate (1) the safety of AGS-004 combined with the investigational drug vorinostat, and (2) how well the combination of AGS-004 plus vorinostat, along with ART, can clear HIV from the body.12,13

Study Names: AGS-004-001; CTN #239; NCT00672191 
Sponsor: Argos Therapeutics
Phase: IIa
Status: This study has been completed.
Location: United States and Canada
Participants:
  • Participants were adults with HIV who had been on their first ART regimen for at least 3 months.
  • Participants had viral load levels of less than 50 copies/mL for at least 90 days before screening, and their viral load levels before starting ART were at least 15,000 copies/mL.
  • Participants had CD4 counts of at least 450 cells/mm3 for at least 90 days before screening, and their lowest CD4 count before starting ART was 200 cells/mm3 or higher.
Purpose: The purpose of this study was to look at AGS-004’s safety and its ability to improve the body’s immune response and control viral load levels after participants stopped taking ART.14,15

Study Names: AGS-004-003; NCT01069809 
Sponsor: Argos Therapeutics
Phase: IIb
Status: This study has been completed.
Location: United States and Canada
Participants:
  • Participants were adults with HIV who had been on an ART regimen for at least 3 months.
  • Participants had viral load levels that were 200 copies/mL or less for at least 3 months before screening and less than 50 copies/mL at screening.
  • Participants had CD4 counts of at least 450 cells/mm3 at screening, and their lowest CD4 count was 200 cells/mm3 or higher.
Purpose: The purpose of this study was to determine the safety and effectiveness of AGS-004 in controlling viral load levels when participants stopped taking ART.4,16

Other completed early-phase studies on AGS-004 include NCT02042248 and NCT00381212.17,18

For more details on the studies listed above, see the Health Professional version.

What side effects might AGS-004 cause?

What side effects might AGS-004 cause?

One goal of HIV research is to identify new therapies, including vaccines, that are safe and have few side effects. The following side effects were observed in some of the studies of AGS-004 listed above.

In both the AGS-004-001 (NCT0067291) and AGS-004-003 (NCT01069809) studies, the most common side effect was mild reactions where AGS-004 was injected (called injection site reactions). No serious side effects were reported in either study.4,14,16,19-20

In the AGS-004-003 study, participants also reported some side effects that may have been related to AGS-004. These side effects included headache, nausea, depression, dizziness, an increase in vivid dreams, swollen lymph nodes, and skin rashes.16

Because AGS-004 is still being studied, information on possible side effects of the vaccine is not complete. As testing of AGS-004 continues, additional information on possible side effects will be gathered.

Where can I get more information about clinical trials studying AGS-004?

Where can I get more information about clinical trials studying AGS-004?

More information about AGS-004-related research studies is available from the AIDSinfo database of ClinicalTrials.gov study summaries. Click on the title of any trial in the list to see the ClinicalTrials.gov trial summary and more information about the study.

How can I find more information about participating in a clinical trial?

How can I find more information about participating in a clinical trial?

Participating in a clinical trial can provide benefits. For example, a volunteer participant can benefit from new research treatments before they are widely available. Participants also receive regular and careful medical attention from a research team that includes doctors and other health professionals. However, clinical trials may also involve risks of varying degrees, such as unpleasant, serious, or even life-threatening side effects from the treatment being studied.10 

Your health care provider can help you decide whether participating in a clinical trial is right for you. For more information, visit NIH Clinical Research Trials and You.

References

References

  1. United States National Library of Medicine. ChemIDplus Advanced. Available at: https://chem.sis.nlm.nih.gov/chemidplus/rn/1807497-10-4. Last accessed on November 15, 2017.
  2. Frick M, Gaudino A, Harrington M, et al. Treatment Action Group. 2017 pipeline report. July 2017. Available at: http://www.pipelinereport.org/sites/default/files/2017%20Pipeline%20Report%20Final.pdf. Last accessed onNovember 15, 2017.
  3. Argos Therapeutics website. HIV clinical trials. Available at: http://www.argostherapeutics.com/hiv-clinical-trials/. Last accessed on November 15, 2017.
  4. Argos Therapeutics. A Randomized, Double-Blind, Phase 2B Study Testing the Efficacy and Safety of AGS-004 on Host Control of HIV Replication During Analytical Treatment Interruption. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on February 16, 2010. NLM Identifier: NCT01069809. Available at: https://clinicaltrials.gov/ct2/show/NCT01069809. Last accessed on November 15, 2017.
  5. The History of Vaccines website. The Development of HIV Vaccines. Available at: https://www.historyofvaccines.org/content/articles/development-hiv-vaccines. Last accessed on November 15, 2017.
  6. Smith PL, Tanner H, Dalgleish A. Developments in HIV-1 immunotherapy and therapeutic vaccination. F1000Prime Rep. 2014 Jun 2; 6:43. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4047951/. Last accessed on November 15, 2017.
  7. Graziani GM and Angel JB. Evaluating the efficacy of therapeutic HIV vaccines through analytical treatment interruptions. J Int AIDS Soc. 2015; 18(1): 20497. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4641978/. Last accessed on November 15, 2017.
  8. HIVdent website. Argos Therapeutics Announces Plans for HIV Eradication Study. Available at: http://www.hivdent.org/_research_/2013/Res_ATAP102013.htm. Last accessed on November 15, 2017.
  9. GeMCRIS: Genetic Modification Clinical Research Information System, Version 6.2. Gene Transfer Protocol Reports: Protocol Number 0912-1015. Non-technical Abstract of Protocol AGS-004-003. Available at: https://www.gemcris.od.nih.gov/Abstracts/1015_nt.pdf. Last accessed on November 15, 2017.
  10. National Institutes of Health (NIH). NIH Clinical Research Trials and You. Available at: https://www.nih.gov/health-information/nih-clinical-research-trials-you. Last accessed on November 15, 2017.
  11. Hudgens MG, Gilbert PB, Self SG. Endpoints in vaccine trials. Stat Methods Med Res. 2004; 13: 1-26. Available at: http://faculty.washington.edu/peterg/Vaccine2006/articles/HudgensGilbertSelfSMMR.pdf. Last accessed on November 15, 2017.
  12. Cynthia L Gay, MD. IGHID 11424 - A Pilot Trial of the Effect of Vorinostat and AGS-004 on Persistent HIV-1 Infection (The VOR VAX Study). In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on March 3, 2016. NLM Identifier: NCT02707900. Available at: https://clinicaltrials.gov/ct2/show/NCT02707900. Last accessed on November 15, 2017.
  13. Argos Therapeutics: Press release, dated April 1, 2015. NIH Funds Study of Fully Personalized Immunotherapy AGS-004 Combined With a Latency Reversing Therapy for the Treatment of HIV. Available at: http://ir.argostherapeutics.com/releasedetail.cfm?releaseid=904466. Last accessed on November 15, 2017.
  14. Argos Therapeutics. A Phase II Study Testing the Activity and Safety of AGS-004 as an Immunotherapeutic in Successfully ART-Treated Subjects Infected With HIV-1 in Combination With ART Followed by ART Interruption. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on May 5, 2008. NLM Identifier: NCT00672191. Available at: https://clinicaltrials.gov/ct2/show/NCT00672191. Last accessed on November 15, 2017.
  15. Routy J-P. Safety and viral load changes in HIV-1 infected subjects treated with autologous dendritic cell immune therapy following ART discontinuation (CTN #239). Slides presented at: AIDS Vaccine 2009; October 19-22, 2009; Paris, France. Available at: http://www.vaccineenterprise.org/conference_archive/2009/pdf_slides/Jean-Pierre-Routy.pdf. Last accessed on November 15, 2017.
  16. Jacobson JM, Routy J-P, Welles S, et al. Dendritic cell immunotherapy for HIV-1 infection using autologous HIV-1 RNA: a randomized, double-blind, placebo-controlled clinical trial. J Acquir Immune Defic Syndr. 2016 May 1; 72(1): 31-8. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4836975/. Last accessed on November 15, 2017
  17. Cynthia L Gay, MD. IGHID 1309 - A Phase I Study to Evaluate the Kinetics of the Immunologic Response and Virologic Impact of AGS-004 in HIV-Infected Individuals Suppressed on Antiretroviral Therapy Initiated During Acute and Chronic HIV Infection. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on January 17, 2014. NLM Identifier: NCT02042248. Available at: https://clinicaltrials.gov/ct2/show/NCT02042248. Last accessed on November 15, 2017.
  18. McGill University Health Center. A Pilot Study (Phase I/II) Testing the Immunologic Activity and Safety of AGS-004, an Autologous HIV Immunotherapeutic, in HIV-Infected Adults on HAART. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on September 25, 2006. NLM Identifier: NCT00381212. Available at: https://clinicaltrials.gov/ct2/show/NCT00381212. Last accessed on November 15, 2017.
  19. Routy J-P, Angel J, Vezina S, et al. Final Analysis of a Phase 2 Study of an Autologous Dendritic Cell Immunotherapy (AGS-004) Showed Positive Outcomes in Primary Endpoint of Viral Load Control, and Favorable Safety and Immunogenicity Profile, in Subjects Undergoing Structured Treatment Interruption of ART. Poster presented at: Conference on Retroviruses and Opportunistic Infections (CROI); February 27-March 2, 2011; Boston, MA. Poster H-114. Available at: http://www.argostherapeutics.com/literature/2011-AGS-004-001-CROI-poster-Final.pdf. Last accessed on October 9, 2016.
  20. ARGOS THERAPEUTICS INC: FORM 10-K (Annual Report), Filed 03/30/16 for the Period Ending 12/31/15. Available at: http://files.shareholder.com/downloads/AMDA-TSH5S/2878656665x0xS1171843-16-8919/1105533/filing.pdf. Last accessed onNovember 15, 2017.

Last Reviewed: November 15, 2017