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?
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’s designed to improve the body’s immune response to HIV in a person who is already infected with HIV.5
HIV researchers are developing and testing therapeutic vaccines (1) to slow down the progression of HIV infection, (2) to eliminate the need for antiretroviral therapy (ART) while still keeping undetectable levels of HIV, and (3) as part of a combination strategy that includes HIV medicines and a therapeutic vaccine to eliminate all HIV from the body. (ART is the recommended treatment for HIV infection and involves using a combination of different HIV medicines to prevent HIV from replicating.) 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 AGS-004 is specialized for each person. Because AGS-004 is made from a person’s own HIV proteins and immune cells, it can stimulate an immune response that is targeted to the specific HIV strain that a person is infected with.8,9
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?
AGS-004 has been studied in a Phase IIb clinical trial.4
What are some studies on AGS-004?
Study Name: IGHID 11424; VORVAX; NCT02707900
Sponsor: Cynthia L Gay, MD
Location: United States
- Participants are HIV-infected adults who have been on ART before (called treatment-experienced). Participants have been on ART for at least 6 months and have been on an ART regimen made up of 3 HIV medicines throughout the 24 weeks before starting the study.
- Participants have had a viral load of less than 50 copies/mL for the past 6 months and at screening. (Viral load is the amount of HIV in a blood sample.)
- Participants have CD4 counts of at least 300 cells/mm3 at screening. (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.)
: 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 persistent HIV from the body.12,13
* This study is currently recruiting participants.
Study Name: AGS-004-001; CTN #239; NCT00672191
Sponsor: Argos Therapeutics
Location: United States and Canada
- Participants were treatment-experienced adults who had chronic HIV infection and who had been on their first ART regimen for at least 3 months.
- Participants had viral loads of less than 50 copies/mL for at least 90 days before screening, and their viral loads before starting ART were at least 15,000/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 Name: AGS-004-003; NCT01069809
Sponsor: Argos Therapeutics
Location: United States and Canada
- Participants were treatment-experienced adults who had chronic HIV infection and who had been on an ART regimen for at least 3 months prior to screening.
- Participants had viral loads that were 400 copies/mL or less for at least 2 months before screening and 50 copies/mL or less at screening.
- Participants had CD4 counts of at least 450 cells/mm3 at screening, and their lowest CD4 count before starting ART was 200 cells/mm3 or higher.
: 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
Other early-phase studies on AGS-004 include NCT02042248
For more details on the studies listed above, see the Health Professional version
What side effects might AGS-004 cause?
In both the AGS-004-001 (NCT0067291) and AGS-004-003 (NCT01069809) studies discussed under the previous question, 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.4,14,18-20
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?
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.
I am interested in participating in a clinical trial of AGS-004. 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.
- United States National Library of Medicine. ChemIDplus Advanced. Available at: https://chem.sis.nlm.nih.gov/chemidplus/rn/1807497-10-4. Last accessed on October 9, 2016.
- Clayden P, Collins S, Frick M, et al. HIV i-BASE/Treatment Action Group. 2016 Pipeline Report. July 2016. Available at: http://www.pipelinereport.org/sites/default/files/2016%20Pipeline%20Report%20Full_0.pdf. Last accessed on October 9, 2016.
- Argos Therapeutics website. Product Pipeline. Available at: http://www.argostherapeutics.com/platform-and-pipeline/product-pipeline/. Last accessed on October 9, 2016.
- 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 October 9, 2016.
- The History of Vaccines website. The Development of HIV Vaccines. Available at: http://www.historyofvaccines.org/content/articles/development-hiv-vaccines. Last accessed on October 9, 2016.
- Smith PL, Tanner H, Dalgleish A. Developments in HIV-1 immunotherapy and therapeutic vaccination. F1000Prime Rep. 2014 Jun 2; 6:43. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4047951/. Last accessed on October 9, 2016.
- 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: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4641978/. Last accessed on October 9, 2016.
- HIVdent website. Argos Therapeutics Announces Plans for HIV Eradication Study. Available at: http://www.hivdent.org/_research_/2013/Res_ATAP102013.htm. Last accessed on October 9, 2016.
- 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 October 9, 2016.
- 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 October 9, 2016.
- 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 October 14, 2016.
- 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 October 9, 2016.
- 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 October 9, 2016.
- 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 October 9, 2016.
- 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 October 9, 2016.
- Cynthia L Gay, MD. IGHID 1309 - A Phase I/II 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 October 9, 2016.
- 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 October 9, 2016.
- 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: 18th 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.
- Jacobson JM, Routy JP, 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/pubmed/26751016. Last accessed on October 9, 2016.
- 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 on October 9, 2016.
Last Reviewed: October 9, 2016