Lexgenleucel-TOther Names: VRX496, VRX496-T Drug Class: Gene Therapy Products Registry Number: 1294006-17-9 (CAS) Organization: VIRxSYS Corporation Phase of Development: II
(Compound details obtained from ChemIDplus Advanced,1 Treatment Action Group website,2 and ClinicalTrials.gov3,4)
What is an investigational drug?
Anis one that is under study and is not approved by the U.S. (FDA) for sale in the United States. Medical research studies are conducted to evaluate the safety and effectiveness of an investigational drug. These research studies are also called clinical trials. Once an investigational drug has been proven safe and effective in clinical trials, FDA may approve the drug for sale in the United States.
To learn more about investigational drugs, read the What is an Investigational HIV Drug? fact sheet.
What is lexgenleucel-T?
Lexgenleucel-T is an investigationalproduct. therapy is an experimental technique that uses genes (short sections of genetic material) to treat or prevent disease. Lexgenleucel-T is a gene therapy product that adds an anti-HIV gene (called an antisense gene) into CD4 cells. (CD4 cells are a type of immune cell that HIV attacks and destroys.)5,6
With lexgenleucel-T, the antisense gene is delivered into the CD4 cell by a carrier called a. The antisense gene becomes a permanent part of the cell’s genetic material. Then, when HIV infects a CD4 cell that has the antisense gene and tries to make copies of itself, the antisense gene is activated. The activated antisense gene prevents the production of an HIV (called an protein) that’s needed for HIV to successfully . Without the envelope protein, HIV cannot multiply.5-8
Lexgenleucel-T is being studied for its ability to help CD4 cells survive during HIVand as a possible strategy to cure HIV.6,7,9
How is lexgenleucel-T made?
Lexgenleucel-T is made by first collecting CD4 cells from a person with HIV. The cells are sent to a laboratory where they are genetically modified to include the antisense gene. The cells are then stimulated to produce many more CD4 cells that also have the antisense gene. Finally, the modified CD4 cells are returned to the person’s body and can multiply in the body. Researchers hope that this treatment will create CD4 cells that permanently block HIV’s ability to make copies of itself.6,7,10
How are clinical trials of investigational drugs conducted?
Clinical trials are conducted in phases. Each phase has a different purpose and helps researchers answer different questions.11
- Phase I trials: Researchers test an investigational drug in a small group of people (20–80) for the first time. The purpose is to evaluate its safety and identify side effects.
- Phase II trials: The investigational drug is administered to a larger group of people (100–300) to determine its effectiveness and to further evaluate its safety.
- Phase III trials: The investigational drug 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 drug to be used safely.11
In most cases, an investigational drug must be proven effective and must show continued safety in a Phase IIIto be considered for approval by FDA for sale in the United States. Some drugs go through FDA’s accelerated approval process and are approved before a Phase III clinical trial is complete. After a drug is approved by FDA and made available to the public, researchers track its safety in Phase IV trials to seek more information about the drug’s risks, benefits, and optimal use.11
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 lexgenleucel-T?
Lexgenleucel-T is being studied in Phase II clinical trials.3,4
What are some studies on lexgenleucel-T?
Study Names: NCT00295477
Sponsor: University of Pennsylvania
Status: This study is ongoing, but not recruiting participants.
Location: United States
- Participants are adults with HIV who are currently on (ART) and who have been on the same ART regimen during the 4 weeks before the start of the study. (ART is the recommended treatment for HIV infection and involves using a combination of different [ARV] drugs to prevent HIV from replicating.)
- Participants have levels (the amount of HIV in a blood sample) that are undetectable (usually less than 20 copies/mL) and CD4 counts greater than 450 cells/mm3 at the start of the study. (A is a laboratory test that measures the number of CD4 cells in a sample of blood and is an important indicator of immune function.)
- Participants are willing to continue their current ART regimen during the study and then stop ART for a short while (called a treatment interruption). During a treatment interruption, researchers evaluate how well an investigational treatment (in this case lexgenleucel-T) can control a person’s HIV without HIV medicines.
Study Names: (1) VRX496-USA-05-002; NCT00131560 and (2) VRX496-USA-05-002-Rollover; NCT00622232
Sponsor: VIRxSYS Corporation
Status: These studies are ongoing, but not recruiting participants.
Location: United States
- Participants are adults with HIV who have received ART at some point before the study. Participants who are on ART when starting the study are willing to continue their current ART regimen during the study. Those who are not receiving ART at the beginning of the study are willing to remain off of therapy during the study.
- While taking at least 1 ART regimen containing 3 drugs, participants had either experienced or stopped taking ART because of side effects or other issues. (Treatment failure is when an ART regimen is unable to control HIV infection.)
- In the 3 months before starting the study, participants have had no significant changes in their viral load. At the start of the study, participants have viral loads between 5,000 and 200,000 copies/mL and CD4 counts of at least 150 cells/mm3.
For more details on the studies listed above, see the Health Professional version.
What side effects might lexgenleucel-T cause?
One goal of HIV research is to identify new drugs that have fewer side effects. The following side effects were observed in the studies of lexgenleucel-T listed above.Protocol 802456; NCT00295477
No safety concerns related to multiple infusions were reported in this study. The most common side effect was a garlic/creamed corn odor occurring during infusions. Other common side effects related to treatment were reactions at the infusion site, such as stinging and a cold sensation.13,14VRX496-USA-05-002; NCT00131560 and VRX496-USA-05-002-Rollover; NCT00622232
Twenty seven participants in these studies have completed 3 years of follow-up safety monitoring with no evidence of long-term safety issues related to lexgenleucel-T treatment.15
Because lexgenleucel-T is still being studied, information on possible side effects of the drug is not complete. As testing of lexgenleucel-T continues, additional information on possible side effects will be gathered.
Where can I get more information about clinical trials studying lexgenleucel-T?
More information about lexgenleucel-T-related research studies is available from the AIDSinfo database of 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?
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.11
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. nlm.nih.gov/chemidplus/rn/1294006-17-9. Last accessed on May 10, 2018.
- Treatment Action Group website. Research toward a cure trials. Available at: http://www.treatmentactiongroup.org/cure/trials. Last accessed on May 10, 2018. [Archived at WebCite]
- VIRxSYS Corporation. A Phase II, open-label, multicenter study to evaluate the safety, tolerability, and biological activity of single and repeated doses of autologous T cells transduced with VRX496 in HIV-positive subjects. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on August 16, 2005. NLM Identifier: NCT00131560. Available at: https://www.clinicaltrials.gov/ct2/show/NCT00131560. Last accessed on May 10, 2018.
- VIRxSYS Corporation. A rollover study to evaluate safety and therapeutic effect of re-infusing subjects who completed participation in the VRX496-USA-05-002 trial with autologous T cells transduced with VRX496. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on February 11, 2008. NLM Identifier: NCT00622232. Available at: https://www.clinicaltrials.gov/ct2/show/NCT00622232. Last accessed on May 10, 2018.
- Horn T. VIRxSYS gene therapy makes progress—Researchers have reported encouraging results from a clinical trial of a gene therapy approach to treat HIV. On European AIDS Treatment Group website. Available at: http://www.eatg.org/news/163817/VIRxSYS_gene_therapy_makes_progress. Last accessed on March 3, 2016.
- VIRxSYS Corporation. FDA biological response modifiers advisory committee meeting briefing package—Autologous T cells transduced with VRX496, an HIV-1 based lentiviral vector for the treatment of patient-subjects infected with HIV-1; October 26th, 2001. Available at: https://wayback.archive-it.org/7993/20170405163710/https://www.fda.gov/ohrms/dockets/ac/01/briefing/3794b3_13_sponsor.pdf. Last accessed onMay 10, 2018. [Archived at WebCite]
- Sheehy J, Zack J, Kiem HP, Handibode J. Cell/gene therapy—HIV cure research training curriculum. Located on the AVAC website (http://www.avac.org/cure-curriculum/module3), under PowerPoint. Available at: http://www.avac.org/sites/default/files/u16/Gene_Cell_Therapy_July.pptx. Last accessed on May 10, 2018.
- Stan R and Zaia JA. Practical considerations in gene therapy for HIV cure. Curr HIV/AIDS Rep. 2014; 11(1): 11–19. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3929767/. Last accessed on May 10, 2018.
- Hartman TL and Buckheit RW Jr. The continuing evolution of HIV-1 therapy: identification and development of novel antiretroviral agents targeting viral and cellular targets. Mol Biol Int. 2012; 2012: 401965. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3400388/. Last accessed on May 10, 2018.
- Humeau LM, Binder GK, Lu X, et al. Efficient lentiviral vector-mediated control of HIV-1 replication in CD4 lymphocytes from diverse HIV+ infected patients grouped according to CD4 count and viral load. Mol Ther. 2004 Jun;9(6):902-13. Available at: http://www.cell.com/molecular-therapy-family/molecular-therapy/fulltext/S1525-0016(04)00101-7. Last accessed on May 10, 2018.
- National Institutes of Health (NIH). NIH clinical tesearch trials and you. Available at: https://www.nih.gov/health-information/nih-clinical-research-trials-you. Last accessed on May 10, 2018.
- University of Pennsylvania. A Phase I/II, open-label, single center study to evaluate the tolerability, trafficking and therapeutic effects of repeated doses of autologous T cells transduced with VRX496 in HIV infected subjects. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on February 21, 2006. NLM Identifier: NCT00295477. Available at: https://www.clinicaltrials.gov/ct2/show/NCT00295477. Last accessed on May 10, 2018.
- Tebas P, Stein D, Binder-Scholl G, et al. Antiviral effects of autologous CD4 T cells genetically modified with a conditionally replicating lentiviral vector expressing long antisense to HIV. Blood. 2013 Feb 28; 121(9): 1524–1533. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3587318/. Last accessed on May 10, 2018.
- Tebas P, Stein D, Zifchak L, et al. Prolonged control of viremia after transfer of autologous CD4 T cells genetically modified with a lentiviral vector expressing long antisense to HIV env (VRX496). Conference on Retroviruses and Opportunistic Infections (CROI); February 16-19, 2010; San Francisco, CA. Levin: Conference Reports for National AIDS Treatment Advocacy Project (NATAP); 2010. Available at: http://www.natap.org/2010/CROI/croi_182.htm. Last accessed on May 10, 2018. [Archived at WebCite]
- Rebello T, Stein D, Blick G, et al. Safety and efficacy of autologous CD4+ T cells transduced with a lentiviral vector delivering anti-HIV RNA antisense env in HIV+ subjects failing one or more HAART regimens. Mol Ther. 2010 May; Vol 18, Supplement 1: S251 (Abstract 646). Available at: http://www.cell.com/molecular-therapy-family/molecular-therapy/pdf/S1525-0016(16)38087-X.pdf. Last accessed May 10, 2018 [Archived at WebCite]
Last Reviewed: May 10, 2018