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LC002

Other Names: DermaVir, DermaVir patch
Drug Class: Therapeutic Vaccines
Company: Genetic Immunity
Phase of Development: LC002 is in Phase II development as a therapeutic HIV vaccine.
Patent Version Content

Pharmacology


Mechanism of Action: Therapeutic vaccine. LC002 is a DNA-based therapeutic HIV vaccine.1 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).3-6 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.7

LC002 is a synthetic nanomedicine constructed of a polymer envelope and a single plasmid DNA core encoding 15 clade B HIV antigens. The vaccine is modified to ensure that its expressed antigens are incapable of integration or replication.2,8-10 LC002 is a topically administered vaccine. After administration, LC002 nanoparticles are absorbed by Langerhans cells on the skin surface; subsequently, Langerhans cells mature into dendritic cells (DC), which then migrate to draining lymph nodes and express the encoded HIV antigens. The 15 expressed HIV proteins assemble into complex virus-like particles (VLP+), allowing for 1) DC presentation of a high number of HIV epitopes to naive T cells 2) precursor/memory T cell activation, and 3) HIV-specific T cell responses capable of destroying HIV-infected cells.8,10 LC002 vaccination may potentially aid in reducing or suppressing viral load without ART and clearing of the latent HIV reservoir when used in a multi-agent combination approach.2,9,11

In a Phase II trial (NCT00711230) involving treatment-naive individuals with HIV, LC002’s immunogenicity and ability to lower plasma viral load was demonstrated at a medium dose level of 0.4 mg.11,12 The immunogencitiy of LC002 has also been shown in some individuals with chronic HIV infection on suppressive ART.8,9


Select Clinical Trials


Study Identifiers: ACTG 5176; A5176; NCT00270205
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Phase: I/II
Status: This study has been completed.
Study Purpose: The purpose of this dose-escalating study was to evaluate the safety, tolerability, and immunogenicity of LC002 in individuals with chronic HIV infection.
Study Population:
  • Participants were adults with chronic HIV who had been receiving a stable ART regimen (with no changes or interruptions for more than 4 consecutive days) for at least 12 weeks before study entry.
  • Participants were receiving ART regimens containing at least 2 different ARV drug classes.
  • Participants had HIV RNA <50 copies/mL in the past 30 days before study entry and CD4 counts >350 cells/mm3 in the past 12 weeks before study entry. Participants had nadir CD4 counts of >250 cells/mm3.
Dosing: Participants were sequentially enrolled into 1 of 3 groups, from low to high dose. Within each group, participants were randomized to receive either LC002 or placebo, each topically administered using a skin preparation device (DermaPrep) and patch.
  • Low-dose: LC002 (0.1 mg) or placebo administered over 2 skin sites at Weeks 1, 7, and 13
  • Medium-dose: LC002 (0.4 mg) or placebo administered over 4 skin sites at Weeks 1, 7, and 13
  • High-dose: LC002 (0.4 mg) or placebo administered over 4 skin sites at Weeks 0, 1, 6, 7, 12, and 13.9,13,14
Selected Study Results:
Study Identifiers: GIEU006; NCT00711230
Sponsor: Genetic Immunity
Phase: II
Status: This study has been completed.
Study Purpose: The purpose of this dose-finding study was to evaluate the safety, tolerability, immunogenicity, and antiviral efficacy of LC002 in treatment-naive individuals with HIV.
Study Population:
  • Participants were treatment-naive adults with HIV.
  • Participants had HIV RNA between 5,000 copies/mL and 150,000 copies/mL and had CD4 counts ≥400 cells/mm3.
Dosing: Participants were randomized to 1 of 3 LC002 doses or placebo, each topically administered using a skin preparation device (DermaPrep) and patch.
  • Low-dose: LC002 (0.2 mg) or placebo administered over 2 skin sites at Weeks 0, 6, 12, and 18
  • Medium-dose: LC002 (0.4 mg) or placebo administered over 4 skin sites at Weeks 0, 6, 12, and 18
  • High-dose: LC002 (0.8 mg) or placebo administered over 8 skin sites at Weeks 0, 6, 12, and 18.1,11,12
Selected Study Results:

Additional clinical trials evaluating LC002 have also been completed, including a Phase II trial (NCT00918840) that evaluated LC002’s immunogenicity and effect on viral load levels during an analytical treatment interruption of ART.15


Adverse Events


ACTG 5176; NCT00270205:

In this Phase I/II trial, analysis was conducted on data from 18 participants who received LC002 (6 each in the low-dose, middle-dose, and high-dose groups) and 7 participants who received placebo. When evaluating the proportion of participants who experienced any AE from the time of their first dose to 28 days after their last dose, there was no significant difference found between treatment groups. Overall, the most common AEs reported were general body complaints (aches/pain/discomfort, asthenia/fatigue/malaise, or fever) occurring in 7 participants, as well as skin AEs (pruritus or rash) and laboratory abnormalities, each occurring in 5 participants.9,13

Treatment-related AEs were not reported among participants in the placebo group. Among those in the LC002 treatment groups, 3 participants in the low-dose group, 1 participant in the middle-dose group, and no participants in the high-dose group reported treatment-related AEs. AEs considered to be possibly, probably, or definitely treatment-related, as well as laboratory abnormalities were all Grade 1 or 2 in severity. No Grade 3 or higher treatment-related AEs occurred. There were no changes to treatment or discontinuations of treatment because of an AE. No anti-double stranded DNA antibodies were detected among participants who had data available.9

GIEU006; NCT00711230:

During this Phase II study, 9 treatment-naive participants were randomized to each group to receive either low, medium, or high doses of LC002 or placebo. All AEs that occurred during the trial were Grade 1 or 2 in severity, and no Grade 3 or higher AEs were reported. The number of AEs that occurred was comparable across all groups. No participants discontinued treatment because of an AE. Only 1 AE – positive Gaenslen’s test – was considered as possibly related to LC002 (low dose) and resolved before the end of the study.11


Drug Interactions


LC002 drug interactions are currently unknown.


References


  1. Treatment Action Group website. Research toward a cure trials. Available at: http://www.treatmentactiongroup.org/cure/trials. Last accessed on June 15, 2018. [Archived at WebCite]
  2. Genetic Immunity website. DermaVir: HIV-specific immune therapy. Available at: https://www.geneticimmunity.com/products.html. Last accessed on June 15, 2018. [Archived at WebCite]
  3. Lederman MM, Rodriguez B, Sieg S. Immunopathogenesis of HIV Infection. In: Coffey S and Volberding P, eds. HIV InSite Knowledge Base. University of California San Francisco; 2004. Available at: http://hivinsite.ucsf.edu/InSite?page=kb-00&doc=kb-02-01-04. Last accessed on June 15, 2018. [Archived at WebCite]
  4. Miller E, Bhardwaj N. Advances in dendritic cell immunotherapies for HIV-1 infection. Expert Opin Biol Ther. 2014 Nov; 14(11): 1545-1549. Available at: https://www.tandfonline.com/doi/citedby/10.1517/14712598.2014.950652?scroll=top&needAccess=true. Last accessed on June 15, 2018.
  5. 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 June 15, 2018.
  6. 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 Feb; 134(2): 140-147. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2818410/. Last accessed on June 15, 2018.
  7. Graziani GM, Angel JB. Evaluating the efficacy of therapeutic HIV vaccines through analytical treatment interruptions. J Int AIDS Soc. 2015 Nov 9;18: 20497. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4641978/. Last accessed on June 15, 2018.
  8. Lisziewicz J, Bakare N, Calarota SA, et al. Single DermaVir immunization: dose-dependent expansion of precursor/memory T cells against all HIV antigens in HIV-1 infected individuals. PLoS One. 2012; 7(5): e35416. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3348904/. Last accessed on June 15, 2018.
  9. Rodriguez B, Asmuth DM, Matining RM, et al. Safety, tolerability and immunogenicity of repeated doses of DermaVir, a candidate therapeutic HIV vaccine, in HIV infected patients receiving combination antiretroviral therapy. Results of the ACTG 5176 trial. J Acquir Immune Defic Syndr. 2013 Dec 1; 64(4): 351-359. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3858388/. Last accessed on June 15, 2018.
  10. Lorincz O, Lisziewicz, J. HIV-specific immunotherapy with synthetic pathogen-like nanoparticles. In: Bawa R, Audette GF, Rubinstein I, eds. Handbook of Clinical Nanomedicine: From Bench to Bedside. Pan Stanford Publishing Pte. Ltd.; 2016. Available at: https://www.researchgate.net/publication/296702506_HIV-Specific_Immunotherapy_with_Synthetic_Pathogen-Like_Nanoparticles. Last accessed on June 15, 2018.
  11. van Lunzen J, Pollard R, Stellbrink H-J, et al. DermaVir for initial treatment of HIV-infected subjects demonstrates preliminary safety, immunogenicity and HIV-RNA reduction versus placebo immunization. Poster presented at: International AIDS Conference; July 18-23, 2010; Vienna, Austria. Available at: https://www.researchgate.net/publication/264848719_DermaVir_for_initial_treatment_of_HIV-infected_subjects_demonstrates_preliminary_safety_immunogenicity_and_HIV-RNA_reduction_versus_placebo_immunization_A-240-0111-_12561. Last accessed on June 15, 2018.
  12. Genetic Immunity. A Phase II randomized, placebo-controlled, multi-center study to evaluate the safety, tolerability, immunogenicity, and antiretroviral activity of DermaVir patch (LC002) in treatment-naïve HIV-1-infected patients. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on July 4, 2008. NLM Identifier: NCT00711230. Available at: https://www.clinicaltrials.gov/ct2/show/NCT00711230. Last accessed on June 15, 2018.
  13. National Institute of Allergy and Infectious Diseases (NIAID). A Phase I/II, randomized, double-blind study to evaluate the safety, tolerability, and immunogenicity of LC002, a DermaVir vaccine, in HIV-1-infected subjects currently under treatment with highly active antiretroviral therapy (HAART). In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on December 21, 2005. NLM Identifier: NCT00270205. Available at: https://www.clinicaltrials.gov/ct2/show/NCT00270205. Last accessed on June 15, 2018.
  14. Rodriguez B, Asmuth D, Matining R, et al. DermaVir as a therapeutic vaccination strategy for HIV infection: results from ACTG protocol A5176. Abstract presented at: International Aids Society (IAS) Conference on HIV Pathogenesis, Treatment and Prevention; July 17-20, 2011; Rome, Italy. Abstract CDB503. Available at: http://www.abstract-archive.org/Abstract/Share/9049. Last accessed on June 15, 2018. [Archived at WebCite]
  15. Genetic Immunity. Antiretroviral-sparing concept: an exploratory Phase II, randomized, single blind placebo-controlled study to investigate the effect of therapeutic immunization on the quantity of HIV-specific T cell precursors during highly active antiretroviral therapy followed by analytical treatment interruption. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on June 8, 2009. NLM Identifier: NCT00918840. Available at: https://www.clinicaltrials.gov/ct2/show/NCT00918840. Last accessed on June 15, 2018.


Last Reviewed: June 15, 2018