We are pleased to offer the following information on our human clinical trials program for our lead product candidate DermaVir, a state of the art immunotherapy for the treatment of HIV/AIDS. DermaVir’s API is a pDNA expressing the broadest HIV antigen repertoire in a Virus-like Particle (VLP+) enclosure currently available. The API is formulated to a pathogen-like nanomedicine. Administration is achieved via DermaPrep, a CE marked medical device.
DermaVir Phase I study
RESULTS: This first-in-human dose escalation study was conducted with three topical DermaVir doses targeted to epidermal Langerhans cells to express fifteen HIV antigens in draining lymph nodes: 0.1 mg DNA targeted to two, 0.4 mg and 0.8 mg DNA targeted to four lymph nodes. Particularly, in the medium dose cohort 0.1 mg DNA was targeted per draining lymph node via ∼8 million Langerhans cells located in 80 cm(2) epidermis area. The 28-days study with 48-week safety follow-up evaluated HIV-specific T cell responses against Gag p17, Gag p24 and Gag p15, Tat and Rev antigens. DermaVir-associated side effects were mild, transient and not dose-dependent. Boosting of HIV-specific effector CD4(+) and CD8(+) T cells expressing IFN-gamma and IL-2 was detected against several antigens in every subject of the medium dose cohort. The striking result was the dose-dependent expansion of HIV-specific precursor/memory T cells with high proliferation capacity. In low, medium and high dose cohorts this HIV-specific T cell population increased by 325-, 136,202 and 50,759 counts after 4 weeks, and by 3,899, 9,878 and 18,382 counts after one year, respectively, compared to baseline.
CONCLUSIONS: Single immunization with the DermaVir candidate therapeutic vaccine was safe and immunogenic in HIV-infected individuals. Based on the potent induction of Gag, Tat and Rev-specific memory T cells, especially in the medium dose cohort, we speculate that DermaVir boost T cell responses specific to all the 15 HIV antigens expressed from the single DNA. For durable immune reactivity repeated DermaVir immunization might be required since the frequency of DermaVir-boosted HIV-specific memory T cells decreased during the 48-week follow up.
DermaVir Phase I/II study
RESULTS: Groups were comparable at baseline. The study intervention was well tolerated, without dose-limiting toxicities. Most responses were highest at week 17 (4 weeks after last vaccination) when Gag p24 responses were significantly greater among intermediate-dose group compared with control subjects [median (IQR): 67,600 (5633-74,368) versus 1194 (9-1667)] net spot-forming units per million cells, P = 0.032. In the intermediate-dose group, there was also a marginal Gag p15 response increase from baseline to week 17 [2859 (1867-56,933), P = 0.06], and this change was significantly greater than in the placebo group [0 (-713 to 297), P = 0.016].
CONCLUSIONS: DermaVir administration was associated with a trend toward greater HIV-specific, predominantly central memory T-cell responses. The intermediate DermaVir dose tended to show the greatest immunogenicity, consistent with previous studies in different HIV-infected patient populations.
DermaVir Phase II study.
GIEU006 was designed to evaluate safety of repeated DermaVir immunizations in antiretroviral-naïve subjects and also test the immunogenicity and antiviral efficacy to guide later development.
36 HIV-infected adults (HIV-RNA: 5,000 to 150,000 copies/mL and CD4: =400 cells/mm3) were randomized to receive one of three DermaVir doses (0.2, 0.4 or 0.8 mg of pDNA) or placebo at weeks 0, 6, 12 and 18. Standard parameters and HIV(gag)-specific precursor T cells were quantified through week 24. ITT was analyzed by non-parametric statistical tests, the treatment effect with Hodges-Lehmann estimator.
Baseline characteristics were comparable across groups (median age: 38 years; CD4: 506 cells/mm3; HIV-RNA: 20,250 copies/mL; 83% Caucasian; 97% male). No subject stopped vaccinations due to an AE and only one subject initiated ARV. No AE =Grade3 occurred, grade 1 and 2 incidences were similar across groups, and only one Grade2 AE was possibly-related to the vaccine. Anti-dsDNA decreased, ANA and CD4 counts did not change and HIV-RNA did not increase. Based on secondary analyses, the 0.4 mg group was superior to others. In this group the HIVgag-specific precursor T cells increased from 5,055 to 9,978 cells/millionPBMC (P=0.07). The median log10 HIV-RNA decreased from 4.5 to 4.0, significantly different from the placebo (P=0.045). The treatment effect compared to placebo at 95% confidence interval was -0.23 (-0.70; 0.09) for log10 HIV-RNA.
DermaVir did not increase viral load nor reduced CD4 counts and was as safe as placebo. Its antiviral and immune-boosting effects in the challenging antiretroviral-naïve setting support further development. The 0.4 mg dose emerged as the vaccine candidate for the early treatment of HIV infection.
DermaVir Phase III study.
GIRU001 is our ongoing trial. It will commence at the end of 2019 with 200 patients enrolled. The study is conducted in Russia to seek marketing approval there. Study results will also be submitted to the FDA to support our US marketing application. The study is undertaken with our Russian partner Pharmadis as part of our Licensing Agreement whereby Pharmadis received exclusive right to market our HIV vaccine in CIS (Commonwealth of Independent States.).
Clinical Trials Involving DermaVir
Location clinicaltrials.gov ID Title Status
A Phase I Study to Evaluate the Tolerability and Safety of DermaVir Immune Therapy in HIV-infected Subject under Treatment with HAART
Excellent safety, tolerability, and immunogenicity.
A Phase I/II, Randomized, Double-Blind Study to Evaluate the Safety, Tolerability and Immunogenicity of DermaVir Immune Therapy in HIV-infected Subjects Currently Under Treatment with HAART
Excellent safety, tolerability, and immunogenicity.
A Phase II, Randomized, Study to Evaluate the Safety, Tolerability, Immunogenicity and Antiviral Activity of DermaVir Immune Therapy in HIV-1 Infected treatment-naïve Subjects
Preliminary safety and efficacy evaluation completed. Trial shows excellent safety and tolerability.
A Phase III study Evaluating the Immunogenicity and Antiviral Activity of DermaVir Immune Therapy in HIV-A Infected patients receiving ART+DermaVir therapy for 18 weeks, then DermaVir alone every six week for 40 weeks. Primarily endpoint is viral-control in absence of ART.
Ongoing trial, enrollment to start in Q2 of 2019.