Date: 2012-09-12
Type of information:
phase: 2
Announcement: presentation of immunological data from the phase 2 study with Vacc-4x during an oral session at the AIDS Vaccine 2012 conference in Boston
Company: Bionor Pharma (Norway)
Product: Vacc-4x
Action
mechanism: Vacc-4x is a therapeutic HIV-vaccine based on four, slightly modified peptides (building blocks of proteins) from conserved parts of the HIV-virus. Endocine is an adjuvant shown to enhance the immune response to vaccine antigens delivered nasally.
This investigational HIV vaccine Vacc-4x has already completed a large exploratory phase II randomized, multinational (USA and 4 European countries), double-blind, placebo-controlled trial. It has shown that patients achieved a statistical significantly lower viral load compared to the placebo group.
Further immunological analysis have documented that the \'quality\' of immune responses between the two groups was different. This qualitative difference in immune responses may have contributed to the killing of HIV infected cells, leading to the above mentioned reduction in viral load.
Disease: HIV-Aids
Therapeutic area: Infectious diseases
Country: USA, Germany, UK, Spain, Italy
Trial
details: The analysis has been conducted on data from the exploratory phase II study on Vacc-4x, with 136 HIV patients. In this randomized, multinational (USA, Germany, UK, Spain and Italy), double-blind, placebo-controlled study, two-thirds of patients received Vacc-4x, while one-third received placebo. Patients given Vacc-4x experienced a statistically significant reduction in viral load set point (stabilized viral load) compared to placebo.
Latest
news: Bionor Pharma has announced that researchers from the Vaccine Immunotherapy Center at the Lausanne University Hospital have presented immunological data from the phase 2 study with Vacc-4x during an oral session at the AIDS Vaccine 2012 conference in Boston.
The data from immunological analysis, which was carried out at the Swiss laboratory, was presented by Kim Ellefsen-Lavoie, CTU (Clinical trials unit) Coordinator, Vaccine and Immunotherapy Center, University Hospital, Lausanne, Switzerland. The data show that patients carrying a genetic variant (HLA B-35) associated with rapid disease progression of untreated HIV infection are just as likely to respond to Vacc-4x as other patients. This supports Bionor’s intention for the vaccine to function across broader patient populations. Complete findings from the analysis will be submitted for publication.
After 6 immunizations on ART over 28 weeks, treatment was interrupted for up to 24 weeks (Vacc-4x n=88; placebo n=38). Immunological analyses (ELISPOT, proliferation, intracellular cytokine staining (ICS)) to HIV p24 were carried out at central laboratories. The HLA class I profile (Vacc-4x n=73, placebo n=32) was also determined.
For subjects that remained off ART until week 52 (Vacc-4x n=56, placebo n=25), there was a log 0.44 reduction in viral load set point between the Vacc-4x and placebo groups (p=0.0397). There was a similar distribution of HLA class I alleles in the two treatment arms, with the exception of the B35 allele (27% of Vacc-4x subjects versus 8% placebo subjects). The viral load of ELISPOT positive Vacc-4x subjects was significantly lower than that of placebo subjects (p=0.023). There was no significant difference in T-cell proliferation responses between Vacc-4x and placebo groups, however, the percentage of subjects showing proliferative CD4 and CD8 T-cell responses to Vacc-4x peptides increased over time only for the Vacc-4x group. ICS analysis showed a predominance of CD8-mediated T-cell responses to p24 that were significantly increased from baseline for the Vacc-4x group (p<0.043) but not for the placebo group (p>0.05). There was also a trend towards higher numbers of polyfunctional T-cells in the Vacc-4x group compared to the placebo group (p=0.188).
Based on the completed phase II study with Vacc-4x, and finalized preclinical studies on Vacc-C5, Bionor Pharma is preparing three further studies that can lead towards phase III:
1. Vacc-4x in combination with Celgene`s immune modulator Revlimid®(Lenalidomide), in patients who fail to regain a normal immune function despite well controlled viral load on ART. The researchers will investigate whether Revlimid can further enhance the effect of Vacc-4x. The study was recently approved by German regulatory authorities to begin at four clinics in Germany.
2. Reboost with Vacc-4x in patients from the phase II study (USA and 4 European countries), to investigate whether this can result in further reduction in viral load.
3. Clinical phase I/II study with Vacc-C5, to investigate whether this vaccine leads to the formation of antibodies against HIV in humans, was recently approved by the Norwegian regulatory authorities to begin at Oslo University Hospital. Subsequent to this Vacc-C5 phase I/II study, Bionor intends to combine Vacc-4x with Vacc-C5, which could form the basis for both a therapeutic and a preventative HIV vaccine.
