 |
|
|
| |
Preventive HIV vaccine Enters Phase 3 Global Study
|
| |
| |
Download the PDF here
Download the PDF here
results of the Phase 1/2a ASCENT study, which support the upcoming launch of Mosaico, the first Phase 3 efficacy study for this vaccine regimen that will be conducted across three continents....
Here are 2 presentations at IAS: ASCENT Phase 2a & APPROACH Phase 1/2a Studies, slide presentation pdfs attached. Abstract below
Late-breaking findings from Phase 1/2a study ASCENT presented at 10th International AIDS Society Conference on HIV Science (IAS 2019)
MEXICO CITY, July 23, 2019 – The Janssen Pharmaceutical Companies of Johnson & Johnson today announced results from a Phase 1/2a study evaluating an investigational mosaic-based preventive vaccine regimen against HIV-1 infection. The study, ASCENT (HPX2003/HVTN 118), found that adding a bivalent soluble protein to the regimen (a combination of Clade C and Mosaic gp140) improved the breadth of immune responses to different HIV strains circulating worldwide. The results were shared today in a late-breaking presentation at the 10th International AIDS Society Conference on HIV Science (IAS 2019) in Mexico City.
Janssen’s mosaic-based vaccine candidate contains mosaic immunogens (molecules capable of inducing an immune response) that have been created using genes from a wide variety of HIV-1 subtypes with the goal of delivering a global vaccine that could be deployed anywhere in the world.
“While the global genetic diversity of HIV poses a considerable scientific challenge, we believe that the mosaic vaccine approach may have the potential to address this problem,” said Hanneke Schuitemaker, Ph.D., Vice President, Head Viral Vaccine Discovery and Translational Medicine, Janssen Vaccines & Prevention B.V. “We are encouraged by the results of the Phase 1/2a ASCENT study, which support the upcoming launch of Mosaico, the first Phase 3 efficacy study for this vaccine regimen that will be conducted across three continents.”
Janssen’s investigational preventive HIV vaccine regimen involves four vaccination visits over one year. The first two vaccination visits involve a single injection of tetravalent mosaic-based adenovirus serotype 26 vector (Ad26.Mos4.HIV). The last two vaccination visits include Ad26.Mos4.HIV plus an injection of a soluble trimeric gp140 protein adjuvanted by aluminum phosphate.
In the ASCENT trial, a bivalent combination of Clade C and Mosaic gp140 was evaluated for immunogenicity (ability to induce an immune response) compared to single-valent Clade C gp140. In the study, both regimens induced high immune responses against a broad range of HIV-1 subtypes. But notably, the study found that bivalent gp140 enhanced immune responses to Clade B, the predominant subtype in the Americas, Western Europe and Australasia. This was achieved without diminishing immune responses to Clade C, which is prevalent in Southern Africa, the horn of Africa, and India.
To further investigate the potential of this approach, on July 15, 2019, Johnson & Johnson announced the formation of a new public-private partnership to support a Phase 3 study called Mosaico (HPX3002/HVTN 706). Mosaico will evaluate the vaccine regimen containing Ad26.Mos4.HIV, and bivalent gp140 adjuvanted by aluminum phosphate. The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), the HIV Vaccine Trials Network (HVTN) based at the Fred Hutchinson Cancer Research Center, and the U.S. Army Medical Research and Development Command (USAMRDC) are joining forces with the Janssen Pharmaceutical Companies of Johnson & Johnson to study the potential global vaccine.
Mosaico will have a target enrollment of 3,800 individuals in eight countries across North America, South America and Europe, and is expected to commence later in 2019.
About ASCENT
The ASCENT study (HPX2003/HVTN 118) was conducted in Kenya, Rwanda, and the United States in 152 healthy adults (18–50 years). Participants were vaccinated with either Ad26.Mos4.HIV and bivalent Clade C/Mosaic gp140 adjuvanted by aluminum phosphate (n=100), Ad26.Mos4.HIV and adjuvanted Clade C gp140 (n=26), or placebo (n=26).
At 52 weeks (four weeks after the last vaccination), both active vaccine regimens induced binding and functional antibodies to all antigens tested. Clade C responses were not reduced by replacing half of the clade C dose with Mosaic gp140, while clade B responses improved. The active regimens were well tolerated and there were no serious adverse events. More information about ASCENT can be found on ClinicalTrials.gov (identifier NCT02935686).
Additional Vaccine Studies at IAS
Janssen’s HIV vaccine presentations at IAS will also include the latest long-term findings from the Phase 1/2a APPROACH study, which examined two regimens of a mosaic-based viral vector with varying doses of the Clade C gp140 soluble protein. Data from an unblinded long-term extension of this study (n=65) demonstrate durable humoral and cellular immune responses through two years, with a 100% antibody response rate being maintained at week 144 (two years post last immunization). The study also found that those participants who had an immune response to the first vaccination in the regimen schedule were more likely to maintain this response over time. Additionally, no safety issues were reported.
----------------------------------
ASCENT: Phase 2a, randomized, double-blind, placebo controlled study evaluating safety and immunogenicity of two HIV-1 prophylactic vaccine regimens comprising Ad26.Mos4.HIV and either clade C gp140 or bivalent gp140
D.J. Stieh1, F. Tomaka2, C.A. Comeaux1, S. Nijs3, K. Callewaert3, J. Hendriks1, Z. Euler1, G.D. Tomaras4, G. Alter5, J. Kublin6, L. Corey6, J. McElrath6, E. Swann7, M. Robb8,9, N. Michael8,9, M. Marovich7, M.G. Pau1, D.H. Barouch5,10, H. Schuitemaker1
1Janssen Vaccines & Prevention B.V, Leiden, Netherlands, 2Janssen Research & Development, Titusville, United States, 3Janssen Research & Development, Beerse, Belgium, 4Duke Human Vaccine Institute, Duke University, Durham, United States, 5Ragon Institute of MGH, MIT and Harvard, Cambridge, United States, 6Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United States, 7Vaccine Research Program, Division of AIDS, National Institutes of Health, Bethesda, United States, 8U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, United States, 9Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, United States, 10Beth Israel Deaconess, Medical Center, Harvard Medical Center, Boston, United States
Background: Mosaic HIV-1 antigens induce broad immune responses and aim to provide protection against diverse HIV-1 strains. Heterologous vaccination regimens including Ad26 and gp140 have conferred significant protection in NHP, and were safe and immunogenic in humans.
To optimize breadth, and refine the vaccine composition, ASCENT assessed adding Mosaic1 gp140 to clade C gp140 in the regimen.
Methods: This study was conducted in adults in Kenya, Rwanda and the USA. Participants were randomized to Ad26.Mos4.HIV at weeks 0 and 12, and Ad26.Mos4.HIV and alum adjuvanted gp140 Env protein (250µg clade C gp140 or bivalent clade C-Mosaic1 gp140, each 125µg) at weeks 24 and 48 or placebo.
Serious adverse events (AEs) were assessed throughout the study, unsolicited AEs until 28 days post-each vaccination, and solicited AEs until 7 days post-each vaccination.
Results: 152 healthy adults (18-50 years; 59% females) were vaccinated with Ad26.Mos4.HIV and clade C gp140 (n=26), Ad26.Mos4.HIV and bivalent gp140 (n=100) or placebo (n=26). Active regimens were well tolerated (most AEs were mild/moderate; no serious AEs).
HIV Env-specific binding antibody levels and subclass distribution showed both regimens induced binding and functional antibodies to all antigens tested (Figure). Clade C responses were not attenuated by replacing half the clade C dose with Mosaic1 gp140, while clade B responses improved (p< 0.05).
At week 28, similar PTE Env ELISpot responses were observed, with medians of 444 and 452 SFU/106 PBMC in bivalent or clade C groups, respectively. CD4+ (but not CD8+) T-cell ICS responses increased to Mos1 gp120 peptides in the bivalent relative to clade C group (0.147% vs 0.123% IL-2 and/or IFNγ+ CD4 T-cells, 81% vs 50% response, respectively).
Conclusions: Both regimens were well tolerated and immunogenic. ASCENT supports using bivalent clade C-Mosaic1 gp140 with Ad26.Mos4.HIV for expanded clade coverage in the phase 3 efficacy study trial starting in 2019.
------------------------------
Two-year post-vaccination follow-up from APPROACH: Phase 1/2a randomized study evaluating safety and immunogenicity of prophylactic HIV vaccine regimens combining Ad26.Mos.HIV and gp140 envelope protein
F. Tomaka1, D.J. Stieh2, D.H. Barouch3, M.L. Robb4,5, N.L. Michael4,5, L. Lavreys6, S. Nijs6, K. Callewaert6, J. Hendriks2, Z. Euler2, M.G. Pau2, H. Schuitemaker2, and the APPROACH Study Team
1Janssen Research and Development, Titusville, United States, 2Janssen Vaccines & Prevention B.V, Leiden, Netherlands, 3Beth Israel Deaconess, Medical Center, Harvard Medical Center, Boston, United States, 4Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, United States, 5Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, United States, 6Janssen Pharmaceutica NV, Beerse, Belgium
Background: Despite increased availability of new options for HIV prevention, the epidemic remains insufficiently controlled, highlighting the need for a prophylactic vaccine. In APPROACH we evaluated seven combinations of viral vectors expressing mosaic HIV-1 Env/Gag/Pol antigens and high-dose (HD) or low-dose (LD) aluminum phosphate adjuvanted clade C Env gp140 protein. All regimens were well tolerated and immunogenic. Two regimens were selected for longer-term follow-up.
Methods: In this unblinded follow-up of APPROACH (phase 1/2a randomized, double-blind, placebo-controlled study) long-term safety and immunogenicity were evaluated at Wk120 and Wk144 in healthy uninfected adults who had received Ad26.Mos.HIV (week [Wk]0 and Wk12) and Ad26.Mos.HIV, gp140HD or LD (Wk24 and Wk48).
Results: 65 participants (18-49 years) vaccinated with Ad26.Mos.HIV, gp140HD (32) or LD (33) entered the long-term follow-up (from Thailand, Rwanda, Uganda, South Africa and USA).
No serious adverse events were reported during follow-up. Immune responses were maintained in both groups with 100% responders to autologous Clade C ELISA at Wk120 and Wk144, in the HD group. Geometric mean titres were 3.5 and 3.3 Log10 at Wk120, and 3.4 and 3.2 Log10 at Wk144, in the HD and LD groups, respectively.
Maintained responses were observed over the second year post last vaccination, remaining in the same range as those measured at Wk78 and Wk96. Comparison to a parallel NHP challenge study showed that Wk120 and Wk144 ELISA titers remained higher than NHP responses at Wk72 when they were protected against SHIV challenge.
Conclusions: In this 2-year post-vaccination follow-up of APPROACH, we observed durable humoral immune responses over 2 years with 100% response rate in the participants receiving the Ad26.Mos.HIV, gp140HD vaccine regimen. No safety issues were seen. Additional immunological analyses and follow-up will continue (approximately 6 year post-vaccination).
|
| |
|
|
|
|
|
