Autor:innen:
S. Sebastian (Cambridge, MA, US)
G. Chichili (Northbrook, IL, US)
R. Smulders (Northbrook, IL, US)
V. Santos (Northbrook, IL, US)
B. Cywin (Northbrook, IL, US)
L. Kovanda (Northbrook, IL, US)
C. VanSant (Northbrook, IL, US)
F. Malinoski (Cambridge, MA, US)
G. Siber (Cambridge, MA, US)
R. Malley (Cambridge, MA, US)
A. Stuendl (München, DE)
Background: Invasive pneumococcal disease, caused by Streptococcus pneumoniae infection, remains prevalent despite availability of pneumococcal vaccines. A multiple antigen-presenting system (MAPS) platform was used to develop the novel 24-valent pneumococcal candidate vaccine, ASP3772 (which has been renamed AFX3772), for induction of robust T-cell–dependent antibody response. Here we present results from a phase 2 study evaluating safety/tolerability and immunogenicity of ASP3772 in elderly participants.
Methods: This phase 2 study (NCT03803202) enrolled elderly adults, aged 65–85 years, into Group A (participants naïve to the 13-valent pneumococcal conjugate vaccine, PCV13) or Group B (participants who previously received PCV13). Group A participants were randomised to one of three ASP3772 doses (1 µg, 2 µg, 5 µg) or PCV13. Group B participants received the 23-valent pneumococcal polysaccharide vaccine, PPSV23. The primary objective was to evaluate safety/tolerability and reactogenicity of ASP3772 versus PCV13 (Group A). The secondary objective was to evaluate the immunogenicity of ASP3772 versus PCV13 (Group A) or PPSV23 (Group B), by assessment of functional opsonophagocytic activity (OPA) titers.
Results: Group A included 390 participants, of whom 293 received ASP3772 (n1 µg=100; n2 µg=107; n5 µg=86) and 97 received PCV13. Group B included 113 participants who received PPSV23. Frequently reported local reactions were tenderness and pain, occurring within the first 2–3 days with no clear difference across ASP3772 and PCV13 cohorts. Frequently reported systemic reactions included fatigue, headache, and myalgia, which tended to increase in frequency with ASP3772 dose. Neither serious vaccine-related adverse events, nor clinically relevant abnormalities (vital signs, ECGs, laboratory parameters), were observed. Day 30 OPA ratios for ASP3772 versus PCV13 were substantially higher for some shared serotypes (serotype 3 at all ASP3772 doses and serotypes 5 and 19F at ASP3772 5 µg), similar for the remaining shared serotypes, and substantially higher for all unique serotypes. Day 30 OPA ratios for the lower ASP3772 doses versus PPSV23 were comparable or higher across serotypes. Day 30 OPA ratios for ASP3772 5 µg versus PPSV23 were substantially higher for 17 serotypes, including seven shared with PCV13.
Conclusions: These results show that the novel multivalent pneumococcal candidate vaccine, ASP3772 (renamed AFX3772), did not raise safety concerns, was well tolerated, and exhibited robust immunogenicity that extended beyond serotypes shared with PCV13 in elderly adults aged 65–85 years.
Funding: Astellas Pharma, Inc.
Acknowledgement: Editorial (Ioana Sima) and coordination support were provided by Akkodis Belgium c/o GSK.