Two phase 1, randomized, double-blind, placebo-controlled, single- ascending-dose studies to investigate the safety, tolerability, and pharmacokinetics of an anti-influenza a virus monoclonal antibody, MHAA4549A, in healthy volunteers

Antimicrobial Agents and Chemotherapy

Volumn 60, Issue 9, 2016, Pages 5437-5444

  Lim, Jeremy J ^a   Deng, Rong ^a   Derby, Michael A ^a   Larouche, Richard ^b   Horn, Priscilla ^a   Anderson, Malia ^a   Maia, Mauricio ^a   Carrier, Stephanie ^b   Pelletier, Isabelle ^b   Burgess, Tracy ^a   Kulkarni, Priya ^a   Newton, Elizabeth ^a   Tavel, Jorge A ^a  

^a GENENTECH INC   (United States)

^b SYNEOS HEALTH   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALANINE AMINOTRANSFERASE; ANTIVIRUS AGENT; CREATINE KINASE; MHAA 4549A; MONOCLONAL ANTIBODY; UNCLASSIFIED DRUG; VIRUS ANTIBODY; INFLUENZA VIRUS HEMAGGLUTININ;

ADULT; ALANINE AMINOTRANSFERASE BLOOD LEVEL; ANTIBODY RESPONSE; AREA UNDER THE CURVE; ARTICLE; CONTROLLED STUDY; CREATINE KINASE BLOOD LEVEL; DOUBLE BLIND PROCEDURE; DRUG HALF LIFE; DRUG SAFETY; DRUG TOLERABILITY; FEMALE; HEADACHE; HUMAN; HUMAN EXPERIMENT; IMMUNOGENICITY; LIMIT OF QUANTITATION; MALE; NORMAL HUMAN; OROPHARYNX PAIN; PHASE 1 CLINICAL TRIAL; PLASMA CONCENTRATION-TIME CURVE; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; RHINOPHARYNGITIS; SIDE EFFECT; VIRUS STRAIN; VOLUME OF DISTRIBUTION AT STEADY-STATE; CLINICAL TRIAL; DRUG ADMINISTRATION; GENE EXPRESSION; GENETICS; HALF LIFE TIME; INFLUENZA, HUMAN; INTRAVENOUS DRUG ADMINISTRATION; METABOLISM; MIDDLE AGED; PATIENT SAFETY; VIROLOGY;

ADULT; ANTIBODIES, MONOCLONAL; ANTIVIRAL AGENTS; DRUG ADMINISTRATION SCHEDULE; FEMALE; GENE EXPRESSION; HALF-LIFE; HEADACHE; HEALTHY VOLUNTEERS; HEMAGGLUTININ GLYCOPROTEINS, INFLUENZA VIRUS; HUMANS; INFLUENZA, HUMAN; INJECTIONS, INTRAVENOUS; MALE; MIDDLE AGED; PATIENT SAFETY;

EID: 84983490282     PISSN: 00664804     EISSN: 10986596     Source Type: Journal    
DOI: 10.1128/AAC.00607-16     Document Type: Article

References (28)

1. Ison MG, de Jong MD, Gilligan KJ, Higgs ES, Pierson J, Hayden FG. 2010. Endpoints for testing influenza antiviral treatments for patients at high risk of severe and life-threatening disease. J Infect Dis 201:1654-1662. http://dx.doi.org/10.1086/652498.
2. World Health Organization. 2014. Influenza (seasonal). Fact sheet no. 211. World Health Organization, Geneva, Switzerland. http://www.who.int/mediacentre/factsheets/fs211/en/.
3. Reed C, Chaves SS, Daily Kirley P, Emerson R, Aragon D, Hancock EB, Butler L, Baumbach J, Hollick G, Bennett NM, Laidler MR, Thomas A, Meltzer MI, Finelli L. 2015. Estimating influenza disease burden from population-based surveillance data in the United States. PLoS One 10: e0118369. http://dx.doi.org/10.1371/journal.pone.0118369.
4. Hadler JL, Yousey-Hindes K, Pérez A, Anderson EJ, Bargsten M, Bohm SR, Hill M, Hogan B, Laidler M, Lindegren ML, Lung KL, Mermel E, Miller L, Morin C, Parker E, Zansky SM, Chaves SS. 2016. Influenzarelated hospitalizations and poverty levels-United States, 2010-2012. MMWR Morb Mortal Wkly Rep 65:101-105. http://dx.doi.org/10.15585/mmwr.mm6505a1.
5. Aoki FY, Macleod MD, Paggiaro P, Carewicz O, El Sawy A, Wat C, Griffiths M, Waalberg E, Ward P, Study Group IMPACT. 2003. Early administration of oral oseltamivir increases the benefits of influenza treatment. J Antimicrob Chemother 51:123-129. http://dx.doi.org/10.1093/jac/dkg007.
6. Muthuri SG, Venkatesan S, Myles PR, Leonardi-Bee J, Al Khuwaitir TS, Al Mamun A, Anovadiya AP, Azziz-Baumgartner E, Báez C, Bassetti M, Beovic B, Bertisch B, Bonmarin I, Booy R, Borja-Aburto VH, Burgmann H, Cao B, Carratala J, Denholm JT, Dominguez SR, Duarte PA, Dubnov-Raz G, Echavarria M, Fanella S, Gao Z, Gérardin P, Giannella M, Gubbels S, Herberg J, Iglesias AL, Hoger PH, Hu X, Islam QT, Jiménez MF, Kandeel A, Keijzers G, Khalili H, Knight M, Kudo K, Kusznierz G, Kuzman I, Kwan AM, Amine IL, Langenegger E, Lankarani KB, Leo YS, Linko R, Liu P, Madanat F, Mayo-Montero E, McGeer A, et al. 2014. Effectiveness of neuraminidase inhibitors in reducing mortality in patients admitted to hospital with influenza A H1N1pdm09 virus infection: a meta-analysis of individual participant data. Lancet Respir Med 2:395-404. http://dx.doi.org/10.1016/S2213-2600(14)70041-4.
7. Nakamura G, Chai N, Park S, Chiang N, Lin Z, Chiu H, Fong R, Yan D, Kim J, Zhang J, Lee WP, Estevez A, Coons M, Xu M, Lupardus P, Balazs M, Swem LR. 2013. An in vivo human-plasmablast enrichment technique allows rapid identification of therapeutic influenza A antibodies. Cell Host Microbe 14:93-103. http://dx.doi.org/10.1016/j.chom.2013.06.004.
8. Chai N, Swem LR, Reichelt M, Chen-Harris H, Luis E, Fouts A, Lupardus P, Wu TD, Li O, McBride J, Laurence M, Xu M, Tan M-W. 2016. Two escape mechanisms of influenza A virus to a broadly neutralizing stalk-binding antibody. PLoS Pathog 12(6):e1005702. http://dx.doi.org/10.1371/journal.ppat.1005702.
9. Mire-Sluis AR, Barrett YC, Devanarayan V, Koren E, Liu H, Maia M, Parish T, Scott G, Shankar G, Shores E, Swanson SJ, Taniguchi G, Wierda D, Zuckerman LA. 2004. Recommendations for the design and optimization of immunoassays used in the detection of host antibodies against biotechnology products. J Immunol Methods 289:1-16. http://dx.doi.org/10.1016/j.jim.2004.06.002.
10. Wakshull E, Coleman D. 2011. Confirmatory immunogenicity assays, p 103-117. In Tovey M (ed), Detection and quantification of antibodies to biopharmaceuticals: practical and applied considerations. John Wiley & Sons, Hoboken, NJ.
11. Koren E, Smith HW, Shores E, Shankar G, Finco-Kent D, Rup B, Barrett YC, Devanarayan V, Gorovits B, Gupta S, Parish T, Quarmby V, Moxness M, Swanson SJ, Taniguchi G, Zuckerman LA, Stebbins CC, Mire-Sluis A. 2008. Recommendations on risk-based strategies for detection and characterization of antibodies against biotechnology products. J Immunol Methods 333:1-9. http://dx.doi.org/10.1016/j.jim.2008.01.001.
12. Bai S, Jorga K, Xin Y, Jin D, Zheng Y, Damico-Beyer LA, Gupta M, Tang M, Allison DE, Lu D, Zhang Y, Joshi A, Dresser MJ. 2012. A guide to rational dosing of monoclonal antibodies. Clin Pharmacokinet 51:119-135. http://dx.doi.org/10.2165/11596370-000000000-00000.
13. Shriver Z, Trevejo JM, Sasisekharan R. 2015. Antibody-based strategies to prevent and treat influenza. Front Immunol 6:315. http://dx.doi.org/10.3389/fimmu.2015.00315.
14. Wang DD, Zhang S, Zhao H, Men AY, Parivar K. 2009. Fixed dosing versus body size-based dosing of monoclonal antibodies in adult clinical trials. J Clin Pharmacol 49:1012-1024. http://dx.doi.org/10.1177/0091270009337512.
15. Lee N, Chan PK, Hui DS, Rainer TH, Wong E, Choi KW, Lui GC, Wong BC, Wong RY, Lam WY, Chu IM, Lai RW, Cockram CS, Sung JJ. 2009. Viral loads and duration of viral shedding in adult patients hospitalized with influenza. J Infect Dis 200:492-500. http://dx.doi.org/10.1086/600383.
16. Leyva-Grado VH, Tan GS, Leon PE, Yondola M, Palese P. 2015. Direct administration in the respiratory tract improves efficacy of broadly neutralizing anti-influenza virus monoclonal antibodies. Antimicrob Agents Chemother 59:4162-4172. http://dx.doi.org/10.1128/AAC.00290-15.
17. Wagner DK, Clements ML, Reimer CB, Snyder M, Nelson DL, Murphy BR. 1987. Analysis of immunoglobulin G antibody responses after administration of live and inactivated influenza A vaccine indicates that nasal wash immunoglobulin G is a transudate from serum. J Clin Microbiol 25:559-562.
18. Jolles S, Sewell WA, Misbah SA. 2005. Clinical uses of intravenous immunoglobulin. Clin Exp Immunol 142:1-11. http://dx.doi.org/10.1111/j.1365-2249.2005.02834.x.
19. Casadevall A, Dadachova E, Pirofski LA. 2004. Passive antibody therapy for infectious diseases. Nat Rev Microbiol 2:695-703. http://dx.doi.org/10.1038/nrmicro974.
20. Pai JC, Sutherland JN, Maynard JA. 2009. Progress towards recombinant anti-infective antibodies. Recent Pat Antiinfect Drug Discov 4:1-17. http://dx.doi.org/10.2174/157489109787236319.
21. Both L, Banyard AC, van Dolleweerd C, Wright E, Ma JK, Fooks AR. 2013. Monoclonal antibodies for prophylactic and therapeutic use against viral infections. Vaccine 31:1553-1559. http://dx.doi.org/10.1016/j.vaccine.2013.01.025.
22. Both L, Banyard AC, van Dolleweerd C, Horton DL, Ma JK, Fooks AR. 2012. Passive immunity in the prevention of rabies. Lancet Infect Dis 12:397-407. http://dx.doi.org/10.1016/S1473-3099(11)70340-1.
23. Goudsmit J, Marissen WE, Weldon WC, Niezgoda M, Hanlon CA, Rice AB, Kruif JD, Dietzschold B, Bakker AB, Rupprecht CE. 2006. Comparison of an anti-rabies human monoclonal antibody combination with human polyclonal anti-rabies immune globulin. J Infect Dis 193:796-801. http://dx.doi.org/10.1086/500470.
24. Marasco WA, Sui J. 2007. The growth and potential of human antiviral monoclonal antibody therapeutics. Nat Biotechnol 25:1421-1434. http://dx.doi.org/10.1038/nbt1363.
25. Saylor C, Dadachova E, Casadevall A. 2009. Monoclonal antibody-based therapies for microbial diseases. Vaccine 27(Suppl 6):G38-G46. http://dx.doi.org/10.1016/j.vaccine.2009.09.105.
26. Chames P, Regenmortel MV, Weiss E, Baty D. 2009. Therapeutic antibodies: successes, limitations and hopes for the future. Br J Pharmacol 157:220-233. http://dx.doi.org/10.1111/j.1476-5381.2009.00190.x.
27. Deng R, Jin F, Prabhu S, Iyer S. 2012. Monoclonal antibodies: what are the pharmacokinetic and pharmacodynamic considerations for drug development? Expert Opin Drug Metab Toxicol 8:141-160. http://dx.doi.org/10.1517/17425255.2012.643868.
28. Ramos EL, Mitcham JL, Koller TD, Bonavia A, Usner DW, Balaratnam G, Fredlund P, Swiderek KM. 2015. Efficacy and safety of treatment with an anti-M2e monoclonal antibody in experimental human influenza. J Infect Dis 211:1038-1044. http://dx.doi.org/10.1093/infdis/jiu539.