Extended Evaluation of Virological, Immunological and Pharmacokinetic Endpoints of CELADEN: A Randomized, Placebo-Controlled Trial of Celgosivir in Dengue Fever Patients

PLoS Neglected Tropical Diseases

Volumn 10, Issue 8, 2016, Pages

  Sung, Cynthia ^a,b   Wei, Yuan ^c   Watanabe, Satoru ^a   Lee, How Sung ^d   Khoo, Yok Moi ^d   Fan, Lu ^d   Rathore, Abhay P S ^a   Chan, Kitti Wing Ki ^a   Choy, Milly M ^e   Kamaraj, Uma S ^a   Sessions, October M ^a   Aw, Pauline ^e   de Sessions, Paola F ^e   Lee, Bernett ^f   Connolly, John E ^f   Hibberd, Martin L ^e   Vijaykrishna, Dhanasekaran ^a   Wijaya, Limin ^g   Ooi, Eng Eong ^a   Low, Jenny Guek Hong ^g   Vasudevan, Subhash G ^a   more..

^a DUKE NUS MEDICAL SCHOOL   (Singapore)

^b HEALTH SCIENCES AUTHORITY   (Singapore)

^c SINGAPORE CLINICAL RESEARCH INSTITUTE   (Singapore)

^d NATIONAL UNIVERSITY OF SINGAPORE   (Singapore)

^e GENOME INSTITUTE OF SINGAPORE   (Singapore)

^f INSTITUTE OF MOLECULAR AND CELL BIOLOGY   (Singapore)

^g NONE   (Singapore)

Author keywords

[No Author keywords available]

Indexed keywords

CASTANOSPERMINE; CASTANOSPERMINE 6 BUTYRATE; IMMUNOGLOBULIN G; IMMUNOGLOBULIN M; PLACEBO; VIRUS RNA; ANTIVIRUS AGENT; CYTOKINE; INDOLIZINE DERIVATIVE;

ADULT; AREA UNDER THE CURVE; ARTICLE; CLINICAL ARTICLE; CONTROLLED STUDY; DENGUE; DOUBLE BLIND PROCEDURE; ENZYME LINKED IMMUNOSORBENT ASSAY; FEMALE; GENE DOSAGE; HELPER CELL; HEMATOCRIT; HUMAN; LIQUID CHROMATOGRAPHY; MALE; MASS SPECTROMETRY; NEXT GENERATION SEQUENCING; NONHUMAN; OUTCOME ASSESSMENT; PHYLOGENY; RANDOMIZED CONTROLLED TRIAL; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; SYNTHESIS; THROMBOCYTE COUNT; VIRAL PLAQUE ASSAY; VIREMIA; VIRUS GENOME; VIRUS REPLICATION; VIRUS STRAIN; BLOOD; CLINICAL TRIAL; DENGUE VIRUS; DRUG EFFECTS; GENETICS; HALF LIFE TIME; HIGH THROUGHPUT SEQUENCING; IMMUNOLOGY; ISOLATION AND PURIFICATION; PHYSIOLOGY; TH1 CELL; VIROLOGY; VIRUS LOAD;

ADULT; ANTIVIRAL AGENTS; CYTOKINES; DENGUE; DENGUE VIRUS; FEMALE; HALF-LIFE; HIGH-THROUGHPUT NUCLEOTIDE SEQUENCING; HUMANS; INDOLIZINES; MALE; PHYLOGENY; TH1 CELLS; VIRAL LOAD; VIREMIA; VIRUS REPLICATION;

EID: 84988691039     PISSN: 19352727     EISSN: 19352735     Source Type: Journal    
DOI: 10.1371/journal.pntd.0004851     Document Type: Article

References (45)

1. Bhatt S, Gething PW, Brady OJ, Messina JP, Farlow AW, Moyes CL, et al. The global distribution and burden of dengue. Nature. 2013;496(7446):504–7. doi: 10.1038/nature1206023563266
2. WHO. Dengue: Guidelines for Diagnosis, Treatment, Prevention and Control: New Edition. Dengue: Guidelines for Diagnosis, Treatment, Prevention and Control: New Edition. WHO Guidelines Approved by the Guidelines Review Committee. Geneva2009.
3. Lee KS, Lo S, Tan SS, Chua R, Tan LK, Xu H, et al. Dengue virus surveillance in Singapore reveals high viral diversity through multiple introductions and in situ evolution. Infect Genet Evol. 2012;12(1):77–85. doi: 10.1016/j.meegid.2011.10.01222036707
4. Communicable Diseases Surveillance in Singapore 2013. www.moh.gov.sg/content/moh_web/home/Publications/Reports/2014/communicable-diseases-surveillance-in-singapore-2013.html [accessed 01 Feb 2016].
5. Wilder-Smith A, Ooi EE, Vasudevan SG, Gubler DJ, Update on dengue: epidemiology, virus evolution, antiviral drugs, and vaccine development. Curr Infect Dis Rep. 2010;12(3):157–64. doi: 10.1007/s11908-010-0102-721308524
6. Guzman MG, Alvarez M, Halstead SB, Secondary infection as a risk factor for dengue hemorrhagic fever/dengue shock syndrome: an historical perspective and role of antibody-dependent enhancement of infection. Arch Virol. 2013;158(7):1445–59. doi: 10.1007/s00705-013-1645-323471635
7. Halstead SB, O'Rourke EJ, Antibody-enhanced dengue virus infection in primate leukocytes. Nature. 1977;265(5596):739–41. 404559
8. Endy TP, Nisalak A, Chunsuttitwat S, Vaughn DW, Green S, Ennis FA, et al. Relationship of preexisting dengue virus (DV) neutralizing antibody levels to viremia and severity of disease in a prospective cohort study of DV infection in Thailand. J Infect Dis. 2004;189(6):990–1000. 14999601
9. Vaughn DW, Green S, Kalayanarooj S, Innis BL, Nimmannitya S, Suntayakorn S, et al. Dengue viremia titer, antibody response pattern, and virus serotype correlate with disease severity. J Infect Dis. 2000;181(1):2–9. 10608744
10. Capeding MR, Tran NH, Hadinegoro SR, Ismail HI, Chotpitayasunondh T, Chua MN, et al. Clinical efficacy and safety of a novel tetravalent dengue vaccine in healthy children in Asia: a phase 3, randomised, observer-masked, placebo-controlled trial. Lancet. 2014;384(9951):1358–65. doi: 10.1016/S0140-6736(14)61060-625018116
11. Villar L, Dayan GH, Arredondo-Garcia JL, Rivera DM, Cunha R, Deseda C, et al. Efficacy of a tetravalent dengue vaccine in children in Latin America. N Engl J Med. 2015;372(2):113–23. doi: 10.1056/NEJMoa141103725365753
12. Hadinegoro SR, Arredondo-Garcia JL, Capeding MR, Deseda C, Chotpitayasunondh T, Dietze R, et al. Efficacy and Long-Term Safety of a Dengue Vaccine in Regions of Endemic Disease. N Engl J Med. 2015;373(13):1195–206. doi: 10.1056/NEJMoa150622326214039
13. Halstead SB, Russell PK, Protective and immunological behavior of chimeric yellow fever dengue vaccine. Vaccine. 2016;34(14): 1643–47. doi: 10.1016/j.vaccine.2016.02.00426873054
14. Tricou V, Minh NN, Van TP, Lee SJ, Farrar J, Wills B, et al. A randomized controlled trial of chloroquine for the treatment of dengue in Vietnamese adults. PLoS Negl Trop Dis. 2010;4(8):e785. doi: 10.1371/journal.pntd.000078520706626
15. Nguyen NM, Tran CN, Phung LK, Duong KT, Huynh Hle A, Farrar J, et al. A randomized, double-blind placebo controlled trial of balapiravir, a polymerase inhibitor, in adult dengue patients. J Infect Dis. 2013;207(9):1442–50. doi: 10.1093/infdis/jis47022807519
16. Tam DT, Ngoc TV, Tien NT, Kieu NT, Thuy TT, Thanh LT, et al. Effects of short-course oral corticosteroid therapy in early dengue infection in Vietnamese patients: a randomized, placebo-controlled trial. Clin Infect Dis. 2012;55(9):1216–24. doi: 10.1093/cid/cis65522865871
17. Low JG, Sung C, Wijaya L, Wei Y, Rathore AP, Watanabe S, et al. Efficacy and safety of celgosivir in patients with dengue fever (CELADEN): a phase 1b, randomised, double-blind, placebo-controlled, proof-of-concept trial. Lancet Infect Dis. 2014;14(8):706–15. doi: 10.1016/S1473-3099(14)70730-324877997
18. Whitehorn J, Nguyen CV, Khanh LP, Kien DT, Quyen NT, Tran NT, et al. Lovastatin for the Treatment of Adult Patients With Dengue: A Randomized, Double-Blind, Placebo-Controlled Trial. Clin Infect Dis. 2016;62(4):468–76. doi: 10.1093/cid/civ94926565005
19. Durantel D, Celgosivir, an alpha-glucosidase I inhibitor for the potential treatment of HCV infection. Curr Opin Investig Drugs. 2009;10(8):860–70. 19649930
20. Sorbera LA, Castaner J, Garcia-Capdevilla L, Celgosivir: α-Glucosidase inhibitor anti-hepatitis C virus drug. Drugs of the future2005;30(6): 545–52.
21. Rathore AP, Paradkar PN, Watanabe S, Tan KH, Sung C, Connolly JE, et al. Celgosivir treatment misfolds dengue virus NS1 protein, induces cellular pro-survival genes and protects against lethal challenge mouse model. Antiviral Res. 2011;92(3):453–60. doi: 10.1016/j.antiviral.2011.10.00222020302
22. Watanabe S, Rathore AP, Sung C, Lu F, Khoo YM, Connolly J, et al. Dose- and schedule-dependent protective efficacy of celgosivir in a lethal mouse model for dengue virus infection informs dosing regimen for a proof of concept clinical trial. Antiviral Res. 2012;96(1):32–5. doi: 10.1016/j.antiviral.2012.07.00822867971
23. Watanabe S, Chan KW, Dow G, Ooi EE, Low JG, Vasudevan SG, Optimizing celgosivir therapy in mouse models of dengue virus infection of serotypes 1 and 2: The search for a window for potential therapeutic efficacy. Antiviral Res. 2016;127:10–9. doi: 10.1016/j.antiviral.2015.12.00826794905
24. Liu PS, Rhinehart BL, Daniel JK. Castanospermine Esters and Glycosides. US Patent 5,017,563. 1991.
25. Kraus AA, Messer W, Haymore LB, de Silva AM, Comparison of plaque- and flow cytometry-based methods for measuring dengue virus neutralization. J Clin Microbiol. 2007;45(11):3777–8017804661
26. Chaterji S., Allen JC., Jr.Chow A, Leo YS, Ooi EE, Evaluation of the NS1 rapid test and the WHO dengue classification schemes for use as bedside diagnosis of acute dengue fever in adults. Am J Trop Med Hyg, 2011. 84(2): p. 224–8. doi: 10.4269/ajtmh.2011.10-031621292888
27. Sessions OM, Wilm A, Kamaraj US, Choy MM, Chow A, Chong Y, et al. Analysis of Dengue Virus Genetic Diversity during Human and Mosquito Infection Reveals Genetic Constraints. PLoS Negl Trop Dis. 2015;9(9):e0004044. doi: 10.1371/journal.pntd.000404426327586
28. Sim S, Aw PP, Wilm A, Teoh G, Hue KD, Nguyen NM, et al. Tracking Dengue Virus Intra-host Genetic Diversity during Human-to-Mosquito Transmission. PLoS Negl Trop Dis. 2015;9(9):e0004052. doi: 10.1371/journal.pntd.000405226325059
29. Li H, Durbin R, Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics. 2009;25(14):1754–60. doi: 10.1093/bioinformatics/btp32419451168
30. McKenna A, Hanna M, Banks E, Sivachenko A, Cibulskis K, Kernytsky A, et al. The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res. 2010;20(9):1297–303. doi: 10.1101/gr.107524.11020644199
31. Wilm A, Aw PP, Bertrand D, Yeo GH, Ong SH, Wong CH, et al. LoFreq: a sequence-quality aware, ultra-sensitive variant caller for uncovering cell-population heterogeneity from high-throughput sequencing datasets, Nucleic Acids Res. 2012:40 (22): 11189–201. doi: 10.1093/nar/gks91823066108
32. Thai KT, Henn MR, Zody MC, Tricou V, Nguyet NM, Charlebois P, et al. High-resolution analysis of intrahost genetic diversity in dengue virus serotype 1 infection identifies mixed infections. Journal of virology. 2012;86(2):835–43. doi: 10.1128/JVI.05985-1122090119
33. Katoh K., Standley D.M., 2013. MAFFT Multiple Sequence Alignment Software Version 7: Improvements in Performance and Usability. Molecular biology and evolution30, 772–780doi: 10.1093/molbev/mst01023329690
34. Stamatakis A., 2014. RAxML Version 8: A tool for Phylogenetic Analysis and Post- Analysis of Large Phylogenies. Bioinformatics30: 1312–1313. doi: 10.1093/bioinformatics/btu03324451623
35. Beatty PR, Puerta-Guardo H, Killingbeck SS, Glasner DR, Hopkins K, Harris E, Dengue virus NS1 triggers endothelial permeability and vascular leak that is prevented by NS1 vaccination. Sci Transl Med. 2015;7(304):304ra141. doi: 10.1126/scitranslmed.aaa378726355030
36. Modhiran N, Watterson D, Muller DA, Panetta AK, Sester DP, Liu L, et al. Dengue virus NS1 protein activates cells via Toll-like receptor 4 and disrupts endothelial cell monolayer integrity. Sci Transl Med. 2015;7(304):304ra142. doi: 10.1126/scitranslmed.aaa386326355031
37. Kang W, Li Y, Zhuang Y, Zhao K, Huang D, Sun Y, Dynamic analysis of Th1/Th2 cytokine concentration during antiretroviral therapy of HIV-1/HCV co-infected patients. BMC Infect Dis. 2012,12, 102. doi: 10.1186/1471-2334-12-10222533731
38. Warfield KL, Plummer EM, Sayce AC, Alonzi DS, Tang W, Tyrrell BE, et. al. Inhibition of endoplasmic reticulum glucosidases is required for in vitro and in vivo dengue antiviral activity by the iminosugar UV-4. Antiviral Res. 2016Mar2. doi: 10.1016/j.antiviral.2016.03.001
39. Pharmacokinetics in Patients with Impaired Renal Function–Study Design, Data Analysis, and Impact on Dosing and Labeling, FDA Draft Guidance for Industry, March 2010.
40. Tricou V, Minh NN, Farrar J, Tran HT, Simmons CP, Kinetics of viremia and NS1 antigenemia are shaped by immune status and virus serotype in adults with dengue. PLoS Negl Trop Dis. 2011;5(9):e1309. doi: 10.1371/journal.pntd.000130921909448
41. Keller TH, Chen YL, Knox JE, et al. Finding new medicines for flaviviral targets. Novartis Foundation symposium2006; 277:102–14; discussion 14–9, 251–3. 17319157
42. World Health Organization. Dengue: Guidelines for Diagnosis, Treatment, Prevention and Control: New Edition. WHO Guidelines Approved by the Guidelines Review Committee. Geneva, 2009.
43. Manokaran G, McPherson K, Simmons CP, Stopping dengue: recent advances and new challenges. 2016Microbiology Australia
44. Sayce AC, Alonzi DS, Killingbeck SS, Tyrrell BE, Hill ML, et. al. Iminosugras inhibit dengue virus production via inhibition of endoplasmic reticulum glucosidases–not glycolipid processing enzymes. 2016PLoS Negl Trop Dis. doi: 10.1371/journal.pntd.0004524
45. Weaver SC, Costa F, Garcia-Blanco MA, Ko AI, Guilherme SR, et alZika virus: History, Emergence, Biology and Prospects for Control. 2016 Antiviral Res. Antiviral Res. 2016Jun;130:69–80. 26996139