Evaluation of the safety, tolerability and pharmacokinetics of ALN-RSV01, a novel RNAi antiviral therapeutic directed against respiratory syncytial virus (RSV)

Antiviral Research

Volumn 77, Issue 3, 2008, Pages 225-231

  DeVincenzo, John ^a   Cehelsky, Jeffrey E ^b   Alvarez, Rene ^b   Elbashir, Sayda ^b   Harborth, Jens ^b   Toudjarska, Iva ^b   Nechev, Lubomir ^b   Murugaiah, Veeravagu ^b   Vliet, Andre Van ^c   Vaishnaw, Akshay K ^b   Meyers, Rachel ^b  

^a UNIVERSITY OF TENNESSEE HEALTH SCIENCE CENTER   (United States)

^b ALNYLAM PHARMACEUTICALS   (United States)

^c PRA Health Sciences   (Netherlands)

Author keywords

ALN RSV01; Antiviral; Respiratory syncytial virus; RNA interference; RNA induced silencing complex; Small interfering RNA

Indexed keywords

ALNRSV 01; ANTIVIRUS AGENT; PLACEBO; RNA; SODIUM CHLORIDE; UNCLASSIFIED DRUG;

ADULT; ARTICLE; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DOSE RESPONSE; DRUG BIOAVAILABILITY; DRUG DELIVERY SYSTEM; DRUG DOSE ESCALATION; DRUG SAFETY; DRUG TOLERABILITY; DRY NOSE; ELECTROCARDIOGRAM; EPISTAXIS; HUMAN; LABORATORY TEST; MAJOR CLINICAL STUDY; MALE; MEDIASTINUM DISEASE; NORMAL HUMAN; NOSE CONGESTION; NOSE DISEASE; NOSE EDEMA; PHARYNX DISEASE; PHYSICAL EXAMINATION; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; RESPIRATORY SYNCYTIAL PNEUMOVIRUS; RESPIRATORY TRACT DISEASE; RHINORRHEA; RNA INTERFERENCE; SORE THROAT; THORAX DISEASE; UPPER RESPIRATORY TRACT INFECTION;

ADMINISTRATION, INTRANASAL; ADOLESCENT; ADULT; ANTIVIRAL AGENTS; HUMANS; MALE; MIDDLE AGED; RESPIRATORY SYNCYTIAL VIRUSES; RNA, SMALL INTERFERING; VIRAL PROTEINS;

RESPIRATORY SYNCYTIAL VIRUS; RICE STRIPE VIRUS;

EID: 38749136602     PISSN: 01663542     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.antiviral.2007.11.009     Document Type: Article

References (23)

1. American Academy of Pediatrics, Committee on Infectious Diseases, 1996. Reassessment of the indications for ribavirin therapy in respiratory syncytial virus infections. Pediatrics 97 (1), 137-140.
2. American Academy of Pediatrics, Committee on Infectious Diseases and Committee on Fetus and Newborn, 2003. Revised indications for the use of palivizumab and respiratory syncytial virus immune globulin intravenous for the prevention of respiratory syncytial virus infections. Pediatrics 112 (6), 1442-1446.
3. Capodici J., Kariko K., and Weissman D. Inhibition of HIV-1 infection by small interfering RNA-mediated RNA interference. J. Immunol. 169 9 (2002) 5196-5201
4. DeVincenzo J.P. Therapy of respiratory syncytial virus infection. Pediatr. Infect. Dis. J. 19 (2000) 786-790
5. DeVincenzo J.P., Cehelsky J., Foote K., Nochur S., Vaishnaw A., and Meyers R. Early clinical evaluation of an RNA interference (RNAi) based therapy for respiratory syncytial virus (RSV) infection. E-PAS (2007) 616295.7
6. Elbashir S.M., Harborth J., Lendeckel W., Yalcin A., Weber K., and Tuschl T. Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature 411 6836 (2001) 494-498
7. Falsey A.R., and Walsh E.E. Respiratory syncytial virus infection in adults. Clin. Microbiol. Rev. 13 3 (2000) 371-384
8. Fire A., Xu S., Montgomery M.K., Kostas S.A., Driver S.E., and Mello C.C. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 391 6669 (1998) 806-811
9. Fisher R., Gruber W., Edwards K., Reed G., Tollefson S., Thompson J., and Wright P. Twenty years of outpatient respiratory Syncytial Virus Infection: a framework for vaccine efficacy trials. Pediatrics 99 2 (1997) 1-5
10. Glezen W.P., and Denny F.W. Epidemiology of acute lower respiratory diseases in children. N. Engl. J. Med. 288 (1973) 498-505
11. Glezen W.P., Greenberg S.B., Atmar R.L., Piedra P.A., and Couch R.B. Impact of respiratory virus infections on persons with chronic underlying conditions. JAMA 283 4 (2000) 499-505
12. Glezen W.P., Taber L.H., Frank A.L., and Kasel J.A. Risk of primary infection and reinfection with respiratory syncytial virus. Am. J. Dis. Child. 140 (1986) 543-546
13. The Impact-RSV Study Group. Palivizumab, a humanized respiratory syncytial virus monoclonal antobody, reduces hospitalization from respiratory syncytial virus infection in high risk infants. Pediatrics 102 3 (1998) 531-537
14. Hamasaki K., Nakao K., Matsumoto K., Ichikawa T., Ishikawa H., and Eguchi K. Short interfering RNA-directed inhibition of hepatitis B virus replication. FEBS Lett. 543 1-3 (2003) 51-54
15. Jia Q., and Sun R. Inhibition of gammaherpesvirus replication by RNA interference. J. Virol. 77 5 (2003) 3301-3306
16. Jiang M., and Milner J. Selective silencing of viral gene expression in HPV-positive human cervical carcinoma cells treated with siRNA, a primer of RNA interference. Oncogene 21 39 (2002) 6041-6048
17. Johnson J.E., Gonzales R.A., Olson S.J., Wright P.F., and Graham B.S. The histopathology of fatal untreated human respiratory syncytial virus infection. Mod. Pathol. 20 1 (2007) 108-119
18. Kimpen J.L., and Schaad U.B. Treatment of respiratory syncytial virus bronchiolitis: 1995 poll of members of the European Society for Paediatric Infectious Diseases. Pediatr. Infect. Dis. J. 16 5 (1997) 479-481
19. Leader S., and Kohlhase K. Respiratory syncytial virus-coded pediatric hospitalizations 1997 to 1999. Pediatr. Infect. Dis. J. 21 7 (2002) 629-632
20. Meyers, R.E., Alvarez, R., Tripp, R., Hadwiger, P., Constein, R., Elbashir, S.J.M., Borland, T., Toudjarska, I., DeVincenzo, J., 2007. ALN-RSV01, an RNAi therapeutic for the treatment of respiratory syncytial virus (RSV) infection. E-PAS2007, 616295.12.
21. Tuschl T., Zamore P.D., Lehmann R., Bartel D.P., and Sharp P.A. Targeted mRNA degradation by double-stranded RNA in vitro. Genes Dev. 13 24 (1999) 3191-3197
22. Yu R.Z., Baker B., Chappell A., Geary R.S., Cheung E., and Levin A.A. Development of an ultrasensitive noncompetitive hybridization-ligation enzyme-linked immunosorbent assay for the determination of phosphorothioate oligodeoxynucleotide in plasma. Anal. Biochem. 304 1 (2002) 19-25
23. Zhang L., Peeples M.E., Boucher R.C., Collins P.L., and Pickles R.J. Respiratory syncytial virus infection of human airway epithelial cells is polarized, specific to ciliated cells, and without obvious cytopathology. J. Virol. 76 11 (2002) 5654-5666