A first-in-human study to assess the safety and pharmacokinetics of monoclonal antibodies against human cytomegalovirus in healthy volunteers

Antimicrobial Agents and Chemotherapy

Volumn 60, Issue 5, 2016, Pages 2881-2887

  Dole, Kiran ^a   Segal, Florencia Pereyra ^a   Feire, Adam ^a   Magnusson, Baldur ^b   Rondon, Juan C ^c   Vemula, Janardhana ^d   Yu, Jing ^a   Pang, Yinuo ^a   Pertel, Peter ^a  

^a NOVARTIS INSTITUTES FOR BIOMEDICAL RESEARCH   (United States)

^b NOVARTIS PHARMA AG   (Switzerland)

^c Elite Research Institute   (United States)

^d Novartis   (India)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIVIRUS AGENT; DRUG ANTIBODY; GLUCOSE; IMMUNOGLOBULIN G1; MONOCLONAL ANTIBODY; MONOCLONAL ANTIBODY LJP538; MONOCLONAL ANTIBODY LJP539; PLACEBO; PROMETHAZINE; UNCLASSIFIED DRUG; IMMUNOGLOBULIN G; VIRUS ANTIBODY;

ABNORMAL LABORATORY RESULT; ADULT; AREA UNDER THE CURVE; ARTICLE; BLEEDING; CONTROLLED STUDY; DIARRHEA; DIZZINESS; DOUBLE BLIND PROCEDURE; DRUG CLEARANCE; DRUG DISPOSITION; DRUG DOSE INCREASE; DRUG SAFETY; DRUG TOLERABILITY; ECG ABNORMALITY; ERYTHEMA; FAINTNESS; FEMALE; FIRST IN HUMAN STUDY; FLU LIKE SYNDROME; FOLLOW UP; GLUCOSE BLOOD LEVEL; HALF LIFE TIME; HEADACHE; HEART PALPITATION; HUMAN; HUMAN CYTOMEGALOVIRUS; HYPOGLYCEMIA; IMMUNOGENICITY; INFUSION RELATED REACTION; MALE; MAXIMUM PLASMA CONCENTRATION; MENORRHAGIA; MIDDLE AGED; MORNING DOSAGE; MYALGIA; NONHUMAN; NORMAL HUMAN; PARESTHESIA; PLASMA CONCENTRATION-TIME CURVE; PRIORITY JOURNAL; PRURITUS; RANDOMIZED CONTROLLED TRIAL; RASH; SIDE EFFECT; SINGLE DRUG DOSE; THROMBOSIS; TRANSIENT ISCHEMIC ATTACK; VIRAL UPPER RESPIRATORY TRACT INFECTION; VITAL SIGN; VOLUME OF DISTRIBUTION AT STEADY-STATE; VOMITING; YOUNG ADULT; CYTOMEGALOVIRUS; DRUG EFFECTS; IMMUNOLOGY; METABOLISM; PATHOGENICITY;

ADULT; ANTIBODIES, MONOCLONAL; ANTIBODIES, VIRAL; ANTIVIRAL AGENTS; CYTOMEGALOVIRUS; DOUBLE-BLIND METHOD; FEMALE; HEALTHY VOLUNTEERS; HUMANS; IMMUNOGLOBULIN G; MALE; MIDDLE AGED; YOUNG ADULT;

EID: 84964875188     PISSN: 00664804     EISSN: 10986596     Source Type: Journal    
DOI: 10.1128/AAC.02698-15     Document Type: Article

References (21)

1. Ho M. 2008. The history of cytomegalovirus and its diseases. Med Microbiol Immunol 197:65-73. http://dx.doi.org/10.1007/s00430-007-0066-x.
2. Biron KK. 2006. Antiviral drugs for cytomegalovirus diseases. Antiviral Res 71:154-163. http://dx.doi.org/10.1016/j.antiviral.2006.05.002.
3. Torres-Madriz G, Boucher HW. 2008. Immunocompromised hosts: perspectives in the treatment and prophylaxis of cytomegalovirus disease in solid-organ transplant recipients. Clin Infect Dis 47:702-711. http://dx.doi.org/10.1086/590934.
4. Snydman DR. 1990. Cytomegalovirus immunoglobulins in the prevention and treatment of cytomegalovirus disease. Rev Infect Dis 12(Suppl 7):S839-S848.
5. Snydman DR, Werner BG, Heinze-Lacey B, Berardi VP, Tilney NL, Kirkman RL, Milford EL, Cho SI, Bush HL, Jr, Levey AS. 1987. Use of cytomegalovirus immune globulin to prevent cytomegalovirus disease in renal-transplant recipients. N Engl J Med 317:1049-1054. http://dx.doi.org/10.1056/NEJM198710223171703.
6. Ishida JH, Patel A, McBride J, Burgess T, Derby MA, Emu B, Feierbach B, Liao XC, Maia M, Deng R, Rosenberger CM, Gennaro LA, Striano NS, Tavel JA. 2015. Phase 2 randomized, double-blind, placebocontrolled trial of RG7667 for prevention of cytomegalovirus infection in high-risk kidney transplant recipients. Abstr 55th Intersci Conf Antimicrob Agents Chemother, San Diego, CA.
7. Macagno A, Bernasconi NL, Vanzetta F, Dander E, Sarasini A, Revello MG, Gerna G, Sallusto F, Lanzavecchia A. 2010. Isolation of human monoclonal antibodies that potently neutralize human cytomegalovirus infection by targeting different epitopes on the gH/gL/UL128-131A complex. J Virol 84:1005-1013. http://dx.doi.org/10.1128/JVI.01809-09.
8. Marshall GS, Rabalais GP, Stout GG, Waldeyer SL. 1992. Antibodies to recombinant-derived glycoprotein B after natural human cytomegalovirus infection correlate with neutralizing activity. J Infect Dis 165:381-384. http://dx.doi.org/10.1093/infdis/165.2.381.
9. Wang D, Li F, Freed DC, Finnefrock AC, Tang A, Grimes SN, Casimiro DR, Fu TM. 2011. Quantitative analysis of neutralizing antibody response to human cytomegalovirus in natural infection. Vaccine 29:9075-9080. http://dx.doi.org/10.1016/j.vaccine.2011.09.056.
10. Fouts AE, Chan P, Stephan JP, Vandlen R, Feierbach B. 2012. Antibodies against the gH/gL/UL128/UL130/UL131 complex comprise the majority of the anti-cytomegalovirus (anti-CMV) neutralizing antibody response in CMV hyperimmune globulin. J Virol 86:7444-7447. http://dx.doi.org/10.1128/JVI.00467-12.
11. Smith BP, Vandenhende FR, DeSante KA, Farid NA, Welch PA, Callaghan JT, Forgue ST. 2000. Confidence interval criteria for assessment of dose proportionality. Pharm Res 17:1278-1283. http://dx.doi.org/10.1023/A:1026451721686.
12. Hahn G, Revello MG, Patrone M, Percivalle E, Campanini G, Sarasini A, Wagner M, Gallina A, Milanesi G, Koszinowski U, Baldanti F, Gerna G. 2004. Human cytomegalovirus UL131-128 genes are indispensable for virus growth in endothelial cells and virus transfer to leukocytes. J Virol 78:10023-10033. http://dx.doi.org/10.1128/JVI.78.18.10023-10033.2004.
13. Wang D, Shenk T. 2005. Human cytomegalovirus virion protein complex required for epithelial and endothelial cell tropism. Proc Natl Acad Sci U S A 102:18153-18158. http://dx.doi.org/10.1073/pnas.0509201102.
14. Jin F, Balthasar JP. 2005. Mechanisms of intravenous immunoglobulin action in immune thrombocytopenic purpura. Hum Immunol 66:403-410. http://dx.doi.org/10.1016/j.humimm.2005.01.029.
15. Yu J, Karcher H, Feire AL, Lowe PJ. 2011. From target selection to the minimum acceptable biological effect level for human study: use of mechanism-based PK/PD modeling to design safe and efficacious biologics. AAPS J 13:169-178. http://dx.doi.org/10.1208/s12248-011-9256-y.
16. Rand KH, Houck H, Ganju A, Babington RG, Elfenbein GJ. 1989. Pharmacokinetics of cytomegalovirus specific IgG antibody following intravenous immunoglobulin in bone marrow transplant patients. Bone Marrow Transpl 4:679-683.
17. Rand KH, Gibbs K, Derendorf H, Graham-Pole J. 1991. Pharmacokinetics of intravenous immunoglobulin (Gammagard) in bone marrow transplant patients. J Clin Pharmacol 31:1151-1154. http://dx.doi.org/10.1002/j.1552-4604.1991.tb03688.x.
18. DeRienzo SY, Chiang KY, O'Neal WM, Godder K, Abhyankar S, Christiansen NP, Bridges KD, Henslee-Downey PJ. 2000. Evaluation of the half-life of intravenous human cytomegalovirus immune globulin in patients receiving partially mismatched related donor bone marrow transplantation. Pharmacotherapy 20:1175-1178. http://dx.doi.org/10.1592/phco.20.15.1175.34592.
19. Boeckh M, Bowden RA, Storer B, Chao NJ, Spielberger R, Tierney DK, Gallez-Hawkins G, Cunningham T, Blume KG, Levitt D, Zaia JA. 2001. Randomized, placebo-controlled, double-blind study of a cytomegalovirus-specific monoclonal antibody (MSL-109) for prevention of cytomegalovirus infection after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transpl 7:343-351. http://dx.doi.org/10.1016/S1083-8791(01)80005-7.
20. Andresen I, Kovarik JM, Spycher M, Bolli R. 2000. Product equivalence study comparing the tolerability, pharmacokinetics, and pharmacodynamics of various human immunoglobulin-G formulations. J Clin Pharmacol 40:722-730. http://dx.doi.org/10.1177/00912700 022009477.
21. Snydman DR, McIver J, Leszczynski J, Cho SI, Werner BG, Berardi VP, LoGerfo F, Heinze-Lacey B, Grady GF. 1984. A pilot trial of a novel cytomegalovirus immune globulin in renal transplant recipients. Transplantation 38:553-557. http://dx.doi.org/10.1097/00007890-198411000-00026.