Safety profile and clinical activity of multiple subcutaneous doses of MEDI-528, a humanized anti-interleukin-9 monoclonal antibody, in two randomized phase 2a studies in subjects with asthma

BMC Pulmonary Medicine

Volumn 11, Issue , 2011, Pages

  Parker, Joseph M ^a   Oh, Chad K ^a   LaForce, Craig ^b   Miller, S David ^c   Pearlman, David S ^d   Le, Chenxiong ^a   Robbie, Gabriel J ^a   White, Wendy I ^a   White, Barbara ^a,e   Molfino, Nestor A ^a  

^a MEDIMMUNE   (United States)

^b North Carolina Clinical Research   (United States)

^c Northeast Medical Research Associates   (United States)

^d Respiratory Institute   (United States)

^e UCB PHARMA   (Belgium)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIASTHMATIC AGENT; BICARBONATE; CHLORIDE; INTERLEUKIN 9; MEDI 528; MONOCLONAL ANTIBODY; PLACEBO; POTASSIUM; TRIACYLGLYCEROL LIPASE; UNCLASSIFIED DRUG; ENOKIZUMAB; MEDI-528;

ADULT; ARTICLE; ASTHMA; BACKACHE; BICARBONATE BLOOD LEVEL; BRONCHOSPASM; CHLORIDE BLOOD LEVEL; CLINICAL EVALUATION; CYST; DISEASE CONTROL; DISEASE EXACERBATION; DOUBLE BLIND PROCEDURE; DRUG ACTIVITY; DRUG BLOOD LEVEL; DRUG DOSE ESCALATION; DRUG EFFICACY; DRUG SAFETY; DRUG TOLERABILITY; ENZYME LINKED IMMUNOSORBENT ASSAY; ETHNICITY; EXERCISE TEST; FEMALE; FORCED EXPIRATORY VOLUME; GLUCOSE BLOOD LEVEL; HUMAN; IMMUNOGENICITY; INFLUENZA; INJECTION SITE CONTUSION; INJECTION SITE IRRITATION; INJECTION SITE PAIN; LOWER RESPIRATORY TRACT INFECTION; LUNG FUNCTION; LYMPHOCYTE COUNT; MALE; MULTICENTER STUDY; NUCLEAR MAGNETIC RESONANCE IMAGING; PHASE 2 CLINICAL TRIAL; POTASSIUM BLOOD LEVEL; QUALITY OF LIFE; RANDOMIZED CONTROLLED TRIAL; RHINOPHARYNGITIS; SIDE EFFECT; SINUSITIS; SORE THROAT; TREATMENT DURATION; TRIACYLGLYCEROL LIPASE BLOOD LEVEL; URINARY TRACT INFECTION; VOMITING; ADOLESCENT; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DOSE RESPONSE; DRUG ANTAGONISM; DRUG TOXICITY; EXERCISE INDUCED ASTHMA; IMMUNOLOGY; LUNG FUNCTION TEST; MIDDLE AGED; PATHOPHYSIOLOGY; SUBCUTANEOUS DRUG ADMINISTRATION; TREATMENT OUTCOME;

ADOLESCENT; ADULT; ANTIBODIES, MONOCLONAL; ASTHMA; ASTHMA, EXERCISE-INDUCED; DOSE-RESPONSE RELATIONSHIP, DRUG; DOUBLE-BLIND METHOD; DRUG TOXICITY; FEMALE; HUMANS; INJECTIONS, SUBCUTANEOUS; INTERLEUKIN-9; MALE; MIDDLE AGED; QUALITY OF LIFE; RESPIRATORY FUNCTION TESTS; TREATMENT OUTCOME; YOUNG ADULT;

EID: 79952049626     PISSN: None     EISSN: 14712466     Source Type: Journal    
DOI: 10.1186/1471-2466-11-14     Document Type: Article

References (30)

1. Eder W, Ege MJ, von Mutius E. The asthma epidemic. N Engl J Med 2006, 355:2226-2235. 10.1056/NEJMra054308, 17124020.
2. Current asthma prevalence percents by age, United States: National health interview survey, 2006. 2008, http://www.cdc.gov/asthma/nhis/06/data.htm
3. Bateman ED, Boushey HA, Bousquet J, Busse WW, Clark TJ, Pauwels RA, Pedersen SE, . GOAL Investigators Group Can guideline-defined asthma control be achieved? The Gaining Optimal Asthma ControL study. Am J Respir Crit Care Med 2004, 170:836-844. 10.1164/rccm.200401-033OC, 15256389, GOAL Investigators Group.
4. Wiener Z, Falus A, Toth S. IL-9 increases the expression of several cytokines in activated mast cells, while the IL-9-induced IL-9 production is inhibited in mast cells of histamine-free transgenic mice. Cytokine 2004, 26:122-130. 10.1016/j.cyto.2004.01.006, 15135806.
5. McNamara PS, Flanagan BF, Baldwin LM, Newland P, Hart CA, Smyth RL. Interleukin 9 production in the lungs of infants with severe respiratory syncytial virus bronchiolitis. Lancet 2004, 363:1031-1037. 10.1016/S0140-6736(04)15838-8, 15051283.
6. Gounni AS, Nutku E, Koussih L, Aris F, Louahed J, Levitt RC, Nicolaides NC, Hamid Q. IL-9 expression by human eosinophils: regulation by IL-1beta and TNF-alpha. J Allergy Clin Immunol 2000, 106:460-466. 10.1067/mai.2000.109172, 10984364.
7. Stassen M, Arnold M, Hultner L, Muller C, Neudorfl C, Reineke T, Schmitt E. Murine bone marrow-derived mast cells as potent producers of IL-9: costimulatory function of IL-10 and kit ligand in the presence of IL-1. J Immunol 2000, 164:5549-5555.
8. Nicolaides NC, Holroyd KJ, Ewart SL, Eleff SM, Kiser MB, Dragwa CR, Sullivan CD, Grasso L, Zhang LY, Messler CJ, Zhou T, Kleeberger SR, Buetow KH, Levitt RC. Interleukin 9: a candidate gene for asthma. Proc Natl Acad Sci USA 1997, 94:13175-13180. 10.1073/pnas.94.24.13175, 24282, 9371819.
9. Temann UA, Geba GP, Rankin JA, Flavell RA. Expression of interleukin 9 in the lungs of transgenic mice causes airway inflammation, mast cell hyperplasia, and bronchial hyperresponsiveness. J Exp Med 1998, 188:1307-1320. 10.1084/jem.188.7.1307, 2212487, 9763610.
10. Temann UA, Ray P, Flavell RA. Pulmonary overexpression of IL-9 induces Th2 cytokine expression, leading to immune pathology. J Clin Invest 2002, 109:29-39. 150821, 11781348.
11. Hauber HP, Bergeron C, Hamid Q. IL-9 in allergic inflammation. Int Arch Allergy Immunol 2004, 134:79-87. 10.1159/000078384, 15133304.
12. van den Brule S, Heymans J, Havaux X, Renauld JC, Lison D, Huaux F, Denis O. Profibrotic effect of IL-9 overexpression in a model of airway remodeling. Am J Respir Cell Mol Biol 2007, 37:202-209. 10.1165/rcmb.2006-0397OC, 17446528.
13. Cheng G, Arima M, Honda K, Hirata H, Eda F, Yoshida N, Fukushima F, Ishii Y, Fukuda T. Anti-interleukin-9 antibody treatment inhibits airway inflammation and hyperreactivity in mouse asthma model. Am J Respir Crit Care Med 2002, 166:409-416. 10.1164/rccm.2105079, 12153980.
14. Kung TT, Luo B, Crawley Y, Garlisi CG, Devito K, Minnicozzi M, Egan RW, Kreutner W, Chapman RW. Effect of anti-mIL-9 antibody on the development of pulmonary inflammation and airway hyperresponsiveness in allergic mice. Am J Respir Cell Mol Biol 2001, 25:600-605.
15. Williams CM, Galli SJ. Mast cells can amplify airway reactivity and features of chronic inflammation in an asthma model in mice. J Exp Med 2000, 192:455-462. 10.1084/jem.192.3.455, 2193222, 10934234.
16. Jones TG, Hallgren J, Humbles A, Burwell T, Finkelman FD, Alcaide P, Austen KF, Gurish MF. Antigen-induced increases in pulmonary mast cell progenitor numbers depend on IL-9 and CD1d-restricted NKT cells. J Immunol 2009, 183:5251-5260. 10.4049/jimmunol.0901471, 2782612, 19783672.
17. Lee TH, Nagy L, Nagakura T, Walport MJ, Kay AB. Identification and partial characterization of an exercise-induced neutrophil chemotactic factor in bronchial asthma. J Clin Invest 1982, 69:889-899. 10.1172/JCI110528, 370143, 7076852.
18. Pliss LB, Ingenito EP, Ingram RH, Pichurko B. Assessment of bronchoalveolar cell and mediator response to isocapnic hyperpnea in asthma. Am Rev Respir Dis 1990, 142:73-78.
19. Van Schoor J, Pauwels R, Joos G. Indirect bronchial hyper-responsiveness: the coming of age of a specific group of bronchial challenges. Clin Exp Allergy 2005, 35:250-261. 10.1111/j.1365-2222.2005.02177.x, 15784100.
20. Shimbara A, Christodoulopoulos P, Soussi-Gounni A, Olivenstein R, Nakamura Y, Levitt RC, Nicolaides NC, Holroyd KJ, Tsicopoulos A, Lafitte JJ, Wallaert B, Hamid QA. IL-9 and its receptor in allergic and nonallergic lung disease: increased expression in asthma. J Allergy Clin Immunol 2000, 105:108-115. 10.1016/S0091-6749(00)90185-4, 10629460.
21. Ying S, Meng Q, Kay AB, Robinson DS. Elevated expression of interleukin-9 mRNA in the bronchial mucosa of atopic asthmatics and allergen-induced cutaneous late-phase reaction: relationships to eosinophils, mast cells and T lymphocytes. Clin Exp Allergy 2002, 32:866-871. 10.1046/j.1365-2222.2002.01376.x, 12047433.
22. Toda M, Tulic MK, Levitt RC, Hamid Q. A calcium-activated chloride channel (HCLCA1) is strongly related to IL-9 expression and mucus production in bronchial epithelium of patients with asthma. J Allergy Clin Immunol 2002, 109:246-250. 10.1067/mai.2002.121555, 11842292.
23. Erpenbeck VJ, Hohlfeld JM, Volkmann B, Hagenberg A, Geldmacher H, Braun A, Krug N. Segmental allergen challenge in patients with atopic asthma leads to increased IL-9 expression in bronchoalveolar lavage fluid lymphocytes. J Allergy Clin Immunol 2003, 111:1319-1327. 10.1067/mai.2003.1485, 12789235.
24. White B, Leon F, White W, Robbie G. Two first-in-human, open-label, phase I dose-escalation safety trials of MEDI-528, a monoclonal antibody against interleukin-9, in healthy adult volunteers. Clin Ther 2009, 31:728-740. 10.1016/j.clinthera.2009.04.019, 19446146.
25. National Heart, and Blood Institute. National Institutes of Health. National Asthma Education and Prevention Program Expert Panel Report 3 (EPR-3): Guidelines for the Diagnosis and Management of Asthma-Summary Report 2007. J Allergy Clin Immunol 2007, 120:S94-138. 10.1016/j.jaci.2007.09.029, 17983880, National Heart, and Blood Institute. National Institutes of Health. National Asthma Education and Prevention Program.
26. Weiler JM, Bonini S, Coifman R, Craig T, Delgado L, Capao-Filipe M, Passali D, Randolph C, Storms W, . Ad Hoc Committee of Sports Medicine Committee of American Academy of Allergy, Asthma & Immunology American Academy of Allergy, Asthma & Immunology Work Group report: exercise-induced asthma. J Allergy Clin Immunol 2007, 119:1349-1358. 10.1016/j.jaci.2007.02.041, 17433829, Ad Hoc Committee of Sports Medicine Committee of American Academy of Allergy, Asthma & Immunology.
27. Crapo RO, Casaburi R, Coates AL, Enright PL, Hankinson JL, Irvin CG, MacIntyre NR, McKay RT, Wanger JS, Anderson SD, Cockcroft DW, Fish JE, Sterk PJ. Guidelines for methacholine and exercise challenge testing-1999. This official statement of the American Thoracic Society was adopted by the ATS Board of Directors, July 1999. Am J Respir Crit Care Med 2000, 161:309-329.
28. Juniper EF, Buist AS, Cox FM, Ferrie PJ, King DR. Validation of a standardized version of the Asthma Quality of Life Questionnaire. Chest 1999, 115:1265-1270. 10.1378/chest.115.5.1265, 10334138.
29. Pepys J. Skin testing. Br J Hosp Med (Lond) 1975, 14:412-417.
30. Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, Crapo R, Enright P, van der Grinten CP, Gustafsson P, Jensen R, Johnson DC, MacIntyre N, McKay R, Navajas D, Pedersen OF, Pellegrino R, Viegi G, Wanger J, . ATS/ERS Task Force Standardisation of spirometry. Eur Respir J 2005, 26:319-338. 10.1183/09031936.05.00034805, 16055882, ATS/ERS Task Force.