AVX-470, an orally delivered anti-tumour necrosis factor antibody for treatment of active ulcerative colitis: Results of a first-in-human trial

Journal of Crohn's and Colitis

Volumn 10, Issue 6, 2016, Pages 631-640

  Harris, M Scott ^a   Hartman, Deborah ^a   Lemos, Brenda R ^a   Erlich, Emma C ^a   Spence, Sharon ^a   Kennedy, Sally ^a   Ptak, Theadore ^b   Pruitt, Ronald ^c   Vermeire, Severine ^d   Fox, Barbara S ^a  

^a Avaxia Biologics Inc   (United States)

^b Toronto Digestive Disease Associates   (Canada)

^c Nashville Medical Research Institute   (United States)

^d UNIVERSITY HOSPITALS LEUVEN   (Belgium)

Author keywords

Anti TNF; Clinical trial; Ulcerative colitis

Indexed keywords

AVX 470; BOVINE IMMUNOGLOBULIN; C REACTIVE PROTEIN; CALGRANULIN; CORTICOSTEROID; IMMUNOSUPPRESSIVE AGENT; INTERLEUKIN 6; PLACEBO; TUMOR NECROSIS FACTOR; TUMOR NECROSIS FACTOR INHIBITOR; UNCLASSIFIED DRUG; ANTIBODY; AVX-470; NONSTEROID ANTIINFLAMMATORY AGENT;

ADULT; ADVERSE OUTCOME; AGED; ALLERGIC REACTION; ANAPHYLAXIS; ARTICLE; ASCENDING COLON; BOVINE; CLINICAL ARTICLE; CLINICAL ASSESSMENT; COLONOSCOPY; COMPARATIVE STUDY; CONTROLLED STUDY; DEMYELINATING DISEASE; DOUBLE BLIND PROCEDURE; DRUG EFFICACY; DRUG SAFETY; DRUG TOLERABILITY; FECES ANALYSIS; FEMALE; FIRST IN HUMAN STUDY; FOLLOW UP; HUMAN; IMMUNOGENICITY; INCIDENCE; INFECTIOUS COMPLICATION; LUPUS ERYTHEMATOSUS; MALE; MULTICENTER STUDY; OPPORTUNISTIC INFECTION; PHARMACODYNAMICS; PHARMACOKINETIC PARAMETERS; PRIORITY JOURNAL; PROTEIN BLOOD LEVEL; RANDOMIZED CONTROLLED TRIAL; REMISSION; TREATMENT DURATION; TREATMENT RESPONSE; ULCERATIVE COLITIS; ADOLESCENT; COLITIS, ULCERATIVE; DRUG ADMINISTRATION; IMMUNOLOGY; MIDDLE AGED; ORAL DRUG ADMINISTRATION; TREATMENT OUTCOME; YOUNG ADULT;

ADMINISTRATION, ORAL; ADOLESCENT; ADULT; AGED; ANTI-INFLAMMATORY AGENTS, NON-STEROIDAL; ANTIBODIES; COLITIS, ULCERATIVE; DOUBLE-BLIND METHOD; DRUG ADMINISTRATION SCHEDULE; FEMALE; FOLLOW-UP STUDIES; HUMANS; MALE; MIDDLE AGED; TREATMENT OUTCOME; YOUNG ADULT;

EID: 84984990092     PISSN: 18739946     EISSN: 18764479     Source Type: Journal    
DOI: 10.1093/ecco-jcc/jjw036     Document Type: Article

References (22)

1. Taylor PC. Pharmacology of TNF blockade in rheumatoid arthritis and other chronic inflammatory diseases. Curr Opin Pharmacol 2010;10:308-15.
2. Kozuch PL, Hanauer SB. Treatment of inflammatory bowel disease: a review of medical therapy. World J Gastroenterol 2008;14:354-77.
3. Atreya R, Zimmer M, Bartsch B, et al. Antibodies against tumor necrosis factor (TNF) induce T-cell apoptosis in patients with inflammatory bowel diseases via TNF receptor 2 and intestinal CD14? macrophages. Gastroenterology 2011;141:2026-38.
4. D'Haens G, Sandborn WJ, Feagan BG, et al. A review of activity indices and efficacy end points for clinical trials of medical therapy in adults with ulcerative colitis. Gastroenterology 2007;132:763-86.
5. Warny M, Fatimi A, Bostwick EF, et al. Bovine immunoglobulin concentrate-Clostridium difficile retains C difficile toxin neutralising activity after passage through the human stomach and small intestine. Gut 1999;44:212-7.
6. Kelly CP, Chetham S, Keates S, et al. Survival of anti-Clostridium difficile bovine immunoglobulin concentrate in the human gastrointestinal tract. Antimicrob Agents Chemother 1997;41:236-41.
7. Tollemar J, Gross N, Dolgiras N, Jarstrand C, Ringdén O, Hammarström L. Fungal prophylaxis by reduction of fungal colonization by oral administration of bovine anti-Candida antibodies in bone marrow transplant recipients. Bone Marrow Transplant 1999;23:283-90.
8. Tacket CO, Losonsky G, Link H, et al. Protection by milk immunoglobulin concentrate against oral challenge with enterotoxigenic Escherichia coli. N Engl J Med 1988;318:1240-3.
9. Mattila E, Anttila VJ, Broas M, et al. A randomized, double-blind study comparing Clostridium difficile immune whey and metronidazole for recurrent Clostridium difficile-associated diarrhoea: efficacy and safety data of a prematurely interrupted trial. Scand J Infect Dis 2008;40:702-8.
10. Greenberg PD, Cello JP. Treatment of severe diarrhea caused by Cryptosporidium parvum with oral bovine immunoglobulin concentrate in patients with AIDS. J Acquir Immune Defic Syndr Hum Retrovirol 1996;13:348-54.
11. Andersen DC, Koch C, Jensen CH, Skjødt K, Brandt J, Teisner B. High prevalence of human anti-bovine IgG antibodies as the major cause of false positive reactions in two-site immunoassays based on monoclonal antibodies. J Immunoassay Immunochem 2004;25:17-30.
12. Bhol KC, Tracey DE, Lemos BR, et al. AVX-470: a novel oral anti-TNF antibody with therapeutic potential in inflammatory bowel disease. Inflamm Bowel Dis 2013:19;2273-81.
13. Sevcik C, Diaz P, D'Suze G. On the presence of antibodies against bovine, equine and poultry immunoglobulins in human IgG preparations, and its implications on antivenom production. Toxicon 2008;51:10-16.
14. Schroeder KW, Tremaine WJ, Ilstrup DM. Coated oral 5-aminosalicylic acid therapy for mildly to moderately active ulcerative colitis. N Engl J Med 1987;317:1625-59.
15. Travis SPL, Schnell D, Krzeski P, et al. Reliability and initial validation of the Ulcerative Colitis Endoscopic Index of Severity. Gastroenterology 2013;145:987-95.
16. Danese S, Colombel J-F, Peyrin-Biroulet L, Rutgeerts P, Reinisch W. Review article: the role of anti-TNF in the management of ulcerative colitis-past, present and future. Aliment Pharmacol Ther 2013;37:855-66.
17. Salim SY, Soderholm JD. Importance of disrupted intestinal barrier in inflammatory bowel diseases. Inflamm Bowel Dis 2011;17:362-81.
18. Ikeya K, Hanai H, Sugimoto K, et al. The Ulcerative Colitis Endoscopic Index of Severity more accurately reflects clinical outcomes and long-term prognosis than the Mayo Endoscopic Score. J Crohns Colitis 2015. pii: jjv210. http://dx.doi.org/10.1093/ecco-jcc/jjv210. [Epub ahead of print].
19. Nielsen OH, Brynskov J, Bendtzen K. Circulating and mucosal concentrations of tumour necrosis factor and inhibitor(s) in chronic inflammatory bowel disease. Dan Med Bull 1993;40:247-9.
20. Umehara Y, Kudo M, Nakaoka R, et al. Serum proinflammatory cytokines and adhesion molecules in ulcerative colitis. Hepatogastroenterology 2006;53:879-82.
21. De Vos M, Louis EJ, Jahnsen J, et al. Consecutive fecal calprotectin measurements to predict relapse in patients with ulcerative colitis receiving infliximab maintenance therapy. Inflamm Bowel Dis 2013;19:2111-7.
22. Calafat M, Cabré E, Mañosa M, Lobatón T, Marín L, Domènech E. High within-day variability of fecal calprotectin levels in patients with active ulcerative colitis: what is the best timing for stool sampling? Inflamm Bowel Dis 2015;21:1072-6.