BACKGROUND AND AIMS: AVX-470 is an oral, polyclonal bovine-derived anti-tumour necrosis factor (TNF) antibody in development for treatment of inflammatory bowel disease (IBD). AVX-470 neutralizes TNF locally in the gastrointestinal tract, minimizing systemic exposure. This was a double-blind, placebo-controlled, first-in-human trial designed to assess the safety, pharmacokinetics, immunogenicity and preliminary efficacy of 4 weeks of AVX-470 in patients with active ulcerative colitis (UC). METHODS:Thirty-seven patients with active UC were randomized and 36 received AVX-470 (0.2, 1.6 or 3.5g/day) or placebo over 4 weeks. Endoscopic activity was assessed by colonoscopy pre- and post-treatment. The primary endpoint was safety. Secondary endpoints included pharmacokinetics and immunogenicity. Clinical and endoscopic response and remission were assessed as exploratory endpoints. RESULTS: Thirty-three (92%) patients completed treatment and follow-up. The incidence of adverse events was similar across treatment groups and no allergic reactions or opportunistic infections were reported. AVX-470 therapy did not induce human anti-bovine antibodies (HABA). Bovine immunoglobulin (Ig) with TNF binding capacity was detected in stool, while bovine Ig levels in serum were low. Across all AVX-470 doses, 25.9% of patients achieved clinical response compared with 11.1% on placebo, with greatest improvements in the 3.5g/day group associated with proximal colon endoscopic improvement and reductions in serum CRP and IL-6. CONCLUSIONS:AVX-470 was safe and well tolerated in this first-in-human trial in UC, with efficacy trends for clinical, endoscopic and biomarker endpoints in the highest dose group (3.5g/day). Results suggest benefit of an orally delivered locally active agent in moderate to severe UC. CLINICAL TRIAL REGISTRATION NUMBER: This trial was registered with Clinicaltrials.gov as study NCT01759056 and with EudraCTas study 2012-004859-27.
RCT Entities:
BACKGROUND AND AIMS: AVX-470 is an oral, polyclonal bovine-derived anti-tumour necrosis factor (TNF) antibody in development for treatment of inflammatory bowel disease (IBD). AVX-470 neutralizes TNF locally in the gastrointestinal tract, minimizing systemic exposure. This was a double-blind, placebo-controlled, first-in-human trial designed to assess the safety, pharmacokinetics, immunogenicity and preliminary efficacy of 4 weeks of AVX-470 in patients with active ulcerative colitis (UC). METHODS: Thirty-seven patients with active UC were randomized and 36 received AVX-470 (0.2, 1.6 or 3.5g/day) or placebo over 4 weeks. Endoscopic activity was assessed by colonoscopy pre- and post-treatment. The primary endpoint was safety. Secondary endpoints included pharmacokinetics and immunogenicity. Clinical and endoscopic response and remission were assessed as exploratory endpoints. RESULTS: Thirty-three (92%) patients completed treatment and follow-up. The incidence of adverse events was similar across treatment groups and no allergic reactions or opportunistic infections were reported. AVX-470 therapy did not induce human anti-bovine antibodies (HABA). Bovine immunoglobulin (Ig) with TNF binding capacity was detected in stool, while bovine Ig levels in serum were low. Across all AVX-470 doses, 25.9% of patients achieved clinical response compared with 11.1% on placebo, with greatest improvements in the 3.5g/day group associated with proximal colon endoscopic improvement and reductions in serum CRP and IL-6. CONCLUSIONS: AVX-470 was safe and well tolerated in this first-in-human trial in UC, with efficacy trends for clinical, endoscopic and biomarker endpoints in the highest dose group (3.5g/day). Results suggest benefit of an orally delivered locally active agent in moderate to severe UC. CLINICAL TRIAL REGISTRATION NUMBER: This trial was registered with Clinicaltrials.gov as study NCT01759056 and with EudraCT as study 2012-004859-27.
Authors: Randall E Burton; Skaison Kim; Rutvij Patel; Deborah S Hartman; Daniel E Tracey; Barbara S Fox Journal: J Biol Chem Date: 2020-07-14 Impact factor: 5.157
Authors: J Scott Crowe; Kevin J Roberts; Timothy M Carlton; Luana Maggiore; Marion F Cubitt; Simon Clare; Katherine Harcourt; Jill Reckless; Thomas T MacDonald; Keith P Ray; Anna Vossenkämper; Michael R West Journal: Sci Rep Date: 2018-03-21 Impact factor: 4.379
Authors: Vipul Jairath; G Y Zou; Claire E Parker; John K MacDonald; Turki AlAmeel; Mohammad Al Beshir; Majid A Almadi; Talal Al-Taweel; Nathan Ss Atkinson; Sujata Biswas; Thomas Chapman; Parambir S Dulai; Mark A Glaire; Daniël R Hoekman; Andreas Koutsoumpas; Elizabeth Minas; Mahmoud H Mosli; Mark Samaan; Reena Khanna; Simon Travis; Geert D'Haens; William J Sandborn; Brian G Feagan Journal: Cochrane Database Syst Rev Date: 2017-09-08
Authors: Bahez Gareb; Antonius T Otten; Henderik W Frijlink; Gerard Dijkstra; Jos G W Kosterink Journal: Pharmaceutics Date: 2020-06-11 Impact factor: 6.321