BACKGROUND: Previous studies have demonstrated a correlation between Clostridium difficile anti-toxin A serum antibodies and protection against symptomatic disease and recurrence. METHODS: A neutralizing monoclonal antibody to C. difficile toxin A (CDA1) developed by MBL and Medarex, Inc. was studied in a phase II, randomized, double-blind, placebo-controlled trial in patients receiving standard of care treatment for C. difficile infection (CDI). Twenty-nine subjects received a single intravenous infusion of 10mg/kg CDA1 and 17 subjects received placebo and were evaluated for recurrence of CDI during the 56-day study period. Serum antibodies against C. difficile toxin A and B were measured by ELISA and cytotoxicity assay at various time points before and after infusion. FINDINGS:CDI recurrence occurred in 5 of 29 (17%) in the CDA1 group and 3 of 17 (18%) (p=NS) in the placebo group with a trend toward delay in time to recurrence in the group treated with CDA1. The geometric mean concentration of antibody to an epitope of the receptor-binding domain of toxin B (0.300 and 1.20microg/ml, respectively; p=0.02) and geometric mean titer of neutralizing B antibody (8.00 and 100, respectively; p=0.02) at study day 28 were lower for those subjects with recurrence compared to those who did not recur. In addition, a significantly greater proportion of subjects who recurred were infected with the epidemic BI/NAP1/027 strain compared with those that did not recur (88% vs. 22%; p=0.002). Finally, in a multiple logistic regression analysis neutralizing anti-toxin B at day 14 (p<0.001), anti-toxin A at day 28 (p<0.001) and infection with the BI/NAP1/027 strain at enrollment (p=0.002) were all predictive of CDI recurrence. INTERPRETATION: In this prospective study, lower concentrations of neutralizing anti-toxin B and anti-toxin A antibody and infection with the BI/NAP1/027 strain of C. difficile were significantly associated with recurrence of CDI.
RCT Entities:
BACKGROUND: Previous studies have demonstrated a correlation between Clostridium difficile anti-toxin A serum antibodies and protection against symptomatic disease and recurrence. METHODS: A neutralizing monoclonal antibody to C. difficile toxin A (CDA1) developed by MBL and Medarex, Inc. was studied in a phase II, randomized, double-blind, placebo-controlled trial in patients receiving standard of care treatment for C. difficileinfection (CDI). Twenty-nine subjects received a single intravenous infusion of 10mg/kg CDA1 and 17 subjects received placebo and were evaluated for recurrence of CDI during the 56-day study period. Serum antibodies against C. difficile toxin A and B were measured by ELISA and cytotoxicity assay at various time points before and after infusion. FINDINGS: CDI recurrence occurred in 5 of 29 (17%) in the CDA1 group and 3 of 17 (18%) (p=NS) in the placebo group with a trend toward delay in time to recurrence in the group treated with CDA1. The geometric mean concentration of antibody to an epitope of the receptor-binding domain of toxin B (0.300 and 1.20microg/ml, respectively; p=0.02) and geometric mean titer of neutralizing B antibody (8.00 and 100, respectively; p=0.02) at study day 28 were lower for those subjects with recurrence compared to those who did not recur. In addition, a significantly greater proportion of subjects who recurred were infected with the epidemic BI/NAP1/027 strain compared with those that did not recur (88% vs. 22%; p=0.002). Finally, in a multiple logistic regression analysis neutralizing anti-toxin B at day 14 (p<0.001), anti-toxin A at day 28 (p<0.001) and infection with the BI/NAP1/027 strain at enrollment (p=0.002) were all predictive of CDI recurrence. INTERPRETATION: In this prospective study, lower concentrations of neutralizing anti-toxin B and anti-toxin A antibody and infection with the BI/NAP1/027 strain of C. difficile were significantly associated with recurrence of CDI.
Authors: Jinfu Xie; Julie Zorman; Lani Indrawati; Melanie Horton; Keri Soring; Joseph M Antonello; Yuhua Zhang; Susan Secore; Matthew Miezeiewski; Su Wang; Anthony D Kanavage; Julie M Skinner; Irene Rogers; Jean-Luc Bodmer; Jon H Heinrichs Journal: Clin Vaccine Immunol Date: 2013-02-06
Authors: Nicola L Davies; Joanne E Compson; Brendon Mackenzie; Victoria L O'Dowd; Amanda K F Oxbrow; James T Heads; Alison Turner; Kaushik Sarkar; Sarah L Dugdale; Mark Jairaj; Louis Christodoulou; David E O Knight; Amanda S Cross; Karine J M Hervé; Kerry L Tyson; Hanna Hailu; Carl B Doyle; Mark Ellis; Marco Kriek; Matthew Cox; Matthew J T Page; Adrian R Moore; Daniel J Lightwood; David P Humphreys Journal: Clin Vaccine Immunol Date: 2013-01-16
Authors: Zhiyong Yang; Jeremy Ramsey; Therwa Hamza; Yongrong Zhang; Shan Li; Harris G Yfantis; Dong Lee; Lorraine D Hernandez; Wolfgang Seghezzi; Jamie M Furneisen; Nicole M Davis; Alex G Therien; Hanping Feng Journal: Infect Immun Date: 2014-12-08 Impact factor: 3.441
Authors: Pragya Rampuria; Gillian A Lang; T Scott Devera; Casey Gilmore; Jimmy D Ballard; Mark L Lang Journal: J Leukoc Biol Date: 2016-08-26 Impact factor: 4.962