609. SHIGATEC Trial: a Phase II Study Assessing Monoclonal Antibodies Against Shiga toxin 1 and 2 in Shiga toxin-producing E. coli-infected Children
Session: Poster Abstract Session: Novel Antimicrobial Agents
Friday, October 21, 2011
Room: Poster Hall B1
Handouts
  • IDSA2011_Poster 609_SHIGATECTrial_DrLopez.pdf (234.2 kB)
  • Background: Shiga toxin-producing E. coli (STEC) are the main pathogens responsible for causing hemolytic uremic syndrome (HUS). There are no approved therapies to prevent HUS. Shigamabs, comprised of two  monoclonal antibodies against Shiga toxin 1 and 2, respectively, has been shown active in preclinical animal models and well tolerated in four Phase I studies

    Methods: Randomized, double blind, placebo controlled Phase II study initiated on November 2010. Two arms: A) standard of care + Shigamabs, or B) standard of care + placebo. Two doses (1 and 3 mg/kg of each antibody) are being tested in two sequential cohorts of 21 children, aged 6 mo to 18 yr, presenting with bloody diarrhea and testing positive for Shiga toxins. Primary endpoints are safety and tolerability; secondary: efficacy and pharmacokinetics. Independent Data Monitoring Committee oversees the safety aspect of the study

    Results: Data is reported for the low-dose cohort, recruited between Nov 2010 - Feb 2011. A total of 305 pts were screened and 22 pts enrolled. Mean age was 3 ½ years (10 mo – 11 yr) with 68% of them <4 yr. One pt progressed to HUS (only SAE reported in this cohort). Overall 13 patients had a total of 34 adverse events (AEs), with 9 pts having no AEs. All reported AEs were mild and none were deemed drug related. Vital signs during infusion day were unremarkable. Hematology and biochemistry parameters did not show any significant anomalies. Human anti-chimeric antibodies are being tested and pharmacokinetic parameters analyzed. Central microbiology laboratory results confirmed for now 14 Shiga toxin-producing E. coli, evenly distributed between O157 and non O157 strains, with a predominance of Shiga toxin 2 producers

    Conclusion: SHIGATEC is the first clinical study testing Shigamabs in infected children for its safety and potential benefits in the prevention of disease and complications induced by Shiga toxin-producing bacteria. None of the reported AEs were reported as drug related. Following the completion of patient enrollment and the prescribed follow-up period of patients from the low dose cohort, the SHIGATEC IDMC met, concluded the lack of any observed safety issue, and therefore recommended proceeding with the high dose cohort


    Subject Category: C. Clinical studies of bacterial infections and antibacterials including sexually transmitted diseases and mycobacterial infections (surveys, epidemiology, and clinical trials)

    Eduardo L. López, MD, Hospital de Niños R. Gutiérrez, Buenos Aires, Argentina, Thomas Cleary, MD, University of Texas Health Science Center at Houston, Houston, TX and Didier Reymond, MD, Thallion Pharmaceuticals Inc., Dorval, QC, Canada

    Disclosures:

    E. L. López, Thallion Pharmaceutical Inc.: Research Contractor, Research support

    T. Cleary, Thallion Pharmaceutical Inc.: Scientific Advisor, Consulting fee

    D. Reymond, Thallion Pharmaceutical Inc.: Employee, Salary

    Findings in the abstracts are embargoed until 12:01 a.m. EST Thursday, Oct. 20 with the exception of research findings presented at IDSA press conferences.