Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Apr;9(3):330-340.
doi: 10.1002/cpdd.729. Epub 2019 Aug 14.

Assessment of Bezlotoxumab Immunogenicity

Diana L Montgomery  1 , Randolph P Matthews  1 , Ka Lai Yee  1 , Lori M Tobias  1 , Mary Beth Dorr  1 , Rebecca E Wrishko  1
Affiliations

Assessment of Bezlotoxumab Immunogenicity

Diana L Montgomery et al. Clin Pharmacol Drug Dev. 2020 Apr.

Abstract

Bezlotoxumab is a fully human monoclonal antibody that binds and neutralizes Clostridium difficile toxin B. This analysis investigated the potential of bezlotoxumab to induce immunogenicity in healthy phase 1 trial participants and in phase 2/3 trial participants receiving oral antibacterial therapy for primary or recurrent C difficile infection. Immunogenicity to bezlotoxumab was evaluated following a single intravenous dose (≤20 mg/kg) or 2 consecutive doses (10 mg/kg) given 84 days apart in healthy participants across 3 phase 1 trials (Protocol MK-3415A-004, N = 30; Protocol CA-GCDX-05-01, N = 54; Protocol MK-3415A-006, N = 12) and following a single 10 mg/kg dose in 1 phase 2 trial (Protocol CA-GCDX-06-02, ClinicalTrials.gov identifier: NCT00350298; N = 97) and 2 phase 3 trials (Protocols MK-3415A-001 and MK-3415A-002, ClinicalTrials.gov identifiers: NCT01241552 and NCT01513239; N = 1414). No treatment-emergent antidrug antibodies were observed following single or repeated dosing of bezlotoxumab. No phase 1 participants and only 1 phase 2 participant tested positive before bezlotoxumab exposure (non-treatment-emergent positive). Nine participants tested non-treatment-emergent positive in phase 3 trials, 1 of whom was neutralizing antibody-positive. Overall, the immunogenicity potential of bezlotoxumab is considered to be low.

Keywords: Antibiotic resistance; drug information; infectious diseases; monoclonal antibodies, immunogenicity.

PubMed Disclaimer

References

    1. Kyne L, Warny M, Qamar A, Kelly CP. Association between antibody response to toxin A and protection against recurrent Clostridium difficile diarrhoea. Lancet. 2001;357(9251):189-193.
    1. Bauer MP, Nibbering PH, Poxton IR, Kuijper EJ, van Dissel JT. Humoral immune response as predictor of recurrence in Clostridium difficile infection. Clin Microbiol Infect. 2014;20(12):1323-1328.
    1. Wilcox MH, Gerding DN, Poxton IR, et al. Bezlotoxumab for prevention of recurrent Clostridium difficile infection. N Engl J Med. 2017;376(4):305-317.
    1. Nelson AL, Dhimolea E, Reichert JM. Development trends for human monoclonal antibody therapeutics. Nat Rev Drug Discov. 2010;9(10):767-774.
    1. Harding FA, Stickler MM, Razo J, DuBridge RB. The immunogenicity of humanized and fully human antibodies: residual immunogenicity resides in the CDR regions. MAbs. 2010;2(3):256-265.

Publication types

MeSH terms

Associated data