Assessment of Bezlotoxumab Immunogenicity

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...

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Bibliographic Details
Published in:Clinical pharmacology in drug development 2020-04, Vol.9 (3), p.330-340
Main Authors: Montgomery, Diana L., Matthews, Randolph P., Yee, Ka Lai, Tobias, Lori M., Dorr, Mary Beth, Wrishko, Rebecca E.
Format: Article
Language:English
Subjects:
Antibiotic resistance
Bacterial infections
Clinical trials
drug information
Drug resistance
infectious diseases
Monoclonal antibodies
monoclonal antibodies, immunogenicity
Pharmacology
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Summary: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.
ISSN:2160-763X
2160-7648
DOI:10.1002/cpdd.729