Vol.65 No.2 March 2017

Safety and immunogenicity of Clostridium difficile toxoid vaccine in Japanese adults

Osamu Matsuoka¹⁾, Dhaval M. Patel²⁾, Shin Sasaki³⁾, Hayato Oka³⁾, Toru Sasaki⁴⁾, Patricia J. Pietrobon²⁾, Thelma Laot⁵⁾, Alain Bouckenooghe⁶⁾, Josemund Menezes⁶⁾ and Guy de Bruyn²⁾

¹⁾ToCROM Clinic
²⁾Sanofi Pasteur, PA, USA
³⁾Sanofi Pasteur Medical, Sanofi K.K., Tokyo Opera City Tower, 3-20-2 Nishi Shinjuku, Shinjuku-ku, Tokyo, Japan
⁴⁾Medical Operation, Sanofi K.K., Tokyo, Japan
⁵⁾Sanofi Pasteur, Manila, Philippines
⁶⁾Sanofi Pasteur, Singapore

Abstract

This was a randomized, placebo-controlled, Phase I/II study conducted in a Japanese cohort to assess the safety and immunogenicity of Clostridium difficile vaccine (same formulation as that used in the ongoing global Phase III study). Healthy Japanese adults aged 40-75 years were randomized to receive either C. difficile vaccine (N = 67) or placebo (N = 34) by intramuscular injection on Days 0, 7 and 30.
Serum IgG specific for toxins A and B was measured by enzyme-linked immunosorbent assay (ELISA) and in vitro functional activity by toxin neutralizing assay (TNA). The seroconversion rate (percentage of participants with a ≥ 4-fold rise in the antibody levels from baseline) was high for both toxin A (ELISA and TNA) and toxin B (ELISA), approaching 100% for each by Day 60. For toxin B assessed by TNA, however, the response rate was lower, with the seroconversion rate not rising significantly beyond the value of 42.9% seen on Day 14 (44.4% at Day 60). Although the response in the participants who were seronegative at baseline was slower than that in those who were seropositive, seroconversion was seen in nearly all (100%) subjects by Day 60, with the exception of the response to toxin B evaluated using TNA (16-18% on Days 14-60).
The proportion of participants with solicited local reactions, solicited systemic reactions, and vaccine-related unsolicited reactions were 67.6%, 19.1%, and 20.6%, respectively. Most of the adverse reactions were mild to moderate in severity, occurring within 3 days post-vaccination, and resolving by 3-6 days post-vaccination. There were no withdrawals due to adverse events, and no serious adverse events.
These data confirm the safety and immunogenicity of C. difficile vaccine in Japanese adults.

Key word

Clostridium difficile, vaccine, safety, immunogenicity

Received

August 8, 2016

Accepted

November 29, 2016

Jpn. J. Chemother. 65 (2): 183-191, 2017