A Phase 2 Extension Study Evaluating the Immunogenicity, Safety, and Tolerability of 3 or 4 Doses of a Clostridioides difficile Vaccine in Healthy US Adults 65 to 85 Years of Age

This phase 2 extension explored long-term antibody persistence of an investigational Clostridioides difficile vaccine and safety/tolerability and immunogenicity of dose 4 ∼12 months postdose 3.One year postdose 3, 300 healthy US 65-85-year-olds were randomized to Dose 4 of vaccine at previously-received antigen levels (100 or 200 μg) or placebo. Assessments included safety and percentages of subjects achieving neutralizing antibody titers above prespecified thresholds (≥219 and ≥2586 neutralization units/mL for toxins A and B, respectively).In subjects previously given three 200-µg doses and placebo in the extension, toxin A and B neutralizing antibodies were above prevaccination levels 48 months postdose 3 (36 months post-placebo); 24.0% and 26.0% had toxin A and B antibodies at or above prespecified thresholds, respectively. Neutralizing antibodies increased postdose 4 (12 months postdose 3) and persisted to 36 months postdose 4. Thirty days postdose 4, all subjects had toxin A and 86.5%‒100% had toxin B titers at or above prespecified thresholds. Local reactions were more frequent in vaccine recipients. Systemic and adverse event frequencies were similar across groups.C difficile vaccine immune responses persisted 48 months postdose 3. Dose 4 was immunogenic and well tolerated, supporting continued development.NCT02561195.