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 Aged 65 to 85 Years
Shon Remich, Nicholas Kitchin, James Peterson, Ping Li, Michael W Pride, Linda Brock, Annaliesa S Anderson, William C Gruber, Kathrin U Jansen, Stephen P Lockhart, Chris Webber- Infectious Diseases
- Immunology and Allergy
Abstract
Background
This phase 2 extension explored the long-term antibody persistence of an investigational Clostridioides difficile vaccine and the safety, tolerability, and immunogenicity of dose 4 approximately 12 months post–dose 3.
Methods
One year post–dose 3, healthy US 65- to 85-year-olds (N = 300) were randomized to dose 4 of vaccine at previously received antigen levels (100 or 200 μg) or placebo. Assessments included safety and percentages of participants achieving neutralizing antibody titers above prespecified thresholds (≥219 and ≥2586 neutralization units/mL for toxins A and B, respectively).
Results
In participants previously given three 200-µg doses and placebo in the extension, toxin A and B neutralizing antibodies were above prevaccination levels 48 months post–dose 3 (36 months after placebo); 24.0% and 26.0% had toxin A and B antibodies at or above prespecified thresholds, respectively. Neutralizing antibodies increased post–dose 4 (12 months post–dose 3) and persisted to 36 months post–dose 4. Thirty days post–dose 4, all participants had toxin A and 86.5% to 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.
Conclusions
C difficile vaccine immune responses persisted 48 months post–dose 3. Dose 4 was immunogenic and well tolerated, supporting continued development.
Clinical Trials Registration. ClinicalTrials.gov NCT02561195.