Novel C. difficile infection (CDI) vaccine shows promise lowering the severity of CDI and in preventing medically attended CDI.
A novel vaccine candidate (PF-06425090, Pfizer) for Clostridioides difficile infection (CDI) showed promising results in a phase 3 trial. In an early analysis of protocol-defined secondary endpoints of the CLOVER trial, PF-06425090 indicated a highly favorable benefit in decreasing the severity of CDI and showed 100% vaccine efficacy in preventing medically attended CDI, according to a Pfizer press release.
“We are encouraged by the promising potential benefit observed against more severe C. difficile infection, as a large portion of cases lead to extended diarrhea episodes that can require hospitalization,” said Kathrin U. Jansen, PhD, Pfizer senior vice president and head of Vaccine Research and Development, in a press release. “We will evaluate next steps for our program in coordination with regulatory agencies. We are grateful to everyone who made the CLOVER study possible, including the study investigators and the trial participants for their contribution to this important research.”
The CLOVER trial enrolled approximately 17,500 adults aged 50 years and older. The investigators anticipated 66 cases of CDI to develop within 2 years of the primary vaccination series. However, because of operational challenges associated with the COVID-19 pandemic, an agreement with the FDA to amend the protocol allowed the final analysis to proceed with 42 cases within 4 years.
The 2 primary efficacy endpoints in CLOVER were first primary episode of CDI ≥14 days following completion of the third dose and first primary episode of CDI ≥14 days following completion of the second dose. Vaccine efficacy under the primary endpoint was 31% after the third dose and 28.6% after the second dose. Vaccine efficacy was noted at 49%, 47%, and 31% up to 12 months, 24 months, and at final analysis, respectively, for all CDI cases recorded 14 days post dose 3.
According to the study authors, the vaccine was well-tolerated and showed a favorable safety profile. Local and systemic reactions were deemed mild to moderate, most of which were pain at the injection site with higher incidence after the second and third doses. Further, the number of participants reporting overall adverse events (AEs), serious AEs, withdrawals, and deaths being similar between the 2 groups.
A favorable benefit was noted in reducing the duration and severity of disease, with the pre-specified secondary endpoint of the proportion of participants who sought medical attention for CDI showing a 0-11 case split, which corresponds to 100% vaccine efficacy. Additionally, none of the participants with CDI in the vaccine group required medical attention compared to the 11 in the placebo group.
Pfizer plans to continue evaluating data from the trial and determine next steps for their CDI vaccine program.
Phase 3 CLOVER Trial for Pfizer’s Investigational Clostridioides Difficile Vaccine Indicates Strong Potential Effect in Reducing Duration and Severity of Disease Based on Secondary Endpoints. Pfizer. March 1, 2022. Accessed March 3, 2022. https://www.pfizer.com/news/press-release/press-release-detail/phase-3-clover-trial-pfizers-investigational-clostridioides