Pfizer’s C Difficile Vaccine Did Not Meet Endpoint for Phase 3 Study

Pfizer reported this week that its investigational C difficile (CDI) vaccine, PF-06425090, did not meet its primary endpoint of prevention of C difficile in its phase 3 CLOVER trial. However, for all CDI cases recorded at 14 days post dose 3, vaccine efficacy was 49%, 47%, and 31% up to 12 months and 24 months respectively.

“We are encouraged by the promising potential benefit observed against more severe C difficile infection,” Kathrin U. Jansen, PhD, senior vice president and head of Vaccine Research & Development, Pfizer, said.

The company reported the median C difficile episode was 1 day vs 4 days and that the mean duration was 3 days vs 16 days comparing vaccine to placebo, corresponding to a 75% and 80% reduction in disease episode, respectively, in vaccinated people.

CLOVER Trial Design and Results

CLOVER was an international, phase 3, placebo-controlled, randomized study to evaluate the efficacy, safety, and tolerability of the company’s C difficile vaccine.

They enrolled approximately 17,500 adults 50 years of age and older. CLOVER included participants who were at high risk of CDI in a proximal time frame to receiving the primary vaccine series. Participants were randomized into 2 cohorts with one group receiving 3 doses of the vaccine (n=8766),or placebo (n=8769) at 0, 1 and 6 months.

The 2 primary efficacy endpoints 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% (96.4% CI -38.7, 66.6) following the third dose and 28.6% (96.4% CI -28.4, 61.0) following the second dose for the C difficile vaccine candidate.

A potential silver lining was that in the vaccine cohort, no one required medical attention including hospitalization (0 out of 17) compared to 11 out of 25 in the placebo group.

The vaccine was very well tolerated and showed a favorable safety profile, according to Pfizer. Secondary endpoints included reduction of incidence of all CDI cases following the second and the third vaccine dose; reduction of the severity of CDI after three doses by the duration of the CDI episodes and the requirement to seek medical attention; reduction of incidence of CDI recurrence after the second and third doses; and for those participants that only received two doses, reduction of the incidence of a first primary episode of CDI and recurrent CDI.

In their statement, Pfizer said some secondary endpoints had not been analyzed including reduction of incidence of all CDI cases following the second and the third dose; reduction of incidence of CDI recurrence after second and third doses; reduction of incidence of a first primary episode of CDI for participants that only received 2 doses; and reduction of incidence of recurrent CDI for participants that only received two doses.

The company has not given further indication of what it plans to do with the vaccine. “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,” Jansen stated.