In the Journals

Phase 2 study shows promising results for C. difficile vaccine

An investigational vaccine for the prevention of Clostridioides difficile infection was safe, well-tolerated and immunogenic in healthy adults aged 65 to 85 years, according to findings from a phase 2 study published in Clinical Infectious Diseases.

The researchers chose to assess the vaccine in adults aged 65 to 85 years because that age group is at an increased risk for C. difficile infection, or CDI. Currently, no vaccine is licensed to prevent CDI. The investigational vaccine, which contains genetically and chemically detoxified toxins A and B, has already entered a phase 3 trial, but Shon A. Remich, MD, senior director of vaccine clinical research and development at Pfizer, told Infectious Disease News that they needed to be sure the vaccine is safe and produces a good immune response before moving to a broader population.

“In addition to health care-associated CDIs, community-associated infections have increased in prevalence in recent years,” Remich said. “These phase 2 study results help bring us one step closer toward a vaccine which, if successful in phase 3 [testing] and approved, may help prevent CDI.”

Remich and colleagues conducted a phase 2, placebo-controlled, randomized, observer-blinded study among 855 healthy adults, aged 65 to 85 years, from July 2015 through March 2017. In a 3:3:1 ratio, participants were randomly assigned to receive the investigational vaccine in either a 100-μg or 200-μg dose or placebo at 0, 1 and 6 months (the “month regimen”), or 1, 8 and 30 days (the “day regimen”).

For both regimens, the researchers observed a higher immune response among participants who received the 200-μg dose compared with participants receiving the 100-μg dose. The month regimen demonstrated stronger and more persistent immune responses compared with the day regimen, and those responses remained elevated 12 months after the third dose.

According to Remich and colleagues, responses for the month regimen peaked at month 7, whereas responses for the day regimen peaked at day 37.

Participant-reported local reactions occurred more frequently among participants who received the vaccine compared with controls, but the rates of systemic events were similar across the groups. Those assigned to the day regimen reported more related adverse events compared with those on the month regimen.

“The results of the phase 2 trial support continued development of the vaccine candidate,” Remich said.

Remich added that the findings helped inform the protocol for the phase 3 study, named CLOVER, or the Clostridium difficile Vaccine Efficacy Trial — which refers the bacterium’s former scientific name. The study will investigate the efficacy of the vaccine among adults aged 50 years or older who, because of age and “increased exposure to healthcare systems,” have an increased risk for CDI. – by Marley Ghizzone

Disclosures: Kitchin is an employee of Pfizer Inc. and reports holding stock and/or stock options. Please see the study for all other authors’ relevant financial disclosures.

An investigational vaccine for the prevention of Clostridioides difficile infection was safe, well-tolerated and immunogenic in healthy adults aged 65 to 85 years, according to findings from a phase 2 study published in Clinical Infectious Diseases.

The researchers chose to assess the vaccine in adults aged 65 to 85 years because that age group is at an increased risk for C. difficile infection, or CDI. Currently, no vaccine is licensed to prevent CDI. The investigational vaccine, which contains genetically and chemically detoxified toxins A and B, has already entered a phase 3 trial, but Shon A. Remich, MD, senior director of vaccine clinical research and development at Pfizer, told Infectious Disease News that they needed to be sure the vaccine is safe and produces a good immune response before moving to a broader population.

“In addition to health care-associated CDIs, community-associated infections have increased in prevalence in recent years,” Remich said. “These phase 2 study results help bring us one step closer toward a vaccine which, if successful in phase 3 [testing] and approved, may help prevent CDI.”

Remich and colleagues conducted a phase 2, placebo-controlled, randomized, observer-blinded study among 855 healthy adults, aged 65 to 85 years, from July 2015 through March 2017. In a 3:3:1 ratio, participants were randomly assigned to receive the investigational vaccine in either a 100-μg or 200-μg dose or placebo at 0, 1 and 6 months (the “month regimen”), or 1, 8 and 30 days (the “day regimen”).

For both regimens, the researchers observed a higher immune response among participants who received the 200-μg dose compared with participants receiving the 100-μg dose. The month regimen demonstrated stronger and more persistent immune responses compared with the day regimen, and those responses remained elevated 12 months after the third dose.

According to Remich and colleagues, responses for the month regimen peaked at month 7, whereas responses for the day regimen peaked at day 37.

Participant-reported local reactions occurred more frequently among participants who received the vaccine compared with controls, but the rates of systemic events were similar across the groups. Those assigned to the day regimen reported more related adverse events compared with those on the month regimen.

“The results of the phase 2 trial support continued development of the vaccine candidate,” Remich said.

Remich added that the findings helped inform the protocol for the phase 3 study, named CLOVER, or the Clostridium difficile Vaccine Efficacy Trial — which refers the bacterium’s former scientific name. The study will investigate the efficacy of the vaccine among adults aged 50 years or older who, because of age and “increased exposure to healthcare systems,” have an increased risk for CDI. – by Marley Ghizzone

Disclosures: Kitchin is an employee of Pfizer Inc. and reports holding stock and/or stock options. Please see the study for all other authors’ relevant financial disclosures.