This article first appeared on our sister site, HCPLive.
Results from a phase 3 study of an Al(OH)3-containing Clostridioides difficile vaccine in healthy adults 65-85 years of age demonstrated the treatment’s lot consistency, immunogenicity, safety, and tolerability.
Neutralizing antibody responses 1 month after dose 3 for both toxin A and toxin B confirmed immunogenicity consistency across C difficile vaccine lots, with further analysis showing it was well tolerated and had similar rates of local reactions and systemic events.1
“Strategies for CDI prevention currently include both antibiotic stewardship programs, which aim to lower risk of CDI through reducing antibiotic use, as well as infection control measures such as hand hygiene, use of disposable equipment, and surface disinfecting,” wrote investigators.1 “Although no vaccine has been approved to date for the prevention of primary or recurrent CDI, vaccine candidates are currently under investigation for prevention of primary CDI.”
A germ causing diarrhea and colitis, C difficile is estimated to cause nearly half a million infections in the US every year. Risk factors include being aged 65 years or older, a recent stay at a hospital or nursing home, a weakened immune system, and previous CDI. Current prevention measures focus primarily on hygiene and disinfection, although vaccine development may offer a promising next step for preventing primary and recurrent CDI.2
The phase 3, randomized, observer-blinded, placebo-controlled study was led by Shane Christensen, MD, of J Lewis Research, and sought to assess the lot-to-lot consistency, immunogenicity, safety, and tolerability of 3 C difficile vaccine doses in healthy older adults. For inclusion, patients were required to be 65-85 years of age, not of childbearing potential, were willing and able to comply with the vaccination plan, along with all scheduled visits and other study procedures, and were able to be contacted by telephone during the study. Patients with preexisting stable chronic medical conditions were permitted.1
Of 1358 patients screened by investigators, 1317 were enrolled in the study and randomly assigned in a 1:1:1:1 ratio to receive C difficile vaccine lot 1 (18–000738), C difficile vaccine lot 2 (18–000615), C difficile vaccine lot 3 (18–000614), or placebo. Prior to vaccination, 3 participants withdrew from the study.1
What You Need to Know
The study demonstrated the lot consistency of the C. difficile vaccine, showing consistent immunogenicity across different vaccine lots.
The safety population comprised 1314 participants, and adverse events were generally more frequent after the vaccine dose compared to the placebo. However, rates of adverse events and severe adverse events were similar between vaccine and placebo groups.
The vaccine was administered in a 3-dose schedule at Months 0, 1, and 6, and the findings support the use of the C. difficile vaccine in this population.
The safety population comprised 1314 participants and included all participants who received ≥1 dose of vaccine or placebo. A total of 96 patients withdrew from the study, the most common reasons being participant decision (n = 39), adverse events (n = 21, and loss to follow-up (n = 13). The evaluable immunogenicity population comprised 1158 participants and included all eligible participants who received the vaccine to which they were randomized, had blood samples taken for assay testing within the specified time frame, had valid and determinate assay results for either toxin A or toxin B, and had no major protocol deviations.1
The mean age among the cohort was 71.7 (SD, 4.97) years and 575 (43.8%) were male. Investigators pointed out baseline demographic data and participant characteristics were similar between treatment groups.1
The primary immunogenicity objective was to compare immune responses induced by 3 lots of C difficile vaccine, as measured by C difficile toxins A- and B-specific neutralizing antibody levels 1 month after the third vaccination when administered in a 3-dose regimen. The primary safety objective was the number and percentage of participants reporting local reactions and systemic events, adverse events, and serious adverse events.1
Investigators noted toxins A- and B-specific neutralizing antibody levels were similar between the various lots of C difficile vaccine both at baseline and 1 month after dose 3. Toxin A-specific neutralizing antibody GMCs 1 month after dose 3 were 878.8 (95% confidence interval [CI], 786.3-982.2) for the first lot, 873.0 (95% CI, 779.2-978.1) for lot 2, and 872.9 (95% CI, 782.6-973.5) for lot 3. Toxin B-specific neutralizing antibody GMCs 1 month after dose 3 were 5823.9 (95% CI, 5041.0-6728.4) for the first lot, 5462.8 (95% CI, 4733.4-6304.7) for lot 2, and 5426.0 (95% CI, 4724.4- 6231.8) for lot 3.1
Further analysis revealed the C difficile vaccine induced greater neutralizing antibody responses than placebo. A greater proportion of participants who received the C difficile vaccine achieved ≥4-, ≥8-, ≥16-, and ≥32-fold increases in toxins A- and B-specific neutralizing antibody levels 1 month after dose 3 than in the placebo group. These improvements were greater among C difficile vaccine recipients than in placebo recipients, regardless of baseline serogroup status.1
Of note, geometric mean fold ratios in toxins A- and B-specific neutralizing antibody levels were consistently greater in participants who were seronegative at baseline for toxins A- and B-specific neutralizing antibodies, respectively, than in those who were seropositive.1
Rates and severity of local reactions and systemic events were similar between vaccine lots and were generally more frequent after the vaccine dose compared to placebo. Rates of adverse events and severe adverse events were similar between participants who received C difficile vaccine (36.5 % and 4.5 %, respectively) and those who received placebo (35.3 % and 6 %, respectively).1
“Results of this study showed that C difficile vaccine lots were consistent and demonstrated that C difficile vaccine induced good neutralizing antibody responses and was well tolerated when administered on a 3-dose schedule at Months 0, 1, and 6 in healthy adults, including those with stable, chronic medical conditions, who were 65 to 85 years old. These findings support those of other studies with the same C difficile vaccine formulation,” concluded investigators.1
References:
- Christensen S, Bouguermouh S, Ilangovan K, et al. A phase 3 study evaluating the lot consistency, immunogenicity, safety, and tolerability of a Clostridioides difficile vaccine in healthy adults 65 to 85 years of age. Vaccine. https://doi.org/10.1016/j.vaccine.2023.11.003
- Centers for Disease Control and Prevention. What is C. diff? C. diff (Clostridioides difficile). September 7, 2022. Accessed November 27, 2023. https://www.cdc.gov/cdiff/what-is.html
