Evaluation Of Clostridium Difficile Vaccine Lot Consistency In Healthy Adults 65 To 85 Years Of Age

GMC was calculated as the mean of the assay results after making the logarithm transformation and then back transformation to its original scale. Confidence intervals (CIs) were back transformations of CIs based on the Student t distribution for the mean logarithm of the concentrations. Clostridium difficile toxin A and toxin B were inactivated by a combination of genetic mutations to decrease toxin activity and chemical treatments were done prior to final purification and formulation of the drug substance.

Time frame: At Month 7

Population: Evaluable immunogenicity(EI)population=enrolled participants who received all 3 doses of investigational product to which they were randomized; blood drawn for analysis within 23-47 days after visit 4(Month 6)had valid, determinate assay results for either toxinA or B for specified analysis and no major protocol deviations. Placebo arm is not reported as GMC was planned to be evaluated only for 3 vaccine lots. Here,'Number Analyzed' refers to number of participants evaluable for specific toxins.

Local reactions included pain at injection site, redness and swelling. These were recorded by participants in an electronic diary (e-diary). Pain at injection site was graded as mild: did not interfere with daily activity, moderate: interfered with daily activity, severe: prevented daily activity, grade 4: emergency room visit or hospitalization. Redness and swelling were measured and recorded in measuring device units. One measuring device unit= 0.5 centimeter (cm) and graded as mild: 2.5 to 5.0 cm, moderate: greater than (\>) 5.0 to 10.0 cm, severe: \>10.0 cm, Grade 4 indicated necrosis or exfoliative dermatitis for redness and necrosis for swelling. The maximum severity was defined as highest grading of each local reaction within 7 days of vaccination. Events were classified as Grade 4 based on study investigator's judgement.

Time frame: Within 7 days after Vaccination 1 at Month 0

Population: Safety analysis population included all participants who received at least 1 dose of the investigational product. Here, Overall Number of Participants Analyzed signifies participants evaluable for this outcome measure.

Local reactions included pain at injection site, redness and swelling. These were recorded by participants in an e-diary. Pain at injection site was graded as mild: did not interfere with daily activity, moderate: interfered with daily activity, severe: prevented daily activity, grade 4: emergency room visit or hospitalization. Redness and swelling were measured and recorded in measuring device units. One measuring device unit= 0.5 cm and graded as mild: 2.5 to 5.0 cm, moderate: \> 5.0 to 10.0 cm, severe: \>10.0 cm, Grade 4 indicated necrosis or exfoliative dermatitis for redness and necrosis for swelling. The maximum severity was defined as highest grading of each local reaction within 7 days of vaccination. Events were classified as Grade 4 based on study investigator's judgement.

Time frame: Within 7 days after Vaccination 2 at Month 1

Population: Safety analysis population included all participants who received at least 1 dose of the investigational product. Here, Overall Number of Participants Analyzed signifies participants evaluable for this outcome measure.

Local reactions included pain at injection site, redness and swelling. These were recorded by participants in an e-diary. Pain at injection site was graded as mild: did not interfere with daily activity, moderate: interfered with daily activity, severe: prevented daily activity, grade 4: emergency room visit or hospitalization. Redness and swelling were measured and recorded in measuring device units. One measuring device unit= 0.5 cm and graded as mild: 2.5 to 5.0 cm, moderate: \> 5.0 to 10.0 cm, severe: \>10.0 cm, Grade 4 indicated necrosis or exfoliative dermatitis for redness and necrosis for swelling. The maximum severity was defined as highest grading of each local reaction within 7 days of vaccination. Events were classified as Grade 4 based on study investigator's judgement.

Time frame: Within 7 days after Vaccination 3 at Month 6

Population: Safety analysis population included all participants who received at least 1 dose of the investigational product. Here, Overall Number of Participants Analyzed signifies participants evaluable for this outcome measure.

An SAE was defined as any untoward medical occurrence at any dose that resulted in any of the following outcomes: death; life-threatening (immediate risk of death); required inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); congenital anomaly/birth defect; or that was considered as an important medical event.

Time frame: From Day 1 to 1 month after last vaccination (Up to Month 7)

Population: Safety analysis population included all participants who received at least 1 dose of the investigational product. Pooled data for Clostridium difficile vaccine (lot 1+lot 2+lot 3) is reported for this outcome measure as pre-specified in the statistical analysis plan.

Systemic events included fever, fatigue, headache, joint pain, muscle pain and vomiting. These were recorded by participants in an e-diary. Fever was categorized as: mild: (38.0 to 38.4 degree Celsius \[deg C\]), moderate: (38.5 to 38.9 deg C), severe (39.0 to 40.0 deg C), grade 4: \>40 deg C. Fatigue, headache, joint pain and muscle pain were graded as mild: did not interfere with activity, moderate: some interference with activity, severe: prevented daily activity, grade 4: emergency room visit or hospitalization. Vomiting was graded as mild: 1 to 2 times in 24 hours, moderate: \>2 times in 24 hours, severe: required intravenous hydration, grade 4: emergency room visit or hospitalization for hypotensive shock. The maximum severity was defined as highest grading of each systemic event within 7 days of vaccination. Events were classified as Grade 4 based on study investigator's judgement.

Time frame: Within 7 days after Vaccination 1 at Month 0

Population: Safety analysis population included all participants who received at least 1 dose of the investigational product. Here, Overall Number of Participants Analyzed signifies participants evaluable for this outcome measure.

Systemic events included fever, fatigue, headache, joint pain, muscle pain and vomiting. These were recorded by participants in an e-diary. Fever was categorized as: mild: (38.0 to 38.4 deg C), moderate: (38.5 to 38.9 deg C), severe (39.0 to 40.0 deg C), grade 4: \>40 deg C. Fatigue, headache, joint pain and muscle pain were graded as mild: did not interfere with activity, moderate: some interference with activity, severe: prevented daily activity, grade 4: emergency room visit or hospitalization. Vomiting was graded as mild: 1 to 2 times in 24 hours, moderate: \>2 times in 24 hours, severe: required intravenous hydration, grade 4: emergency room visit or hospitalization for hypotensive shock. The maximum severity was defined as highest grading of each systemic event within 7 days of vaccination. Events were classified as Grade 4 based on study investigator's judgement.

Time frame: Within 7 days after Vaccination 2 at Month 1

Population: Safety analysis population included all participants who received at least 1 dose of the investigational product. Here, Overall Number of Participants Analyzed signifies participants evaluable for this outcome measure.

Systemic events included fever, fatigue, headache, joint pain, muscle pain and vomiting. These were recorded by participants in an e-diary. Fever was categorized as: mild: (38.0 to 38.4 deg C), moderate: (38.5 to 38.9 deg C), severe (39.0 to 40.0 deg C), grade 4: \>40 deg C. Fatigue, headache, joint pain and muscle pain were graded as mild: did not interfere with activity, moderate: some interference with activity, severe: prevented daily activity, grade 4: emergency room visit or hospitalization. Vomiting was graded as mild: 1 to 2 times in 24 hours, moderate: \>2 times in 24 hours, severe: required intravenous hydration, grade 4: emergency room visit or hospitalization for hypotensive shock. The maximum severity was defined as highest grading of each systemic event within 7 days of vaccination. Events were classified as Grade 4 based on study investigator's judgement.

Time frame: Within 7 days after Vaccination 3 at Month 6

Population: Safety analysis population included all participants who received at least 1 dose of the investigational product. Here, Overall Number of Participants Analyzed signifies participants evaluable for this outcome measure.

An AE was defined as any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. AEs included both serious and all non-serious adverse events (NSAEs). Only AEs and NSAEs collected by non-systematic assessment (i.e., excluding local reactions and systemic events) were reported in this outcome measure.

Time frame: From Day 1 to 1 month after last vaccination (Up to Month 7)

Population: Safety analysis population included all participants who received at least 1 dose of the investigational product. Pooled data for Clostridium difficile vaccine (lot 1+lot 2+lot 3) is reported for this outcome measure as pre-specified in the statistical analysis plan.