Trial Outcomes & Findings for Evaluation Of Clostridium Difficile Vaccine Lot Consistency In Healthy Adults 65 To 85 Years Of Age (NCT NCT03579459)

Last Updated: 2023-01-19

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1317 participants

Primary outcome timeframe

At Month 7

Results posted on

2023-01-19

Participant Flow

1358 participants signed the informed consent form (ICF). 41 participants were screen failures who did not meet eligibility criteria and were not enrolled. Out of 1317 randomized participants, only 1314 participants received at least one 1 dose of the investigational product.

Participant milestones

Participant milestones
Measure	Clostridium Difficile Vaccine: Lot 1 Participants were randomized to receive Clostridium difficile vaccine Lot 1 (200 microgram total toxoid per dose) intramuscularly at Months 0, 1 and 6.	Clostridium Difficile Vaccine: Lot 2 Participants were randomized to receive Clostridium difficile vaccine Lot 2 (200 microgram total toxoid per dose) intramuscularly at Months 0, 1 and 6.	Clostridium Difficile Vaccine: Lot 3 Participants were randomized to receive Clostridium difficile vaccine Lot 3 (200 microgram total toxoid per dose) intramuscularly at Months 0, 1 and 6.	Placebo Participants were randomized to receive placebo (0.9% sodium chloride injection, in a 0.5 mL dose) intramuscularly at Months 0, 1 and 6.
Overall Study STARTED	330	327	328	332
Overall Study Dose 1	330	325	328	331
Overall Study Dose 2	324	318	319	322
Overall Study Dose 3	305	305	307	309
Overall Study COMPLETED	301	304	305	308
Overall Study NOT COMPLETED	29	23	23	24

Reasons for withdrawal

Reasons for withdrawal
Measure	Clostridium Difficile Vaccine: Lot 1 Participants were randomized to receive Clostridium difficile vaccine Lot 1 (200 microgram total toxoid per dose) intramuscularly at Months 0, 1 and 6.	Clostridium Difficile Vaccine: Lot 2 Participants were randomized to receive Clostridium difficile vaccine Lot 2 (200 microgram total toxoid per dose) intramuscularly at Months 0, 1 and 6.	Clostridium Difficile Vaccine: Lot 3 Participants were randomized to receive Clostridium difficile vaccine Lot 3 (200 microgram total toxoid per dose) intramuscularly at Months 0, 1 and 6.	Placebo Participants were randomized to receive placebo (0.9% sodium chloride injection, in a 0.5 mL dose) intramuscularly at Months 0, 1 and 6.
Overall Study Adverse Event	7	6	2	6
Overall Study Death	1	0	1	2
Overall Study Lost to Follow-up	6	2	4	1
Overall Study Physician Decision	0	1	0	1
Overall Study Protocol Violation	1	2	3	5
Overall Study Withdrawal by Subject	12	8	11	8
Overall Study Medication error without associated adverse event	2	1	1	0
Overall Study Other	0	1	1	0
Overall Study Randomized not vaccinated	0	2	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Clostridium Difficile Vaccine: Lot 1 n=330 Participants Participants received Clostridium difficile vaccine Lot 1 (200 microgram total toxoid per dose) intramuscularly at Months 0, 1 and 6.	Clostridium Difficile Vaccine: Lot 2 n=325 Participants Participants received Clostridium difficile vaccine Lot 2 (200 microgram total toxoid per dose) intramuscularly at Months 0, 1 and 6.	Clostridium Difficile Vaccine: Lot 3 n=328 Participants Participants received Clostridium difficile vaccine Lot 3 (200 microgram total toxoid per dose) intramuscularly at Months 0, 1 and 6.	Placebo n=331 Participants Participants received placebo (0.9% sodium chloride injection, in a 0.5 mL dose) intramuscularly at Months 0, 1 and 6.	Total n=1314 Participants Total of all reporting groups
Age, Continuous	71.7 Years STANDARD_DEVIATION 5.01 • n=5 Participants	72.0 Years STANDARD_DEVIATION 5.03 • n=7 Participants	71.1 Years STANDARD_DEVIATION 4.83 • n=5 Participants	72.1 Years STANDARD_DEVIATION 4.99 • n=4 Participants	71.7 Years STANDARD_DEVIATION 4.97 • n=21 Participants
Sex: Female, Male Female	189 Participants n=5 Participants	186 Participants n=7 Participants	186 Participants n=5 Participants	178 Participants n=4 Participants	739 Participants n=21 Participants
Sex: Female, Male Male	141 Participants n=5 Participants	139 Participants n=7 Participants	142 Participants n=5 Participants	153 Participants n=4 Participants	575 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	38 Participants n=5 Participants	29 Participants n=7 Participants	26 Participants n=5 Participants	32 Participants n=4 Participants	125 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	289 Participants n=5 Participants	291 Participants n=7 Participants	299 Participants n=5 Participants	297 Participants n=4 Participants	1176 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	5 Participants n=7 Participants	3 Participants n=5 Participants	2 Participants n=4 Participants	13 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants	8 Participants n=21 Participants
Race (NIH/OMB) Asian	5 Participants n=5 Participants	5 Participants n=7 Participants	6 Participants n=5 Participants	6 Participants n=4 Participants	22 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants	2 Participants n=4 Participants	7 Participants n=21 Participants
Race (NIH/OMB) Black or African American	38 Participants n=5 Participants	25 Participants n=7 Participants	29 Participants n=5 Participants	25 Participants n=4 Participants	117 Participants n=21 Participants
Race (NIH/OMB) White	285 Participants n=5 Participants	289 Participants n=7 Participants	285 Participants n=5 Participants	292 Participants n=4 Participants	1151 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants	5 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	4 Participants n=21 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Clostridium Difficile Vaccine: Lot 1 n=286 Participants Participants received Clostridium difficile vaccine Lot 1 (200 microgram total toxoid per dose) intramuscularly at Months 0, 1 and 6.	Clostridium Difficile Vaccine: Lot 2 n=284 Participants Participants received Clostridium difficile vaccine Lot 2 (200 microgram total toxoid per dose) intramuscularly at Months 0, 1 and 6.	Clostridium Difficile Vaccine: Lot 3 n=296 Participants Participants received Clostridium difficile vaccine Lot 3 (200 microgram total toxoid per dose) intramuscularly at Months 0, 1 and 6.	Placebo Participants received placebo (0.9% sodium chloride injection, in a 0.5 mL dose) intramuscularly at Months 0, 1 and 6.
Geometric Mean Concentrations (GMCs) of Clostridium Difficile Toxin A and Toxin B Specific Neutralizing Antibodies at Month 7 Toxin A	878.8 Neutralization units per mL Interval 786.3 to 982.2	873.0 Neutralization units per mL Interval 779.2 to 978.1	872.9 Neutralization units per mL Interval 782.6 to 973.5	—
Geometric Mean Concentrations (GMCs) of Clostridium Difficile Toxin A and Toxin B Specific Neutralizing Antibodies at Month 7 Toxin B	5823.9 Neutralization units per mL Interval 5041.0 to 6728.4	5462.8 Neutralization units per mL Interval 4733.4 to 6304.7	5426.0 Neutralization units per mL Interval 4724.4 to 6231.8	—

PRIMARY outcome

Timeframe: 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 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.

Outcome measures

Outcome measures
Measure	Clostridium Difficile Vaccine: Lot 1 n=325 Participants Participants received Clostridium difficile vaccine Lot 1 (200 microgram total toxoid per dose) intramuscularly at Months 0, 1 and 6.	Clostridium Difficile Vaccine: Lot 2 n=320 Participants Participants received Clostridium difficile vaccine Lot 2 (200 microgram total toxoid per dose) intramuscularly at Months 0, 1 and 6.	Clostridium Difficile Vaccine: Lot 3 n=322 Participants Participants received Clostridium difficile vaccine Lot 3 (200 microgram total toxoid per dose) intramuscularly at Months 0, 1 and 6.	Placebo n=325 Participants Participants received placebo (0.9% sodium chloride injection, in a 0.5 mL dose) intramuscularly at Months 0, 1 and 6.
Percentage of Participants Reporting Local Reactions by Maximum Severity Within 7 Days After Vaccination 1 Pain at injection site: Mild	14.2 Percentage of participants Interval 10.6 to 18.4	15.9 Percentage of participants Interval 12.1 to 20.4	17.4 Percentage of participants Interval 13.4 to 22.0	4.9 Percentage of participants Interval 2.8 to 7.9
Percentage of Participants Reporting Local Reactions by Maximum Severity Within 7 Days After Vaccination 1 Pain at injection site: Moderate	2.5 Percentage of participants Interval 1.1 to 4.8	0.3 Percentage of participants Interval 0.0 to 1.7	0.9 Percentage of participants Interval 0.2 to 2.7	0 Percentage of participants Interval 0.0 to 1.1
Percentage of Participants Reporting Local Reactions by Maximum Severity Within 7 Days After Vaccination 1 Pain at injection site: Severe	0 Percentage of participants Interval 0.0 to 1.1	0 Percentage of participants Interval 0.0 to 1.1	0.3 Percentage of participants Interval 0.0 to 1.7	0 Percentage of participants Interval 0.0 to 1.1
Percentage of Participants Reporting Local Reactions by Maximum Severity Within 7 Days After Vaccination 1 Pain at injection site: Grade 4	0 Percentage of participants Interval 0.0 to 1.1	0 Percentage of participants Interval 0.0 to 1.1	0 Percentage of participants Interval 0.0 to 1.1	0 Percentage of participants Interval 0.0 to 1.1
Percentage of Participants Reporting Local Reactions by Maximum Severity Within 7 Days After Vaccination 1 Redness: Mild	0.6 Percentage of participants Interval 0.1 to 2.2	1.6 Percentage of participants Interval 0.5 to 3.6	2.2 Percentage of participants Interval 0.9 to 4.4	0.6 Percentage of participants Interval 0.1 to 2.2
Percentage of Participants Reporting Local Reactions by Maximum Severity Within 7 Days After Vaccination 1 Redness: Moderate	0.6 Percentage of participants Interval 0.1 to 2.2	0 Percentage of participants Interval 0.0 to 1.1	0.3 Percentage of participants Interval 0.0 to 1.7	0 Percentage of participants Interval 0.0 to 1.1
Percentage of Participants Reporting Local Reactions by Maximum Severity Within 7 Days After Vaccination 1 Redness: Severe	0.3 Percentage of participants Interval 0.0 to 1.7	0 Percentage of participants Interval 0.0 to 1.1	0 Percentage of participants Interval 0.0 to 1.1	0 Percentage of participants Interval 0.0 to 1.1
Percentage of Participants Reporting Local Reactions by Maximum Severity Within 7 Days After Vaccination 1 Redness: Grade 4	0 Percentage of participants Interval 0.0 to 1.1	0 Percentage of participants Interval 0.0 to 1.1	0 Percentage of participants Interval 0.0 to 1.1	0 Percentage of participants Interval 0.0 to 1.1
Percentage of Participants Reporting Local Reactions by Maximum Severity Within 7 Days After Vaccination 1 Swelling: Mild	1.5 Percentage of participants Interval 0.5 to 3.6	0.9 Percentage of participants Interval 0.2 to 2.7	1.6 Percentage of participants Interval 0.5 to 3.6	0 Percentage of participants Interval 0.0 to 1.1
Percentage of Participants Reporting Local Reactions by Maximum Severity Within 7 Days After Vaccination 1 Swelling: Moderate	0.9 Percentage of participants Interval 0.2 to 2.7	0.6 Percentage of participants Interval 0.1 to 2.2	0.3 Percentage of participants Interval 0.0 to 1.7	0.6 Percentage of participants Interval 0.1 to 2.2
Percentage of Participants Reporting Local Reactions by Maximum Severity Within 7 Days After Vaccination 1 Swelling: Severe	0 Percentage of participants Interval 0.0 to 1.1	0 Percentage of participants Interval 0.0 to 1.1	0.6 Percentage of participants Interval 0.1 to 2.2	0 Percentage of participants Interval 0.0 to 1.1
Percentage of Participants Reporting Local Reactions by Maximum Severity Within 7 Days After Vaccination 1 Swelling: Grade 4	0 Percentage of participants Interval 0.0 to 1.1	0 Percentage of participants Interval 0.0 to 1.1	0 Percentage of participants Interval 0.0 to 1.1	0 Percentage of participants Interval 0.0 to 1.1

PRIMARY outcome

Timeframe: Within 7 days after Vaccination 2 at Month 1

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.

Outcome measures

Outcome measures
Measure	Clostridium Difficile Vaccine: Lot 1 n=316 Participants Participants received Clostridium difficile vaccine Lot 1 (200 microgram total toxoid per dose) intramuscularly at Months 0, 1 and 6.	Clostridium Difficile Vaccine: Lot 2 n=309 Participants Participants received Clostridium difficile vaccine Lot 2 (200 microgram total toxoid per dose) intramuscularly at Months 0, 1 and 6.	Clostridium Difficile Vaccine: Lot 3 n=314 Participants Participants received Clostridium difficile vaccine Lot 3 (200 microgram total toxoid per dose) intramuscularly at Months 0, 1 and 6.	Placebo n=313 Participants Participants received placebo (0.9% sodium chloride injection, in a 0.5 mL dose) intramuscularly at Months 0, 1 and 6.
Percentage of Participants Reporting Local Reactions by Maximum Severity Within 7 Days After Vaccination 2 Pain at injection site: Mild	22.2 Percentage of participants Interval 17.7 to 27.1	26.9 Percentage of participants Interval 22.0 to 32.2	22.0 Percentage of participants Interval 17.5 to 27.0	4.2 Percentage of participants Interval 2.2 to 7.0
Percentage of Participants Reporting Local Reactions by Maximum Severity Within 7 Days After Vaccination 2 Pain at injection site: Moderate	2.2 Percentage of participants Interval 0.9 to 4.5	2.9 Percentage of participants Interval 1.3 to 5.5	1.6 Percentage of participants Interval 0.5 to 3.7	0.3 Percentage of participants Interval 0.0 to 1.8
Percentage of Participants Reporting Local Reactions by Maximum Severity Within 7 Days After Vaccination 2 Pain at injection site: Severe	0.3 Percentage of participants Interval 0.0 to 1.8	0 Percentage of participants Interval 0.0 to 1.2	0 Percentage of participants Interval 0.0 to 1.2	0 Percentage of participants Interval 0.0 to 1.2
Percentage of Participants Reporting Local Reactions by Maximum Severity Within 7 Days After Vaccination 2 Pain at injection site: Grade 4	0 Percentage of participants Interval 0.0 to 1.2	0 Percentage of participants Interval 0.0 to 1.2	0 Percentage of participants Interval 0.0 to 1.2	0 Percentage of participants Interval 0.0 to 1.2
Percentage of Participants Reporting Local Reactions by Maximum Severity Within 7 Days After Vaccination 2 Redness: Mild	3.5 Percentage of participants Interval 1.8 to 6.1	3.9 Percentage of participants Interval 2.0 to 6.7	1.3 Percentage of participants Interval 0.3 to 3.2	1.0 Percentage of participants Interval 0.2 to 2.8
Percentage of Participants Reporting Local Reactions by Maximum Severity Within 7 Days After Vaccination 2 Redness: Moderate	1.9 Percentage of participants Interval 0.7 to 4.1	1.3 Percentage of participants Interval 0.4 to 3.3	1.3 Percentage of participants Interval 0.3 to 3.2	0.3 Percentage of participants Interval 0.0 to 1.8
Percentage of Participants Reporting Local Reactions by Maximum Severity Within 7 Days After Vaccination 2 Redness: Severe	1.3 Percentage of participants Interval 0.3 to 3.2	0.6 Percentage of participants Interval 0.1 to 2.3	0 Percentage of participants Interval 0.0 to 1.2	0 Percentage of participants Interval 0.0 to 1.2
Percentage of Participants Reporting Local Reactions by Maximum Severity Within 7 Days After Vaccination 2 Redness: Grade 4	0 Percentage of participants Interval 0.0 to 1.2	0 Percentage of participants Interval 0.0 to 1.2	0 Percentage of participants Interval 0.0 to 1.2	0 Percentage of participants Interval 0.0 to 1.2
Percentage of Participants Reporting Local Reactions by Maximum Severity Within 7 Days After Vaccination 2 Swelling: Mild	3.5 Percentage of participants Interval 1.8 to 6.1	3.9 Percentage of participants Interval 2.0 to 6.7	1.9 Percentage of participants Interval 0.7 to 4.1	0.3 Percentage of participants Interval 0.0 to 1.8
Percentage of Participants Reporting Local Reactions by Maximum Severity Within 7 Days After Vaccination 2 Swelling: Moderate	2.5 Percentage of participants Interval 1.1 to 4.9	1.6 Percentage of participants Interval 0.5 to 3.7	1.6 Percentage of participants Interval 0.5 to 3.7	0 Percentage of participants Interval 0.0 to 1.2
Percentage of Participants Reporting Local Reactions by Maximum Severity Within 7 Days After Vaccination 2 Swelling: Severe	0.9 Percentage of participants Interval 0.2 to 2.7	1.3 Percentage of participants Interval 0.4 to 3.3	0.3 Percentage of participants Interval 0.0 to 1.8	0 Percentage of participants Interval 0.0 to 1.2
Percentage of Participants Reporting Local Reactions by Maximum Severity Within 7 Days After Vaccination 2 Swelling: Grade 4	0 Percentage of participants Interval 0.0 to 1.2	0 Percentage of participants Interval 0.0 to 1.2	0 Percentage of participants Interval 0.0 to 1.2	0 Percentage of participants Interval 0.0 to 1.2

PRIMARY outcome

Timeframe: Within 7 days after Vaccination 3 at Month 6

Outcome measures

Outcome measures
Measure	Clostridium Difficile Vaccine: Lot 1 n=293 Participants Participants received Clostridium difficile vaccine Lot 1 (200 microgram total toxoid per dose) intramuscularly at Months 0, 1 and 6.	Clostridium Difficile Vaccine: Lot 2 n=295 Participants Participants received Clostridium difficile vaccine Lot 2 (200 microgram total toxoid per dose) intramuscularly at Months 0, 1 and 6.	Clostridium Difficile Vaccine: Lot 3 n=298 Participants Participants received Clostridium difficile vaccine Lot 3 (200 microgram total toxoid per dose) intramuscularly at Months 0, 1 and 6.	Placebo n=303 Participants Participants received placebo (0.9% sodium chloride injection, in a 0.5 mL dose) intramuscularly at Months 0, 1 and 6.
Percentage of Participants Reporting Local Reactions by Maximum Severity Within 7 Days After Vaccination 3 Pain at injection site: Mild	22.5 Percentage of participants Interval 17.9 to 27.7	23.4 Percentage of participants Interval 18.7 to 28.6	27.9 Percentage of participants Interval 22.8 to 33.3	2.6 Percentage of participants Interval 1.1 to 5.1
Percentage of Participants Reporting Local Reactions by Maximum Severity Within 7 Days After Vaccination 3 Pain at injection site: Moderate	1.7 Percentage of participants Interval 0.6 to 3.9	2.0 Percentage of participants Interval 0.7 to 4.4	1.3 Percentage of participants Interval 0.4 to 3.4	0.3 Percentage of participants Interval 0.0 to 1.8
Percentage of Participants Reporting Local Reactions by Maximum Severity Within 7 Days After Vaccination 3 Pain at injection site: Severe	0 Percentage of participants Interval 0.0 to 1.3	0 Percentage of participants Interval 0.0 to 1.2	0 Percentage of participants Interval 0.0 to 1.2	0 Percentage of participants Interval 0.0 to 1.2
Percentage of Participants Reporting Local Reactions by Maximum Severity Within 7 Days After Vaccination 3 Pain at injection site: Grade 4	0 Percentage of participants Interval 0.0 to 1.3	0 Percentage of participants Interval 0.0 to 1.2	0 Percentage of participants Interval 0.0 to 1.2	0 Percentage of participants Interval 0.0 to 1.2
Percentage of Participants Reporting Local Reactions by Maximum Severity Within 7 Days After Vaccination 3 Redness: Mild	2.4 Percentage of participants Interval 1.0 to 4.9	3.7 Percentage of participants Interval 1.9 to 6.6	2.0 Percentage of participants Interval 0.7 to 4.3	0.7 Percentage of participants Interval 0.1 to 2.4
Percentage of Participants Reporting Local Reactions by Maximum Severity Within 7 Days After Vaccination 3 Redness: Moderate	1.0 Percentage of participants Interval 0.2 to 3.0	2.0 Percentage of participants Interval 0.7 to 4.4	0.7 Percentage of participants Interval 0.1 to 2.4	0.3 Percentage of participants Interval 0.0 to 1.8
Percentage of Participants Reporting Local Reactions by Maximum Severity Within 7 Days After Vaccination 3 Redness: Severe	0.3 Percentage of participants Interval 0.0 to 1.9	0 Percentage of participants Interval 0.0 to 1.2	0.3 Percentage of participants Interval 0.0 to 1.9	0 Percentage of participants Interval 0.0 to 1.2
Percentage of Participants Reporting Local Reactions by Maximum Severity Within 7 Days After Vaccination 3 Redness: Grade 4	0 Percentage of participants Interval 0.0 to 1.3	0 Percentage of participants Interval 0.0 to 1.2	0 Percentage of participants Interval 0.0 to 1.2	0 Percentage of participants Interval 0.0 to 1.2
Percentage of Participants Reporting Local Reactions by Maximum Severity Within 7 Days After Vaccination 3 Swelling: Mild	2.4 Percentage of participants Interval 1.0 to 4.9	5.8 Percentage of participants Interval 3.4 to 9.1	3.7 Percentage of participants Interval 1.9 to 6.5	0.7 Percentage of participants Interval 0.1 to 2.4
Percentage of Participants Reporting Local Reactions by Maximum Severity Within 7 Days After Vaccination 3 Swelling: Moderate	1.0 Percentage of participants Interval 0.2 to 3.0	2.7 Percentage of participants Interval 1.2 to 5.3	1.7 Percentage of participants Interval 0.5 to 3.9	0 Percentage of participants Interval 0.0 to 1.2
Percentage of Participants Reporting Local Reactions by Maximum Severity Within 7 Days After Vaccination 3 Swelling: Severe	0.3 Percentage of participants Interval 0.0 to 1.9	0 Percentage of participants Interval 0.0 to 1.2	0.3 Percentage of participants Interval 0.0 to 1.9	0.3 Percentage of participants Interval 0.0 to 1.8
Percentage of Participants Reporting Local Reactions by Maximum Severity Within 7 Days After Vaccination 3 Swelling: Grade 4	0 Percentage of participants Interval 0.0 to 1.3	0 Percentage of participants Interval 0.0 to 1.2	0 Percentage of participants Interval 0.0 to 1.2	0 Percentage of participants Interval 0.0 to 1.2

PRIMARY outcome

Timeframe: Within 7 days after Vaccination 1 at Month 0

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.

Outcome measures

PRIMARY outcome

Timeframe: Within 7 days after Vaccination 2 at Month 1

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.

Outcome measures

PRIMARY outcome

Timeframe: Within 7 days after Vaccination 3 at Month 6

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.

Outcome measures

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Clostridium Difficile Vaccine: Lot 1 n=983 Participants Participants received Clostridium difficile vaccine Lot 1 (200 microgram total toxoid per dose) intramuscularly at Months 0, 1 and 6.	Clostridium Difficile Vaccine: Lot 2 n=331 Participants Participants received Clostridium difficile vaccine Lot 2 (200 microgram total toxoid per dose) intramuscularly at Months 0, 1 and 6.	Clostridium Difficile Vaccine: Lot 3 Participants received Clostridium difficile vaccine Lot 3 (200 microgram total toxoid per dose) intramuscularly at Months 0, 1 and 6.	Placebo Participants received placebo (0.9% sodium chloride injection, in a 0.5 mL dose) intramuscularly at Months 0, 1 and 6.
Percentage of Participants With Adverse Events (AEs) Through 1 Month After Last Study Vaccination Any AEs	35.5 Percentage of participants	33.5 Percentage of participants	—	—
Percentage of Participants With Adverse Events (AEs) Through 1 Month After Last Study Vaccination NSAEs	34.1 Percentage of participants	31.7 Percentage of participants	—	—

PRIMARY outcome

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

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.

Outcome measures

Outcome measures
Measure	Clostridium Difficile Vaccine: Lot 1 n=983 Participants Participants received Clostridium difficile vaccine Lot 1 (200 microgram total toxoid per dose) intramuscularly at Months 0, 1 and 6.	Clostridium Difficile Vaccine: Lot 2 n=331 Participants Participants received Clostridium difficile vaccine Lot 2 (200 microgram total toxoid per dose) intramuscularly at Months 0, 1 and 6.	Clostridium Difficile Vaccine: Lot 3 Participants received Clostridium difficile vaccine Lot 3 (200 microgram total toxoid per dose) intramuscularly at Months 0, 1 and 6.	Placebo Participants received placebo (0.9% sodium chloride injection, in a 0.5 mL dose) intramuscularly at Months 0, 1 and 6.
Percentage of Participants Reporting Serious Adverse Events (SAEs)	4.2 Percentage of participants	4.5 Percentage of participants	—	—

Adverse Events

Clostridium Difficile Vaccine (Pooled Lots)

Serious events: 41 serious events

Other events: 694 other events

Deaths: 2 deaths

Placebo

Serious events: 15 serious events

Other events: 175 other events

Deaths: 2 deaths

Serious adverse events

Other adverse events

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer Inc.

Phone: 1-800-718-1021

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Publication restrictions are in place

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Measure	Clostridium Difficile Vaccine: Lot 1 n=325 Participants Participants received Clostridium difficile vaccine Lot 1 (200 microgram total toxoid per dose) intramuscularly at Months 0, 1 and 6.	Clostridium Difficile Vaccine: Lot 2 n=320 Participants Participants received Clostridium difficile vaccine Lot 2 (200 microgram total toxoid per dose) intramuscularly at Months 0, 1 and 6.	Clostridium Difficile Vaccine: Lot 3 n=322 Participants Participants received Clostridium difficile vaccine Lot 3 (200 microgram total toxoid per dose) intramuscularly at Months 0, 1 and 6.	Placebo n=325 Participants Participants received placebo (0.9% sodium chloride injection, in a 0.5 mL dose) intramuscularly at Months 0, 1 and 6.
Percentage of Participants Reporting Systemic Events by Maximum Severity Within 7 Days After Vaccination 1 Fever: 38.0-38.4 deg C	0.9 Percentage of participants Interval 0.2 to 2.6	0.6 Percentage of participants Interval 0.1 to 2.2	0 Percentage of participants Interval 0.0 to 1.1	0 Percentage of participants Interval 0.0 to 1.1
Percentage of Participants Reporting Systemic Events by Maximum Severity Within 7 Days After Vaccination 1 Fever: 38.5-38.9 deg C	0 Percentage of participants Interval 0.0 to 1.1	0 Percentage of participants Interval 0.0 to 1.1	0 Percentage of participants Interval 0.0 to 1.1	0 Percentage of participants Interval 0.0 to 1.1
Percentage of Participants Reporting Systemic Events by Maximum Severity Within 7 Days After Vaccination 1 Fever: 39.0-40.0 deg C	0 Percentage of participants Interval 0.0 to 1.1	0 Percentage of participants Interval 0.0 to 1.1	0 Percentage of participants Interval 0.0 to 1.1	0 Percentage of participants Interval 0.0 to 1.1
Percentage of Participants Reporting Systemic Events by Maximum Severity Within 7 Days After Vaccination 1 Fever: >40 deg C	0 Percentage of participants Interval 0.0 to 1.1	0 Percentage of participants Interval 0.0 to 1.1	0 Percentage of participants Interval 0.0 to 1.1	0 Percentage of participants Interval 0.0 to 1.1
Percentage of Participants Reporting Systemic Events by Maximum Severity Within 7 Days After Vaccination 1 Fatigue: Mild	11.7 Percentage of participants Interval 8.3 to 15.5	10.9 Percentage of participants Interval 7.6 to 14.7	14.0 Percentage of participants Interval 10.2 to 17.9	8.3 Percentage of participants Interval 5.4 to 11.6
Percentage of Participants Reporting Systemic Events by Maximum Severity Within 7 Days After Vaccination 1 Fatigue: Moderate	12.0 Percentage of participants Interval 8.5 to 15.8	9.1 Percentage of participants Interval 6.1 to 12.6	9.6 Percentage of participants Interval 6.5 to 13.1	10.2 Percentage of participants Interval 7.0 to 13.7
Percentage of Participants Reporting Systemic Events by Maximum Severity Within 7 Days After Vaccination 1 Fatigue: Severe	0.3 Percentage of participants Interval 0.0 to 1.7	0 Percentage of participants Interval 0.0 to 1.1	0.9 Percentage of participants Interval 0.2 to 2.6	0 Percentage of participants Interval 0.0 to 1.1
Percentage of Participants Reporting Systemic Events by Maximum Severity Within 7 Days After Vaccination 1 Fatigue: Grade 4	0 Percentage of participants Interval 0.0 to 1.1	0 Percentage of participants Interval 0.0 to 1.1	0 Percentage of participants Interval 0.0 to 1.1	0 Percentage of participants Interval 0.0 to 1.1
Percentage of Participants Reporting Systemic Events by Maximum Severity Within 7 Days After Vaccination 1 Headache: Mild	13.2 Percentage of participants Interval 9.6 to 17.1	11.3 Percentage of participants Interval 7.9 to 15.0	6.5 Percentage of participants Interval 4.0 to 9.6	7.7 Percentage of participants Interval 4.9 to 10.9
Percentage of Participants Reporting Systemic Events by Maximum Severity Within 7 Days After Vaccination 1 Headache: Moderate	3.7 Percentage of participants Interval 1.9 to 6.3	4.1 Percentage of participants Interval 2.1 to 6.7	5.3 Percentage of participants Interval 3.0 to 8.2	3.4 Percentage of participants Interval 1.7 to 5.9
Percentage of Participants Reporting Systemic Events by Maximum Severity Within 7 Days After Vaccination 1 Headache: Severe	0 Percentage of participants Interval 0.0 to 1.1	0 Percentage of participants Interval 0.0 to 1.1	0.6 Percentage of participants Interval 0.1 to 2.2	0.3 Percentage of participants Interval 0.0 to 1.7
Percentage of Participants Reporting Systemic Events by Maximum Severity Within 7 Days After Vaccination 1 Headache: Grade 4	0 Percentage of participants Interval 0.0 to 1.1	0 Percentage of participants Interval 0.0 to 1.1	0 Percentage of participants Interval 0.0 to 1.1	0 Percentage of participants Interval 0.0 to 1.1
Percentage of Participants Reporting Systemic Events by Maximum Severity Within 7 Days After Vaccination 1 Joint pain: Mild	4.9 Percentage of participants Interval 2.8 to 7.8	3.8 Percentage of participants Interval 1.9 to 6.4	4.0 Percentage of participants Interval 2.1 to 6.7	2.2 Percentage of participants Interval 0.9 to 4.3
Percentage of Participants Reporting Systemic Events by Maximum Severity Within 7 Days After Vaccination 1 Joint pain: Moderate	3.7 Percentage of participants Interval 1.9 to 6.3	2.8 Percentage of participants Interval 1.3 to 5.2	4.3 Percentage of participants Interval 2.4 to 7.1	3.1 Percentage of participants Interval 1.5 to 5.5
Percentage of Participants Reporting Systemic Events by Maximum Severity Within 7 Days After Vaccination 1 Joint pain: Severe	0 Percentage of participants Interval 0.0 to 1.1	0.3 Percentage of participants Interval 0.0 to 1.7	0.3 Percentage of participants Interval 0.0 to 1.7	0 Percentage of participants Interval 0.0 to 1.1
Percentage of Participants Reporting Systemic Events by Maximum Severity Within 7 Days After Vaccination 1 Joint pain: Grade 4	0 Percentage of participants Interval 0.0 to 1.1	0 Percentage of participants Interval 0.0 to 1.1	0 Percentage of participants Interval 0.0 to 1.1	0 Percentage of participants Interval 0.0 to 1.1
Percentage of Participants Reporting Systemic Events by Maximum Severity Within 7 Days After Vaccination 1 Muscle pain: Mild	4.6 Percentage of participants Interval 2.6 to 7.4	3.1 Percentage of participants Interval 1.5 to 5.6	3.4 Percentage of participants Interval 1.7 to 5.9	5.2 Percentage of participants Interval 3.0 to 8.1
Percentage of Participants Reporting Systemic Events by Maximum Severity Within 7 Days After Vaccination 1 Muscle pain: Moderate	4.6 Percentage of participants Interval 2.6 to 7.4	4.7 Percentage of participants Interval 2.6 to 7.5	3.1 Percentage of participants Interval 1.5 to 5.5	4.6 Percentage of participants Interval 2.6 to 7.4
Percentage of Participants Reporting Systemic Events by Maximum Severity Within 7 Days After Vaccination 1 Muscle pain: Severe	0.3 Percentage of participants Interval 0.0 to 1.7	0 Percentage of participants Interval 0.0 to 1.1	0.3 Percentage of participants Interval 0.0 to 1.7	0 Percentage of participants Interval 0.0 to 1.1
Percentage of Participants Reporting Systemic Events by Maximum Severity Within 7 Days After Vaccination 1 Muscle pain: Grade 4	0 Percentage of participants Interval 0.0 to 1.1	0 Percentage of participants Interval 0.0 to 1.1	0 Percentage of participants Interval 0.0 to 1.1	0 Percentage of participants Interval 0.0 to 1.1
Percentage of Participants Reporting Systemic Events by Maximum Severity Within 7 Days After Vaccination 1 Vomiting: Mild	0.3 Percentage of participants Interval 0.0 to 1.7	0.9 Percentage of participants Interval 0.2 to 2.7	0.9 Percentage of participants Interval 0.2 to 2.6	0.3 Percentage of participants Interval 0.0 to 1.7
Percentage of Participants Reporting Systemic Events by Maximum Severity Within 7 Days After Vaccination 1 Vomiting: Moderate	0.9 Percentage of participants Interval 0.2 to 2.6	0.3 Percentage of participants Interval 0.0 to 1.7	0.3 Percentage of participants Interval 0.0 to 1.7	0.3 Percentage of participants Interval 0.0 to 1.7
Percentage of Participants Reporting Systemic Events by Maximum Severity Within 7 Days After Vaccination 1 Vomiting: Severe	0 Percentage of participants Interval 0.0 to 1.1	0 Percentage of participants Interval 0.0 to 1.1	0 Percentage of participants Interval 0.0 to 1.1	0 Percentage of participants Interval 0.0 to 1.1
Percentage of Participants Reporting Systemic Events by Maximum Severity Within 7 Days After Vaccination 1 Vomiting: Grade 4	0 Percentage of participants Interval 0.0 to 1.1	0 Percentage of participants Interval 0.0 to 1.1	0 Percentage of participants Interval 0.0 to 1.1	0 Percentage of participants Interval 0.0 to 1.1

Measure	Clostridium Difficile Vaccine: Lot 1 n=293 Participants Participants received Clostridium difficile vaccine Lot 1 (200 microgram total toxoid per dose) intramuscularly at Months 0, 1 and 6.	Clostridium Difficile Vaccine: Lot 2 n=295 Participants Participants received Clostridium difficile vaccine Lot 2 (200 microgram total toxoid per dose) intramuscularly at Months 0, 1 and 6.	Clostridium Difficile Vaccine: Lot 3 n=298 Participants Participants received Clostridium difficile vaccine Lot 3 (200 microgram total toxoid per dose) intramuscularly at Months 0, 1 and 6.	Placebo n=303 Participants Participants received placebo (0.9% sodium chloride injection, in a 0.5 mL dose) intramuscularly at Months 0, 1 and 6.
Percentage of Participants Reporting Systemic Events by Maximum Severity Within 7 Days After Vaccination 3 Fatigue: Mild	10.6 Percentage of participants Interval 7.0 to 14.1	8.5 Percentage of participants Interval 5.4 to 11.9	10.4 Percentage of participants Interval 7.0 to 14.0	5.0 Percentage of participants Interval 2.8 to 7.9
Percentage of Participants Reporting Systemic Events by Maximum Severity Within 7 Days After Vaccination 3 Fever: 38.0-38.4 deg C	0.3 Percentage of participants Interval 0.0 to 1.8	0.3 Percentage of participants Interval 0.0 to 1.8	0.3 Percentage of participants Interval 0.0 to 1.8	0 Percentage of participants Interval 0.0 to 1.2
Percentage of Participants Reporting Systemic Events by Maximum Severity Within 7 Days After Vaccination 3 Fever: 38.5-38.9 deg C	0 Percentage of participants Interval 0.0 to 1.2	0 Percentage of participants Interval 0.0 to 1.2	0 Percentage of participants Interval 0.0 to 1.2	0.7 Percentage of participants Interval 0.1 to 2.3
Percentage of Participants Reporting Systemic Events by Maximum Severity Within 7 Days After Vaccination 3 Fever: 39.0-40.0 deg C	0 Percentage of participants Interval 0.0 to 1.2	0 Percentage of participants Interval 0.0 to 1.2	0 Percentage of participants Interval 0.0 to 1.2	0 Percentage of participants Interval 0.0 to 1.2
Percentage of Participants Reporting Systemic Events by Maximum Severity Within 7 Days After Vaccination 3 Fever: >40 deg C	0 Percentage of participants Interval 0.0 to 1.2	0 Percentage of participants Interval 0.0 to 1.2	0 Percentage of participants Interval 0.0 to 1.2	0 Percentage of participants Interval 0.0 to 1.2
Percentage of Participants Reporting Systemic Events by Maximum Severity Within 7 Days After Vaccination 3 Fatigue: Moderate	10.6 Percentage of participants Interval 7.0 to 14.1	7.8 Percentage of participants Interval 4.8 to 11.1	5.7 Percentage of participants Interval 3.3 to 8.7	8.6 Percentage of participants Interval 5.6 to 12.1
Percentage of Participants Reporting Systemic Events by Maximum Severity Within 7 Days After Vaccination 3 Fatigue: Severe	0 Percentage of participants Interval 0.0 to 1.2	1.0 Percentage of participants Interval 0.2 to 2.8	1.0 Percentage of participants Interval 0.2 to 2.8	0 Percentage of participants Interval 0.0 to 1.2
Percentage of Participants Reporting Systemic Events by Maximum Severity Within 7 Days After Vaccination 3 Fatigue: Grade 4	0 Percentage of participants Interval 0.0 to 1.2	0 Percentage of participants Interval 0.0 to 1.2	0 Percentage of participants Interval 0.0 to 1.2	0 Percentage of participants Interval 0.0 to 1.2
Percentage of Participants Reporting Systemic Events by Maximum Severity Within 7 Days After Vaccination 3 Headache: Mild	12.6 Percentage of participants Interval 8.7 to 16.3	8.8 Percentage of participants Interval 5.6 to 12.2	7.0 Percentage of participants Interval 4.3 to 10.3	5.9 Percentage of participants Interval 3.5 to 9.1
Percentage of Participants Reporting Systemic Events by Maximum Severity Within 7 Days After Vaccination 3 Headache: Moderate	3.4 Percentage of participants Interval 1.6 to 5.9	3.7 Percentage of participants Interval 1.8 to 6.4	2.7 Percentage of participants Interval 1.1 to 5.1	1.7 Percentage of participants Interval 0.5 to 3.7
Percentage of Participants Reporting Systemic Events by Maximum Severity Within 7 Days After Vaccination 3 Headache: Severe	0.7 Percentage of participants Interval 0.1 to 2.3	0.3 Percentage of participants Interval 0.0 to 1.8	0 Percentage of participants Interval 0.0 to 1.2	0 Percentage of participants Interval 0.0 to 1.2
Percentage of Participants Reporting Systemic Events by Maximum Severity Within 7 Days After Vaccination 3 Headache: Grade 4	0 Percentage of participants Interval 0.0 to 1.2	0 Percentage of participants Interval 0.0 to 1.2	0 Percentage of participants Interval 0.0 to 1.2	0 Percentage of participants Interval 0.0 to 1.2
Percentage of Participants Reporting Systemic Events by Maximum Severity Within 7 Days After Vaccination 3 Joint pain: Mild	2.0 Percentage of participants Interval 0.7 to 4.2	2.7 Percentage of participants Interval 1.1 to 5.1	2.7 Percentage of participants Interval 1.1 to 5.1	3.0 Percentage of participants Interval 1.3 to 5.5
Percentage of Participants Reporting Systemic Events by Maximum Severity Within 7 Days After Vaccination 3 Joint pain: Moderate	2.7 Percentage of participants Interval 1.1 to 5.1	1.7 Percentage of participants Interval 0.5 to 3.8	2.7 Percentage of participants Interval 1.1 to 5.1	0.7 Percentage of participants Interval 0.1 to 2.3
Percentage of Participants Reporting Systemic Events by Maximum Severity Within 7 Days After Vaccination 3 Joint pain: Severe	0.3 Percentage of participants Interval 0.0 to 1.8	0.3 Percentage of participants Interval 0.0 to 1.8	0 Percentage of participants Interval 0.0 to 1.2	0 Percentage of participants Interval 0.0 to 1.2
Percentage of Participants Reporting Systemic Events by Maximum Severity Within 7 Days After Vaccination 3 Joint pain: Grade 4	0 Percentage of participants Interval 0.0 to 1.2	0 Percentage of participants Interval 0.0 to 1.2	0 Percentage of participants Interval 0.0 to 1.2	0 Percentage of participants Interval 0.0 to 1.2
Percentage of Participants Reporting Systemic Events by Maximum Severity Within 7 Days After Vaccination 3 Muscle pain: Mild	3.1 Percentage of participants Interval 1.4 to 5.5	3.1 Percentage of participants Interval 1.4 to 5.5	5.0 Percentage of participants Interval 2.8 to 7.9	2.6 Percentage of participants Interval 1.1 to 5.1
Percentage of Participants Reporting Systemic Events by Maximum Severity Within 7 Days After Vaccination 3 Muscle pain: Moderate	2.4 Percentage of participants Interval 0.9 to 4.7	2.0 Percentage of participants Interval 0.7 to 4.2	3.0 Percentage of participants Interval 1.3 to 5.5	1.7 Percentage of participants Interval 0.5 to 3.7
Percentage of Participants Reporting Systemic Events by Maximum Severity Within 7 Days After Vaccination 3 Muscle pain: Severe	0.3 Percentage of participants Interval 0.0 to 1.8	0.3 Percentage of participants Interval 0.0 to 1.8	0 Percentage of participants Interval 0.0 to 1.2	0 Percentage of participants Interval 0.0 to 1.2
Percentage of Participants Reporting Systemic Events by Maximum Severity Within 7 Days After Vaccination 3 Muscle pain: Grade 4	0 Percentage of participants Interval 0.0 to 1.2	0 Percentage of participants Interval 0.0 to 1.2	0 Percentage of participants Interval 0.0 to 1.2	0 Percentage of participants Interval 0.0 to 1.2
Percentage of Participants Reporting Systemic Events by Maximum Severity Within 7 Days After Vaccination 3 Vomiting: Mild	0.3 Percentage of participants Interval 0.0 to 1.8	0 Percentage of participants Interval 0.0 to 1.2	0 Percentage of participants Interval 0.0 to 1.2	0.7 Percentage of participants Interval 0.1 to 2.3
Percentage of Participants Reporting Systemic Events by Maximum Severity Within 7 Days After Vaccination 3 Vomiting: Moderate	0.7 Percentage of participants Interval 0.1 to 2.3	0.7 Percentage of participants Interval 0.1 to 2.3	0 Percentage of participants Interval 0.0 to 1.2	0 Percentage of participants Interval 0.0 to 1.2
Percentage of Participants Reporting Systemic Events by Maximum Severity Within 7 Days After Vaccination 3 Vomiting: Severe	0 Percentage of participants Interval 0.0 to 1.2	0 Percentage of participants Interval 0.0 to 1.2	0 Percentage of participants Interval 0.0 to 1.2	0 Percentage of participants Interval 0.0 to 1.2
Percentage of Participants Reporting Systemic Events by Maximum Severity Within 7 Days After Vaccination 3 Vomiting: Grade 4	0 Percentage of participants Interval 0.0 to 1.2	0 Percentage of participants Interval 0.0 to 1.2	0 Percentage of participants Interval 0.0 to 1.2	0 Percentage of participants Interval 0.0 to 1.2