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A Study To Investigate Two 3-dose Schedules Of A Clostridium Difficile Vaccine In Healthy Adults Aged 65 to 85 Years

Primary Purpose

Clostridium Difficile Associated Disease

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Clostridium difficile Vaccine

Placebo

About this trial

This is an interventional prevention trial for Clostridium Difficile Associated Disease focused on measuring Clostridium difficile, Vaccine.

Eligibility Criteria

65 Years - 85 Years (Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

Healthy male and female subjects
Aged 65 to 85 years

Additional Inclusion Criteria for the extension Stage:

Receipt of all 3 doses of C difficile vaccine (100 µg or 200 µg antigen dose level) in the original portion of the study.

Exclusion Criteria:

Proven or suspected prior episode of Clostridium difficile associated diarrhea
Unstable chronic medical condition
Disease requiring significant change in therapy or hospitalization for worsening disease within 8 weeks before receipt of study vaccine
Serious chronic disorders
Congenital or acquired immunodeficiency disorders
Rheumatologic disorders or other illnesses requiring chronic treatment with known immunosuppressant medications.
Active or treated leukemia or lymphoma or bone marrow disorder
Any contraindication to vaccination or vaccine components including previous anaphylactic reaction to any vaccine or vaccine-related components

Additional Exclusion Criteria for the Extension Stage:

Subjects originally randomized to placebo during the original portion of the study.
Subjects who have already completed Visit 9 prior to study unblinding.

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Arm Label

Low-dose C. difficile Vaccine (accelerated schedule)

High-dose C. difficile Vaccine (accelerated schedule)

Placebo (accelerated schedule)

Low-dose C. difficile Vaccine (non-accelerated schedule)

High-Dose C. difficile Vaccine (non-accelerated schedule)

Placebo (non-accelerated schedule)

Arm Description

Outcomes

Primary Outcome Measures

Day 1, 8 and 30 Regimen: Percentage of Participants Achieving Prespecified Antibody Titer Level for Toxin A at Day 37

Toxin A antibodies (threshold >= 219 neutralization units/mL) were measured using neutralization assay.

Month 0, 1 and 6 Regimen: Percentage of Participants Achieving Prespecified Antibody Titer Level for Toxin A at Month 7

Toxin A antibodies (threshold >= 219 neutralization units/mL) were measured using neutralization assay.

Day 1, 8 and 30 Regimen: Percentage of Participants Achieving Prespecified Antibody Titer Level for Toxin B at Day 37

Toxin B antibodies (threshold >= 2586 neutralization units/mL) were measured using neutralization assay.

Month 0, 1 and 6 Regimen: Percentage of Participants Achieving Prespecified Antibody Titer Level for Toxin B at Month 7

Toxin B antibodies (threshold >= 2586 neutralization units/mL) were measured using neutralization assay.

Day 1, 8 and 30 Regimen: Percentage of Participants Achieving Prespecified Antibody Titer Level for Both Toxin A and Toxin B at Day 37

Toxin A and B antibodies (threshold >= 219 and 2586 neutralization units/mL) were measured using neutralization assay.

Month 0, 1 and 6 Regimen: Percentage of Participants Achieving Prespecified Antibody Titer Level for Both Toxin A and Toxin B at Month 7

Toxin A and B antibodies (threshold >= 219 and 2586 neutralization units/mL) were measured using neutralization assay.

Day 1, 8 and 30 Regimen: Percentage of Participants With Local Reactions by Severity Within 7 Days After Vaccination 1

Local reactions included pain at injection site, swelling and redness collected by using an electronic diary (e-diary). Pain was graded as: mild (grade 1) (did not interfere with activity), moderate (grade 2)(interfered with activity), severe (grade 3) (prevented daily activity) and grade 4 (emergency room visit or hospitalization). Redness and swelling were graded as: mild (2.5-5.0 centimeter [cm]), moderate (>5.0 to 10.0 cm), severe (>10.0 cm) and grade 4 (necrosis).

Month 0, 1 and 6 Regimen: Percentage of Participants With Local Reactions by Severity Within 14 Days After Vaccination 1

Local reactions included pain at injection site, swelling and redness collected by using an electronic diary (e-diary). Pain was graded as: mild (did not interfere with activity), moderate (interfered with activity), severe (prevented daily activity) and grade 4 (emergency room visit or hospitalization). Redness and swelling were graded as: mild (2.5-5.0 cm), moderate (>5.0 to 10.0 cm), severe (>10.0 cm) and grade 4 (necrosis).

Day 1, 8 and 30 Regimen: Percentage of Participants With Local Reactions by Severity Within 14 Days After Vaccination 2

Month 0, 1 and 6 Regimen: Percentage of Participants With Local Reactions by Severity Within 14 Days After Vaccination 2

Day 1, 8 and 30 Regimen: Percentage of Participants With Local Reactions by Severity Within 14 Days After Vaccination 3

Month 0, 1 and 6 Regimen: Percentage of Participants With Local Reactions by Severity Within 14 Days After Vaccination 3

Day 1, 8 and 30 Regimen: Percentage of Participants With Systemic Events by Severity Within 7 Days After Vaccination 1

Systemic events included fever, vomiting, diarrhea, headache, fatigue, new or worsening muscle pain, new or worsening joint pain and were recorded by using an e-diary. Fever was graded as mild (38.0 to 38.4 degree Celsius (C)), moderate (38.5 to 38.9 degree C), severe (39.0 to 40.0 degree C), grade 4 (>40.0 degree C). Vomiting was graded as mild (1-2 times in 24 hours), moderate (>2 times in 24 hours), severe (required intravenous hydration) and grade 4 (hospitalization for hypotensive shock). Diarrhea was graded as mild (2-3 loose stools in 24 hours), moderate (4-5 loose stools in 24 hours), severe (>=6 stools in 24 hours) and grade 4 (hospitalization). Headache, fatigue, new or worsening muscle pain and new or worsening joint pain was graded as mild (no interference with activity), moderate (some interference with activity), severe (prevents daily activity) and grade 4 (hospitalization).

Month 0, 1 and 6 Regimen: Percentage of Participants With Systemic Events by Severity Within 14 Days After Vaccination 1

Systemic events included fever, vomiting, diarrhea, headache, fatigue, new or worsening muscle pain, new or worsening joint pain and were recorded by using an e-diary. Fever was graded as mild (38.0 to 38.4 C), moderate (38.5 to 38.9 degree C), severe (39.0 to 40.0 degree C), grade 4 (>40.0 degree C). Vomiting was graded as mild (1-2 times in 24 hours), moderate (>2 times in 24 hours), severe (required intravenous hydration) and grade 4 (hospitalization for hypotensive shock). Diarrhea was graded as mild (2-3 loose stools in 24 hours), moderate (4-5 loose stools in 24 hours), severe (>=6 stools in 24 hours) and grade 4 (hospitalization). Headache, fatigue, new or worsening muscle pain and new or worsening joint pain was graded as mild (no interference with activity), moderate (some interference with activity), severe (prevents daily activity) and grade 4 (hospitalization).

Day 1, 8 and 30 Regimen: Percentage of Participants With Systemic Events by Severity Within 14 Days After Vaccination 2

Systemic events included fever, vomiting, diarrhea, headache, fatigue, new or worsening muscle pain, new or worsening joint pain and were recorded by using an e-diary. Fever was graded as mild (38.0 to 38.4 C), moderate (38.5 to 38.9 degree C), severe (39.0 to 40.0 degree C), grade 4 (>40.0 degree C). Vomiting was graded as mild (1-2 times in 24 hours), moderate (>2 times in 24 hours), severe (required intravenous hydration) and grade 4 (hospitalization for hypotensive shock). Diarrhea was graded as mild (2-3 loose stools in 24 hours), moderate (4-5 loose stools in 24 hours), severe (>=6 stools in 24 hours) and grade 4 (hospitalization). Headache, fatigue, new or worsening muscle pain and new or worsening joint pain was graded as mild (no interference with activity), moderate (some interference with activity), severe (prevents daily activity) and grade 4 (hospitalization).

Month 0, 1 and 6 Regimen: Percentage of Participants With Systemic Events by Severity Within 14 Days After Vaccination 2

Systemic events included fever, vomiting, diarrhea, headache, fatigue, new or worsening muscle pain, new or worsening joint pain and were recorded by using an e-diary. Fever was graded as mild (38.0 to 38.4 C), moderate (38.5 to 38.9 degree C), severe (39.0 to 40.0 degree C), grade 4 (>40.0 degree C). Vomiting was graded as mild (1-2 times in 24 hours), moderate (>2 times in 24 hours), severe (required intravenous hydration) and grade 4 (hospitalization for hypotensive shock). Diarrhea was graded as mild (2-3 loose stools in 24 hours), moderate (4-5 loose stools in 24 hours), severe (>=6 stools in 24 hours) and grade 4 (hospitalization). Headache, fatigue, new or worsening muscle pain and new or worsening joint pain was graded as mild (no interference with activity), moderate (some interference with activity), severe (prevents daily activity) and grade 4 (hospitalization).

Day 1, 8 and 30 Regimen: Percentage of Participants With Systemic Events by Severity Within 14 Days After Vaccination 3

Systemic events included fever, vomiting, diarrhea, headache, fatigue, new or worsening muscle pain, new or worsening joint pain and were recorded by using an e-diary. Fever was graded as mild (38.0 to 38.4 C), moderate (38.5 to 38.9 degree C), severe (39.0 to 40.0 degree C), grade 4 (>40.0 degree C). Vomiting was graded as mild (1-2 times in 24 hours), moderate (>2 times in 24 hours), severe (required intravenous hydration) and grade 4 (hospitalization for hypotensive shock). Diarrhea was graded as mild (2-3 loose stools in 24 hours), moderate (4-5 loose stools in 24 hours), severe (>=6 stools in 24 hours) and grade 4 (hospitalization). Headache, fatigue, new or worsening muscle pain and new or worsening joint pain was graded as mild (no interference with activity), moderate (some interference with activity), severe (prevents daily activity) and grade 4 (hospitalization).

Month 0, 1 and 6 Regimen: Percentage of Participants With Systemic Events by Severity Within 14 Days After Vaccination 3

Systemic events included fever, vomiting, diarrhea, headache, fatigue, new or worsening muscle pain, new or worsening joint pain and were recorded by using an e-diary. Fever was graded as mild (38.0 to 38.4 C), moderate (38.5 to 38.9 degree C), severe (39.0 to 40.0 degree C), grade 4 (>40.0 degree C). Vomiting was graded as mild (1-2 times in 24 hours), moderate (>2 times in 24 hours), severe (required intravenous hydration) and grade 4 (hospitalization for hypotensive shock). Diarrhea was graded as mild (2-3 loose stools in 24 hours), moderate (4-5 loose stools in 24 hours), severe (>=6 stools in 24 hours) and grade 4 (hospitalization). Headache, fatigue, new or worsening muscle pain and new or worsening joint pain was graded as mild (no interference with activity), moderate (some interference with activity), severe (prevents daily activity) and grade 4 (hospitalization).

Day 1, 8 and 30 Regimen: Percentage of Participants With Treatment Emergent Adverse Events (AEs)

An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose of study drug that were absent before treatment or that worsened relative to pretreatment state.

Month 0, 1 and 6 Regimen: Percentage of Participants With Treatment Emergent Adverse Events (AEs)

Day 1, 8 and 30 Regimen: Percentage of Participants With Treatment Emergent Serious Adverse Events (SAEs)

An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; lack of efficacy in an approved indication. Treatment-emergent serious adverse events are events between first dose of study drug and up to 6 months after last dose of study drug that were absent before treatment or that worsened relative to pretreatment state.

Month 0, 1 and 6 Regimen: Percentage of Participants With Treatment Emergent Serious Adverse Events (SAEs)

Secondary Outcome Measures

Day 1, 8 and 30 Regimen: Percentage of Participants Achieving Prespecified Antibody Titer Level for Toxin A at Day 1, 8, 15, 30, and Month 2, 4, 7, 13

Toxin A antibodies were measured using neutralization assay.

Day 1, 8 and 30 Regimen: Percentage of Participants Achieving Prespecified Antibody Titer Level for Toxin B at Day 1, 8, 15, 30 and Month 2, 4, 7, 13

Toxin B antibodies were measured using neutralization assay.

Day 1, 8 and 30 Regimen: Percentage of Participants Achieving Prespecified Antibody Titer Level for Both Toxin A and Toxin B at Day 1, 8, 15, 30 and Month 2, 4, 7, 13

Toxin A and toxin B antibodies were measured using neutralization assay.

Month 0, 1 and 6 Regimen: Percentage of Participants Achieving Prespecified Antibody Titer Level for Toxin A at Day 1, 30, 37, 187 and Month 2, 6, 12, 18

Toxin A antibodies were measured using neutralization assay.

Month 0, 1 and 6 Regimen: Percentage of Participants Achieving Prespecified Antibody Titer Level for for Toxin B at Day 1, 30, 37, 187 and Month 2, 6, 12, 18

Toxin B antibodies were measured using neutralization assay.

Month 0, 1 and 6 Regimen: Percentage of Participants Achieving Prespecified Antibody Titer Level for Both Toxin A and Toxin B at Day 1, 30, 37, 187 and Month 2, 6, 12, 18

Toxin A and toxin B antibodies were measured using neutralization assay.

Day 1, 8 and 30 Regimen: Geometric Mean Concentration of Toxin A Specific Neutralizing Antibody Levels at Day 1, 8, 15, 30, 37 and Month 2, 4, 7, 13

Geometric mean concentration (GMC) of toxin A specific antibody levels was calculated using back transformations of the logarithmically transformed means of assay results. Confidence interval (CI) for GMC were back transformations of a CI based on the Student t distribution for the mean logarithm of concentrations.

Day 1, 8 and 30 Regimen: Geometric Mean Concentration of Toxin B Specific Neutralizing Antibody Levels at Day 1, 8, 15, 30, 37 and Month 2, 4, 7, 13

GMC of toxin B specific antibody levels was calculated using back transformations of the logarithmically transformed means of assay results. CI for GMC were back transformations of a CI based on the Student t distribution for the mean logarithm of concentrations.

Month 0, 1 and 6 Regimen: Geometric Mean Concentration of Toxin A Specific Neutralizing Antibody Levels at Day 1, 30, 37, 187 and Month 2, 6, 7, 12, 18

GMC of toxin A specific antibody levels was calculated using back transformations of the logarithmically transformed means of assay results. CI for GMC were back transformations of a CI based on the Student t distribution for the mean logarithm of concentrations.

Month 0, 1 and 6 Regimen: Geometric Mean Concentration of Toxin B Specific Neutralizing Antibody Levels at Day 1, 30, 37, 187 and Month 2, 6, 7, 12, 18

Day 1, 8 and 30 Regimen: Geometric Mean Fold Rise in Toxin A Specific Neutralizing Antibody Levels From Baseline at Day 8, 15, 30, 37 and Month 2, 4, 7, 13

Geometric mean fold rise (GMFR) in toxin A specific antibody levels was calculated using back transformations of the logarithmically transformed means of fold rise from baseline with assay results. CI for GMFR were back transformations of a CI based on the Student t distribution for the mean logarithm of the mean fold rise.

Day 1, 8 and 30 Regimen: Geometric Mean Fold Rise in Toxin B Specific Neutralizing Antibody Levels From Baseline at Day 8, 15, 30, 37 and Month 2, 4, 7, 13

GMFR in toxin B specific antibody levels was calculated using back transformations of the logarithmically transformed means of fold rise from baseline with assay results. CI for GMFR were back transformations of a CI based on the Student t distribution for the mean logarithm of the mean fold rise.

Month 0, 1 and 6 Regimen: Geometric Mean Fold Rise in Toxin A Specific Neutralizing Antibody Levels From Baseline at Day 30, 37, 187 and Month 2, 6, 7, 12, 18

GMFR in toxin A specific antibody levels was calculated using back transformations of the logarithmically transformed means of fold rise from baseline with assay results. CI for GMFR were back transformations of a CI based on the Student t distribution for the mean logarithm of the mean fold rise.

Month 0, 1 and 6 Regimen: Geometric Mean Fold Rise in Toxin B Specific Neutralizing Antibody Levels From Baseline at Day 30, 37, 187 and Month 2, 6, 7, 12, 18

GMFR for toxin B specific antibody levels was calculated using back transformations of the logarithmically transformed means of fold rise from baseline with assay results. CI for GMFR were back transformations of a CI based on the Student t distribution for the mean logarithm of the mean fold rise.

Day 1, 8 and 30 Regimen: Percentage of Participants Achieving >=4, >=8, >=16 and >=32 Fold Rise From Baseline in Toxin A Specific Antibody Levels at Day 8, 15, 30, 37 and Month 2, 4, 7, 13

Toxin A antibodies were measured using neutralization assay.

Day 1, 8 and 30 Regimen: Percentage of Participants Achieving >=4, >=8, >=16 and >=32 Fold Rise From Baseline in Toxin B Specific Antibody Levels at Day 8, 15, 30, 37 and Month 2, 4, 7, 13

Toxin B antibodies were measured using neutralization assay.

Day 1, 8 and 30 Regimen: Percentage of Participants Achieving>=4,>=8,>=16,>=32 Fold Rise From Baseline in Both Toxin A and Toxin B Specific Antibody Levels at Day 8, 15, 30, 37 and Month 2, 4, 7, 13

Toxin A and toxin B antibodies were measured using neutralization assay.

Month 0, 1 and 6 Regimen: Percentage of Participants Achieving >=4, >=8, >=16 and >=32 Fold Rise From Baseline in Toxin A Specific Antibody Levels at Day 30, 37, 187 and Month 2, 6, 7, 12, 18

Toxin A antibodies were measured using neutralization assay.

Month 0, 1 and 6 Regimen: Percentage of Participants Achieving >=4, >=8, >=16 and >=32 Fold Rise From Baseline in Toxin B Specific Antibody Levels at Day 30, 37, 187 and Month 2, 6, 7, 12, 18

Toxin A antibodies were measured using neutralization assay.

Month 0, 1 and 6 Regimen: Percentage of Participants Achieving>=4,>=8,>=16,>=32 Fold Rise From Baseline in Both Toxin A and Toxin B Antibody Levels at Day 30, 37, 187 and Month 2, 6, 7, 12, 18

Toxin A and toxin B antibodies were measured using neutralization assay.

Extension Stage Day 1, 8 and 30 Regimen: Percentage of Participants Achieving Prespecified Antibody Titer Level for Toxin A at Days 1, 8, 30 and Months 6, 12, 18, 24, 30, 36

Toxin A antibodies (threshold >= 219 neutralization units/mL) were measured using neutralization assay.

Extension Stage Day 1, 8 and 30 Regimen: Percentage of Participants Achieving Prespecified Antibody Titer Level for Toxin B at Days 1, 8, 30 and Months 6, 12, 18, 24, 30, 36

Toxin B antibodies (threshold >= 2586 neutralization units/mL) were measured using neutralization assay.

Extension Stage Day 1, 8 and 30 Regimen: Percentage of Participants Achieving Prespecified Antibody Titer Level for Both Toxin A and Toxin B at Days 1, 8, 30 and Months 6, 12, 18, 24, 30, 36

Toxin A and B antibodies (threshold >= 219 and 2586 neutralization units/mL) were measured using neutralization assay.

Extension Stage Month 0, 1 and 6 Regimen: Percentage of Participants Achieving Prespecified Antibody Titer Level for Toxin A at Days 1, 8, 30 and Months 6, 12, 18, 24, 30, 36

Toxin A antibodies (threshold >= 219 neutralization units/mL) were measured using neutralization assay.

Extension Stage Month 0, 1 and 6 Regimen: Percentage of Participants Achieving Prespecified Antibody Titer Level for Toxin B at Days 1, 8, 30 and Months 6, 12, 18, 24, 30, 36

Toxin B antibodies (threshold >= 2586 neutralization units/mL) were measured using neutralization assay.

Extension Stage Month 0, 1 and 6 Regimen: Percentage of Participants Achieving Prespecified Antibody Titer Level for Both Toxin A and Toxin B at Days 1, 8, 30 and Months 6, 12, 18, 24, 30, 36

Toxin A and B antibodies (threshold >= 219 and 2586 neutralization units/mL) were measured using neutralization assay.

Extension Stage Day 1, 8 and 30 Regimen: Geometric Mean Concentration for Toxin A Specific Neutralizing Antibody Levels at Days 1, 8, 30 and Months 6, 12, 18, 24, 30, 36

Extension Stage Day 1, 8 and 30 Regimen: Geometric Mean Concentration for Toxin B Specific Neutralizing Antibody Levels at Days 1, 8, 30 and Months 6, 12, 18, 24, 30, 36

Extension Stage Month 0, 1 and 6 Regimen: Geometric Mean Concentration for Toxin A Specific Neutralizing Antibody Levels at Days 1, 8, 30 and Months 6, 12, 18, 24, 30, 36

Extension Stage Month 0, 1 and 6 Regimen: Geometric Mean Concentration for Toxin B Specific Neutralizing Antibody Levels at Days 1, 8, 30 and Months 6, 12, 18, 24, 30, 36

Extension Stage Day 1, 8 and 30 Regimen: Geometric Mean Fold Rise in Toxin A Specific Neutralizing Antibody Levels From Baseline at Days 8, 30 and Months 6, 12, 18, 24, 30, 36

Extension Stage Day 1, 8 and 30 Regimen: Geometric Mean Fold Rise in Toxin B Specific Neutralizing Antibody Levels From Baseline at Day 8, 30 and Months 6, 12, 18, 24, 30, 36

Extension Stage Month 0, 1 and 6 Regimen: Geometric Mean Fold Rise in Toxin A Specific Neutralizing Antibody Levels From Baseline at Days 8, 30 and Months 6, 12, 18, 24, 30, 36

Extension Stage Month 0, 1 and 6 Regimen: Geometric Mean Fold Rise in Toxin B Specific Neutralizing Antibody Levels From Baseline at Days 8, 30 and Months 6, 12, 18, 24, 30, 36

Extension Stage Day 1, 8 and 30 Regimen: Percentage of Participants Achieving >=4, >=8, >=16 and >=32 Fold Rise From Baseline in Toxin A Specific Antibody Levels at Days 8, 30 and Months 6, 12, 18, 24, 30, 36

Toxin A antibodies were measured using neutralization assay.

Extension Stage Day 1, 8 and 30 Regimen: Percentage of Participants Achieving >=4, >=8, >=16 and >=32 Fold Rise From Baseline in Toxin B Specific Antibody Levels at Days 8, 30 and Months 6, 12, 18, 24, 30, 36

Toxin B antibodies were measured using neutralization assay.

Extension Stage Day 1, 8 and 30 Regimen: Percentage of Participants Achieving >=4, >=8, >=16 and >=32 Fold Rise From Baseline in Both Toxin A and Toxin B Specific Antibody Levels at Days 8, 30 and Months 6, 12, 18, 24, 30, 36

Toxin A and B antibodies were measured using neutralization assay.

Extension Stage Month 0, 1 and 6 Regimen: Percentage of Participants Achieving >=4, >=8, >=16 and >=32 Fold Rise From Baseline in Toxin A Specific Antibody Levels at Days 8, 30 and Months 6, 12, 18, 24, 30, 36

Toxin A antibodies were measured using neutralization assay.

Extension Stage Month 0, 1 and 6 Regimen: Percentage of Participants Achieving >=4, >=8, >=16 and >=32 Fold Rise From Baseline in Toxin B Specific Antibody Levels at Days 8, 30 and Months 6, 12, 18, 24, 30, 36

Toxin B antibodies were measured using neutralization assay.

Extension Stage Month 0, 1 and 6 Regimen: Percentage of Participants Achieving >=4, >=8, >=16 and >=32 Fold Rise From Baseline in Both Toxin A and Toxin B Specific Antibody Levels at Days 8, 30 and Months 6, 12, 18, 24, 30, 36

Toxin A and B antibodies were measured using neutralization assay.

Extension Stage Day 1, 8 and 30 Regimen: Percentage of Participants With Local Reactions by Severity Within 14 Days After Vaccination 4

Local reactions included pain at injection site, swelling and redness collected by using an electronic diary (e-diary). Pain was graded as: mild (grade 1) (did not interfere with activity), moderate (grade 2) (interfered with activity), severe (grade 3) (prevented daily activity) and grade 4 (emergency room visit or hospitalization). Redness and swelling were graded as: mild (2.5-5.0 cm), moderate (>5.0 to 10.0 cm), severe (>10.0 cm) and grade 4 (necrosis). Any local reaction referred to any injection site pain, any swelling, or any redness.

Extension Stage Month 0, 1 and 6 Regimen: Percentage of Participants With Local Reactions by Severity Within 14 Days After Vaccination 4

Local reactions included pain at injection site, swelling and redness collected by using an electronic diary (e-diary). Pain was graded as: mild (grade 1) (did not interfere with activity), moderate (grade 2) (interfered with activity), severe (grade 3) (prevented daily activity) and grade 4 (emergency room visit or hospitalization). Redness and swelling were graded as: mild (2.5-5.0 cm), moderate (>5.0 to 10.0 cm), severe (>10.0 cm) and grade 4 (necrosis). Any local reaction referred to any injection site pain, any swelling, or any redness.

Extension Stage Day 1, 8 and 30 Regimen: Percentage of Participants With Systemic Events by Severity Within 14 Days After Vaccination 4

Systemic events included following events: Fever was graded as mild (38.0 to 38.4 degree C), moderate (38.5 to 38.9 degree C), severe (39.0 to 40.0 degree C), grade (G) 4 (>40.0 degree C). Vomiting was graded as mild (1-2 times in 24 hours), moderate (>2 times in 24 hours), severe (required intravenous hydration)/grade 4 (hospitalization for hypotensive shock). Diarrhea was graded as mild (2-3 loose stools in 24 hours), moderate (4-5 loose stools in 24 hours), severe (>=6 stools in 24 hours) and G4 (hospitalization). Headache, fatigue, new/worsening muscle pain and new/worsening joint pain was graded as mild (no interference with activity), moderate (some interference with activity), severe (prevents daily activity) and G4 (hospitalization). Any systemic event referred to any fever >= 38.0 degree C, any vomiting, any diarrhea, any headache, any fatigue, any new/worsening muscle pain, or any new or worsening joint pain.

Extension Stage Month 0, 1 and 6 Regimen: Percentage of Participants With Systemic Events by Severity Within 14 Days After Vaccination 4

Extension Stage Day 1, 8 and 30 Regimen: Number of Participants With Treatment Emergent Adverse Events (AEs)

An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. Treatment-emergent adverse events are events from dose 4 of study drug to 28 days after dose 4 of study drug that were absent before treatment or that worsened relative to pretreatment state.

Extension Stage Month 0, 1 and 6 Regimen: Number of Participants With Treatment Emergent Adverse Events (AEs)

Extension Stage Day 1, 8 and 30 Regimen: Number of Participants With Treatment Emergent Serious Adverse Events (SAEs)

An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; lack of efficacy in an approved indication. Treatment-emergent serious adverse events are events from dose 4 of study drug to 6 months after dose 4 of study drug that were absent before treatment or that worsened relative to pretreatment state.

Extension Stage Month 0, 1 and 6 Regimen: Number of Participants With Treatment Emergent Serious Adverse Events (SAEs)

An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; lack of efficacy in an approved indication. Treatment-emergent serious adverse events are events from dose 4 of study drug to 6 months after dose 4 of study drug that were absent before treatment or that worsened relative to pretreatment state.

Full Information

NCT ID

NCT02561195

First Posted

July 9, 2015

Last Updated

February 11, 2021

Sponsor

Pfizer

1. Study Identification

Unique Protocol Identification Number

NCT02561195

Brief Title

A Study To Investigate Two 3-dose Schedules Of A Clostridium Difficile Vaccine In Healthy Adults Aged 65 to 85 Years

Official Title

A PHASE 2, PLACEBO-CONTROLLED, RANDOMIZED, OBSERVER-BLINDED STUDY TO EVALUATE THE SAFETY, TOLERABILITY, AND IMMUNOGENICITY OF TWO 3-DOSE REGIMENS OF A CLOSTRIDIUM DIFFICILE VACCINE IN HEALTHY ADULTS AGED 65 TO 85 YEARS

Study Type

Interventional

2. Study Status

Record Verification Date

February 2021

Overall Recruitment Status

Completed

Study Start Date

July 16, 2015 (Actual)

Primary Completion Date

March 7, 2017 (Actual)

Study Completion Date

February 13, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Pfizer

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This study will investigate a Clostridium difficile vaccine in healthy adults aged 65-85 years. Each subject will initially receive 3 doses of vaccine on 1 of 2 vaccination schedules. The study will assess the safety and tolerability of the vaccine as well as the subjects' immune response to the vaccine. One year after the third dose subjects that did not receive placebo will be randomized to receive a fourth dose. Subjects will be followed for up to 4 years after their third vaccination.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Clostridium Difficile Associated Disease

Keywords

Clostridium difficile, Vaccine.

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

300 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Low-dose C. difficile Vaccine (accelerated schedule)

Arm Type

Experimental

Arm Title

High-dose C. difficile Vaccine (accelerated schedule)

Arm Type

Experimental

Arm Title

Placebo (accelerated schedule)

Arm Type

Placebo Comparator

Arm Title

Low-dose C. difficile Vaccine (non-accelerated schedule)

Arm Type

Experimental

Arm Title

High-Dose C. difficile Vaccine (non-accelerated schedule)

Arm Type

Experimental

Arm Title

Placebo (non-accelerated schedule)

Arm Type

Placebo Comparator

Intervention Type

Biological

Intervention Name(s)

Clostridium difficile Vaccine

Intervention Description

0.5 mL intramuscular injection.

Intervention Type

Biological

Intervention Name(s)

Placebo

Intervention Description

0.5 mL intramuscular injection

Primary Outcome Measure Information:

Title

Day 1, 8 and 30 Regimen: Percentage of Participants Achieving Prespecified Antibody Titer Level for Toxin A at Day 37

Description

Toxin A antibodies (threshold >= 219 neutralization units/mL) were measured using neutralization assay.

Time Frame

Day 37 (7 days after Vaccination 3 of Day 1, 8 and 30 regimen)

Title

Month 0, 1 and 6 Regimen: Percentage of Participants Achieving Prespecified Antibody Titer Level for Toxin A at Month 7

Description

Toxin A antibodies (threshold >= 219 neutralization units/mL) were measured using neutralization assay.

Time Frame

Month 7 (1 month after Vaccination 3 of Month 0, 1 and 6 regimen)

Title

Day 1, 8 and 30 Regimen: Percentage of Participants Achieving Prespecified Antibody Titer Level for Toxin B at Day 37

Description

Toxin B antibodies (threshold >= 2586 neutralization units/mL) were measured using neutralization assay.

Time Frame

Day 37 (7 days after Vaccination 3 of Day 1, 8 and 30 regimen)

Title

Month 0, 1 and 6 Regimen: Percentage of Participants Achieving Prespecified Antibody Titer Level for Toxin B at Month 7

Description

Toxin B antibodies (threshold >= 2586 neutralization units/mL) were measured using neutralization assay.

Time Frame

Month 7 (1 month after Vaccination 3 of Month 0, 1 and 6 regimen)

Title

Day 1, 8 and 30 Regimen: Percentage of Participants Achieving Prespecified Antibody Titer Level for Both Toxin A and Toxin B at Day 37

Description

Toxin A and B antibodies (threshold >= 219 and 2586 neutralization units/mL) were measured using neutralization assay.

Time Frame

Day 37 (7 days after Vaccination 3 of Day 1, 8 and 30 regimen)

Title

Month 0, 1 and 6 Regimen: Percentage of Participants Achieving Prespecified Antibody Titer Level for Both Toxin A and Toxin B at Month 7

Description

Toxin A and B antibodies (threshold >= 219 and 2586 neutralization units/mL) were measured using neutralization assay.

Time Frame

Month 7 (1 month after Vaccination 3 of Month 0, 1 and 6 regimen)

Title

Day 1, 8 and 30 Regimen: Percentage of Participants With Local Reactions by Severity Within 7 Days After Vaccination 1

Description

Time Frame

within 7 days After Vaccination 1

Title

Month 0, 1 and 6 Regimen: Percentage of Participants With Local Reactions by Severity Within 14 Days After Vaccination 1

Description

Time Frame

within 14 days After Vaccination 1

Title

Day 1, 8 and 30 Regimen: Percentage of Participants With Local Reactions by Severity Within 14 Days After Vaccination 2

Description

Time Frame

within 14 days After Vaccination 2

Title

Month 0, 1 and 6 Regimen: Percentage of Participants With Local Reactions by Severity Within 14 Days After Vaccination 2

Description

Time Frame

within 14 days after Vaccination 2

Title

Day 1, 8 and 30 Regimen: Percentage of Participants With Local Reactions by Severity Within 14 Days After Vaccination 3

Description

Time Frame

within 14 days after Vaccination 3

Title

Month 0, 1 and 6 Regimen: Percentage of Participants With Local Reactions by Severity Within 14 Days After Vaccination 3

Description

Time Frame

within 14 days after Vaccination 3

Title

Day 1, 8 and 30 Regimen: Percentage of Participants With Systemic Events by Severity Within 7 Days After Vaccination 1

Description

Time Frame

within 7 days after Vaccination 1

Title

Month 0, 1 and 6 Regimen: Percentage of Participants With Systemic Events by Severity Within 14 Days After Vaccination 1

Description

Systemic events included fever, vomiting, diarrhea, headache, fatigue, new or worsening muscle pain, new or worsening joint pain and were recorded by using an e-diary. Fever was graded as mild (38.0 to 38.4 C), moderate (38.5 to 38.9 degree C), severe (39.0 to 40.0 degree C), grade 4 (>40.0 degree C). Vomiting was graded as mild (1-2 times in 24 hours), moderate (>2 times in 24 hours), severe (required intravenous hydration) and grade 4 (hospitalization for hypotensive shock). Diarrhea was graded as mild (2-3 loose stools in 24 hours), moderate (4-5 loose stools in 24 hours), severe (>=6 stools in 24 hours) and grade 4 (hospitalization). Headache, fatigue, new or worsening muscle pain and new or worsening joint pain was graded as mild (no interference with activity), moderate (some interference with activity), severe (prevents daily activity) and grade 4 (hospitalization).

Time Frame

within 14 days after Vaccination 1

Title

Day 1, 8 and 30 Regimen: Percentage of Participants With Systemic Events by Severity Within 14 Days After Vaccination 2

Description

Systemic events included fever, vomiting, diarrhea, headache, fatigue, new or worsening muscle pain, new or worsening joint pain and were recorded by using an e-diary. Fever was graded as mild (38.0 to 38.4 C), moderate (38.5 to 38.9 degree C), severe (39.0 to 40.0 degree C), grade 4 (>40.0 degree C). Vomiting was graded as mild (1-2 times in 24 hours), moderate (>2 times in 24 hours), severe (required intravenous hydration) and grade 4 (hospitalization for hypotensive shock). Diarrhea was graded as mild (2-3 loose stools in 24 hours), moderate (4-5 loose stools in 24 hours), severe (>=6 stools in 24 hours) and grade 4 (hospitalization). Headache, fatigue, new or worsening muscle pain and new or worsening joint pain was graded as mild (no interference with activity), moderate (some interference with activity), severe (prevents daily activity) and grade 4 (hospitalization).

Time Frame

within 14 days after Vaccination 2

Title

Month 0, 1 and 6 Regimen: Percentage of Participants With Systemic Events by Severity Within 14 Days After Vaccination 2

Description

Systemic events included fever, vomiting, diarrhea, headache, fatigue, new or worsening muscle pain, new or worsening joint pain and were recorded by using an e-diary. Fever was graded as mild (38.0 to 38.4 C), moderate (38.5 to 38.9 degree C), severe (39.0 to 40.0 degree C), grade 4 (>40.0 degree C). Vomiting was graded as mild (1-2 times in 24 hours), moderate (>2 times in 24 hours), severe (required intravenous hydration) and grade 4 (hospitalization for hypotensive shock). Diarrhea was graded as mild (2-3 loose stools in 24 hours), moderate (4-5 loose stools in 24 hours), severe (>=6 stools in 24 hours) and grade 4 (hospitalization). Headache, fatigue, new or worsening muscle pain and new or worsening joint pain was graded as mild (no interference with activity), moderate (some interference with activity), severe (prevents daily activity) and grade 4 (hospitalization).

Time Frame

within 14 days after Vaccination 2

Title

Day 1, 8 and 30 Regimen: Percentage of Participants With Systemic Events by Severity Within 14 Days After Vaccination 3

Description

Systemic events included fever, vomiting, diarrhea, headache, fatigue, new or worsening muscle pain, new or worsening joint pain and were recorded by using an e-diary. Fever was graded as mild (38.0 to 38.4 C), moderate (38.5 to 38.9 degree C), severe (39.0 to 40.0 degree C), grade 4 (>40.0 degree C). Vomiting was graded as mild (1-2 times in 24 hours), moderate (>2 times in 24 hours), severe (required intravenous hydration) and grade 4 (hospitalization for hypotensive shock). Diarrhea was graded as mild (2-3 loose stools in 24 hours), moderate (4-5 loose stools in 24 hours), severe (>=6 stools in 24 hours) and grade 4 (hospitalization). Headache, fatigue, new or worsening muscle pain and new or worsening joint pain was graded as mild (no interference with activity), moderate (some interference with activity), severe (prevents daily activity) and grade 4 (hospitalization).

Time Frame

within 14 days after Vaccination 3

Title

Month 0, 1 and 6 Regimen: Percentage of Participants With Systemic Events by Severity Within 14 Days After Vaccination 3

Description

Systemic events included fever, vomiting, diarrhea, headache, fatigue, new or worsening muscle pain, new or worsening joint pain and were recorded by using an e-diary. Fever was graded as mild (38.0 to 38.4 C), moderate (38.5 to 38.9 degree C), severe (39.0 to 40.0 degree C), grade 4 (>40.0 degree C). Vomiting was graded as mild (1-2 times in 24 hours), moderate (>2 times in 24 hours), severe (required intravenous hydration) and grade 4 (hospitalization for hypotensive shock). Diarrhea was graded as mild (2-3 loose stools in 24 hours), moderate (4-5 loose stools in 24 hours), severe (>=6 stools in 24 hours) and grade 4 (hospitalization). Headache, fatigue, new or worsening muscle pain and new or worsening joint pain was graded as mild (no interference with activity), moderate (some interference with activity), severe (prevents daily activity) and grade 4 (hospitalization).

Time Frame

within 14 days after Vaccination 3

Title

Day 1, 8 and 30 Regimen: Percentage of Participants With Treatment Emergent Adverse Events (AEs)

Description

Time Frame

From Vaccination 1 up to 28 days after Vaccination 3 (Day 58)

Title

Month 0, 1 and 6 Regimen: Percentage of Participants With Treatment Emergent Adverse Events (AEs)

Description

Time Frame

From Vaccination 1 up to 28 days after Vaccination 3 (Day 208)

Title

Day 1, 8 and 30 Regimen: Percentage of Participants With Treatment Emergent Serious Adverse Events (SAEs)

Description

Time Frame

From Vaccination 1 up to 6 months after Vaccination 3 (Month 7)

Title

Month 0, 1 and 6 Regimen: Percentage of Participants With Treatment Emergent Serious Adverse Events (SAEs)

Description

Time Frame

From Vaccination 1 up to 6 months after Vaccination 3 (Month 12)

Secondary Outcome Measure Information:

Title

Day 1, 8 and 30 Regimen: Percentage of Participants Achieving Prespecified Antibody Titer Level for Toxin A at Day 1, 8, 15, 30, and Month 2, 4, 7, 13

Description

Toxin A antibodies were measured using neutralization assay.

Time Frame

Day 1, 8, 15, 30 and Month 2, 4, 7, 13

Title

Day 1, 8 and 30 Regimen: Percentage of Participants Achieving Prespecified Antibody Titer Level for Toxin B at Day 1, 8, 15, 30 and Month 2, 4, 7, 13

Description

Toxin B antibodies were measured using neutralization assay.

Time Frame

Day 1, 8, 15, 30 and Month 2, 4, 7, 13

Title

Day 1, 8 and 30 Regimen: Percentage of Participants Achieving Prespecified Antibody Titer Level for Both Toxin A and Toxin B at Day 1, 8, 15, 30 and Month 2, 4, 7, 13

Description

Toxin A and toxin B antibodies were measured using neutralization assay.

Time Frame

Day 1, 8, 15, 30 and Month 2, 4, 7, 13

Title

Month 0, 1 and 6 Regimen: Percentage of Participants Achieving Prespecified Antibody Titer Level for Toxin A at Day 1, 30, 37, 187 and Month 2, 6, 12, 18

Description

Toxin A antibodies were measured using neutralization assay.

Time Frame

Day 1, 30, 37, 187 and Month 2, 6, 12, 18

Title

Month 0, 1 and 6 Regimen: Percentage of Participants Achieving Prespecified Antibody Titer Level for for Toxin B at Day 1, 30, 37, 187 and Month 2, 6, 12, 18

Description

Toxin B antibodies were measured using neutralization assay.

Time Frame

Day 1, 30, 37, 187 and Month 2, 6, 12, 18

Title

Month 0, 1 and 6 Regimen: Percentage of Participants Achieving Prespecified Antibody Titer Level for Both Toxin A and Toxin B at Day 1, 30, 37, 187 and Month 2, 6, 12, 18

Description

Toxin A and toxin B antibodies were measured using neutralization assay.

Time Frame

Day 1, 30, 37, 187 and Month 2, 6, 12, 18

Title

Day 1, 8 and 30 Regimen: Geometric Mean Concentration of Toxin A Specific Neutralizing Antibody Levels at Day 1, 8, 15, 30, 37 and Month 2, 4, 7, 13

Description

Time Frame

Day 1, 8, 15, 30, 37 and Month 2, 4, 7, 13

Title

Day 1, 8 and 30 Regimen: Geometric Mean Concentration of Toxin B Specific Neutralizing Antibody Levels at Day 1, 8, 15, 30, 37 and Month 2, 4, 7, 13

Description

Time Frame

Day 1, 8, 15, 30, 37 and Month 2, 4, 7, 13

Title

Month 0, 1 and 6 Regimen: Geometric Mean Concentration of Toxin A Specific Neutralizing Antibody Levels at Day 1, 30, 37, 187 and Month 2, 6, 7, 12, 18

Description

Time Frame

Day 1, 30, 37, 187 and Month 2, 6, 7, 12, 18

Title

Month 0, 1 and 6 Regimen: Geometric Mean Concentration of Toxin B Specific Neutralizing Antibody Levels at Day 1, 30, 37, 187 and Month 2, 6, 7, 12, 18

Description

Time Frame

Day 1, 30, 37, 187 and Month 2, 6, 7, 12, 18

Title

Day 1, 8 and 30 Regimen: Geometric Mean Fold Rise in Toxin A Specific Neutralizing Antibody Levels From Baseline at Day 8, 15, 30, 37 and Month 2, 4, 7, 13

Description

Time Frame

Day 8, 15, 30, 37 and Month 2, 4, 7, 13

Title

Day 1, 8 and 30 Regimen: Geometric Mean Fold Rise in Toxin B Specific Neutralizing Antibody Levels From Baseline at Day 8, 15, 30, 37 and Month 2, 4, 7, 13

Description

Time Frame

Day 8, 15, 30, 37 and Month 2, 4, 7, 13

Title

Month 0, 1 and 6 Regimen: Geometric Mean Fold Rise in Toxin A Specific Neutralizing Antibody Levels From Baseline at Day 30, 37, 187 and Month 2, 6, 7, 12, 18

Description

Time Frame

Day 30, 37, 187 and Month 2, 6, 7, 12, 18

Title

Month 0, 1 and 6 Regimen: Geometric Mean Fold Rise in Toxin B Specific Neutralizing Antibody Levels From Baseline at Day 30, 37, 187 and Month 2, 6, 7, 12, 18

Description

Time Frame

Day 30, 37, 187 and Month 2, 6, 7, 12, 18

Title

Day 1, 8 and 30 Regimen: Percentage of Participants Achieving >=4, >=8, >=16 and >=32 Fold Rise From Baseline in Toxin A Specific Antibody Levels at Day 8, 15, 30, 37 and Month 2, 4, 7, 13

Description

Toxin A antibodies were measured using neutralization assay.

Time Frame

Day 8, 15, 30, 37 and Month 2, 4, 7, 13

Title

Day 1, 8 and 30 Regimen: Percentage of Participants Achieving >=4, >=8, >=16 and >=32 Fold Rise From Baseline in Toxin B Specific Antibody Levels at Day 8, 15, 30, 37 and Month 2, 4, 7, 13

Description

Toxin B antibodies were measured using neutralization assay.

Time Frame

Day 8, 15, 30, 37 and Month 2, 4, 7, 13

Title

Day 1, 8 and 30 Regimen: Percentage of Participants Achieving>=4,>=8,>=16,>=32 Fold Rise From Baseline in Both Toxin A and Toxin B Specific Antibody Levels at Day 8, 15, 30, 37 and Month 2, 4, 7, 13

Description

Toxin A and toxin B antibodies were measured using neutralization assay.

Time Frame

Day 8, 15, 30, 37 and Month 2, 4, 7, 13

Title

Month 0, 1 and 6 Regimen: Percentage of Participants Achieving >=4, >=8, >=16 and >=32 Fold Rise From Baseline in Toxin A Specific Antibody Levels at Day 30, 37, 187 and Month 2, 6, 7, 12, 18

Description

Toxin A antibodies were measured using neutralization assay.

Time Frame

Day 30, 37, 187 and Month 2, 6, 7, 12, 18

Title

Month 0, 1 and 6 Regimen: Percentage of Participants Achieving >=4, >=8, >=16 and >=32 Fold Rise From Baseline in Toxin B Specific Antibody Levels at Day 30, 37, 187 and Month 2, 6, 7, 12, 18

Description

Toxin A antibodies were measured using neutralization assay.

Time Frame

Day 30, 37, 187 and Month 2, 6, 7, 12, 18

Title

Month 0, 1 and 6 Regimen: Percentage of Participants Achieving>=4,>=8,>=16,>=32 Fold Rise From Baseline in Both Toxin A and Toxin B Antibody Levels at Day 30, 37, 187 and Month 2, 6, 7, 12, 18

Description

Toxin A and toxin B antibodies were measured using neutralization assay.

Time Frame

Day 30, 37, 187 and Month 2, 6, 7, 12, 18

Title

Extension Stage Day 1, 8 and 30 Regimen: Percentage of Participants Achieving Prespecified Antibody Titer Level for Toxin A at Days 1, 8, 30 and Months 6, 12, 18, 24, 30, 36

Description

Toxin A antibodies (threshold >= 219 neutralization units/mL) were measured using neutralization assay.

Time Frame

Days 1, 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4

Title

Extension Stage Day 1, 8 and 30 Regimen: Percentage of Participants Achieving Prespecified Antibody Titer Level for Toxin B at Days 1, 8, 30 and Months 6, 12, 18, 24, 30, 36

Description

Toxin B antibodies (threshold >= 2586 neutralization units/mL) were measured using neutralization assay.

Time Frame

Days 1, 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4

Title

Extension Stage Day 1, 8 and 30 Regimen: Percentage of Participants Achieving Prespecified Antibody Titer Level for Both Toxin A and Toxin B at Days 1, 8, 30 and Months 6, 12, 18, 24, 30, 36

Description

Toxin A and B antibodies (threshold >= 219 and 2586 neutralization units/mL) were measured using neutralization assay.

Time Frame

Days 1, 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4

Title

Extension Stage Month 0, 1 and 6 Regimen: Percentage of Participants Achieving Prespecified Antibody Titer Level for Toxin A at Days 1, 8, 30 and Months 6, 12, 18, 24, 30, 36

Description

Toxin A antibodies (threshold >= 219 neutralization units/mL) were measured using neutralization assay.

Time Frame

Days 1, 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4

Title

Extension Stage Month 0, 1 and 6 Regimen: Percentage of Participants Achieving Prespecified Antibody Titer Level for Toxin B at Days 1, 8, 30 and Months 6, 12, 18, 24, 30, 36

Description

Toxin B antibodies (threshold >= 2586 neutralization units/mL) were measured using neutralization assay.

Time Frame

Days 1, 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4

Title

Extension Stage Month 0, 1 and 6 Regimen: Percentage of Participants Achieving Prespecified Antibody Titer Level for Both Toxin A and Toxin B at Days 1, 8, 30 and Months 6, 12, 18, 24, 30, 36

Description

Toxin A and B antibodies (threshold >= 219 and 2586 neutralization units/mL) were measured using neutralization assay.

Time Frame

Days 1, 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4

Title

Extension Stage Day 1, 8 and 30 Regimen: Geometric Mean Concentration for Toxin A Specific Neutralizing Antibody Levels at Days 1, 8, 30 and Months 6, 12, 18, 24, 30, 36

Description

Time Frame

Days 1, 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4

Title

Extension Stage Day 1, 8 and 30 Regimen: Geometric Mean Concentration for Toxin B Specific Neutralizing Antibody Levels at Days 1, 8, 30 and Months 6, 12, 18, 24, 30, 36

Description

Time Frame

Extension Stage Days 1, 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4

Title

Extension Stage Month 0, 1 and 6 Regimen: Geometric Mean Concentration for Toxin A Specific Neutralizing Antibody Levels at Days 1, 8, 30 and Months 6, 12, 18, 24, 30, 36

Description

Time Frame

Days 1, 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4

Title

Extension Stage Month 0, 1 and 6 Regimen: Geometric Mean Concentration for Toxin B Specific Neutralizing Antibody Levels at Days 1, 8, 30 and Months 6, 12, 18, 24, 30, 36

Description

Time Frame

Days 1, 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4

Title

Extension Stage Day 1, 8 and 30 Regimen: Geometric Mean Fold Rise in Toxin A Specific Neutralizing Antibody Levels From Baseline at Days 8, 30 and Months 6, 12, 18, 24, 30, 36

Description

Time Frame

Days 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4

Title

Extension Stage Day 1, 8 and 30 Regimen: Geometric Mean Fold Rise in Toxin B Specific Neutralizing Antibody Levels From Baseline at Day 8, 30 and Months 6, 12, 18, 24, 30, 36

Description

Time Frame

Days 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4

Title

Extension Stage Month 0, 1 and 6 Regimen: Geometric Mean Fold Rise in Toxin A Specific Neutralizing Antibody Levels From Baseline at Days 8, 30 and Months 6, 12, 18, 24, 30, 36

Description

Time Frame

Days 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4

Title

Extension Stage Month 0, 1 and 6 Regimen: Geometric Mean Fold Rise in Toxin B Specific Neutralizing Antibody Levels From Baseline at Days 8, 30 and Months 6, 12, 18, 24, 30, 36

Description

Time Frame

Days 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4

Title

Description

Toxin A antibodies were measured using neutralization assay.

Time Frame

Days 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4

Title

Description

Toxin B antibodies were measured using neutralization assay.

Time Frame

Days 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4

Title

Description

Toxin A and B antibodies were measured using neutralization assay.

Time Frame

Days 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4

Title

Description

Toxin A antibodies were measured using neutralization assay.

Time Frame

Days 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4

Title

Description

Toxin B antibodies were measured using neutralization assay.

Time Frame

Days 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4

Title

Description

Toxin A and B antibodies were measured using neutralization assay.

Time Frame

Days 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4

Title

Extension Stage Day 1, 8 and 30 Regimen: Percentage of Participants With Local Reactions by Severity Within 14 Days After Vaccination 4

Description

Local reactions included pain at injection site, swelling and redness collected by using an electronic diary (e-diary). Pain was graded as: mild (grade 1) (did not interfere with activity), moderate (grade 2) (interfered with activity), severe (grade 3) (prevented daily activity) and grade 4 (emergency room visit or hospitalization). Redness and swelling were graded as: mild (2.5-5.0 cm), moderate (>5.0 to 10.0 cm), severe (>10.0 cm) and grade 4 (necrosis). Any local reaction referred to any injection site pain, any swelling, or any redness.

Time Frame

Within 14 days after Vaccination 4

Title

Extension Stage Month 0, 1 and 6 Regimen: Percentage of Participants With Local Reactions by Severity Within 14 Days After Vaccination 4

Description

Local reactions included pain at injection site, swelling and redness collected by using an electronic diary (e-diary). Pain was graded as: mild (grade 1) (did not interfere with activity), moderate (grade 2) (interfered with activity), severe (grade 3) (prevented daily activity) and grade 4 (emergency room visit or hospitalization). Redness and swelling were graded as: mild (2.5-5.0 cm), moderate (>5.0 to 10.0 cm), severe (>10.0 cm) and grade 4 (necrosis). Any local reaction referred to any injection site pain, any swelling, or any redness.

Time Frame

Within 14 days after Vaccination 4

Title

Extension Stage Day 1, 8 and 30 Regimen: Percentage of Participants With Systemic Events by Severity Within 14 Days After Vaccination 4

Description

Time Frame

Within 14 days after Vaccination 4

Title

Extension Stage Month 0, 1 and 6 Regimen: Percentage of Participants With Systemic Events by Severity Within 14 Days After Vaccination 4

Description

Time Frame

within 14 days after Vaccination 4

Title

Extension Stage Day 1, 8 and 30 Regimen: Number of Participants With Treatment Emergent Adverse Events (AEs)

Description

Time Frame

From Vaccination 4 up to 28 days after Vaccination 4

Title

Extension Stage Month 0, 1 and 6 Regimen: Number of Participants With Treatment Emergent Adverse Events (AEs)

Description

Time Frame

From Vaccination 4 up to 28 days after Vaccination 4

Title

Extension Stage Day 1, 8 and 30 Regimen: Number of Participants With Treatment Emergent Serious Adverse Events (SAEs)

Description

An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; lack of efficacy in an approved indication. Treatment-emergent serious adverse events are events from dose 4 of study drug to 6 months after dose 4 of study drug that were absent before treatment or that worsened relative to pretreatment state.

Time Frame

From Vaccination 4 up to 6 months after Vaccination 4

Title

Extension Stage Month 0, 1 and 6 Regimen: Number of Participants With Treatment Emergent Serious Adverse Events (SAEs)

Description

An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; lack of efficacy in an approved indication. Treatment-emergent serious adverse events are events from dose 4 of study drug to 6 months after dose 4 of study drug that were absent before treatment or that worsened relative to pretreatment state.

Time Frame

From Vaccination 4 up to 6 months after Vaccination 4

10. Eligibility

Sex

All

Minimum Age & Unit of Time

65 Years

Maximum Age & Unit of Time

85 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Healthy male and female subjects Aged 65 to 85 years Additional Inclusion Criteria for the extension Stage: Receipt of all 3 doses of C difficile vaccine (100 µg or 200 µg antigen dose level) in the original portion of the study. Exclusion Criteria: Proven or suspected prior episode of Clostridium difficile associated diarrhea Unstable chronic medical condition Disease requiring significant change in therapy or hospitalization for worsening disease within 8 weeks before receipt of study vaccine Serious chronic disorders Congenital or acquired immunodeficiency disorders Rheumatologic disorders or other illnesses requiring chronic treatment with known immunosuppressant medications. Active or treated leukemia or lymphoma or bone marrow disorder Any contraindication to vaccination or vaccine components including previous anaphylactic reaction to any vaccine or vaccine-related components Additional Exclusion Criteria for the Extension Stage: Subjects originally randomized to placebo during the original portion of the study. Subjects who have already completed Visit 9 prior to study unblinding.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Pfizer CT.gov Call Center

Organizational Affiliation

Pfizer

Official's Role

Study Director

Facility Information:

Facility Name

Avail Clinical Research, LLC

City

DeLand

State/Province

Florida

ZIP/Postal Code

32720

Country

United States

Facility Name

QPS-MRA, LLC (Broward Research Group)

City

Hollywood

State/Province

Florida

ZIP/Postal Code

33024

Country

United States

Facility Name

QPS-MRA, LLC (Miami Research Associates)

City

South Miami

State/Province

Florida

ZIP/Postal Code

33143

Country

United States

Facility Name

East-West Medical Research Institute

City

Honolulu

State/Province

Hawaii

ZIP/Postal Code

96814

Country

United States

Facility Name

Vince & Associates Clinical Research, Inc.

City

Overland Park

State/Province

Kansas

ZIP/Postal Code

66212

Country

United States

Facility Name

Vince & Associates Clinical Research, Inc

City

Overland Park

State/Province

Kansas

ZIP/Postal Code

66212

Country

United States

Facility Name

Meridian Clinical Research, LLC

City

Omaha

State/Province

Nebraska

ZIP/Postal Code

68134

Country

United States

Facility Name

Clinical Research Center of Nevada LLC

City

Las Vegas

State/Province

Nevada

ZIP/Postal Code

89104

Country

United States

Facility Name

Wake Research Associates, LLC

City

Raleigh

State/Province

North Carolina

ZIP/Postal Code

27612

Country

United States

Facility Name

PMG Research of Wilmington, LLC

City

Wilmington

State/Province

North Carolina

ZIP/Postal Code

28401

Country

United States

Facility Name

Cincinnati Childrens Hospital Medical Center

City

Cincinnati

State/Province

Ohio

ZIP/Postal Code

45206

Country

United States

Facility Name

Cincinnati Childrens Hospital Medical Center

City

Cincinnati

State/Province

Ohio

ZIP/Postal Code

45229

Country

United States

Facility Name

Benchmark Research

City

Austin

State/Province

Texas

ZIP/Postal Code

78705

Country

United States

Facility Name

Texas Center For Drug Development, Inc.

City

Houston

State/Province

Texas

ZIP/Postal Code

77081

Country

United States

Facility Name

Clinical Trials of Texas, Inc.

City

San Antonio

State/Province

Texas

ZIP/Postal Code

78229

Country

United States

Facility Name

J. Lewis Research, Inc. / Foothill Family Clinic

City

Salt Lake City

State/Province

Utah

ZIP/Postal Code

84109

Country

United States

Facility Name

J. Lewis Research, Inc. / Foothill Family Clinic South

City

Salt Lake City

State/Province

Utah

ZIP/Postal Code

84121

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

IPD Sharing URL

https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

Citations:

PubMed Identifier

31125055

Citation

Kitchin N, Remich SA, Peterson J, Peng Y, Gruber WC, Jansen KU, Pride MW, Anderson AS, Knirsch C, Webber C. A Phase 2 Study Evaluating the Safety, Tolerability, and Immunogenicity of Two 3-Dose Regimens of a Clostridium difficile Vaccine in Healthy US Adults Aged 65 to 85 Years. Clin Infect Dis. 2020 Jan 1;70(1):1-10. doi: 10.1093/cid/ciz153.

Results Reference

derived

Links:

URL

https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=B5091009&StudyName=A%20Phase%202%2C%20Placebo-controlled%2C%20Randomized%2C%20Observer-blinded%20Study%20To%20Evaluate%20The%20Safety%2C%20Tolerability%2C%20And%20Immunogenicity%20Of%20Two%203-dose%20Regimens%20Of%20A%20Clostridium%20Difficile%20Vaccine%20In%20Healthy%20Adults%20Aged%2065%20To%2085%20Years

Description

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A Study To Investigate Two 3-dose Schedules Of A Clostridium Difficile Vaccine In Healthy Adults Aged 65 to 85 Years

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A Study To Investigate Two 3-dose Schedules Of A Clostridium Difficile Vaccine In Healthy Adults Aged 65 to 85 Years

Clostridium Difficile Associated Disease

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial