Phase 2
N=855
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
Bottom Line
View on ClinicalTrials.gov: NCT02561195 ↗Enrolled (actual)
855
Serious AEs
7.9%
Results posted
Mar 2018
Primary outcome: Primary: Day 1, 8 and 30 Regimen: Percentage of Participants Achieving Prespecified Antibody Titer Level for Toxin A at Day 37 — 12.5; 68.4; 85.5 percentage of participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Clostridium difficile Vaccine (Biological); Placebo (Biological)
- Age
- Older Adult · 65+ yrs
- Sex
- All
- Sponsor
- Pfizer
- Primary completion
- Mar 2017
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Day 1, 8 and 30 Regimen: Percentage of Participants Achieving Prespecified Antibody Titer Level for Toxin A at Day 37 |
12.5; 68.4; 85.5 | — |
| PRIMARY Month 0, 1 and 6 Regimen: Percentage of Participants Achieving Prespecified Antibody Titer Level for Toxin A at Month 7 |
1.9; 98.2; 95.6 | — |
| PRIMARY Day 1, 8 and 30 Regimen: Percentage of Participants Achieving Prespecified Antibody Titer Level for Toxin B at Day 37 |
1.8; 29.8; 38.8 | — |
| PRIMARY Month 0, 1 and 6 Regimen: Percentage of Participants Achieving Prespecified Antibody Titer Level for Toxin B at Month 7 |
7.5; 74.8; 87.3 | — |
| PRIMARY Day 1, 8 and 30 Regimen: Percentage of Participants Achieving Prespecified Antibody Titer Level for Both Toxin A and Toxin B at Day 37 |
0.0; 26.3; 38.8 | — |
| PRIMARY Month 0, 1 and 6 Regimen: Percentage of Participants Achieving Prespecified Antibody Titer Level for Both Toxin A and Toxin B at Month 7 |
0.0; 74.2; 86.1 | — |
| PRIMARY Day 1, 8 and 30 Regimen: Percentage of Participants With Local Reactions by Severity Within 7 Days After Vaccination 1 |
6.6; 19.0; 15.8; 6.6; 17.9; 14.2 | — |
| PRIMARY Month 0, 1 and 6 Regimen: Percentage of Participants With Local Reactions by Severity Within 14 Days After Vaccination 1 |
8.2; 24.2; 19.8; 6.6; 22.0; 19.2 | — |
| PRIMARY Day 1, 8 and 30 Regimen: Percentage of Participants With Local Reactions by Severity Within 14 Days After Vaccination 2 |
0.0; 31.7; 41.3; 0.0; 25.6; 36.3 | — |
| PRIMARY Month 0, 1 and 6 Regimen: Percentage of Participants With Local Reactions by Severity Within 14 Days After Vaccination 2 |
5.1; 27.8; 27.7; 5.1; 23.3; 25.4 | — |
| PRIMARY Day 1, 8 and 30 Regimen: Percentage of Participants With Local Reactions by Severity Within 14 Days After Vaccination 3 |
3.5; 22.9; 22.2; 3.5; 18.9; 21.1 | — |
| PRIMARY Month 0, 1 and 6 Regimen: Percentage of Participants With Local Reactions by Severity Within 14 Days After Vaccination 3 |
1.9; 22.0; 26.1; 0.0; 19.6; 21.7 | — |
| PRIMARY Day 1, 8 and 30 Regimen: Percentage of Participants With Systemic Events by Severity Within 7 Days After Vaccination 1 |
0.0; 0.0; 0.5; 0.0; 0.0; 0.5 | — |
| PRIMARY Month 0, 1 and 6 Regimen: Percentage of Participants With Systemic Events by Severity Within 14 Days After Vaccination 1 |
0.0; 0.5; 0.0; 0.0; 0.5; 0.0 | — |
| PRIMARY Day 1, 8 and 30 Regimen: Percentage of Participants With Systemic Events by Severity Within 14 Days After Vaccination 2 |
0.0; 0.6; 0.0; 0.0; 0.0; 0.0 | — |
| PRIMARY Month 0, 1 and 6 Regimen: Percentage of Participants With Systemic Events by Severity Within 14 Days After Vaccination 2 |
0.0; 1.1; 0.6; 0.0; 1.1; 0.6 | — |
| PRIMARY Day 1, 8 and 30 Regimen: Percentage of Participants With Systemic Events by Severity Within 14 Days After Vaccination 3 |
0.0; 0.6; 1.8; 0.0; 0.6; 1.2 | — |
| PRIMARY Month 0, 1 and 6 Regimen: Percentage of Participants With Systemic Events by Severity Within 14 Days After Vaccination 3 |
0.0; 1.2; 0.6; 0.0; 1.2; 0.6 | — |
| PRIMARY Day 1, 8 and 30 Regimen: Percentage of Participants With Treatment Emergent Adverse Events (AEs) |
27.9; 23.6; 36.4 | — |
| PRIMARY Month 0, 1 and 6 Regimen: Percentage of Participants With Treatment Emergent Adverse Events (AEs) |
54.1; 53.6; 55.7 | — |
| PRIMARY Day 1, 8 and 30 Regimen: Percentage of Participants With Treatment Emergent Serious Adverse Events (SAEs) |
0.0; 6.0; 3.3 | — |
| PRIMARY Month 0, 1 and 6 Regimen: Percentage of Participants With Treatment Emergent Serious Adverse Events (SAEs) |
3.3; 10.4; 12.0 | — |
| SECONDARY 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 |
0.0; 1.2; 0.6; 0.0; 4.7; 6.7 | — |
| SECONDARY 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 |
5.4; 4.7; 3.7; 3.6; 9.9; 11.5 | — |
| SECONDARY 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 |
0.0; 0.0; 0.0; 0.0; 3.5; 4.8 | — |
| SECONDARY 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 |
1.9; 0.6; 1.3; 0.0; 17.3; 19.1 | — |
| SECONDARY 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 |
3.8; 2.5; 4.4; 1.9; 25.9; 36.9 | — |
| SECONDARY 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 |
0.0; 0.0; 0.0; 0.0; 10.5; 13.4 | — |
| SECONDARY 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 |
86; 83; 85; 88; 98; 104 | — |
| SECONDARY 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 |
193; 187; 188; 190; 273; 290 | — |
| SECONDARY 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 |
83; 85; 87; 82; 137; 149 | — |
| SECONDARY 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 |
231; 177; 191; 209; 570; 909 | — |
| SECONDARY 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 |
1.03; 1.19; 1.22; 0.95; 1.73; 2.27 | — |
| SECONDARY 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 |
0.99; 1.46; 1.55; 0.98; 4.31; 5.86 | — |
| SECONDARY 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 |
0.98; 1.61; 1.71; 1.12; 2.70; 3.78 | — |
| SECONDARY 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 |
0.90; 3.28; 4.75; 0.94; 3.75; 5.59 | — |
| SECONDARY 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 |
0.0; 3.5; 4.9; 0.0; 2.9; 4.3 | — |
| SECONDARY 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 |
0.0; 11.7; 14.6; 0.0; 8.2; 8.5 | — |
| SECONDARY 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 |
0.0; 3.5; 3.0; 0.0; 2.9; 1.8 | — |
| SECONDARY 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 |
0.0; 14.2; 14.0; 0.0; 12.3; 11.5 | — |
| SECONDARY 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 |
3.8; 34.0; 43.3; 1.9; 29.6; 38.9 | — |
| SECONDARY 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 |
0.0; 11.7; 12.1; 0.0; 9.3; 9.6 | — |
| SECONDARY 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 |
6.3; 22.2; 20.8; 30.0; 6.3; 100.0 | — |
| SECONDARY 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 |
12.5; 44.4; 29.2; 40.0; 12.5; 88.9 | — |
| SECONDARY 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 |
0.0; 11.1; 8.3; 15.0; 0.0; 88.9 | — |
| SECONDARY 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 |
54.2; 32.7; 50.0; 61.0; 50.0; 94.2 | — |
| SECONDARY 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 |
39.6; 15.4; 41.4; 50.8; 33.3; 69.2 | — |
| SECONDARY 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 |
29.2; 9.6; 27.6; 40.7; 25.0; 69.2 | — |
| SECONDARY 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 |
88; 142; 120; 198; 88; 2161 | — |
| SECONDARY 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 |
267; 1352; 791; 1632; 256; 14754 | — |
| SECONDARY 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 |
230; 152; 249; 281; 235; 1188 | — |
| SECONDARY 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 |
1424; 704; 1925; 2186; 1347; 5011 | — |
| SECONDARY 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 |
1.00; 15.25; 0.98; 19.13; 1.08; 38.41 | — |
| SECONDARY 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 |
0.96; 10.91; 1.02; 11.54; 1.09; 18.70 | — |
| SECONDARY 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 |
1.02; 7.80; 1.09; 8.17; 0.87; 21.57 | — |
| SECONDARY 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 |
0.95; 7.12; 0.97; 7.87; 0.93; 16.88 | — |
| SECONDARY 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 |
0.0; 88.9; 0.0; 85.0; 0.0; 66.7 | — |
| SECONDARY 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 |
0.0; 77.8; 0.0; 75.0; 0.0; 55.6 | — |
| SECONDARY 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 |
0.0; 72.2; 0.0; 65.0; 0.0; 50.0 | — |
| SECONDARY 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 |
0.0; 75.0; 1.7; 71.2; 0.0; 50.0 | — |
| SECONDARY 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 |
0.0; 65.4; 0.0; 69.5; 0.0; 48.1 | — |
| SECONDARY 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 |
0.0; 59.6; 0.0; 59.3; 0.0; 34.6 | — |
| SECONDARY Extension Stage Day 1, 8 and 30 Regimen: Percentage of Participants With Local Reactions by Severity Within 14 Days After Vaccination 4 |
6.3; 5.6; 0.0; 27.3; 6.3; 0.0 | — |
| SECONDARY Extension Stage Month 0, 1 and 6 Regimen: Percentage of Participants With Local Reactions by Severity Within 14 Days After Vaccination 4 |
6.0; 23.1; 3.4; 20.3; 6.0; 21.2 | — |
| SECONDARY Extension Stage Day 1, 8 and 30 Regimen: Percentage of Participants With Systemic Events by Severity Within 14 Days After Vaccination 4 |
0.0; 0.0; 4.2; 0.0; 0.0; 0.0 | — |
| SECONDARY Extension Stage Month 0, 1 and 6 Regimen: Percentage of Participants With Systemic Events by Severity Within 14 Days After Vaccination 4 |
0.0; 1.9; 0.0; 0.0; 0.0; 1.9 | — |
| SECONDARY Extension Stage Day 1, 8 and 30 Regimen: Number of Participants With Treatment Emergent Adverse Events (AEs) |
1; 0; 4; 3 | — |
| SECONDARY Extension Stage Month 0, 1 and 6 Regimen: Number of Participants With Treatment Emergent Adverse Events (AEs) |
10; 8; 17; 16 | — |
| SECONDARY Extension Stage Day 1, 8 and 30 Regimen: Number of Participants With Treatment Emergent Serious Adverse Events (SAEs) |
0; 0; 1; 1 | — |
| SECONDARY Extension Stage Month 0, 1 and 6 Regimen: Number of Participants With Treatment Emergent Serious Adverse Events (SAEs) |
2; 1; 1; 3 | — |
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.
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.
Data sourced from ClinicalTrials.gov (NCT02561195). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.