Clinical trial NCT02561195: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Clostridium Difficile Associated Disease
Keywords: Clostridium difficile, Vaccine.
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2015-09-25
Enrollment: 300
Sex: ALL
Minimum age (years): 65
Maximum age (years): 85
Standard ages: OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


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.

Primary outcomes:
measure: Day 1, 8 and 30 Regimen: Percentage of Participants Achieving Prespecified Antibody Titer Level for Toxin A at Day 37
timeFrame: Day 37 (7 days after Vaccination 3 of Day 1, 8 and 30 regimen)
measure: Month 0, 1 and 6 Regimen: Percentage of Participants Achieving Prespecified Antibody Titer Level for Toxin A at Month 7
timeFrame: Month 7 (1 month after Vaccination 3 of Month 0, 1 and 6 regimen)
measure: Day 1, 8 and 30 Regimen: Percentage of Participants Achieving Prespecified Antibody Titer Level for Toxin B at Day 37
timeFrame: Day 37 (7 days after Vaccination 3 of Day 1, 8 and 30 regimen)
measure: Month 0, 1 and 6 Regimen: Percentage of Participants Achieving Prespecified Antibody Titer Level for Toxin B at Month 7
timeFrame: Month 7 (1 month after Vaccination 3 of Month 0, 1 and 6 regimen)
measure: Day 1, 8 and 30 Regimen: Percentage of Participants Achieving Prespecified Antibody Titer Level for Both Toxin A and Toxin B at Day 37
timeFrame: Day 37 (7 days after Vaccination 3 of Day 1, 8 and 30 regimen)
measure: Month 0, 1 and 6 Regimen: Percentage of Participants Achieving Prespecified Antibody Titer Level for Both Toxin A and Toxin B at Month 7
timeFrame: Month 7 (1 month after Vaccination 3 of Month 0, 1 and 6 regimen)
measure: Day 1, 8 and 30 Regimen: Percentage of Participants With Local Reactions by Severity Within 7 Days After Vaccination 1
timeFrame: within 7 days After Vaccination 1
measure: Month 0, 1 and 6 Regimen: Percentage of Participants With Local Reactions by Severity Within 14 Days After Vaccination 1
timeFrame: within 14 days After Vaccination 1
measure: Day 1, 8 and 30 Regimen: Percentage of Participants With Local Reactions by Severity Within 14 Days After Vaccination 2
timeFrame: within 14 days After Vaccination 2
measure: Month 0, 1 and 6 Regimen: Percentage of Participants With Local Reactions by Severity Within 14 Days After Vaccination 2
timeFrame: within 14 days after Vaccination 2
measure: Day 1, 8 and 30 Regimen: Percentage of Participants With Local Reactions by Severity Within 14 Days After Vaccination 3
timeFrame: within 14 days after Vaccination 3
measure: Month 0, 1 and 6 Regimen: Percentage of Participants With Local Reactions by Severity Within 14 Days After Vaccination 3
timeFrame: within 14 days after Vaccination 3
measure: Day 1, 8 and 30 Regimen: Percentage of Participants With Systemic Events by Severity Within 7 Days After Vaccination 1
timeFrame: within 7 days after Vaccination 1
measure: Month 0, 1 and 6 Regimen: Percentage of Participants With Systemic Events by Severity Within 14 Days After Vaccination 1
timeFrame: within 14 days after Vaccination 1
measure: Day 1, 8 and 30 Regimen: Percentage of Participants With Systemic Events by Severity Within 14 Days After Vaccination 2
timeFrame: within 14 days after Vaccination 2
measure: Month 0, 1 and 6 Regimen: Percentage of Participants With Systemic Events by Severity Within 14 Days After Vaccination 2
timeFrame: within 14 days after Vaccination 2
measure: Day 1, 8 and 30 Regimen: Percentage of Participants With Systemic Events by Severity Within 14 Days After Vaccination 3
timeFrame: within 14 days after Vaccination 3
measure: Month 0, 1 and 6 Regimen: Percentage of Participants With Systemic Events by Severity Within 14 Days After Vaccination 3
timeFrame: within 14 days after Vaccination 3
measure: Day 1, 8 and 30 Regimen: Percentage of Participants With Treatment Emergent Adverse Events (AEs)
timeFrame: From Vaccination 1 up to 28 days after Vaccination 3 (Day 58)
measure: Month 0, 1 and 6 Regimen: Percentage of Participants With Treatment Emergent Adverse Events (AEs)
timeFrame: From Vaccination 1 up to 28 days after Vaccination 3 (Day 208)
measure: Day 1, 8 and 30 Regimen: Percentage of Participants With Treatment Emergent Serious Adverse Events (SAEs)
timeFrame: From Vaccination 1 up to 6 months after Vaccination 3 (Month 7)
measure: Month 0, 1 and 6 Regimen: Percentage of Participants With Treatment Emergent Serious Adverse Events (SAEs)
timeFrame: From Vaccination 1 up to 6 months after Vaccination 3 (Month 12)
Secondary outcomes:
measure: 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
timeFrame: Day 1, 8, 15, 30 and Month 2, 4, 7, 13
measure: 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
timeFrame: Day 1, 8, 15, 30 and Month 2, 4, 7, 13
measure: 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
timeFrame: Day 1, 8, 15, 30 and Month 2, 4, 7, 13
measure: 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
timeFrame: Day 1, 30, 37, 187 and Month 2, 6, 12, 18
measure: 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
timeFrame: Day 1, 30, 37, 187 and Month 2, 6, 12, 18
measure: 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
timeFrame: Day 1, 30, 37, 187 and Month 2, 6, 12, 18
measure: 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
timeFrame: Day 1, 8, 15, 30, 37 and Month 2, 4, 7, 13
measure: 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
timeFrame: Day 1, 8, 15, 30, 37 and Month 2, 4, 7, 13
measure: 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
timeFrame: Day 1, 30, 37, 187 and Month 2, 6, 7, 12, 18
measure: 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
timeFrame: Day 1, 30, 37, 187 and Month 2, 6, 7, 12, 18
measure: 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
timeFrame: Day 8, 15, 30, 37 and Month 2, 4, 7, 13
measure: 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
timeFrame: Day 8, 15, 30, 37 and Month 2, 4, 7, 13
measure: 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
timeFrame: Day 30, 37, 187 and Month 2, 6, 7, 12, 18
measure: 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
timeFrame: Day 30, 37, 187 and Month 2, 6, 7, 12, 18
measure: 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
timeFrame: Day 8, 15, 30, 37 and Month 2, 4, 7, 13
measure: 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
timeFrame: Day 8, 15, 30, 37 and Month 2, 4, 7, 13
measure: 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
timeFrame: Day 8, 15, 30, 37 and Month 2, 4, 7, 13
measure: 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
timeFrame: Day 30, 37, 187 and Month 2, 6, 7, 12, 18
measure: 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
timeFrame: Day 30, 37, 187 and Month 2, 6, 7, 12, 18
measure: 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
timeFrame: Day 30, 37, 187 and Month 2, 6, 7, 12, 18
measure: 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
timeFrame: Days 1, 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4
measure: 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
timeFrame: Days 1, 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4
measure: 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
timeFrame: Days 1, 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4
measure: 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
timeFrame: Days 1, 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4
measure: 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
timeFrame: Days 1, 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4
measure: 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
timeFrame: Days 1, 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4
measure: 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
timeFrame: Days 1, 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4
measure: 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
timeFrame: Extension Stage Days 1, 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4
measure: 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
timeFrame: Days 1, 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4
measure: 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
timeFrame: Days 1, 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4
measure: 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
timeFrame: Days 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4
measure: 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
timeFrame: Days 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4
measure: 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
timeFrame: Days 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4
measure: 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
timeFrame: Days 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4
measure: 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
timeFrame: Days 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4
measure: 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
timeFrame: Days 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4
measure: 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
timeFrame: Days 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4
measure: 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
timeFrame: Days 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4
measure: 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
timeFrame: Days 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4
measure: 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
timeFrame: Days 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4
measure: Extension Stage Day 1, 8 and 30 Regimen: Percentage of Participants With Local Reactions by Severity Within 14 Days After Vaccination 4
timeFrame: Within 14 days after Vaccination 4
measure: Extension Stage Month 0, 1 and 6 Regimen: Percentage of Participants With Local Reactions by Severity Within 14 Days After Vaccination 4
timeFrame: Within 14 days after Vaccination 4
measure: Extension Stage Day 1, 8 and 30 Regimen: Percentage of Participants With Systemic Events by Severity Within 14 Days After Vaccination 4
timeFrame: Within 14 days after Vaccination 4
measure: Extension Stage Month 0, 1 and 6 Regimen: Percentage of Participants With Systemic Events by Severity Within 14 Days After Vaccination 4
timeFrame: within 14 days after Vaccination 4
measure: Extension Stage Day 1, 8 and 30 Regimen: Number of Participants With Treatment Emergent Adverse Events (AEs)
timeFrame: From Vaccination 4 up to 28 days after Vaccination 4
measure: Extension Stage Month 0, 1 and 6 Regimen: Number of Participants With Treatment Emergent Adverse Events (AEs)
timeFrame: From Vaccination 4 up to 28 days after Vaccination 4
measure: Extension Stage Day 1, 8 and 30 Regimen: Number of Participants With Treatment Emergent Serious Adverse Events (SAEs)
timeFrame: From Vaccination 4 up to 6 months after Vaccination 4
measure: Extension Stage Month 0, 1 and 6 Regimen: Number of Participants With Treatment Emergent Serious Adverse Events (SAEs)
timeFrame: From Vaccination 4 up to 6 months after Vaccination 4
Other outcomes:
Locations:
city: DeLand
country: United States
facility: Avail Clinical Research, LLC
state: Florida
city: Hollywood
country: United States
facility: QPS-MRA, LLC (Broward Research Group)
state: Florida
city: South Miami
country: United States
facility: QPS-MRA, LLC (Miami Research Associates)
state: Florida
city: Honolulu
country: United States
facility: East-West Medical Research Institute
state: Hawaii
city: Overland Park
country: United States
facility: Vince & Associates Clinical Research, Inc.
state: Kansas
city: Overland Park
country: United States
facility: Vince & Associates Clinical Research, Inc
state: Kansas
city: Omaha
country: United States
facility: Meridian Clinical Research, LLC
state: Nebraska
city: Las Vegas
country: United States
facility: Clinical Research Center of Nevada LLC
state: Nevada
city: Raleigh
country: United States
facility: Wake Research Associates, LLC
state: North Carolina
city: Wilmington
country: United States
facility: PMG Research of Wilmington, LLC
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Childrens Hospital Medical Center
state: Ohio
city: Cincinnati
country: United States
facility: Cincinnati Childrens Hospital Medical Center
state: Ohio
city: Austin
country: United States
facility: Benchmark Research
state: Texas
city: Houston
country: United States
facility: Texas Center For Drug Development, Inc.
state: Texas
city: San Antonio
country: United States
facility: Clinical Trials of Texas, Inc.
state: Texas
city: Salt Lake City
country: United States
facility: J. Lewis Research, Inc. / Foothill Family Clinic
state: Utah
city: Salt Lake City
country: United States
facility: J. Lewis Research, Inc. / Foothill Family Clinic South
state: Utah
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
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.