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

NCT02561195 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: B5091009
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 17

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.

Conditions

Clostridium Difficile Associated Disease

Keywords

Clostridium difficile, Vaccine.

Outcome Measures

Primary Outcomes (22)

• 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.

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

• 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.

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

• 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.

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

• 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.

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

• 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.

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

• 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.

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

• 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).

  within 7 days After Vaccination 1

• 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).

  within 14 days After Vaccination 1

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

  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).

  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

  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).

  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

  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).

  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

  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).

  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).

  within 7 days after Vaccination 1

• 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).

  within 14 days after Vaccination 1

• 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).

  within 14 days after Vaccination 2

• 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).

  within 14 days after Vaccination 2

• 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).

  within 14 days after Vaccination 3

• 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).

  within 14 days after Vaccination 3

• 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.

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

• Month 0, 1 and 6 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.

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

• 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.

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

• Month 0, 1 and 6 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.

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

Secondary Outcomes (48)

• 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

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

• 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

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

• 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

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

• 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

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

• 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

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

Study Arms (6)

Low-dose C. difficile Vaccine (accelerated schedule)

EXPERIMENTAL

Biological: Clostridium difficile Vaccine

High-dose C. difficile Vaccine (accelerated schedule)

EXPERIMENTAL

Biological: Clostridium difficile Vaccine

Placebo (accelerated schedule)

PLACEBO COMPARATOR

Biological: Placebo

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

EXPERIMENTAL

Biological: Clostridium difficile Vaccine

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

EXPERIMENTAL

Biological: Clostridium difficile Vaccine

Placebo (non-accelerated schedule)

PLACEBO COMPARATOR

Biological: Placebo

Interventions

Clostridium difficile Vaccine BIOLOGICAL

0.5 mL intramuscular injection.

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

Placebo BIOLOGICAL

0.5 mL intramuscular injection

Placebo (accelerated schedule); Placebo (non-accelerated schedule)

Eligibility Criteria

• Age: 65 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Older Adult (65+)

You may qualify if:

• Healthy male and female subjects
• Aged 65 to 85 years
• Receipt of all 3 doses of C difficile vaccine (100 µg or 200 µg antigen dose level) in the original portion of the study.

You may not qualify if:

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

Sponsors & Collaborators

• Pfizer: lead

Study Sites (17)

Avail Clinical Research, LLC

DeLand, Florida, 32720, United States

Location

QPS-MRA, LLC (Broward Research Group)

Hollywood, Florida, 33024, United States

Location

QPS-MRA, LLC (Miami Research Associates)

South Miami, Florida, 33143, United States

Location

East-West Medical Research Institute

Honolulu, Hawaii, 96814, United States

Location

Vince & Associates Clinical Research, Inc.

Overland Park, Kansas, 66212, United States

Location

Vince & Associates Clinical Research, Inc

Overland Park, Kansas, 66212, United States

Location

Meridian Clinical Research, LLC

Omaha, Nebraska, 68134, United States

Location

Clinical Research Center of Nevada LLC

Las Vegas, Nevada, 89104, United States

Location

Wake Research Associates, LLC

Raleigh, North Carolina, 27612, United States

Location

PMG Research of Wilmington, LLC

Wilmington, North Carolina, 28401, United States

Location

Cincinnati Childrens Hospital Medical Center

Cincinnati, Ohio, 45206, United States

Location

Cincinnati Childrens Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Benchmark Research

Austin, Texas, 78705, United States

Location

Texas Center For Drug Development, Inc.

Houston, Texas, 77081, United States

Location

Clinical Trials of Texas, Inc.

San Antonio, Texas, 78229, United States

Location

J. Lewis Research, Inc. / Foothill Family Clinic

Salt Lake City, Utah, 84109, United States

Location

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

Salt Lake City, Utah, 84121, United States

Location

Related Publications (2)

• Remich S, Kitchin N, Peterson J, Li P, Pride MW, Brock L, Anderson AS, Gruber WC, Jansen KU, Lockhart SP, Webber C. A Phase 2 Extension Study Evaluating the Immunogenicity, Safety, and Tolerability of 3 or 4 Doses of a Clostridioides difficile Vaccine in Healthy US Adults Aged 65 to 85 Years. J Infect Dis. 2024 Feb 14;229(2):367-375. doi: 10.1093/infdis/jiad307.

  PMID: 37531657 DERIVED

• 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.

  PMID: 31125055 DERIVED

Related Links

• To obtain contact information for a study center near you, click here.

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 9, 2015
• First Posted: September 25, 2015
• Study Start: July 16, 2015
• Primary Completion: March 7, 2017
• Study Completion: February 13, 2020
• Last Updated: March 8, 2021
• Results First Posted: March 30, 2018

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will share

Locations

US (17)