Clostridium Difficile Vaccine 2-Dose Versus 3-Dose Study

A PHASE 3, RANDOMIZED OBSERVER-BLINDED STUDY TO EVALUATE THE IMMUNOGENICITY, SAFETY, AND TOLERABILITY OF 2 DOSES COMPARED TO 3 DOSES OF CLOSTRIDIUM DIFFICILE VACCINE IN ADULTS 50 YEARS OF AGE AND OLDER

This study will investigate a Clostridium difficile vaccine in adults 50 years of age and older. In half the adults, all 3 doses given are the Clostridium difficile vaccine, and in half the adults, 2 of the 3 doses are the Clostridium difficile vaccine with the other dose containing no active ingredients. The study will look at the subjects' immune response to the vaccine and assess the safety and tolerability of a 2-dose regimen of Clostridium difficile vaccine compared to a 3-dose regimen of Clostridium difficile vaccine.

Study Overview

• Status: Completed
• Conditions: Clostridium Difficile Associated Disease
• Intervention / Treatment: Biological: Placebo; Biological: Clostridium difficile

Detailed Description

Serology for B5091019 will be forthcoming. There have been delays due to discussions with the FDA on statistical analysis as well as delays attributable to the COVID pandemic.

• Study Type: Interventional
• Enrollment (Actual): 1994
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Athens, Alabama, United States, 35611
      • North Alabama Research Center, LLC
    • Huntsville, Alabama, United States, 35801
      • Medical Affiliated Research Center
  • Arizona
    • Chandler, Arizona, United States, 85224
      • East Valley Gastroenterology and Hepatology Associates
    • Peoria, Arizona, United States, 85381
      • The Pain Center of Arizona
    • Phoenix, Arizona, United States, 85018
      • Hope Research Institute
    • Phoenix, Arizona, United States, 85018
      • The Pain Center of Arizona
    • Phoenix, Arizona, United States, 85032
      • The Pain Center of Arizona
  • California
    • La Mesa, California, United States, 91942
      • Paradigm Clinical Research Centers, Inc.
    • Redding, California, United States, 96001
      • Paradigm Clinical Research Centers, Inc.
  • Colorado
    • Wheat Ridge, Colorado, United States, 80033
      • Paradigm Research
  • Florida
    • Clearwater, Florida, United States, 33756
      • Innovative Research of West Florida, Inc.
    • DeLand, Florida, United States, 32720
      • Accel Research Sites - DeLand Clinical Research Unit
    • Miami, Florida, United States, 33142
      • Acevedo Clinical Research Associates
    • Orlando, Florida, United States, 32801
      • Clinical Neuroscience Solutions, Inc.
    • Orlando, Florida, United States, 32806
      • Clinical Neuroscience Solutions, Inc.
    • Pembroke Pines, Florida, United States, 33026
      • Pines Care Research Center, LLC
    • Port Orange, Florida, United States, 32127
      • Progressive Medical Research
  • Georgia
    • Savannah, Georgia, United States, 31406
      • Meridian Clinical Research, LLC
  • Idaho
    • Idaho Falls, Idaho, United States, 83404
      • Snake River Research, PLLC
  • Indiana
    • Mishawaka, Indiana, United States, 46544
      • MOC Research
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • MedPharmics, LLC
  • Mississippi
    • Gulfport, Mississippi, United States, 39503
      • MedPharmics, LLC
  • Missouri
    • Chesterfield, Missouri, United States, 63005
      • Clinical Research Professionals Inc.
  • New Jersey
    • Raritan, New Jersey, United States, 08869
      • Amici Clinical Research
  • New York
    • Rochester, New York, United States, 14609
      • Rochester Clinical Research, Inc
  • North Carolina
    • Charlotte, North Carolina, United States, 28209
      • PMG Research of Charlotte LLC
    • Greensboro, North Carolina, United States, 27408
      • PharmQuest
    • Hickory, North Carolina, United States, 28601
      • Accellacare - Hickory
    • Raleigh, North Carolina, United States, 27609
      • PMG Research of Raleigh
    • Wilmington, North Carolina, United States, 28401
      • PMG Research of Wilmington, LLC
    • Winston-Salem, North Carolina, United States, 27103
      • PMG Research of Winston-Salem, LLC
  • North Dakota
    • Fargo, North Dakota, United States, 58104
      • Lillestol Research LLC
  • Ohio
    • Columbus, Ohio, United States, 43213
      • Aventiv Research Inc.
    • Dayton, Ohio, United States, 45419
      • PriMed Clinical Research
  • South Carolina
    • Goose Creek, South Carolina, United States, 29445
      • Medical Research South
    • Little River, South Carolina, United States, 29566
      • Main Street Physician's Care - Waterway
    • North Charleston, South Carolina, United States, 29405
      • Coastal Carolina Research Center
  • Tennessee
    • Bristol, Tennessee, United States, 37620
      • Holston Medical Group
  • Texas
    • Austin, Texas, United States, 78726
      • ARC Clinical Research at Wilson Parke
    • Bellaire, Texas, United States, 77401
      • Bellaire Doctor's Clinic
    • Fort Worth, Texas, United States, 76104
      • Ventavia Research Group, LLC
    • Fort Worth, Texas, United States, 76104
      • Texas Health Care, PLLC
    • Houston, Texas, United States, 77081
      • Texas Center for Drug Development, Inc.
    • San Antonio, Texas, United States, 78229
      • Diagnostics Research Group
    • Tomball, Texas, United States, 77375
      • Martin Diagnostic Clinic
    • Tomball, Texas, United States, 77375
      • DM Clinical Research
  • Utah
    • Draper, Utah, United States, 84020
      • J. Lewis Research Inc. / Foothill Family Clinic Draper
    • Salt Lake City, Utah, United States, 84109
      • J. Lewis Research, Inc. / Foothill Family Clinic
    • Salt Lake City, Utah, United States, 84121
      • J. Lewis Research, Inc. / Foothill Family Clinic South
    • South Jordan, Utah, United States, 84095
      • J. Lewis Research, Inc. / Jordan River Family Medicine
  • Virginia
    • Midlothian, Virginia, United States, 23114
      • Virginia Research Center LLC
  • Washington
    • Wenatchee, Washington, United States, 98801
      • Wenatchee Valley Hospital & Clinics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Evidence of a personally signed and dated informed consent document.
• Willing and able to comply with study procedures.
• Subjects with an increased risk of future contact with healthcare systems or subjects who have received systemic antibiotics in the previous 12 weeks.
• Ability to be contacted by telephone during study participation.

Exclusion Criteria:

• Pregnant female participants; breastfeeding female participants; positive urine pregnancy test for women of childbearing potential (WOCBP); and WOCBP who are, in the opinion of the investigator, sexually active and at risk for pregnancy and are unwilling or unable to use effective methods of contraception as outlined in this protocol from the signing of the informed consent until at least 28 days after the last dose of investigational product.
• Prior episode of CDI, confirmed by either laboratory test or diagnosis of pseudomembranous colitis at colonoscopy, at surgery, or histopathologically.

• Participants who may be unable to respond to vaccination due to:

  • Metastatic malignancy; or
  • End-stage renal disease (glomerular filtration rate <15 mL/min/1.73 m2 or on dialysis).
  • Any serious medical disorder that in the investigator's opinion is likely to be fatal within the next 12 months.
  • Congenital or acquired immunodeficiency.
• Known infection with human immunodeficiency virus (HIV).
• Any bleeding disorder or anticoagulant therapy that would contraindicate IM injection.
• Any contraindication to vaccination or vaccine components, including previous anaphylactic reaction to any vaccine or vaccine-related components.
• Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inappropriate for entry into this study.
• Previous administration of an investigational C difficile vaccine or C difficile mAb therapy.
• Receipt of systemic corticosteroids for greater than or equal to 14 days within 28 days before enrollment.
• Receipt of chronic systemic treatment with other known immunosuppressant medications, or radiotherapy, within 6 months before enrollment.
• Receipt of blood products or immunoglobulins within 6 months before enrollment.
• Participation in other studies involving investigational drug(s)/vaccine(s) within 28 days prior to study entry until 1 month after the third vaccination.
• Investigator site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or Pfizer employees, including their family members, directly involved in the conduct of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Clostridium difficile vaccine - 3 dose; All 3 doses are the Clostridium difficile vaccine	Biological: Clostridium difficile; Toxoid-based Clostridium difficile vaccine
Experimental: Clostridium difficile vaccine - 2 dose; 2 of the 3 doses are the Clostridium difficile vaccine with the other being placebo	Biological: Placebo; Normal saline solution (0.9% sodium chloride); Biological: Clostridium difficile; Toxoid-based Clostridium difficile vaccine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adjusted Geometric Mean Concentration (GMC) of Clostridium Difficile Toxin A and Toxin B Specific Neutralizing Antibodies at Month 7 for Evaluable Immunogenicity Population (EIP)	Adjusted GMCs and 2-sided 95% confidence intervals (CIs) of toxin A and toxin B specific neutralizing antibody levels were calculated by exponentiating the least square (LS) means and the corresponding CIs based on analysis of logarithmically transformed concentrations using a linear regression model with terms of baseline concentration (log scale) and vaccine group. EIP at Month 7 (EI7): all enrolled participants who received all 3 doses of investigational product; had blood drawn for assay testing within 28 to 47 days after visit 4; had valid and determinate assay results for either toxin A or B for the specified analysis at Month 7; had no major protocol deviations.	Month 7
Percentage of Participants Achieving Seroresponse for Clostridium Difficile Toxin A and Toxin B at Month 7 for EIP	Seroresponse was defined as at least a 4-fold rise from the baseline neutralizing antibody level following vaccination. 95% CI was based on Clopper-Pearson method. EI7: all enrolled participants who received all 3 doses of investigational product; had blood drawn for assay testing within 28 to 47 days after visit 4; had valid and determinate assay results for either toxin A or B for the specified analysis at Month 7; had no major protocol deviations.	Month 7
Percentage of Participants With Local Reactions by Maximum Severity Through 7 Days After Dose 1	Local reactions included pain at injection site, redness and swelling. These were recorded by participants in an electronic diary (e-diary). Redness and swelling were measured and recorded in measuring device units, where 1 measuring device unit= 0.5 centimeter (cm). Redness and swelling were graded as mild: 2.5-5.0 cm, moderate: greater than (>) 5.0-10.0 cm, severe: >10.0 cm, potentially life threatening: necrosis or exfoliative dermatitis for redness, or necrosis for swelling. Pain at injection site was graded as mild: did not interfere with daily activity, moderate: interfered with daily activity, severe: prevented daily activity, potentially life threatening: emergency room visit or hospitalization. The maximum severity was defined as highest grading of each local reaction through 7 days of vaccination.	Up to 7 days after Dose 1 of investigational product at Month 0
Percentage of Participants With Local Reactions by Maximum Severity Through 7 Days After Dose 2	Local reactions included pain at injection site, redness and swelling. These were recorded by participants in an e-diary. Redness and swelling were measured and recorded in measuring device units, where 1 measuring device unit= 0.5 cm. Redness and swelling were graded as mild: 2.5-5.0 cm, moderate: >5.0-10.0 cm, severe: >10.0 cm, potentially life threatening: necrosis or exfoliative dermatitis for redness, or necrosis for swelling. Pain at injection site was graded as mild: did not interfere with daily activity, moderate: interfered with daily activity, severe: prevented daily activity, potentially life threatening: emergency room visit or hospitalization. The maximum severity was defined as highest grading of each local reaction through 7 days of vaccination.	Up to 7 days after Dose 2 of investigational product at Month 1
Percentage of Participants With Local Reactions by Maximum Severity Through 7 Days After Dose 3	Local reactions included pain at injection site, redness and swelling. These were recorded by participants in an e-diary. Redness and swelling were measured and recorded in measuring device units, where 1 measuring device unit= 0.5 cm. Redness and swelling were graded as mild: 2.5-5.0 cm, moderate: >5.0-10.0 cm, severe: >10.0 cm, potentially life threatening: necrosis or exfoliative dermatitis for redness, or necrosis for swelling. Pain at injection site was graded as mild: did not interfere with daily activity, moderate: interfered with daily activity, severe: prevented daily activity, potentially life threatening: emergency room visit or hospitalization. The maximum severity was defined as highest grading of each local reaction through 7 days of vaccination.	Up to 7 days after Dose 3 of investigational product at Month 6
Percentage of Participants With Systemic Events by Maximum Severity Through 7 Days After Dose 1	Systemic events included fever, fatigue, headache, joint pain, muscle pain and vomiting. These were recorded by participants in an e-diary. Fever was categorized as: mild (38.0 to 38.4 degree [deg] Celsius [C]), moderate (38.5 to 38.9 deg C), severe (39.0 to 40.0 deg C) and potentially life threatening (>40.0 deg C). Fatigue, headache, muscle pain and joint pain were graded as mild: did not interfere with activity, moderate: some interference with activity, severe: prevented daily routine activity and potentially life threatening: emergency room visit or hospitalization. Vomiting was graded as mild: 1 to 2 times in 24 hours(h), moderate: >2 times in 24h, severe: required intravenous hydration and potentially life threatening: emergency room visit or hospitalization for hypotensive shock. The maximum severity was defined as highest grading of each systemic event through 7 days of vaccination.	Up to 7 days after Dose 1 of investigational product at Month 0
Percentage of Participants With Systemic Events by Maximum Severity Through 7 Days After Dose 2	Systemic events included fever, fatigue, headache, joint pain, muscle pain and vomiting. These were recorded by participants in an e-diary. Fever was categorized as: mild (38.0 to 38.4 deg C), moderate (38.5 to 38.9 deg C), severe (39.0 to 40.0 deg C) and potentially life threatening (>40.0 deg C). Fatigue, headache, muscle pain and joint pain were graded as mild: did not interfere with activity, moderate: some interference with activity, severe: prevented daily routine activity and potentially life threatening: emergency room visit or hospitalization. Vomiting was graded as mild: 1 to 2 times in 24h, moderate: >2 times in 24h, severe: required intravenous hydration and potentially life threatening: emergency room visit or hospitalization for hypotensive shock. The maximum severity was defined as highest grading of each systemic event through 7 days of vaccination.	Up to 7 days after Dose 2 of investigational product at Month 1
Percentage of Participants With Systemic Events by Maximum Severity Through 7 Days After Dose 3	Systemic events included fever, fatigue, headache, joint pain, muscle pain and vomiting. These were recorded by participants in an e-diary. Fever was categorized as: mild (38.0 to 38.4 deg C), moderate (38.5 to 38.9 deg C), severe (39.0 to 40.0 deg C) and potentially life threatening (>40.0 deg C). Fatigue, headache, muscle pain and joint pain were graded as mild: did not interfere with activity, moderate: some interference with activity, severe: prevented daily routine activity and potentially life threatening: emergency room visit or hospitalization. Vomiting was graded as mild: 1 to 2 times in 24h, moderate: >2 times in 24h, severe: required intravenous hydration and potentially life threatening: emergency room visit or hospitalization for hypotensive shock. The maximum severity was defined as highest grading of each systemic event through 7 days of vaccination.	Up to 7 days after Dose 3 of investigational product at Month 6
Percentage of Participants With Adverse Events Through 1 Month After Last Study Vaccination	An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. Percentage of participants with any AEs (both serious and all non-serious AEs) and non-serious AEs through 1 month after last study vaccination were reported in this outcome measure. Only AEs and non-SAEs collected by non-systematic assessment (i.e., excluding local reactions and systemic events) were reported in this outcome measure.	From day of first dose up to 1 month after last dose (up to Month 7)
Percentage of Participants With Serious Adverse Events (SAEs) Through 6 Months After Last Study Vaccination	SAE was any untoward medical occurrence that at any dose resulted 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.	From day of first dose up to 6 months after last dose (up to Month 12)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adjusted Geometric Mean Concentration for Clostridium Difficile Toxin A and Toxin B Specific Neutralizing Antibody at Month 12 for EIP	Adjusted GMCs and 2-sided 95% CIs of toxin A and toxin B specific neutralizing antibody levels were calculated by exponentiating the LS means and the corresponding CIs based on analysis of logarithmically transformed concentrations using a linear regression model with terms of baseline concentration (log scale) and vaccine group. EI12: all enrolled participants who received all 3 doses of investigational product; had blood drawn for assay testing within 165 to 200 days after visit 4; had valid and determinate assay results for either toxin A or B for the specified analysis at Month 12; had no major protocol deviations.	Month 12
Percentage of Participants Achieving Seroresponse for Clostridium Difficile Toxin A and Toxin B at Month 12 for EIP	Seroresponse was defined as at least a 4-fold rise from the baseline neutralizing antibody following vaccination. 95% CI was based on Clopper-Pearson method. EI12: all enrolled participants who received all 3 doses of investigational product; had blood drawn for assay testing within 165 to 200 days after visit 4; had valid and determinate assay results for either toxin A or B for the specified analysis at Month 12; had no major protocol deviations.	Month 12

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2019
• Primary Completion (Actual): December 22, 2020
• Study Completion (Actual): December 22, 2020

Study Registration Dates

• First Submitted: April 2, 2019
• First Submitted That Met QC Criteria: April 15, 2019
• First Posted (Actual): April 17, 2019

Study Record Updates

• Last Update Posted (Actual): January 10, 2024
• Last Update Submitted That Met QC Criteria: December 18, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: vaccine; Clostridium Difficile
• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Clostridium Infections
• Other Study ID Numbers: B5091019

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No