Clinical trial NCT03918629: Clostridium Difficile Vaccine 2-Dose Versus 3-Dose Study
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Clostridium Difficile Associated Disease
Keywords: Clostridium Difficile
vaccine
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2019-04-17
Enrollment: 1994
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
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 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Adjusted Geometric Mean Concentration (GMC) of Clostridium Difficile Toxin A and Toxin B Specific Neutralizing Antibodies at Month 7 for Evaluable Immunogenicity Population (EIP)
timeFrame: Month 7
measure: Percentage of Participants Achieving Seroresponse for Clostridium Difficile Toxin A and Toxin B at Month 7 for EIP
timeFrame: Month 7
measure: Percentage of Participants With Local Reactions by Maximum Severity Through 7 Days After Dose 1
timeFrame: Up to 7 days after Dose 1 of investigational product at Month 0
measure: Percentage of Participants With Local Reactions by Maximum Severity Through 7 Days After Dose 2
timeFrame: Up to 7 days after Dose 2 of investigational product at Month 1
measure: Percentage of Participants With Local Reactions by Maximum Severity Through 7 Days After Dose 3
timeFrame: Up to 7 days after Dose 3 of investigational product at Month 6
measure: Percentage of Participants With Systemic Events by Maximum Severity Through 7 Days After Dose 1
timeFrame: Up to 7 days after Dose 1 of investigational product at Month 0
measure: Percentage of Participants With Systemic Events by Maximum Severity Through 7 Days After Dose 2
timeFrame: Up to 7 days after Dose 2 of investigational product at Month 1
measure: Percentage of Participants With Systemic Events by Maximum Severity Through 7 Days After Dose 3
timeFrame: Up to 7 days after Dose 3 of investigational product at Month 6
measure: Percentage of Participants With Adverse Events Through 1 Month After Last Study Vaccination
timeFrame: From day of first dose up to 1 month after last dose (up to Month 7)
measure: Percentage of Participants With Serious Adverse Events (SAEs) Through 6 Months After Last Study Vaccination
timeFrame: From day of first dose up to 6 months after last dose (up to Month 12)
Secondary outcomes:
measure: Adjusted Geometric Mean Concentration for Clostridium Difficile Toxin A and Toxin B Specific Neutralizing Antibody at Month 12 for EIP
timeFrame: Month 12
measure: Percentage of Participants Achieving Seroresponse for Clostridium Difficile Toxin A and Toxin B at Month 12 for EIP
timeFrame: Month 12
Other outcomes:
Locations:
city: Athens
country: United States
facility: North Alabama Research Center, LLC
state: Alabama
city: Huntsville
country: United States
facility: Medical Affiliated Research Center
state: Alabama
city: Chandler
country: United States
facility: East Valley Gastroenterology and Hepatology Associates
state: Arizona
city: Peoria
country: United States
facility: The Pain Center of Arizona
state: Arizona
city: Phoenix
country: United States
facility: HOPE Research Institute
state: Arizona
city: Phoenix
country: United States
facility: The Pain Center of Arizona
state: Arizona
city: Phoenix
country: United States
facility: The Pain Center of Arizona
state: Arizona
city: La Mesa
country: United States
facility: Paradigm Clinical Research Centers, Inc.
state: California
city: Redding
country: United States
facility: Paradigm Clinical Research Centers, Inc.
state: California
city: Wheat Ridge
country: United States
facility: Paradigm Research
state: Colorado
city: Clearwater
country: United States
facility: Innovative Research of West Florida, Inc.
state: Florida
city: DeLand
country: United States
facility: Accel Research Sites - DeLand Clinical Research Unit
state: Florida
city: Miami
country: United States
facility: Acevedo Clinical Research Associates
state: Florida
city: Orlando
country: United States
facility: Clinical Neuroscience Solutions, Inc.
state: Florida
city: Orlando
country: United States
facility: Clinical Neuroscience Solutions, Inc.
state: Florida
city: Pembroke Pines
country: United States
facility: Pines Care Research Center, LLC
state: Florida
city: Port Orange
country: United States
facility: Progressive Medical Research
state: Florida
city: Savannah
country: United States
facility: Meridian Clinical Research, LLC
state: Georgia
city: Idaho Falls
country: United States
facility: Snake River Research, PLLC
state: Idaho
city: Mishawaka
country: United States
facility: MOC Research
state: Indiana
city: Metairie
country: United States
facility: MedPharmics, LLC
state: Louisiana
city: Gulfport
country: United States
facility: MedPharmics, LLC
state: Mississippi
city: Chesterfield
country: United States
facility: Clinical Research Professionals Inc.
state: Missouri
city: Raritan
country: United States
facility: Amici Clinical Research
state: New Jersey
city: Rochester
country: United States
facility: Rochester Clinical Research, Inc
state: New York
city: Charlotte
country: United States
facility: PMG Research of Charlotte LLC
state: North Carolina
city: Greensboro
country: United States
facility: PharmQuest
state: North Carolina
city: Hickory
country: United States
facility: Accellacare - Hickory
state: North Carolina
city: Raleigh
country: United States
facility: PMG Research of Raleigh
state: North Carolina
city: Wilmington
country: United States
facility: PMG Research of Wilmington, LLC
state: North Carolina
city: Winston-Salem
country: United States
facility: PMG Research of Winston-Salem, LLC
state: North Carolina
city: Fargo
country: United States
facility: Lillestol Research LLC
state: North Dakota
city: Columbus
country: United States
facility: Aventiv Research Inc.
state: Ohio
city: Dayton
country: United States
facility: PriMed Clinical Research
state: Ohio
city: Goose Creek
country: United States
facility: Medical Research South
state: South Carolina
city: Little River
country: United States
facility: Main Street Physician's Care - Waterway
state: South Carolina
city: North Charleston
country: United States
facility: Coastal Carolina Research Center
state: South Carolina
city: Bristol
country: United States
facility: Holston Medical Group
state: Tennessee
city: Austin
country: United States
facility: ARC Clinical Research at Wilson Parke
state: Texas
city: Bellaire
country: United States
facility: Bellaire Doctor's Clinic
state: Texas
city: Fort Worth
country: United States
facility: Texas Health Care, PLLC
state: Texas
city: Fort Worth
country: United States
facility: Ventavia Research Group, LLC
state: Texas
city: Houston
country: United States
facility: Texas Center for Drug Development, Inc.
state: Texas
city: San Antonio
country: United States
facility: Diagnostics Research Group
state: Texas
city: Tomball
country: United States
facility: DM Clinical Research
state: Texas
city: Tomball
country: United States
facility: Martin Diagnostic Clinic
state: Texas
city: Draper
country: United States
facility: J. Lewis Research Inc. / Foothill Family Clinic Draper
state: Utah
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
city: South Jordan
country: United States
facility: J. Lewis Research, Inc. / Jordan River Family Medicine
state: Utah
city: Midlothian
country: United States
facility: Virginia Research Center LLC
state: Virginia
city: Wenatchee
country: United States
facility: Wenatchee Valley Hospital & Clinics
state: Washington
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: