Clostridium Difficile Vaccine 2-Dose Versus 3-Dose Study

NCT03918629 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: B5091019
• Study Type: interventional
• Target: 1,994
• Locations: 1 country
• Sites: 52

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.

Conditions

Clostridium Difficile Associated Disease

Keywords

Clostridium Difficile; vaccine

Outcome Measures

Primary Outcomes (10)

• 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 Outcomes (2)

• Adjusted Geometric Mean Concentration for Clostridium Difficile Toxin A and Toxin B Specific Neutralizing Antibody at Month 12 for EIP

  Month 12

• Percentage of Participants Achieving Seroresponse for Clostridium Difficile Toxin A and Toxin B at Month 12 for EIP

  Month 12

Study Arms (2)

Clostridium difficile vaccine - 3 dose

EXPERIMENTAL

All 3 doses are the Clostridium difficile vaccine

Biological: Clostridium difficile

Clostridium difficile vaccine - 2 dose

EXPERIMENTAL

2 of the 3 doses are the Clostridium difficile vaccine with the other being placebo

Biological: Clostridium difficile; Biological: Placebo

Interventions

Clostridium difficile BIOLOGICAL

Toxoid-based Clostridium difficile vaccine

Clostridium difficile vaccine - 2 dose; Clostridium difficile vaccine - 3 dose

Placebo BIOLOGICAL

Normal saline solution (0.9% sodium chloride)

Clostridium difficile vaccine - 2 dose

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (52)

North Alabama Research Center, LLC

Athens, Alabama, 35611, United States

Location

Medical Affiliated Research Center

Huntsville, Alabama, 35801, United States

Location

East Valley Gastroenterology and Hepatology Associates

Chandler, Arizona, 85224, United States

Location

The Pain Center of Arizona

Peoria, Arizona, 85381, United States

Location

HOPE Research Institute

Phoenix, Arizona, 85018, United States

Location

The Pain Center of Arizona

Phoenix, Arizona, 85018, United States

Location

The Pain Center of Arizona

Phoenix, Arizona, 85032, United States

Location

Paradigm Clinical Research Centers, Inc.

La Mesa, California, 91942, United States

Location

Paradigm Clinical Research Centers, Inc.

Redding, California, 96001, United States

Location

Paradigm Research

Wheat Ridge, Colorado, 80033, United States

Location

Innovative Research of West Florida, Inc.

Clearwater, Florida, 33756, United States

Location

Accel Research Sites - DeLand Clinical Research Unit

DeLand, Florida, 32720, United States

Location

Acevedo Clinical Research Associates

Miami, Florida, 33142, United States

Location

Clinical Neuroscience Solutions, Inc.

Orlando, Florida, 32801, United States

Location

Clinical Neuroscience Solutions, Inc.

Orlando, Florida, 32806, United States

Location

Pines Care Research Center, LLC

Pembroke Pines, Florida, 33026, United States

Location

Progressive Medical Research

Port Orange, Florida, 32127, United States

Location

Meridian Clinical Research, LLC

Savannah, Georgia, 31406, United States

Location

Snake River Research, PLLC

Idaho Falls, Idaho, 83404, United States

Location

MOC Research

Mishawaka, Indiana, 46544, United States

Location

MedPharmics, LLC

Metairie, Louisiana, 70006, United States

Location

MedPharmics, LLC

Gulfport, Mississippi, 39503, United States

Location

Clinical Research Professionals Inc.

Chesterfield, Missouri, 63005, United States

Location

Amici Clinical Research

Raritan, New Jersey, 08869, United States

Location

Rochester Clinical Research, Inc

Rochester, New York, 14609, United States

Location

PMG Research of Charlotte LLC

Charlotte, North Carolina, 28209, United States

Location

PharmQuest

Greensboro, North Carolina, 27408, United States

Location

Accellacare - Hickory

Hickory, North Carolina, 28601, United States

Location

PMG Research of Raleigh

Raleigh, North Carolina, 27609, United States

Location

PMG Research of Wilmington, LLC

Wilmington, North Carolina, 28401, United States

Location

PMG Research of Winston-Salem, LLC

Winston-Salem, North Carolina, 27103, United States

Location

Lillestol Research LLC

Fargo, North Dakota, 58104, United States

Location

Aventiv Research Inc.

Columbus, Ohio, 43213, United States

Location

PriMed Clinical Research

Dayton, Ohio, 45419, United States

Location

Medical Research South

Goose Creek, South Carolina, 29445, United States

Location

Main Street Physician's Care - Waterway

Little River, South Carolina, 29566, United States

Location

Coastal Carolina Research Center

North Charleston, South Carolina, 29405, United States

Location

Holston Medical Group

Bristol, Tennessee, 37620, United States

Location

ARC Clinical Research at Wilson Parke

Austin, Texas, 78726, United States

Location

Bellaire Doctor's Clinic

Bellaire, Texas, 77401, United States

Location

Texas Health Care, PLLC

Fort Worth, Texas, 76104, United States

Location

Ventavia Research Group, LLC

Fort Worth, Texas, 76104, United States

Location

Texas Center for Drug Development, Inc.

Houston, Texas, 77081, United States

Location

Diagnostics Research Group

San Antonio, Texas, 78229, United States

Location

DM Clinical Research

Tomball, Texas, 77375, United States

Location

Martin Diagnostic Clinic

Tomball, Texas, 77375, United States

Location

J. Lewis Research Inc. / Foothill Family Clinic Draper

Draper, Utah, 84020, 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

J. Lewis Research, Inc. / Jordan River Family Medicine

South Jordan, Utah, 84095, United States

Location

Virginia Research Center LLC

Midlothian, Virginia, 23114, United States

Location

Wenatchee Valley Hospital & Clinics

Wenatchee, Washington, 98801, United States

Location

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 3
• 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: April 2, 2019
• First Posted: April 17, 2019
• Study Start: April 1, 2019
• Primary Completion: December 22, 2020
• Study Completion: December 22, 2020
• Last Updated: January 10, 2024
• Results First Posted: January 10, 2024

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will share

Locations

US (52)