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Completed

NCT Number: NCT03918629

Clostridium Difficile Vaccine 2-Dose Versus 3-Dose Study

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.

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Key information

Conditions

Clostridium Difficile Associated Disease

Age range

50 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

North Alabama Research Center, LLC, Athens, Alabama, United States

Loading trial locations.

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Clostridium difficile

Biological

Toxoid-based Clostridium difficile vaccine

Placebo

Biological

Normal saline solution (0.9% sodium chloride)

Primary outcomes

  1. Adjusted Geometric Mean Concentration (GMC) of Clostridium Difficile Toxin A and Toxin B Specific Neutralizing Antibodies at Month 7 for Evaluable Immunogenicity Population (EIP)

    Time frame: Month 7

    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.

  2. Percentage of Participants Achieving Seroresponse for Clostridium Difficile Toxin A and Toxin B at Month 7 for EIP

    Time frame: Month 7

    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.

  3. Percentage of Participants With Local Reactions by Maximum Severity Through 7 Days After Dose 1

    Time frame: Up to 7 days after Dose 1 of investigational product at Month 0

    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.

  4. Percentage of Participants With Local Reactions by Maximum Severity Through 7 Days After Dose 2

    Time frame: Up to 7 days after Dose 2 of investigational product at Month 1

    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.

  5. Percentage of Participants With Local Reactions by Maximum Severity Through 7 Days After Dose 3

    Time frame: Up to 7 days after Dose 3 of investigational product at Month 6

    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.

  6. Percentage of Participants With Systemic Events by Maximum Severity Through 7 Days After Dose 1

    Time frame: Up to 7 days after Dose 1 of investigational product at Month 0

    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.

  7. Percentage of Participants With Systemic Events by Maximum Severity Through 7 Days After Dose 2

    Time frame: Up to 7 days after Dose 2 of investigational product at Month 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 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.

  8. Percentage of Participants With Systemic Events by Maximum Severity Through 7 Days After Dose 3

    Time frame: Up to 7 days after Dose 3 of investigational product at Month 6

    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.

  9. Percentage of Participants With Adverse Events Through 1 Month After Last Study Vaccination

    Time frame: From day of first dose up to 1 month after last dose (up to Month 7)

    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.

  10. Percentage of Participants With Serious Adverse Events (SAEs) Through 6 Months After Last Study Vaccination

    Time frame: From day of first dose up to 6 months after last dose (up to Month 12)

    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.

Secondary outcomes

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

    Time frame: Month 12

    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.

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

    Time frame: Month 12

    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.

Sponsors and collaborators

Lead sponsor

Pfizer

Industry

Registry information

Official study 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

Important dates

Study start
2019
Primary completion
2020
Study completion
2020
First posted
Apr 17, 2019
Registry last updated
Jan 10, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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