Evaluation Of Clostridium Difficile Vaccine Lot Consistency In Healthy Adults 65 To 85 Years Of Age

Clostridium Difficile Associated Disease Clinical Trial

Official title:

A PHASE 3, PLACEBO-CONTROLLED, RANDOMIZED, OBSERVER-BLINDED STUDY TO EVALUATE THE LOT CONSISTENCY, SAFETY, TOLERABILITY, AND IMMUNOGENICITY OF A CLOSTRIDIUM DIFFICILE VACCINE IN HEALTHY ADULTS 65 TO 85 YEARS OF AGE

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03579459
• Other study ID #: B5091008
• Status: Completed
• Phase: Phase 3
• Start date: July 31, 2018
• Est. completion date: August 6, 2019

Study information

• Verified date: December 2022
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will investigate a Clostridium difficile vaccine in healthy adults 65 to 85 years of age, who will each receive 3 doses of vaccine. The study will assess the lot consistency, safety, and tolerability of the vaccine, and also look at the subjects' immune response to the vaccine.

Description:

Serology for B5091008 was delayed due to discussions with the FDA on statistical analysis as well as delays attributed to the COVID pandemic.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1317
• Est. completion date: August 6, 2019
• Est. primary completion date: August 6, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 65 Years to 85 Years

Eligibility

Inclusion Criteria:

• Evidence of a personally signed and dated informed consent document.

• Willing and able to comply with study procedures.

• Healthy adults 65 to 85 years of age.

• Male subjects or female subjects who are not of childbearing potential.

• Ability to be contacted by telephone during study participation.

Exclusion Criteria:

• 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 subjects who are Pfizer employees, including their family members, directly involved in the conduct of the study.

• Participation in other studies involving investigational drug(s)/vaccine(s) within 28 days prior to study entry through conclusion of the study.

• Previous administration of an investigational C difficile vaccine or C difficile monoclonal antibody therapy.

• Proven or suspected prior episode of C difficile infection.

• Unstable chronic medical condition or disease requiring significant change in therapy or hospitalization for worsening disease within 8 weeks before receipt of investigational product.

• Serious chronic medical disorders, including metastatic malignancy, severe chronic obstructive pulmonary disease (COPD) requiring supplemental oxygen, end-stage renal disease with or without dialysis, clinically unstable cardiac disease.

• Any bleeding disorder or anticoagulant therapy that would contraindicate intramuscular injection.

• Any contraindication to vaccination or vaccine components, including previous anaphylactic reaction to any vaccine or vaccine-related components.

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

• Congenital or acquired immunodeficiency.

• Receipt of systemic corticosteroids (greater than or equal to 20 mg/day of prednisone or equivalent) for greater than or equal to 14 days within 28 days of enrollment.

• Receipt of chronic systemic treatment with other known immunosuppressant medications, or radiotherapy, within 6 months of enrollment.

• Underlying bone marrow disorder treated within the past year, such as myelodysplasia, myeloma, or myeloproliferative disorder, treated within the past year, or any history of bone marrow transplant.

• Malignancy that required treatment with chemotherapy (including the use of adjunctive and hormonal therapy), immunotherapy, radiation therapy, or antineoplastic target therapies within the past 24 months.

• Receipt of blood products or immunoglobulins within 6 months before enrollment through conclusion of the study.

• Residence in a nursing home or other long-term care facility, or requirement for semiskilled nursing care or assisted living. An ambulatory subject who lives in an autonomous manner in a retirement home or village is eligible for the trial.

• A known infection with human immunodeficiency virus (HIV).

• Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavioral 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.

• Female subjects of childbearing potential; pregnant female subjects; breastfeeding female subjects; fertile male subjects who are unwilling or unable to use a highly effective method of contraception as outlined in this protocol for the duration of the study and for at least 28 days after the last dose of investigational product.

Related Conditions & MeSH terms

• Clostridium Difficile Associated Disease
• Clostridium Infections

Intervention

Biological:
• Clostridium difficile vaccine
Toxoid based Clostridium difficile vaccine
• placebo
Normal saline solution

Locations

Country	Name	City	State
United States	Atlanta Center for Medical Research	Atlanta	Georgia
United States	Benchmark Research	Austin	Texas
United States	PMG Research of Charlotte, LLC	Charlotte	North Carolina
United States	Clinical Research of South Florida	Coral Gables	Florida
United States	Avail Clinical Research, LLC	DeLand	Florida
United States	J. Lewis Research Inc. / Foothill Family Clinic Draper	Draper	Utah
United States	Medical Research South, LLC	Goose Creek	South Carolina
United States	Research Centers of America, LLC	Hollywood	Florida
United States	East-West Medical Research Institute	Honolulu	Hawaii
United States	Advanced Clinical Research	Meridian	Idaho
United States	Coastal Clinical Research, Inc.	Mobile	Alabama
United States	Ochsner Clinic Foundation	New Orleans	Louisiana
United States	Meridian Clinical Research, LLC	Norfolk	Nebraska
United States	Lynn Health Science Institute	Oklahoma City	Oklahoma
United States	Meridian Clinical Research, LLC	Omaha	Nebraska
United States	Amici Clinical Research	Raritan	New Jersey
United States	Paradigm Clinical Research Centers, Inc.	Redding	California
United States	J. Lewis Research, Inc./ Foothill Family Clinic South	Salt Lake City	Utah
United States	J. Lewis Research, Incorporated/Foothill Family Clinic South	Salt Lake City	Utah
United States	Diagnostics Research Group	San Antonio	Texas
United States	J. Lewis Research, Inc. / Jordan River Family Medicine	South Jordan	Utah
United States	Clinical Research Atlanta	Stockbridge	Georgia
United States	Heartland Research Associates, LLC	Wichita	Kansas
United States	PMG Research of Wilmington, LLC	Wilmington	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Geometric Mean Concentrations (GMCs) of Clostridium Difficile Toxin A and Toxin B Specific Neutralizing Antibodies at Month 7	GMC was calculated as the mean of the assay results after making the logarithm transformation and then back transformation to its original scale. Confidence intervals (CIs) were back transformations of CIs based on the Student t distribution for the mean logarithm of the concentrations. Clostridium difficile toxin A and toxin B were inactivated by a combination of genetic mutations to decrease toxin activity and chemical treatments were done prior to final purification and formulation of the drug substance.	At Month 7
Primary	Percentage of Participants Reporting Local Reactions by Maximum Severity Within 7 Days After Vaccination 1	Local reactions included pain at injection site, redness and swelling. These were recorded by participants in an electronic diary (e-diary). Pain at injection site was graded as mild: did not interfere with daily activity, moderate: interfered with daily activity, severe: prevented daily activity, grade 4: emergency room visit or hospitalization. Redness and swelling were measured and recorded in measuring device units. One measuring device unit= 0.5 centimeter (cm) and graded as mild: 2.5 to 5.0 cm, moderate: greater than (>) 5.0 to 10.0 cm, severe: >10.0 cm, Grade 4 indicated necrosis or exfoliative dermatitis for redness and necrosis for swelling. The maximum severity was defined as highest grading of each local reaction within 7 days of vaccination. Events were classified as Grade 4 based on study investigator's judgement.	Within 7 days after Vaccination 1 at Month 0
Primary	Percentage of Participants Reporting Local Reactions by Maximum Severity Within 7 Days After Vaccination 2	Local reactions included pain at injection site, redness and swelling. These were recorded by participants in an e-diary. Pain at injection site was graded as mild: did not interfere with daily activity, moderate: interfered with daily activity, severe: prevented daily activity, grade 4: emergency room visit or hospitalization. Redness and swelling were measured and recorded in measuring device units. One measuring device unit= 0.5 cm and graded as mild: 2.5 to 5.0 cm, moderate: > 5.0 to 10.0 cm, severe: >10.0 cm, Grade 4 indicated necrosis or exfoliative dermatitis for redness and necrosis for swelling. The maximum severity was defined as highest grading of each local reaction within 7 days of vaccination. Events were classified as Grade 4 based on study investigator's judgement.	Within 7 days after Vaccination 2 at Month 1
Primary	Percentage of Participants Reporting Local Reactions by Maximum Severity Within 7 Days After Vaccination 3	Local reactions included pain at injection site, redness and swelling. These were recorded by participants in an e-diary. Pain at injection site was graded as mild: did not interfere with daily activity, moderate: interfered with daily activity, severe: prevented daily activity, grade 4: emergency room visit or hospitalization. Redness and swelling were measured and recorded in measuring device units. One measuring device unit= 0.5 cm and graded as mild: 2.5 to 5.0 cm, moderate: > 5.0 to 10.0 cm, severe: >10.0 cm, Grade 4 indicated necrosis or exfoliative dermatitis for redness and necrosis for swelling. The maximum severity was defined as highest grading of each local reaction within 7 days of vaccination. Events were classified as Grade 4 based on study investigator's judgement.	Within 7 days after Vaccination 3 at Month 6
Primary	Percentage of Participants Reporting Systemic Events by Maximum Severity Within 7 Days After Vaccination 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 Celsius [deg C]), moderate: (38.5 to 38.9 deg C), severe (39.0 to 40.0 deg C), grade 4: >40 deg C. Fatigue, headache, joint pain and muscle pain were graded as mild: did not interfere with activity, moderate: some interference with activity, severe: prevented daily activity, grade 4: emergency room visit or hospitalization. Vomiting was graded as mild: 1 to 2 times in 24 hours, moderate: >2 times in 24 hours, severe: required intravenous hydration, grade 4: emergency room visit or hospitalization for hypotensive shock. The maximum severity was defined as highest grading of each systemic event within 7 days of vaccination. Events were classified as Grade 4 based on study investigator's judgement.	Within 7 days after Vaccination 1 at Month 0
Primary	Percentage of Participants Reporting Systemic Events by Maximum Severity Within 7 Days After Vaccination 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), grade 4: >40 deg C. Fatigue, headache, joint pain and muscle pain were graded as mild: did not interfere with activity, moderate: some interference with activity, severe: prevented daily activity, grade 4: emergency room visit or hospitalization. Vomiting was graded as mild: 1 to 2 times in 24 hours, moderate: >2 times in 24 hours, severe: required intravenous hydration, grade 4: emergency room visit or hospitalization for hypotensive shock. The maximum severity was defined as highest grading of each systemic event within 7 days of vaccination. Events were classified as Grade 4 based on study investigator's judgement.	Within 7 days after Vaccination 2 at Month 1
Primary	Percentage of Participants Reporting Systemic Events by Maximum Severity Within 7 Days After Vaccination 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), grade 4: >40 deg C. Fatigue, headache, joint pain and muscle pain were graded as mild: did not interfere with activity, moderate: some interference with activity, severe: prevented daily activity, grade 4: emergency room visit or hospitalization. Vomiting was graded as mild: 1 to 2 times in 24 hours, moderate: >2 times in 24 hours, severe: required intravenous hydration, grade 4: emergency room visit or hospitalization for hypotensive shock. The maximum severity was defined as highest grading of each systemic event within 7 days of vaccination. Events were classified as Grade 4 based on study investigator's judgement.	Within 7 days after Vaccination 3 at Month 6
Primary	Percentage of Participants With Adverse Events (AEs) Through 1 Month After Last Study Vaccination	An AE was defined as any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. AEs included both serious and all non-serious adverse events (NSAEs). Only AEs and NSAEs collected by non-systematic assessment (i.e., excluding local reactions and systemic events) were reported in this outcome measure.	From Day 1 to 1 month after last vaccination (Up to Month 7)
Primary	Percentage of Participants Reporting Serious Adverse Events (SAEs)	An SAE was defined as any untoward medical occurrence at any dose that resulted in any of the following outcomes: death; life-threatening (immediate risk of death); required inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); congenital anomaly/birth defect; or that was considered as an important medical event.	From Day 1 to 1 month after last vaccination (Up to Month 7)

External Links

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