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
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 1,317
- 试验地点
- 24
- 主要终点
- Geometric Mean Concentrations (GMCs) of Clostridium Difficile Toxin A and Toxin B Specific Neutralizing Antibodies at Month 7
研究概览
简要总结
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.
详细描述
Serology for B5091008 was delayed due to discussions with the FDA on statistical analysis as well as delays attributed to the COVID pandemic.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 65 Years 至 85 Years（Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Placebo
Normal saline solution (0.9% sodium chloride)
干预措施: placebo (Biological)
Clostridium difficile vaccine Lot 3
干预措施: Clostridium difficile vaccine (Biological)
Clostridium difficile vaccine Lot 2
干预措施: Clostridium difficile vaccine (Biological)
Clostridium difficile vaccine Lot 1
干预措施: Clostridium difficile vaccine (Biological)
结局指标
主要结局
Geometric Mean Concentrations (GMCs) of Clostridium Difficile Toxin A and Toxin B Specific Neutralizing Antibodies at Month 7
时间窗: 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.
Percentage of Participants Reporting Local Reactions by Maximum Severity Within 7 Days After Vaccination 1
时间窗: Within 7 days after Vaccination 1 at Month 0
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.
Percentage of Participants Reporting Local Reactions by Maximum Severity Within 7 Days After Vaccination 2
时间窗: Within 7 days after Vaccination 2 at Month 1
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.
Percentage of Participants Reporting Local Reactions by Maximum Severity Within 7 Days After Vaccination 3
时间窗: Within 7 days after Vaccination 3 at Month 6
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.
Percentage of Participants Reporting Systemic Events by Maximum Severity Within 7 Days After Vaccination 1
时间窗: Within 7 days after Vaccination 1 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 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.
Percentage of Participants Reporting Systemic Events by Maximum Severity Within 7 Days After Vaccination 2
时间窗: Within 7 days after Vaccination 2 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), 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.
Percentage of Participants Reporting Systemic Events by Maximum Severity Within 7 Days After Vaccination 3
时间窗: Within 7 days after Vaccination 3 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), 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.
Percentage of Participants With Adverse Events (AEs) Through 1 Month After Last Study Vaccination
时间窗: From Day 1 to 1 month after last vaccination (Up to Month 7)
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.
Percentage of Participants Reporting Serious Adverse Events (SAEs)
时间窗: From Day 1 to 1 month after last vaccination (Up to Month 7)
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.
次要结局
未报告次要终点