A PHASE 1/2 RANDOMIZED STUDY TO EVALUATE THE SAFETY, TOLERABILITY, IMMUNOGENICITY, AND IMMUNOPERSISTENCE OF A CLOSTRIDIOIDES DIFFICILE VACCINE ADMINISTERED WITH NOVEL ADJUVANTS IN HEALTHY ADULTS
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- Pfizer
- 入组人数
- 936
- 试验地点
- 43
- 主要终点
- Phase 2: Percentage of participants reporting adverse events
研究概览
简要总结
An antibody is a substance your body makes to fight off infection. This study will explore the safety and antibody response of a vaccine to prevent severe diarrhea caused by a germ called Clostridoides difficile (C. diff). Three new formulations of the C. diff vaccine will be used in this study, in addition to a C. diff vaccine formulation that has been studied in previous clinical trials.
The purpose of this study is to understand if giving the new C. diff vaccine formulations helps people make as many antibodies as giving the previously studied C. diff vaccine formulation.
The study is divided into 2 phases.
Phase 1 will evaluate 3 new formulations of the C. diff vaccine and 2 dosing schedules spread out over 2 months or 6 months.
The Phase 1 portion of the study is seeking participants:
- who are healthy adults of 65 to 84 years of age
- who have not had a C. diff infection before
- who have not received a C. diff vaccine or C. diff monoclonal antibody therapy before.
All participants in Phase 1 will receive study injections with active vaccine or placebo at each vaccination visit, depending on the vaccine group to which they are assigned. A placebo does not contain any active ingredients. Participants in Phase 1 will attend at least 9 study visits and will take part in the study for approximately 18 months. Based on the results of Phase 1, 1 or 2 of the new C. diff vaccine formulations will be chosen for further study in Phase 2.
Phase 2 will evaluate the safety and effects of the new C. diff vaccine formulation(s) chosen in Phase 1.
The Phase 2 portion of the study is seeking participants:
- who are healthy adults ≥65 years of age; and 50 through 64 years of age (Cohort 4 only)
- who have not had a C. diff infection before
- who have not received a C. diff vaccine or C. diff monoclonal antibody therapy before.
Phase 2 participants will receive active C. diff vaccine or placebo at each vaccination visit. Participants in Phase 2 will attend at least 6 and up to 12 study visits and will take part in the study for up to 4 years.
A booster stage for selected participants in Phase 2 will have participants receive active C. diff vaccine or placebo to examine immune persistence. The booster stage participants will attend at least 10 additional study visits and will take part in the study for 6 years.
A newly added cohort will evaluate the safety and effects of active C. diff vaccine formulation in participants 50 through 64 years of age. Participants will receive C. diff vaccine or placebo and will attend at least 6 study visits over a period of 18 months.
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
- 50 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Each phase of the study will enroll participants in different age categories:
- •Phase 1: Participants ≥65 to <85 years of age; Phase 2: Participants ≥65 years of age; Cohort 4 Participants 50 through 64 years of age.
- •Healthy participants as determined by medical history, clinical assessment, and the judgment of the investigator.
- •Participants who are willing and able to comply with all scheduled visits, investigational plan, laboratory tests, lifestyle considerations, and other study procedures.
- •Capable of giving personally signed informed consent, which includes compliance with the requirements and restrictions listed in the ICD and in this protocol.
排除标准
- •Fertile male participants and WOCBP who are unwilling or unable to use an effective method of contraception from the signing of informed consent until at least 28 days after the last dose of study intervention.
- •Serious chronic disorder, including history of metastatic malignancy, severe COPD requiring supplemental oxygen, end-stage renal disease with or without dialysis, cirrhosis of the liver, clinically unstable cardiac disease, or any other disorder that, in the investigator's opinion, would make the participant inappropriate for entry into the study.
- •Any contraindication to vaccination or vaccine components, including previous hypersensitivity or anaphylactic reaction to any vaccine or vaccine-related components.
- •Prior episode of CDI, confirmed by either laboratory test or diagnosis of pseudomembranous colitis at colonoscopy, at surgery, or histopathologically.
- •Any bleeding disorder or anticoagulant therapy that would contraindicate intramuscular injection.
- •Known or suspected immunodeficiency or other conditions associated with immunosuppression, including, but not limited to, leukocyte, lymphocyte, or immunoglobulin class/subclass deficiencies or abnormalities, generalized malignancy, HIV infection, leukemia, lymphoma, or organ or bone marrow transplant.
- •Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
- •Previous receipt of an investigational C difficile vaccine or C difficile mAb therapy.
- •Receipt of blood product or immunoglobulin within 6 months before enrollment.
- •Currently receives treatment with immunosuppressive therapy, including cytotoxic agents or systemic corticosteroids, or planned receipt throughout the study. Participants may not be enrolled if corticosteroids were administered within 28 days before study intervention administration.
- •Participation in other studies involving investigational drugs, investigational vaccines, or investigational devices within 28 days prior to study entry through 12 months after the last dose of study intervention.
- •Phase 1 only: Any screening hematology and/or blood chemistry laboratory value that meets the definition of a ≥ Grade 1 abnormality.
- •Investigator site staff directly involved in the conduct of the study and their family members, site staff otherwise supervised by the investigator, and sponsor and sponsor delegate employees directly involved in the conduct of the study and their family members.
研究组 & 干预措施
C. difficile vaccine formulation 2, Schedule 4 (Phase 2)
Novel vaccine formulation 2
干预措施: Saline Placebo. (Other)
C. difficile vaccine formulation 2, Schedule 5 (Phase 2)
Novel vaccine formulation 2
干预措施: C. difficile vaccine formulation 2. (Biological)
C. difficile vaccine formulation 2, Schedule 4 (Phase 1)
Novel vaccine formulation 2
干预措施: C. difficile vaccine formulation 2. (Biological)
C. difficile vaccine formulation 3, Schedule 4 (Phase 1)
Novel vaccine formulation 3
干预措施: Saline Placebo. (Other)
C. difficile vaccine (previously studied formulation) Schedule 1 (Phase 1)
Previously studied C. difficile vaccine formulation
干预措施: Saline Placebo. (Other)
C difficile vaccine formulation 2, Schedule 1 (Phase 2)
Novel vaccine formulation 2
干预措施: C. difficile vaccine formulation 2. (Biological)
C difficile vaccine formulation 2, Schedule 1 (Phase 2)
Novel vaccine formulation 2
干预措施: Saline Placebo. (Other)
C. difficile vaccine formulation 2, Schedule 4 (Phase 2)
Novel vaccine formulation 2
干预措施: C. difficile vaccine formulation 2. (Biological)
C. difficile vaccine formulation 2, Schedule 7 (Phase 2)
Novel vaccine formulation 2
干预措施: Saline Placebo. (Other)
C. difficile vaccine (previously studied formulation) , Schedule 1 (Phase 2)
Previously studied C. difficile vaccine formulation
干预措施: Saline Placebo. (Other)
C. difficile vaccine formulation 2, Schedule 5 (Phase 2)
Novel vaccine formulation 2
干预措施: Saline Placebo. (Other)
C. difficile vaccine formulation 2, Schedule 6 (Phase 2)
Novel vaccine formulation 2
干预措施: C. difficile vaccine formulation 2. (Biological)
C. difficile vaccine (previously studied formulation) , Schedule 1 (Phase 2)
Previously studied C. difficile vaccine formulation
干预措施: C. difficile vaccine (previously studied formulation). (Biological)
C. difficile vaccine formulation 1, Schedule 4 (Phase 1)
Novel vaccine formulation 1
干预措施: Saline Placebo. (Other)
C. difficile vaccine formulation 1, Schedule 2 (Phase 1)
Novel vaccine formulation 1
干预措施: C. difficile vaccine formulation 1. (Biological)
C. difficile vaccine formulation 1, Schedule 2 (Phase 1)
Novel vaccine formulation 1
干预措施: Saline Placebo. (Other)
C. difficile vaccine formulation 2, Schedule 3 (Phase 1)
Novel vaccine formulation 2
干预措施: C. difficile vaccine formulation 2. (Biological)
C. difficile vaccine formulation 2, Schedule 3 (Phase 1)
Novel vaccine formulation 2
干预措施: Saline Placebo. (Other)
C. difficile vaccine formulation 3, Schedule 2 (Phase 1)
Novel vaccine formulation 3
干预措施: C. difficile vaccine formulation 3. (Biological)
C. difficile vaccine formulation 3, Schedule 2 (Phase 1)
Novel vaccine formulation 3
干预措施: Saline Placebo. (Other)
C. difficile vaccine formulation 2, Schedule 4 (Phase 1)
Novel vaccine formulation 2
干预措施: Saline Placebo. (Other)
C. difficile vaccine formulation 3, Schedule 4 (Phase 1)
Novel vaccine formulation 3
干预措施: C. difficile vaccine formulation 3. (Biological)
C. difficile vaccine (previously studied formulation) Schedule 1 (Phase 1)
Previously studied C. difficile vaccine formulation
干预措施: C. difficile vaccine (previously studied formulation). (Biological)
C. difficile vaccine formulation 2, Schedule 7 (Phase 2)
Novel vaccine formulation 2
干预措施: C. difficile vaccine formulation 2. (Biological)
C. difficile vaccine formulation 2, Schedule 4, (Phase 2)
Novel vaccine formulation 2
干预措施: Saline Placebo. (Other)
C. difficile vaccine formulation 2, Schedule 9, (Phase 2)
Novel vaccine formulation 2
干预措施: C. difficile vaccine formulation 2. (Biological)
C. difficile vaccine formulation 2, Schedule 9, (Phase 2)
Novel vaccine formulation 2
干预措施: Saline Placebo. (Other)
Saline placebo, Schedule 4 (Phase 2)
Saline placebo
干预措施: Saline Placebo. (Other)
C. difficile vaccine formulation 2, Schedule 8, (Phase 2)
Novel vaccine formulation 2
干预措施: C. difficile vaccine formulation 2. (Biological)
C. difficile vaccine formulation 2, Schedule 1, (Phase 2)
Novel vaccine formulation 2
干预措施: C. difficile vaccine formulation 2. (Biological)
C. difficile vaccine formulation 2, Schedule 4, (Phase 2)
Novel vaccine formulation 2
干预措施: C. difficile vaccine formulation 2. (Biological)
C. difficile vaccine formulation 2, Schedule 8, (Phase 2)
Novel vaccine formulation 2
干预措施: Saline Placebo. (Other)
结局指标
主要结局
Phase 2: Percentage of participants reporting adverse events
时间窗: From each dose of study intervention through 1 month after each dose of study intervention
As elicited by investigational site staff
Phase 2: Geometric mean concentration (GMT) of C. difficile toxin A- and toxin B-specific neutralizing antibodies
时间窗: 1 month after the last dose of study intervention
As measured at the central laboratory
Phase 2: Geometric mean ratio (GMR) of C. difficile toxin A- and toxin B-specific neutralizing antibodies
时间窗: At Month 7 comparing data from ≥65 years of age to data from 50 through 64 years of age
As measured at the central laboratory
Phase 1: Percentage of participants reporting local reactions
时间窗: For 7 days after each vaccination
Injection site pain, redness, and swelling as self-reported in electronic diaries
Phase 1: Percentage of participants reporting systemic events
时间窗: For 7 days after each vaccination
Vomiting, diarrhea, headache, fatigue, new or worsening muscle pain, new or worsening joint pain, and fever, as self-reported in electronic diaries
Phase 1: Percentage of participants reporting adverse events
时间窗: From each vaccination through 1 month after vaccination
As elicited by investigational site staff
Phase 1: Percentage of participants reporting serious adverse events
时间窗: From Dose 1 (Day 1) through 6 months after the last dose
As elicited by investigational site staff
Phase 1: Percentage of participants reporting medically attended adverse events
时间窗: From Dose 1 (Day 1) through 6 months after the last dose of study intervention
As elicited by investigational site staff
Phase 1: Percentage of participants with abnormal hematology and chemistry laboratory values
时间窗: 1 week after Dose 1 (Day 7) and 1 month after each dose (through Month 7)
As measured at the central laboratory
Phase 2: Percentage of participants reporting local reactions
时间窗: For 7 days after each vaccination
Injection site pain, redness, and swelling as self-reported in electronic diaries
Phase 2: Percentage of participants reporting systemic events
时间窗: For 7 days after each vaccination
Vomiting, diarrhea, headache, fatigue, new or worsening muscle pain, new or worsening joint pain, and fever, as self-reported in electronic diaries
Phase 2: Percentage of participants reporting adverse events
时间窗: From the first dose of study intervention through 1 month after the last dose of study intervention
As elicited by investigational site staff
Phase 2: Percentage of participants reporting medically attended adverse events
时间窗: From the first dose of study intervention through 6 months after the last dose of study intervention
As elicited by investigational site staff
Phase 2: Percentage of participants reporting serious adverse events
时间窗: From the first dose of study intervention through 6 months after the last dose of study intervention
As elicited by investigational site staff
Phase 2: Geometric mean ratio (GMR) of C. difficile toxin A- and toxin B- specific neutralizing antibodies
时间窗: 1 month after the last dose of study intervention
As measured at the central laboratory
Phase 2: Geometric mean fold-rise (GMFR) of C. difficile toxin A- and toxin B-specific neutralizing antibody concentrations
时间窗: From before vaccination to 1 month after the last dose
As measured at the central laboratory
次要结局
- Phase 1: Geometric mean fold-rise (GMFR) of C. difficile toxin A- and toxin B-specific neutralizing antibody concentrations(From before Dose 1 (Day 1) to 1 month after each dose, and to 6 months and 12 months after the last dose)
- Phase 1: Percentage of participants reporting serious adverse events(From 6 months through 12 months after the last dose of study intervention)
- Phase 1: Percentage of participants reporting medically attended adverse events(From 6 months through 12 months after the last dose of study intervention)
- Phase 2: Percentage of participants reporting medically attended adverse events(From 6 month through 12 months after the last dose of study intervention)
- Phase 2: Percentage of participants reporting serious adverse events(From 6 month through 12 months after the last dose)
- Phase 1: Geometric mean concentration (GMC) of C. difficile toxin A- and toxin B-specific neutralizing antibodies(1 month after each dose, before the last dose, 6 months after the last dose, and 12 months after the last dose)
- Phase 2: The percentage of participants with a greater than or equal to 4-fold rise in C. difficile toxin A- and toxin B-specific neutralizing antibody concentrations(From before vaccination to each planned vaccination time point)
- Phase 2: Geometric mean fold-rise (GMFR) of C. difficile toxin A- and toxin B- specific neutralizing antibodies(From before vaccination to each planned persistence time point)
- Phase 2: Geometric mean ratio (GMR) of C. difficile toxin A- and toxin B-specific neutralizing antibodies(At each planned post vaccination time point)
- Phase 2: Geometric mean fold-rise (GMFR) of C. difficile toxin A- and toxin B-specific neutralizing antibody concentrations(From before vaccination to each planned post vaccination time point)
- Phase 2: Geometric mean concentration (GMT) of C. difficile toxin A- and toxin B-specific neutralizing antibodies(At each planned post vaccination time point)
- Phase 2: Geometric mean concentration (GMT) of C. difficile toxin A- and toxin B- specific neutralizing antibodies(At each planned persistence time point)