Clinical trial NCT05805826: To Understand the Safety and Effects of a C. Difficile Vaccine With New Adds-Ons That Will Be Given to Healthy Adults
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Clostridoides Difficile Associated Disease
Keywords: Clostridioides difficile
Clostridium difficile
C. diff
Persistence
Vaccine
Cohort
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2023-04-10
Enrollment: 689
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Parallel assignment
Primary purpose: PREVENTION

Brief summary: 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
* 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.


Eligibility criteria: Inclusion Criteria:

1. 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.
2. Healthy participants as determined by medical history, clinical assessment, and the judgment of the investigator.
3. Participants who are willing and able to comply with all scheduled visits, investigational plan, laboratory tests, lifestyle considerations, and other study procedures.
4. Capable of giving personally signed informed consent, which includes compliance with the requirements and restrictions listed in the ICD and in this protocol.

Exclusion Criteria:

1. 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.
2. 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.
3. Any contraindication to vaccination or vaccine components, including previous hypersensitivity or anaphylactic reaction to any vaccine or vaccine-related components.
4. Prior episode of CDI, confirmed by either laboratory test or diagnosis of pseudomembranous colitis at colonoscopy, at surgery, or histopathologically.
5. Any bleeding disorder or anticoagulant therapy that would contraindicate intramuscular injection.
6. 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.
7. 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.
8. Previous receipt of an investigational C difficile vaccine or C difficile mAb therapy.
9. Receipt of blood product or immunoglobulin within 6 months before enrollment.
10. 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.
11. 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.
12. Phase 1 only: Any screening hematology and/or blood chemistry laboratory value that meets the definition of a ≥ Grade 1 abnormality.
13. 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.

Primary outcomes:
measure: Phase 1: Percentage of participants reporting local reactions
timeFrame: For 7 days after each vaccination
measure: Phase 1: Percentage of participants reporting systemic events
timeFrame: For 7 days after each vaccination
measure: Phase 1: Percentage of participants reporting adverse events
timeFrame: From each vaccination through 1 month after vaccination
measure: Phase 1: Percentage of participants reporting serious adverse events
timeFrame: From Dose 1 (Day 1) through 6 months after the last dose
measure: Phase 1: Percentage of participants reporting medically attended adverse events
timeFrame: From Dose 1 (Day 1) through 6 months after the last dose of study intervention
measure: Phase 1: Percentage of participants with abnormal hematology and chemistry laboratory values
timeFrame: 1 week after Dose 1 (Day 7) and 1 month after each dose (through Month 7)
measure: Phase 2: Percentage of participants reporting local reactions
timeFrame: For 7 days after each vaccination
measure: Phase 2: Percentage of participants reporting systemic events
timeFrame: For 7 days after each vaccination
measure: Phase 2: Percentage of participants reporting adverse events
timeFrame: From each dose of study intervention through 1 month after each dose of study intervention
measure: Phase 2: Percentage of participants reporting adverse events
timeFrame: From the first dose of study intervention through 1 month after the last dose of study intervention
measure: Phase 2: Percentage of participants reporting medically attended adverse events
timeFrame: From the first dose of study intervention through 6 months after the last dose of study intervention
measure: Phase 2: Percentage of participants reporting serious adverse events
timeFrame: From the first dose of study intervention through 6 months after the last dose of study intervention
measure: Phase 2: Geometric mean concentration (GMC) of C. difficile toxin A- and toxin B-specific neutralizing antibodies
timeFrame: 1 month after the last dose of study intervention
measure: Phase 2: Geometric mean ratio (GMR) of C. difficile toxin A- and toxin B- specific neutralizing antibodies
timeFrame: 1 month after the last dose of study intervention
measure: Phase 2: Geometric mean fold-rise (GMFR) of C. difficile toxin A- and toxin B-specific neutralizing antibody concentrations
timeFrame: From before vaccination to 1 month after the last dose
Secondary outcomes:
measure: Phase 1: Percentage of participants reporting serious adverse events
timeFrame: From 6 months through 12 months after the last dose of study intervention
measure: Phase 1: Percentage of participants reporting medically attended adverse events
timeFrame: From 6 months through 12 months after the last dose of study intervention
measure: Phase 1: Geometric mean concentration (GMC) of C. difficile toxin A- and toxin B-specific neutralizing antibodies
timeFrame: 1 month after each dose, before the last dose, 6 months after the last dose, and 12 months after the last dose
measure: Phase 1: Geometric mean fold-rise (GMFR) of C. difficile toxin A- and toxin B-specific neutralizing antibody concentrations
timeFrame: From before Dose 1 (Day 1) to 1 month after each dose, and to 6 months and 12 months after the last dose
measure: Phase 2: Percentage of participants reporting medically attended adverse events
timeFrame: From 6 month through 12 months after the last dose of study intervention
measure: Phase 2: Percentage of participants reporting serious adverse events
timeFrame: From 6 month through 12 months after the last dose
measure: Phase 2: Geometric mean concentration (GMC) of C. difficile toxin A- and toxin B-specific neutralizing antibodies
timeFrame: At each planned post vaccination time point
measure: Phase 2: Geometric mean ratio (GMR) of C. difficile toxin A- and toxin B-specific neutralizing antibodies
timeFrame: At each planned post vaccination time point
measure: Phase 2: Geometric mean fold-rise (GMFR) of C. difficile toxin A- and toxin B-specific neutralizing antibody concentrations
timeFrame: From before vaccination to each planned post vaccination time point
measure: 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
timeFrame: From before vaccination to each planned vaccination time point
measure: Phase 2: Geometric mean concentration (GMC) of C. difficile toxin A- and toxin B- specific neutralizing antibodies
timeFrame: At each planned persistence time point
measure: Phase 2: Geometric mean fold-rise (GMFR) of C. difficile toxin A- and toxin B- specific neutralizing antibodies
timeFrame: From before vaccination to each planned persistence time point
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Hope Research Institute
state: Arizona
city: Phoenix
country: United States
facility: The Pain Center of Arizona
state: Arizona
city: Phoenix
country: United States
facility: HOPE Research Institute
state: Arizona
city: Anaheim
country: United States
facility: Anaheim Clinical Trials, LLC
state: California
city: Coral Gables
country: United States
facility: Alliance for Multispecialty Research, LLC
state: Florida
city: Hialeah
country: United States
facility: Indago Research & Health Center, Inc
state: Florida
city: Hollywood
country: United States
facility: Research Centers of America ( Hollywood )
state: Florida
city: Hollywood
country: United States
facility: Research Centers of America
state: Florida
city: Miami Lakes
country: United States
facility: Charisma Medical and Research Center
state: Florida
city: Miami
country: United States
facility: Miami Clinical Research
state: Florida
city: Miami
country: United States
facility: New Horizon Research Center
state: Florida
city: Pembroke Pines
country: United States
facility: Private Practice - Dr. Hector Fabregas
state: Florida
city: Pembroke Pines
country: United States
facility: DBC Research USA
state: Florida
city: Plantation
country: United States
facility: BRCR Medical Center Inc.
state: Florida
city: Tampa
country: United States
facility: Clinical Research Trials of Florida
state: Florida
city: Chicago
country: United States
facility: Great Lakes Clinical Trials - Ravenswood
state: Illinois
city: Gurnee
country: United States
facility: Great Lakes Clinical Trials - Gurnee
state: Illinois
city: Wichita
country: United States
facility: Alliance for Multispecialty Research, LLC
state: Kansas
city: Saint Paul
country: United States
facility: Prism Research LLC dba Nucleus Network
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: New York
country: United States
facility: NYU Langone Health
state: New York
city: Rochester
country: United States
facility: Rochester Clinical Research, LLC
state: New York
city: Cincinnati
country: United States
facility: CTI Clinical Research Center
state: Ohio
city: Austin
country: United States
facility: Benchmark Research
state: Texas
city: Tomball
country: United States
facility: DM Clinical Research - MDC
state: Texas
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: