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To Understand the Safety and Effects of a C. Difficile Vaccine With New Adds-Ons That Will Be Given to Healthy Adults

Phase 2
Active, not recruiting
Conditions
Clostridoides Difficile Associated Disease
Interventions
Biological: C. difficile vaccine formulation 1.
Biological: C. difficile vaccine formulation 2.
Biological: C. difficile vaccine formulation 3.
Biological: C. difficile vaccine (previously studied formulation).
Other: Saline Placebo.
Registration Number
NCT05805826
Lead Sponsor
Pfizer
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
689
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
C. difficile vaccine formulation 1, Schedule 2 (Phase 1)C. difficile vaccine formulation 1.Novel vaccine formulation 1
C. difficile vaccine formulation 1, Schedule 2 (Phase 1)Saline Placebo.Novel vaccine formulation 1
C. difficile vaccine formulation 2, Schedule 3 (Phase 1)C. difficile vaccine formulation 2.Novel vaccine formulation 2
C. difficile vaccine formulation 2, Schedule 3 (Phase 1)Saline Placebo.Novel vaccine formulation 2
C. difficile vaccine formulation 3, Schedule 2 (Phase 1)C. difficile vaccine formulation 3.Novel vaccine formulation 3
C. difficile vaccine formulation 3, Schedule 2 (Phase 1)Saline Placebo.Novel vaccine formulation 3
C. difficile vaccine formulation 1, Schedule 4 (Phase 1)Saline Placebo.Novel vaccine formulation 1
C. difficile vaccine formulation 2, Schedule 4 (Phase 1)C. difficile vaccine formulation 2.Novel vaccine formulation 2
C. difficile vaccine formulation 2, Schedule 4 (Phase 1)Saline Placebo.Novel vaccine formulation 2
C. difficile vaccine formulation 3, Schedule 4 (Phase 1)C. difficile vaccine formulation 3.Novel vaccine formulation 3
C. difficile vaccine formulation 3, Schedule 4 (Phase 1)Saline Placebo.Novel vaccine formulation 3
C. difficile vaccine (previously studied formulation) Schedule 1 (Phase 1)C. difficile vaccine (previously studied formulation).Previously studied C. difficile vaccine formulation
C. difficile vaccine (previously studied formulation) Schedule 1 (Phase 1)Saline Placebo.Previously studied C. difficile vaccine formulation
C difficile vaccine formulation 2, Schedule 1 (Phase 2)C. difficile vaccine formulation 2.Novel vaccine formulation 2
C difficile vaccine formulation 2, Schedule 1 (Phase 2)Saline Placebo.Novel vaccine formulation 2
C. difficile vaccine formulation 2, Schedule 4 (Phase 2)C. difficile vaccine formulation 2.Novel vaccine formulation 2
C. difficile vaccine formulation 2, Schedule 4 (Phase 2)Saline Placebo.Novel vaccine formulation 2
C. difficile vaccine formulation 2, Schedule 5 (Phase 2)C. difficile vaccine formulation 2.Novel vaccine formulation 2
C. difficile vaccine formulation 2, Schedule 5 (Phase 2)Saline Placebo.Novel vaccine formulation 2
C. difficile vaccine formulation 2, Schedule 6 (Phase 2)C. difficile vaccine formulation 2.Novel vaccine formulation 2
C. difficile vaccine (previously studied formulation) , Schedule 1 (Phase 2)C. difficile vaccine (previously studied formulation).Previously studied C. difficile vaccine formulation
C. difficile vaccine (previously studied formulation) , Schedule 1 (Phase 2)Saline Placebo.Previously studied C. difficile vaccine formulation
C. difficile vaccine formulation 2, Schedule 7 (Phase 2)C. difficile vaccine formulation 2.Novel vaccine formulation 2
C. difficile vaccine formulation 2, Schedule 7 (Phase 2)Saline Placebo.Novel vaccine formulation 2
C. difficile vaccine formulation 2, Schedule 1, (Phase 2)C. difficile vaccine formulation 2.Novel vaccine formulation 2
C. difficile vaccine formulation 2, Schedule 4, (Phase 2)C. difficile vaccine formulation 2.Novel vaccine formulation 2
C. difficile vaccine formulation 2, Schedule 4, (Phase 2)Saline Placebo.Novel vaccine formulation 2
Primary Outcome Measures
NameTimeMethod
Phase 2: Percentage of participants reporting medically attended adverse eventsFrom 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 eventsFrom the first dose of study intervention through 6 months after the last dose of study intervention

As elicited by investigational site staff

Phase 1: Percentage of participants reporting local reactionsFor 7 days after each vaccination

Injection site pain, redness, and swelling as self-reported in electronic diaries

Phase 1: Percentage of participants reporting systemic eventsFor 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 eventsFrom each vaccination through 1 month after vaccination

As elicited by investigational site staff

Phase 1: Percentage of participants reporting serious adverse eventsFrom 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 eventsFrom 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 values1 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 reactionsFor 7 days after each vaccination

Injection site pain, redness, and swelling as self-reported in electronic diaries

Phase 2: Percentage of participants reporting systemic eventsFor 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 eventsFrom the first dose of study intervention through 1 month after the last dose of study intervention

As elicited by investigational site staff

Phase 2: Geometric mean concentration (GMC) of C. difficile toxin A- and toxin B-specific neutralizing antibodies1 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 antibodies1 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 concentrationsFrom before vaccination to 1 month after the last dose

As measured at the central laboratory

Secondary Outcome Measures
NameTimeMethod
Phase 1: Geometric mean fold-rise (GMFR) of C. difficile toxin A- and toxin B-specific neutralizing antibody concentrationsFrom before Dose 1 (Day 1) to 1 month after each dose, and to 6 months and 12 months after the last dose

As measured at the central laboratory

Phase 1: Percentage of participants reporting serious adverse eventsFrom 6 months through 12 months after the last dose of study intervention

As elicited by investigational site

Phase 1: Percentage of participants reporting medically attended adverse eventsFrom 6 months through 12 months after the last dose of study intervention

As elicited by investigational site

Phase 2: Percentage of participants reporting medically attended adverse eventsFrom 6 month through 12 months after the last dose of study intervention

As elicited by investigational site

Phase 2: Percentage of participants reporting serious adverse eventsFrom 6 month through 12 months after the last dose

As elicited by investigational site

Phase 2: Geometric mean concentration (GMC) of C. difficile toxin A- and toxin B-specific neutralizing antibodiesAt each planned post vaccination time point

As measured at the central laboratory

Phase 1: Geometric mean concentration (GMC) of C. difficile toxin A- and toxin B-specific neutralizing antibodies1 month after each dose, before the last dose, 6 months after the last dose, and 12 months after the last dose

As measured at the central laboratory

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 concentrationsFrom before vaccination to each planned vaccination time point

As measured at the central laboratory

Phase 2: Geometric mean concentration (GMC) of C. difficile toxin A- and toxin B- specific neutralizing antibodiesAt each planned persistence time point

As measured at the central laboratory

Phase 2: Geometric mean fold-rise (GMFR) of C. difficile toxin A- and toxin B- specific neutralizing antibodiesFrom before vaccination to each planned persistence time point

As measured at the central laboratory

Phase 2: Geometric mean ratio (GMR) of C. difficile toxin A- and toxin B-specific neutralizing antibodiesAt each planned post vaccination time point

As measured at the central laboratory

Phase 2: Geometric mean fold-rise (GMFR) of C. difficile toxin A- and toxin B-specific neutralizing antibody concentrationsFrom before vaccination to each planned post vaccination time point

As measured at the central laboratory

Trial Locations

Locations (24)

HOPE Research Institute

🇺🇸

Phoenix, Arizona, United States

Hope Research Institute

🇺🇸

Phoenix, Arizona, United States

The Pain Center of Arizona

🇺🇸

Phoenix, Arizona, United States

Anaheim Clinical Trials, LLC

🇺🇸

Anaheim, California, United States

Alliance for Multispecialty Research, LLC

🇺🇸

Wichita, Kansas, United States

Indago Research & Health Center, Inc

🇺🇸

Hialeah, Florida, United States

Research Centers of America ( Hollywood )

🇺🇸

Hollywood, Florida, United States

Research Centers of America

🇺🇸

Hollywood, Florida, United States

Charisma Medical and Research Center

🇺🇸

Miami Lakes, Florida, United States

Miami Clinical Research

🇺🇸

Miami, Florida, United States

New Horizon Research Center

🇺🇸

Miami, Florida, United States

Private Practice - Dr. Hector Fabregas

🇺🇸

Pembroke Pines, Florida, United States

DBC Research USA

🇺🇸

Pembroke Pines, Florida, United States

BRCR Medical Center Inc.

🇺🇸

Plantation, Florida, United States

Clinical Research Trials of Florida

🇺🇸

Tampa, Florida, United States

Great Lakes Clinical Trials - Ravenswood

🇺🇸

Chicago, Illinois, United States

Great Lakes Clinical Trials - Gurnee

🇺🇸

Gurnee, Illinois, United States

Prism Research LLC dba Nucleus Network

🇺🇸

Saint Paul, Minnesota, United States

Washington University School of Medicine

🇺🇸

Saint Louis, Missouri, United States

NYU Langone Health

🇺🇸

New York, New York, United States

Rochester Clinical Research, LLC

🇺🇸

Rochester, New York, United States

CTI Clinical Research Center

🇺🇸

Cincinnati, Ohio, United States

Benchmark Research

🇺🇸

Austin, Texas, United States

DM Clinical Research - MDC

🇺🇸

Tomball, Texas, United States

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