To Understand the Safety and Effects of a C. Difficile Vaccine With New Adds-Ons. It Will Be Given Twice Over a Period of Time to Healthy Adults

A Phase 1/2 Randomized Study to Evaluate the Safety, Tolerability, Immunogenicity, and Immunopersistence of a Clostridioides Difficile Vaccine Administered in a 2-Dose Regimen With Novel Adjuvants in Healthy Adults

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.

All 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 11 study visits and will take part in the study for approximately 4.5 years.

Study Overview

• Status: Active, not recruiting
• Conditions: Clostridoides Difficile Associated Disease
• Intervention / Treatment: Biological: C. difficile vaccine formulation 1.; Other: Saline Placebo.; Biological: C. difficile vaccine formulation 2.; Biological: C. difficile vaccine formulation 3.; Biological: C. difficile vaccine (previously studied formulation).

• Study Type: Interventional
• Enrollment (Estimated): 550
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Pfizer CT.gov Call Center; Phone Number: 1-800-718-1021; Email: ClinicalTrials.gov_Inquiries@pfizer.com

Study Locations

• United States
  • California
    • Anaheim, California, United States, 92801
      • Anaheim Clinical Trials, LLC
  • Florida
    • Hialeah, Florida, United States, 33012
      • Indago Research & Health Center, Inc
    • Hollywood, Florida, United States, 33024
      • Research Centers of America ( Hollywood )
    • Miami, Florida, United States, 33165
      • New Horizon Research Center
    • Pembroke Pines, Florida, United States, 33029
      • DBC Research USA
    • Pembroke Pines, Florida, United States, 33026
      • Private Practice - Dr. Hector Fabregas
    • Plantation, Florida, United States, 33322
      • BRCR Medical Center Inc.
    • Tampa, Florida, United States, 33607
      • Clinical Research Trials of Florida
  • Minnesota
    • Saint Paul, Minnesota, United States, 55114
      • Prism Research LLC dba Nucleus Network
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New York
    • Rochester, New York, United States, 14609
      • Rochester Clinical Research, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 84 years (Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

12

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: C. difficile vaccine formulation 2, 2-month schedule (Phase 1); Novel vaccine formulation 2	Other: Saline Placebo.; 0.9% sodium chloride solution given as an intramuscular injection; Biological: C. difficile vaccine formulation 2.; C. difficile vaccine formulation 2 given as an intramuscular injection
Experimental: C. difficile vaccine formulation 3, 2-month schedule (Phase 1); Novel vaccine formulation 3	Other: Saline Placebo.; 0.9% sodium chloride solution given as an intramuscular injection; Biological: C. difficile vaccine formulation 3.; C. difficile vaccine formulation 3 given as an intramuscular injection
Experimental: C. difficile vaccine formulation 1, 6-month schedule (Phase 1); Novel vaccine formulation 1	Biological: C. difficile vaccine formulation 1.; C. difficile vaccine formulation 1 given as an intramuscular injection; Other: Saline Placebo.; 0.9% sodium chloride solution given as an intramuscular injection
Experimental: C. difficile vaccine formulation 2, 6-month schedule (Phase 1); Novel vaccine formulation 2	Other: Saline Placebo.; 0.9% sodium chloride solution given as an intramuscular injection; Biological: C. difficile vaccine formulation 2.; C. difficile vaccine formulation 2 given as an intramuscular injection
Experimental: C. difficile vaccine formulation 3, 6-month schedule (Phase 1); Novel vaccine formulation 3	Other: Saline Placebo.; 0.9% sodium chloride solution given as an intramuscular injection; Biological: C. difficile vaccine formulation 3.; C. difficile vaccine formulation 3 given as an intramuscular injection
Experimental: C. difficile vaccine formulation 1, 2-month schedule(Phase 1); Novel vaccine formulation 1	Biological: C. difficile vaccine formulation 1.; C. difficile vaccine formulation 1 given as an intramuscular injection; Other: Saline Placebo.; 0.9% sodium chloride solution given as an intramuscular injection
Active Comparator: C. difficile vaccine (previously studied formulation) 6-months schedule (Phase 1); Previously studied C. difficile vaccine formulation	Other: Saline Placebo.; 0.9% sodium chloride solution given as an intramuscular injection; Biological: C. difficile vaccine (previously studied formulation).; Toxoid based Clostridioides difficile vaccine (previously studied formulation) given as an intramuscular injection
Experimental: C difficile vaccine formulation 2. Schedule 1 with booster (Phase 2); Novel vaccine formulation 2	Other: Saline Placebo.; 0.9% sodium chloride solution given as an intramuscular injection; Biological: C. difficile vaccine formulation 2.; C. difficile vaccine formulation 2 given as an intramuscular injection
Experimental: C. difficile vaccine formulation 2. Schedule 1 (Phase 2); Novel vaccine formulation 2	Other: Saline Placebo.; 0.9% sodium chloride solution given as an intramuscular injection; Biological: C. difficile vaccine formulation 2.; C. difficile vaccine formulation 2 given as an intramuscular injection
Experimental: C. difficile vaccine formulation 2. Schedule 2 with booster (Phase 2); Novel vaccine formulation 2	Other: Saline Placebo.; 0.9% sodium chloride solution given as an intramuscular injection; Biological: C. difficile vaccine formulation 2.; C. difficile vaccine formulation 2 given as an intramuscular injection
Experimental: C. difficile vaccine formulation 2. Schedule 2 (Phase 2); Novel vaccine formulation 2	Other: Saline Placebo.; 0.9% sodium chloride solution given as an intramuscular injection; Biological: C. difficile vaccine formulation 2.; C. difficile vaccine formulation 2 given as an intramuscular injection
Active Comparator: C. difficile vaccine (previously studied formulation) , 6-month schedule (Phase 2); Previously studied C. difficile vaccine formulation	Other: Saline Placebo.; 0.9% sodium chloride solution given as an intramuscular injection; Biological: C. difficile vaccine (previously studied formulation).; Toxoid based Clostridioides difficile vaccine (previously studied formulation) given as an intramuscular injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1: Percentage of participants reporting local reactions	Injection site pain, redness, and swelling as self-reported in electronic diaries	For 7 days after each vaccination (through Month 6)
Phase 1: Percentage of participants reporting systemic events	Vomiting, diarrhea, headache, fatigue, new or worsening muscle pain, new or worsening joint pain, and fever, as self-reported in electronic diaries	For 7 days after each vaccination (through Month 6)
Phase 1: Percentage of participants reporting adverse events	As elicited by investigational site staff	From Dose 1 (Day 1) through 1 month after the last dose (Month 7)
Phase 1: Percentage of participants reporting serious adverse events	As elicited by investigational site staff	From Dose 1 (Day 1) through 6 months after the last dose (Month 12)
Phase 1: Percentage of participants with abnormal hematology and chemistry laboratory values	As measured at the central laboratory	1 week after Dose 1 (Day 7) and 1 month after each dose (through Month 7)
Phase 1: Percentage of participants reporting medically attended adverse events	As elicited by investigational site staff	From Dose 1 (Day 1) through 6 months after the last dose (Month 12)
Phase 2: Percentage of participants reporting local reactions	Injection site pain, redness, and swelling as self-reported in electronic diaries	For 7 days after each dose in the initial vaccination series (through Month 6)
Phase 2: Percentage of participants reporting systemic events	Vomiting, diarrhea, headache, fatigue, new or worsening muscle pain, new or worsening joint pain, and fever, as self-reported in electronic diaries	For 7 days after each dose in the initial vaccination series (through Month 6)
Phase 2: Percentage of participants reporting adverse events	As elicited by investigational site staff	From Dose 1 (Day 1) through 1 month after the last dose of study intervention in the initial vaccination series (through Month 7)
Phase 2: Percentage of participants reporting medically attended adverse events	As elicited by investigational site staff	From Dose 1 (Day 1) through 6 months after the last dose of study intervention in the initial vaccination series (through Month 12)
Phase 2: Percentage of participants reporting serious adverse events	As elicited by investigational site staff	From Dose 1 (Day 1) through 6 months after the last dose of study intervention in the initial vaccination series (through Month 12)
Phase 2: Geometric mean concentration (GMC) of C. difficile toxin A- and toxin B-specific neutralizing antibodies	As measured at the central laboratory	1 month after the last dose in the initial series (Month 7)
Phase 2: Geometric mean ration (GMR) of C. difficile toxine A- and toxin B- specific neutralizing antibodies	As measured at the central laboratory	1 month after the last dose in the initial series (Month 7)
Phase 2: Geometric mean fold-rise (GMFR) of C. difficile toxin A- and toxin B-specific neutralizing antibody concentrations	As measured at the central laboratory	From before Dose 1 (Day 1) to 1 month after the last dose in the initial vaccination series (Month 7)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1: Percentage of participants reporting serious adverse events	As elicited by investigational site	From 6 month (Month 12) through 12 months after the last dose (Month 18)
Phase 1: Percentage of participants reporting medically attended adverse events	As elicited by investigational site	From 6 month (Month 12) through 12 months after the last dose (Month 18)
Phase 1: Geometric mean concentration (GMC) of C. difficile toxin A- and toxin B-specific neutralizing antibodies	As measured at the central laboratory	1 month after each dose (through Month 7), 6 months aftre the first and last dose (Months 6 and 12), and 12 months aftre the last dose
Phase 1: Geometric mean fold-rise (GMFR) of C. difficile toxin A- and toxin B-specific neutralizing antibody concentrations	As measured at the central laboratory	From before Dose 1 (Day 1) to 1 month after each dose (through month 7), and to 6 months and 12 months after the last dose (through Month 18)
Phase 2: Percentage of participants reporting local reactions	Injection site pain, redness, and swelling as self-reported in the electronic diaries	For 7 days after vaccination 5 (Month 13 or 14)
Phase 2: Percentage of participants reporting systemic events	fever, vomiting, diarrhea, headache, fatigue, new or worsening muscle pain, and new or worsening joint pain) as self-reportedin the elctronic diaries	For 7 days after vaccination 5 (Month 13 or 14)
Phase 2: Percentage of participants reporting adverse events	As elicited by the investigational site	From vaccination 5 (Month 13 or 14) through 1 month after vaccination 5 (Month 14 or 15)
Phase 2: Percentage of participants reporting medically attended adverse events (MAAEs)	As elicited by investigational site staff	From vaccination 5 (Month 13 or 14) through 6 months after vaccination 5 (Month 19 or 20)
Phase 2: Percentage of participants reporting serious adverse events	As elicited by investigational site staff	From vaccination 5 (Month 13 or 14) through 6 months after vaccination 5 (Month 19 or 20)
Phase 2: Percentage of participants reporting medically attended adverse events	As elicited by investigational site	From 6 month through 12 months after the last dose (through Month 26)
Phase 2: Percentage of participants reporting serious adverse events	As elicited by investigational site	From 6 month through 12 months after the last dose (through Month 26)
Phase 2: Geometric mean concentration (GMC) of C. difficile toxin A- and toxin B-specific neutralizing antibodies	As measured at the central laboratory	At each planned time point in the initial vaccination series (through Month 7)
Phase 2: Geometric mean ratio (GMR) of C. difficile toxin A- and toxin B-specific neutralizing antibodies	As measured at the central laboratory	At each planned time point in the initial vaccination series (through Month 7)
Phase 2: Geometric mean fold-rise (GMFR) of C. difficile toxin A- and toxin B-specific neutralizing antibody concentrations	As measured at the central laboratory	From before Dose 1 (Day 1) to each planned time point in the initial vaccination series (through Month 7)
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	As measured at the central laboratory	From before Dose 1 (Day 1) to each planned time point in the initial vaccination series (through Month 7)
Phase 2: Geometric mean concentration (GMC) of C. difficile toxin A- and toxin B-specific neutralizing antibodies	As measured at the central laboratory	At 1 month after vaccination 5 (Month 14 or 15)
Phase 2: Geometric mean fold-rise (GMFR) of C. difficile toxin A- and toxin B-specific neutralizing antibody concentrations	As measured at the central laboratory	From before Dose 1 (Day 1) to 1 month after vaccination 5 (Month 14 or 15)
Phase 2: Geometric mean fold-rise (GMFR) of C. difficile toxin A- and toxin B-specific neutralizing antibody concentrations	As measured at the central laboratory	From before vaccination 5 (Month 13 or 14) to 1 month after vaccnation 5 (Month 14 or 15)
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	As measured at the central laboratory	From before vaccination (Day 1) to 1 month after vaccination 5 (Month 14 or 15)
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	As measured at the central laboratory	From before vaccination 5 (Month 13 or 14) to 1 month after vaccination 5 (Month 14 or 15)
Phase 2: Geometric mean concentration (GMC) of C. difficile toxin A- and toxin B- specific neutralizing antibodies	As measured at the central laboratory	At each planned persistence time point (Month, 13 or 14, 26, 38, 50)
Phase 2: Geometric mean fold-rise (GMFR) of C. difficile toxin A- and toxin B- specific neutralizing antibodies	As measured at the central laboratory	From before vaccination (Day 1), each planned persistence time point (Month 13 or 14, 26, 38, 50)
Phase 2: Geometric mean fold-rise (GMFR) of C. difficile toxin A- and toxin B- specific neutralizing antibodies	As measured at the central laboratory	From before vaccination 5 (Month 13 or 14), each planned persistence time point (Month 26, 38 and 50)

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): March 23, 2023
• Primary Completion (Estimated): February 9, 2025
• Study Completion (Estimated): September 2, 2028

Study Registration Dates

• First Submitted: March 21, 2023
• First Submitted That Met QC Criteria: April 6, 2023
• First Posted (Actual): April 10, 2023

Study Record Updates

• Last Update Posted (Actual): April 9, 2024
• Last Update Submitted That Met QC Criteria: April 8, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Vaccine; Clostridium difficile; Persistence; C. diff; Clostridioides difficile
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: C4771001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No