Clostridium Difficile Vaccine Efficacy Trial (Clover)

• ClinicalTrials.gov Identifier: NCT03090191
• Recruitment Status: Active, not recruiting
• First Posted: March 24, 2017
• Last Update Posted: November 26, 2019
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Study Description

Brief Summary:

The Clover trial is evaluating an investigational vaccine that may help to prevent Clostridium difficile infection. Participants in the study are adults 50 years of age and older, who are at risk of developing Clostridium difficile infection. The study will assess whether the vaccine prevents the disease, and whether it is safe and well tolerated.

Each subject will receive 3 doses of Clostridium difficile vaccine or placebo and be followed for up to 3 years after vaccination for potential Clostridium difficile infection.

Condition or disease	Intervention/treatment	Phase
Clostridium Difficile Infection	Biological: Clostridium difficile vaccine; Biological: Placebo	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 17525 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: A PHASE 3, PLACEBO-CONTROLLED, RANDOMIZED, OBSERVER-BLINDED STUDY TO EVALUATE THE EFFICACY, SAFETY, AND TOLERABILITY OF A CLOSTRIDIUM DIFFICILE VACCINE IN ADULTS 50 YEARS OF AGE AND OLDER
• Actual Study Start Date: March 29, 2017
• Estimated Primary Completion Date: September 28, 2020
• Estimated Study Completion Date: September 28, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: Clostridium difficile vaccine	Biological: Clostridium difficile vaccine; Toxoid-based Clostridium difficile vaccine
Placebo Comparator: Placebo	Biological: Placebo; Normal saline solution (0.9% sodium chloride)

Outcome Measures

Primary Outcome Measures :

1. First primary case CDI incidence [ Time Frame: Up to 3 years after the 3rd dose ]
   Per 1000 person-years of follow-up (confirmed at the central laboratory)
2. First primary case CDI incidence [ Time Frame: Up to 3.4 years after the 2nd dose ]
   Per 1000 person-years of follow-up (confirmed at the central laboratory)
3. Percentage of subjects reporting local reactions [ Time Frame: Up to 7 days following each vaccination, 1, 2, and 3 ]
   Pain, erythema, and induration, as self-reported on electronic diaries
4. Percentage of subjects reporting systemic events [ Time Frame: Up to 7 days following each vaccination, 1, 2, and 3 ]
   Fever, vomiting, headache, fatigue, new or worsening muscle pain, and new or worsening joint pain, as self-reported on electronic diaries
5. Percentage of subjects reporting nonserious adverse events [ Time Frame: Up to 7 months after the first dose ]
   As elicited by investigational site staff
6. Percentage of subjects reporting serious adverse events [ Time Frame: Up to 12 months after the first dose ]
   As elicited by investigational site staff

Secondary Outcome Measures :

1. All case CDI incidence [ Time Frame: Up to 3 years after the 3rd dose ]
   Per 1000 person-years of follow-up (confirmed at the central laboratory)
2. Mean time to resolution of diarrhea in first primary cases of CDI [ Time Frame: Up to 3.5 years after enrolment ]
   Confirmed at the central laboratory
3. Proportion of subjects experiencing a first primary episode of CDI who have a non-protocol-related medically attended visit during the CDI episode [ Time Frame: Up to 3.5 years after enrolment ]
   Confirmed at the central laboratory
4. Recurrent case CDI incidence [ Time Frame: Up to 3 years after the 3rd dose ]
   Per 1000 person-years of follow-up (confirmed at the central laboratory)
5. All case CDI incidence [ Time Frame: Up to 3.4 years after the 2nd dose ]
   Per 1000 person-years of follow-up (confirmed at the central laboratory)
6. Recurrent case CDI incidence [ Time Frame: Up to 3.4 years after the 2nd dose ]
   Per 1000 person-years of follow-up (confirmed at the central laboratory)
7. In subjects that receive only 2 doses, first primary CDI incidence [ Time Frame: Up to 3.4 years after the 2nd dose ]
   Per 1000 person-years of follow-up (confirmed at the central laboratory)
8. In subjects that receive only 2 doses, recurrent case CDI incidence [ Time Frame: Up to 3.4 years after the 2nd dose ]
   Per 1000 person-years of follow-up (confirmed at the central laboratory)

Eligibility Criteria

• Ages Eligible for Study: 50 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Evidence of a personally signed and dated informed consent document.
• Willing and able to comply with study procedures.
• Subjects with an increased risk of future contact with healthcare systems or subjects who have received systemic antibiotics in the previous 12 weeks.
• Ability to be contacted by telephone during study participation.
• Negative urine pregnancy test for female subjects of childbearing potential.

Exclusion Criteria:

• 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 until 1 month after the third vaccination.
• Previous administration of an investigational C difficile vaccine or C difficile mAb therapy.
• Prior episode of CDI..
• Receipt of blood products or immunoglobulins within 6 months before enrollment.

• Subjects who may be unable to respond to vaccination due to:

  • Metastatic malignancy; or
  • End-stage renal disease; or
  • Any serious medical disorder likely to be fatal within the next 12 months; or
  • Congenital or acquired immunodeficiency; or
  • Receipt of high dose systemic corticosteroids for 14 days within 28 days of enrollment; or
  • Receipt of chronic systemic treatment with other known immunosuppressant medications, or radiotherapy, within 6 months of enrollment.
• Known infection with human immunodeficiency virus (HIV).
• 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.
• Prior small- or large-bowel resection.
• Any condition or treatment resulting in frequent diarrhea.
• Other acute or chronic condition or abnormality that may increase the risk associated with study participation or IP administration or may interfere with interpretation of study results
• Pregnant or breastfeeding female subjects; male subjects and female subjects who are sexually active and at risk for pregnancy and will not/cannot use 2 methods of contraception

Contacts and Locations

  Show 425 Study Locations

Sponsors and Collaborators

Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

More Information

Additional Information:

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

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT03090191 History of Changes
• Other Study ID Numbers: B5091007; 2016-003866-14 ( EudraCT Number ); CLOVER ( Other Identifier: Alias Study Number )
• First Posted: March 24, 2017
• Last Update Posted: November 26, 2019
• Last Verified: November 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• 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.
• URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Clostridium Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Vaccines; Immunologic Factors; Physiological Effects of Drugs