A study to assess whether a vaccine against Clostridium difficile prevents the disease, and whether it is safe and well tolerated when given to adults 50 years of age and older

• Register: EUCTR
• Last refreshed on: 14 March 2022
• Main ID: EUCTR2016-003866-14-BG
• Date of registration: 05/04/2017
• Prospective Registration: Yes
• Primary sponsor: Pfizer Inc. 235 East 42nd Street, New York, NY 10017
• Public title: A study to assess whether a vaccine against Clostridium difficile prevents the disease, and whether it is safe and well tolerated when given to adults 50 years of age and older
• Scientific 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 - CLOVER
• Date of first enrolment: 06/06/2017
• Target sample size: 17476
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-003866-14
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: yes; Other trial design description: observer blinded; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Belgium, Bulgaria, Canada, Chile, Colombia, Czech Republic, Czechia, Finland, France, Germany, Hungary, Japan, Korea, Republic of, Peru, Poland, Portugal, Slovakia, Spain, Sweden, Taiwan, United Kingdom, United States

Contacts

• Name: Clinical Trials.gov Call Center
• Affiliation: Pfizer Inc

• Name: Clinical Trials.gov Call Center
• Affiliation: Pfizer Inc

Key inclusion & exclusion criteria

Inclusion criteria:
Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study:
1.Evidence of a personally signed and dated ICD indicating that the subject has been informed of all pertinent aspects of the study.
2.Willing and able to comply with scheduled visits, vaccination plan, and other study procedures.
3.50 Years or older at enrollment.
4.Subjects with an increased risk of future contact with healthcare systems by virtue of:
•At least 1 inpatient hospitalization =2 nights’ duration in the previous 12 months; or
•At least 2 emergency room visits in the previous 12 months; or
•At least 10 outpatient visits (primary and/or secondary care visits; defined as an in-person visit to the office/clinic of a prescribing healthcare provider for the purposes of the diagnosis, treatment, or ongoing management of a medical condition, excluding pharmacy and mental health visits) in the previous 12 months; or
•Residence in a skilled nursing facility (a residential institution that provides professional nursing care and rehabilitation services, usually following discharge from the hospital); or
•Residence in a nursing home (a residential institution that provides assistance with activities of daily living); or
•Inpatient hospitalization =2 nights’ duration scheduled =37 days after randomization.
Or subjects who have received systemic (ie, oral or injected) antibiotics for a minimum of 48 hours at any time in the previous 12 weeks.
5.Ability to be contacted by telephone during study participation.
6.Negative urine pregnancy test for female subjects of childbearing potential.
Female subjects of nonchildbearing potential must meet at least 1 of the following criteria:
a.Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; status may be confirmed with a serum follicle-stimulating hormone (FSH) level confirming the postmenopausal state;
b.Have undergone a documented hysterectomy and/or bilateral oophorectomy;
c.Have medically confirmed ovarian failure.
All other female subjects (including female subjects with tubal ligations) are considered to be of childbearing potential.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 4000
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 12000

Exclusion criteria:
Subjects with any of the following characteristics/conditions will not be included in the study:
1.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.
2.Participation in other studies involving investigational drug(s)/vaccine(s) within 28 days prior to study entry until Visit 5 (1 month after the third vaccination).
3.Previous administration of an investigational C difficile vaccine or C difficile mAb therapy.
4.Prior episode of CDI, confirmed by either laboratory test or diagnosis of pseudomembranous colitis at colonoscopy, at surgery, or histopathologically.
5.Receipt of blood products or immunoglobulins within 6 months before enrollment.
6.Subjects who may be unable to respond to vaccination because of:
•Metastatic malignancy; or
•End-stage renal disease (glomerular filtration rate <15 mL/min/1.73 m2 or on dialysis); or
•Any serious medical disorder that in the investigator’s opinion is likely to be fatal within the next 12 months; or
•Congenital or acquired immunodeficiency; or
•Receipt of systemic corticosteroids (=20 mg/day of prednisone or equivalent) 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.
7.Known infection with human immunodeficiency virus (HIV).
8.Any bleeding disorder or anticoagulant therapy that would contraindicate intramuscular injection.
9.Any contraindication to vaccination or vaccine components, including previous anaphylactic reaction to any vaccine or vaccine-related components.
10.Prior small- or large-bowel resection (does not include appendectomy).
11.Any condition or treatment resulting in frequent diarrhea (=3 loose stools per day more than once per month), as reported by the subject.
12.Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavioral or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.
13.Pregnant female subjects; breastfeeding female subjects; fertile male subjects and female subjects of childbearing potential who are, in the opinion of the investigator, sexually active and at risk for pregnancy with their partner(s) and are unwilling or unable to use 2 highly effective methods of contraception as outlined in this protocol from the signing of the informed consent until at least 28 days after the last dose of investigational product.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Primary C difficile infection (CDI)
MedDRA version: 20.0 Level: PT Classification code 10054236 Term: Clostridium difficile infection System Organ Class: 10021881 - Infections and infestations
MedDRA version: 20.0 Level: LLT Classification code 10012748 Term: Diarrhoea, Clostridium difficile System Organ Class: 10021881 - Infections and infestations

Therapeutic area: Diseases [C] - Bacterial Infections and Mycoses [C01]

Intervention(s)

Product Code: PF-06425090
Pharmaceutical Form: Powder and suspension for suspension for injection
INN or Proposed INN: N/A
CAS Number: N/A
Current Sponsor code: CLOSTRIDIUM DIFFICILE TOXOID (A AND B)
Other descriptive name: PF-06425090
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 200-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Intramuscular use

Primary Outcome(s)

Secondary Objective: 3-Dose Family
To evaluate the efficacy of Pfizer's C difficile vaccine in reducing:
- incidence of all CDI cases
To evaluate the efficacy of Pfizer's C difficile vaccine in reducing the
severity of CDI, defined by:
-The duration of CDI episodes
-The requirement to seek medical attention.
To evaluate the efficacy of Pfizer's C difficile vaccine in reducing the
incidence of recurrent CDI.
At-Least-2-Dose/Only-2-Dose Family
To evaluate the efficacy of Pfizer's C difficile vaccine in reducing:
- incidence of all CDI cases
-incidence of recurrent CDI
In subjects who receive only 2 doses of vaccine, to evaluate the efficacy
of Pfizer's C difficile vaccine in reducing:
-The incidence of a first primary episode of CDI.
-The incidence of recurrent CDI.

Primary end point(s): Primary Efficacy Endpoint:
CDI incidence per 1000 person-years of follow-up

Primary Safety Endpoints:
•Local reactions (pain, erythema, and induration)
•Systemic events (fever, vomiting, headache, fatigue, new or worsening muscle pain, and new or worsening joint pain) as self-reported on
electronic diaries (e-diaries)
•Nonserious AEs
•SAEs

Timepoint(s) of evaluation of this end point: • CDI incidence per 1000 person-years of follow-up is assessed during up to 2 time periods :
- After receipt of the third dose of investigational product onwards.
- After receipt of the second dose of investigational product onwards.

• Local reactions: for up to 7 days following each dose of investigational product.
•Systemic events: for up to 7 days following each dose of investigational product.
•Nonserious AEs: from the signing of the informed consent document (ICD) to 1 month after receipt of the third dose of investigational product.
•SAEs: from the signing of the ICD to 6 months after receipt of third dose of investigational product.

Main Objective: Primary Efficacy Objective:
To demonstrate that Pfizer’s C difficile vaccine is effective in reducing the incidence of a first primary episode of CDI

Primary Safety Objective:
To evaluate the safety profile of Pfizer’s C difficile vaccine as measured by the percentage of subjects reporting local reactions and systemic events, AEs, and SAEs.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: CDI incidence per 1000 person-years of follow-up is assessed during 2 time periods:
- After receipt of the third dose of investigational product onwards.(3-
Dose Family)
- After receipt of the second dose of investigational product onwards.(At
Least-2-Dose/Only-2-Dose Family).

Secondary end point(s): 3-Dose Family
•CDI incidence per 1000 person-years of follow-up
•Mean time to resolution of diarrhea in first primary episodes of CDI
•Proportion of subjects experiencing a first primary episode of CDI who have a non–protocol-related medically attended visit during the CDI episode.
•CDI incidence per 1000 person-years of follow-up, assessed after the
third dose of investigational product onwards.
At Least-2-Dose/Only-2-Dose Family
•CDI incidence per 1000 person-years of follow-up

Secondary ID(s)

2016-003866-14-SK

B5091007

Source(s) of Monetary Support

Pfizer Inc, 235 East 42nd Street, New York, NY 10017

Ethics review

Status: Approved
Approval date: 11/05/2017
Contact: