E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Primary C difficile infection (CDI) |
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E.1.1.1 | Medical condition in easily understood language |
Clostridium difficile is a bacterium that can infect the bowel and cause severe diarrhoea |
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E.1.1.2 | Therapeutic area | Diseases [C] - Bacterial Infections and Mycoses [C01] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10054236 |
E.1.2 | Term | Clostridium difficile infection |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10012748 |
E.1.2 | Term | Diarrhoea, Clostridium difficile |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
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E.2.2 | Secondary objectives of the trial |
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. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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.
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E.4 | Principal 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.
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E.5 End points |
E.5.1 | 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 |
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E.5.1.1 | 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. |
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E.5.2 | 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
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E.5.2.1 | 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. (3Dose Family) - After receipt of the second dose of investigational product onwards. (At Least-2-Dose/Only-2-Dose Family). |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 128 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Canada |
Chile |
Colombia |
Japan |
Korea, Republic of |
Peru |
Taiwan |
United States |
Belgium |
Bulgaria |
Finland |
France |
Germany |
Hungary |
Poland |
Portugal |
Slovakia |
Spain |
Sweden |
United Kingdom |
Czechia |
Argentina |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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End of trial in a Member State of the European Union is defined as the time at which it is deemed that a sufficient number of subjects have been recruited and completed the study as stated in the regulatory application and ethics application in the Member State. Poor recruitment (recruiting less than the anticipated number in the CTA) by a Member State is not a reason for premature termination but is considered a normal conclusion to the study in that Member State. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 30 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 30 |