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C. difficile investigational vaccine based on the F2 antigen

Phase 1

Clostridium Infections | Monoclonal antibody | Infectious Disease |GSK plc|Last Updated: Sep 23, 2024

Success Probability

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Trial Design

RandomizedDouble-BlindPLACEBO_CONTROLLED
Total Trials1
Total Enrollment140

FDA Designations

No designations recorded

Clinical trial landscape

C. difficile investigational vaccine based on the F2 antigen · 1 trial · 1 indication

Phase 1 1
NCT04026009Safety and Immunogenicity Study of GSK's Clostridium Difficile Vaccine 2904545A When Administered in Healthy Adults Aged 18-45 Years and 50-70 YearsClostridium Infections
COMPLETED140 Analytics
PHASE1COMPLETED
Safety and Immunogenicity Study of GSK's Clostridium Difficile Vaccine 2904545A When Administered in Healthy Adults Aged 18-45 Years and 50-70 Years
Clostridium InfectionsUnlock trial analytics

Study Endpoints

Primary Endpoints

Number of Subjects With Any and Grade 3 Solicited Local Symptoms, After Each Vaccine Dose
During the 7-day follow-up period (from the day of vaccination up to 6 subsequent days) after each vaccination

Assessed solicited local symptoms are pain at injection site, redness at injection site and swelling at injection site. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = significant pain at rest, pain that pre-vents normal every day activities. Grade 3 redness/swelling = redness/swelling with a maximum diameter greater (\>) than 100 millimeters (mm).

Number of Subjects With Any, Grade 3, Related and Grade 3 Related Solicited General Symptoms, After Each Vaccine Dose
During the 7-day follow-up period (from the day of vaccination up to 6 subsequent days) after each vaccination

Assessed solicited general symptoms are fatigue, fever \[defined as oral temperature equal to or higher than (\>=) 38 degrees Celsius (°C)\], gastrointestinal symptoms (nausea, vomiting, diarrhea, and/or abdominal pain), headache, myalgia, shivering and arthralgia. Any = occurrence of the symptom regardless of intensity grade and relationship to vaccination. Grade 3 symptom = symptom that prevents normal, everyday activities. Grade 3 fever = oral temperature higher (\>) than 39.0°C. Related symptom = symptom assessed by the investigator as causally related to the study vaccination. Grade 3 related symptom = Grade 3 symptom assessed by the investigator as causally related to the study vaccination.

Number of Subjects With Any, Grade 3, Related, Grade 3 Related and Medically Attended Unsolicited Adverse Events (AEs)
During the 30-day follow-up period (from the day of vaccination up to 29 subsequent days) after any vaccination

An unsolicited AE is any adverse event reported in addition to those solicited during the clinical study. Also, any "solicited" symptom with onset outside the specified period of follow-up for solicited symptoms is reported as an unsolicited adverse event. Potential unsolicited AEs may be medically attended (defined as symptoms or illnesses requiring hospitalization, or emergency room visit, or visit to/by a health care provider) or were of concern to the subjects. Any = occurrence of the symptom regardless of intensity grade and relationship to vaccination. Grade 3 symptom = symptom that prevents normal, everyday activities. Related symptom = symptom assessed by the investigator as causally related to the study vaccination. Grade 3 related symptom = Grade 3 symptom assessed by the investigator as causally related to the study vaccination.

Number of Subjects With Serious Adverse Events (SAEs)
From Day 1 up to and including Day 390 (Epoch 001)

An SAE is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, represents a congenital anomaly/birth defect in the offspring of a study subject.

Number of Subjects With Potential Immune-mediated Diseases (pIMDs)
During the whole study period (from Day 1 up to Day 390 [for subjects receiving 2 vaccine doses] and from Day 1 up to Day 670 [for subjects receiving 3 vaccine doses])

pIMDs are a subset of adverse events of specific interest (AESIs) that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune etiology.

Number of Subjects With Hematological, Biochemical, and Urinary Laboratory Abnormalities at Screening
At Screening (from Day -15 up to Day -1 [for subjects receiving 2 vaccine doses] and at Day 476 [for subjects receiving 3 vaccine doses])

Hematological (white blood cells, platelet count, hemoglobin level), biochemical (alanine aminotransferase, aspartate aminotransferase, creatinine, C-reactive protein and urate/uric acid) and urinary (protein, glucose and red blood cells) parameters are assessed. C-reactive protein is only assessed during the screening visit. Grades are based on the local laboratory normal ranges and derived from the FDA Toxicity Grading Scale for laboratory abnormalities.

Number of Subjects With Hematological and Biochemical Laboratory Abnormalities at Day 8
At Day 8

Hematological (white blood cells, platelet count, hemoglobin level), biochemical (alanine aminotransferase, aspartate aminotransferase, creatinine and urate/uric acid) parameters are assessed. Grades are based on the local laboratory normal ranges and derived from the FDA Toxicity Grading Scale for laboratory abnormalities.

Number of Subjects With Hematological and Biochemical Laboratory Abnormalities at Day 31
At Day 31

Hematological (white blood cells, platelet count, hemoglobin level), biochemical (alanine aminotransferase, aspartate aminotransferase, creatinine and urate/uric acid) parameters are assessed. Grades are based on the local laboratory normal ranges and derived from the FDA Toxicity Grading Scale for laboratory abnormalities.

Number of Subjects With Hematological and Biochemical Laboratory Abnormalities at Day 38
At Day 38

Hematological (white blood cells, platelet count, hemoglobin level), biochemical (alanine aminotransferase, aspartate aminotransferase, creatinine and urate/uric acid) parameters are assessed. Grades are based on the local laboratory normal ranges and derived from the FDA Toxicity Grading Scale for laboratory abnormalities.

Number of Subjects With Hematological and Biochemical Laboratory Abnormalities at Day 180
At Day 180

Hematological (white blood cells, platelet count, hemoglobin level), biochemical (alanine aminotransferase, aspartate aminotransferase, creatinine and urate/uric acid) parameters are assessed. Grades are based on the local laboratory normal ranges and derived from the FDA Toxicity Grading Scale for laboratory abnormalities.

Number of Subjects With Hematological and Biochemical Laboratory Abnormalities at Day 390
At Day 390

Hematological (white blood cells, platelet count, hemoglobin level), biochemical (alanine aminotransferase, aspartate aminotransferase, creatinine and urate/uric acid) parameters are assessed. Grades are based on the local laboratory normal ranges and derived from the FDA Toxicity Grading Scale for laboratory abnormalities.

Number of Subjects With Hematological and Biochemical Laboratory Abnormalities at Day 476
At Day 476

Hematological (white blood cells, platelet count, hemoglobin level), biochemical (alanine aminotransferase, aspartate aminotransferase, creatinine and urate/uric acid) parameters are assessed. Grades are based on the local laboratory normal ranges and derived from the FDA Toxicity Grading Scale for laboratory abnormalities.

Number of Subjects With Hematological and Biochemical Laboratory Abnormalities at Day 491
At Day 491

Hematological (white blood cells, platelet count, hemoglobin level), biochemical (alanine aminotransferase, aspartate aminotransferase, creatinine and urate/uric acid) parameters are assessed. Grades are based on the local laboratory normal ranges and derived from the FDA Toxicity Grading Scale for laboratory abnormalities.

Number of Subjects With Hematological and Biochemical Laboratory Abnormalities at Day 670
At Day 670

Hematological (white blood cells, platelet count, hemoglobin level), biochemical (alanine aminotransferase, aspartate aminotransferase, creatinine and urate/uric acid) parameters are assessed. Grades are based on the local laboratory normal ranges and derived from the FDA Toxicity Grading Scale for laboratory abnormalities.

Secondary Endpoints

Serum Neutralizing Anti-Toxin A and Anti-Toxin B Antibody Titers, as Measured by Toxin Neutralization Assay (TNA)
At Day 1, Day 31, Day 61, Day 180, Day 390, Day 491, Day 521 and Day 670
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Study Design & Arms

AllocationRANDOMIZED
MaskingQUADRUPLE
ModelSEQUENTIAL
PurposePREVENTION

Treatment Arms

ArmTypeDescription
CDIFF Ag 18 - 45 Years GroupEXPERIMENTALHealthy male and female subjects, aged between and including 18 and 45 years old, who receive CDIFF antigen (Ag) vaccine administered intramuscularly in the deltoid, according to a 0, 1-month vaccination schedule.
Placebo 18 - 45 Years GroupPLACEBO_COMPARATORHealthy male and female subjects, aged between and including 18 and 45 years old, who receive Placebo administered intramuscularly in the deltoid, according to a 0, 1-month vaccination schedule.
CDIFF Ag 50 - 70 Years GroupEXPERIMENTALHealthy male and female subjects, aged between and including 50 and 70 years old, who receive CDIFF antigen (Ag) vaccine administered intramuscularly in the deltoid, according to a 0, 1-month vaccination schedule. A third dose of CDIFF Ag vaccine is to be administered to a subcohort of subjects aged 50-70 years, approximately 15 months after the administration of the second dose.
CDIFF Ag + AS01B 50 - 70 Years GroupEXPERIMENTALHealthy male and female subjects, aged between and including 50 and 70 years old, who receive CDIFF Ag + AS01B adjuvant vaccine administered intramuscularly in the deltoid, according to a 0, 1-month vaccination schedule. A third dose of CDIFF Ag + AS01B adjuvant vaccine is to be administered to a subcohort of subjects aged 50-70 years, approximately 15 months after the administration of the second dose.
Placebo 50 - 70 Years GroupPLACEBO_COMPARATORHealthy male and female subjects, aged between and including 50 and 70 years old, who receive Placebo administered intramuscularly in the deltoid, according to a 0, 1-month vaccination schedule.

Interventions

NameTypeDescription
C. difficile investigational vaccine based on the F2 antigen (GSK2904545A)BIOLOGICALSubjects in CDIFF Ag 18 - 45 Years and CDIFF Ag 50 - 70 Years Groups will receive 2 or 3 doses (0.5 mL each) of CDIFF Ag vaccine. The vaccine will be administered intramuscularly in the deltoid, at a 0, 1-month dose interval. The third dose will be administered approximately 15 months after the second dose.
C. difficile investigational vaccine based on the F2 antigen (GSK2904545A) adjuvanted with AS01BBIOLOGICALSubjects in CDIFF Ag + AS01B 50 - 70 Years Group will receive 2 or 3 doses (0.5 mL each) of CDIFF Ag + AS01B vaccine. The vaccine will be administered intramuscularly in the deltoid, at a 0, 1-month dose interval. The third dose will be administered approximately 15 months after the second dose.
PlaceboDRUGSubjects will receive 2 doses (0.5 mL each) of Placebo, administered intramuscularly in the deltoid, at a 0, 1-month dose interval.
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Eligibility Criteria

Age Range18 Years to 70 Years
SexALL
Healthy VolunteersYes
Study Sites1

Inclusion Criteria: 1. Subjects who, in the opinion of the Investigator, can and will comply with the requirements of the protocol. 2. Written or witnessed/thumb print informed consent obtained from the subject prior to performance of any study specific procedure. 3. For Step 1 only: A male or fema...

Countries:Belgium
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