Clostridium InfectionsPhase 1NCT04026009

Safety and Immunogenicity Study of GSK's Clostridium Difficile Vaccine 2904545A When Administered in Healthy Adults Aged 18-45 Years and 50-70 Years

A Phase 1 study testing C. difficile investigational vaccine based on the F2 antigen (GSK2904545A) and C. difficile investigational vaccine based on the F2 antigen (GSK2904545A) adjuvanted with AS01B in people with Clostridium Infections, run by GlaxoSmithKline at 1 site in Belgium.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The purpose of this study is to generate safety, reactogenicity (assessment of any expected or unexpected side effect of the vaccine) and immunogenicity (ability to induce an immune response) data for the development of a candidate Clostridium difficile (C. Read more about this study

Who is it for?: Ages 18 to 70 yearsHealthy volunteers can take part
Conditions the study is for: Clostridium Infections
What is being tested?: C. difficile investigational vaccine based on the F2 antigen (GSK2904545A) and C. difficile investigational vaccine based on the F2 antigen (GSK2904545A) adjuvanted with AS01B
Type of treatment: Vaccines, Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 140 participants
Where: 1 siteBelgium
Study dates: 5 Aug 2019to 10 May 2022
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 70 years
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

Subjects who, in the opinion of the Investigator, can and will comply with the requirements of the protocol.
Written or witnessed/thumb print informed consent obtained from the subject prior to performance of any study specific procedure.
For Step 1 only: A male or female between, and including, 18-45 years of age at the time of the first vaccination.
For Steps 2, 3, and 4: A male or female between, and including, 50-70 years of age at the time of the first vaccination.
Healthy subjects as established by medical history and clinical examination before entering into the study.
Subjects free of any uncontrolled chronic illnesses as established by medical history and clinical examination before entering into the study.

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Female subjects of non-childbearing potential may be enrolled in the study.
Non-childbearing potential is defined as premenarche, current bilateral tubal ligation or occlusion, hysterectomy, bilateral ovariectomy, or post-menopause.
Female subjects of childbearing potential may be enrolled in the study, if the subject:
Has practiced adequate contraception for 30 days prior to vaccination, and
Has a negative urine pregnancy test on the day of vaccination, and
Has agreed to continue adequate contraception during the entire treatment period and for 2 months after completion of the vaccination series.

Who cannot join

Health condition that, in the opinion of the Investigator, may interfere with optimal participation in the study or place the volunteer at increased risk of AEs. Study clinicians, in consultation with the Principal Investigator will use clinical judgment on a case by case basis to assess safety risks under this criterion. The Principal Investigator will consult with the Medical Monitor as appropriate.
Use of any investigational or nonregistered product other than the study vaccine(s) during the period starting 30 days before the first dose of study vaccine(s) (Day 29 to Day 1), or planned use during the study period.
Any medical condition that in the judgment of the Investigator would make IM injection unsafe and subjects under treatment with anticoagulant therapy.
Chronic administration of immunosuppressants or other immune modifying drugs during the period starting 3 months prior to the first vaccination. For corticosteroids, this will mean prednisone ≥ 5 milligrams per day (mg/day) (for adult subjects), or equivalent. Inhaled and topical steroids are allowed.
Administration of long acting immune modifying drugs at any time during the study period.
Administration of immunosuppressive therapy, including chemotherapeutic agents used to treat cancer or other conditions, and treatments associated with organ or bone marrow transplantation or autoimmune disease.

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Administration of immunoglobulins and/or any blood products during the period starting 3 months before the first vaccination of study treatment or planned administration during the study period.
Planned administration/administration of a vaccine not foreseen by the study protocol in the period starting 6 weeks before the first vaccination and ending 6 weeks after the last vaccination, with the exception of inactivated influenza vaccine which can be administered up to 14 days before or from 30 days after the last study vaccination.
In case an emergency mass vaccination for an unforeseen public health threat (eg, a pandemic) is recommended and/or organized by public health authorities outside the routine immunization program, the time period described above can be reduced if, necessary for that vaccine, provided it is used according to the local governmental recommendations and that the Sponsor is notified accordingly.
Planned administration of GSK's Herpes Zoster vaccine marketed as Shingrix or an adjuvanted recombinant varicella zoster virus envelope gE subunit vaccine (HZ/su) within 180 days before the first dose and within 180 days after the last dose of the study vaccine.
Planned elective surgery during the study period.
Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational vaccine/product.
Body mass index < 19 kg/m^2 or ≥ 35 kg/m^2.
Clinically relevant physical examination abnormalities.
For subjects aged 18 - 45 years, Grade 2 or higher abnormal hematological, biochemical, and urinary parameters.
For subjects aged 50 - 70 years, Grade 3 or higher abnormal hematological, biochemical, and urinary parameters.
Documentation of current or prior episode of CDI.
Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required).
Recurrent history or uncontrolled neurological disorders or seizures.
Family history of congenital or hereditary immunodeficiency.
History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccines.
Acute disease and/or fever at the time of enrollment.
Fever is defined as temperature ≥ 38.0°C/100.4°F. The preferred location for measuring temperature in this study will be the oral cavity.
Subjects with a minor illness, without fever, may be enrolled at the discretion of the Investigator.
Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic, or renal functional abnormality, as determined by physical examination or laboratory screening tests.
Pregnant or lactating female.
History of intestinal bleeding or history of diverticular intestinal bleeding.
Surgery for gastrointestinal malignancy in the period starting 3 months prior to the first vaccination.
History of chronic alcohol consumption and/or drug abuse as deemed by the Investigator to render the potential subject unable/unlikely to provide accurate safety reports.
Female planning to become pregnant or planning to discontinue contraceptive precautions.
Documented human immunodeficiency virus positive subject, known positivity for the surface antigen of the hepatitis B virus or known positive serologic test for the hepatitis C virus.
Involvement in the planning and/or conduct of the study.

Trial locations and contacts

1 site in 1 country.

Belgium1 site

GSK Investigational Site
Ghent, 9000

Other trials in Belgium

About this study

Official title: A Phase I, Single-center, Randomized, Observer-blind, Placebo-controlled Study to Evaluate Safety, Reactogenicity and Immunogenicity of GSK's Clostridium Difficile Investigational Vaccine Based on the F2 Antigen With or Without AS01B Adjuvant, When Administered Intramuscularly According to a 0, 1-month Schedule to Healthy Adults Aged Between 18-45 Years and Between 50-70 Years, Followed by an Additional Dose Administered in a Partial Blind Manner Within an Interval of Approximately 15 Months After Dose 2, in a Subcohort of Subjects Aged 50-70 Years

Clostridium difficile infection is a major cause of gastrointestinal illness with approximately 500,000 infections and the leading cause of gastroenteritis associated death with 29,000 deaths annually in the United States of America (USA). The emergence of extremely infectious varieties/types of C. difficile has contributed to increase the number and severity of CDI cases. In recent years, some countries (United Kingdom) have implemented hospital hygiene and other measures which resulted in significant reductions in the number of cases. The burden is, however, expected to remain significant until vaccination is available.

Conditions: Clostridium Infections
Being tested: C. difficile investigational vaccine based on the F2 antigen (GSK2904545A), C. difficile investigational vaccine based on the F2 antigen (GSK2904545A) adjuvanted with AS01B, Placebo
Medical subject headings: Clostridium Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

C. difficile investigational vaccine based on the F2 antigen (GSK2904545A)Biological
Also called CDIFF Ag
Subjects 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 AS01BBiological
Also called CDIFF Ag + AS01B
Subjects 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.
PlaceboDrug
Subjects will receive 2 doses (0.5 mL each) of Placebo, administered intramuscularly in the deltoid, at a 0, 1-month dose interval.

Study groups in NCT04026009
Study group	Role	What they receive
CDIFF Ag 18 - 45 Years Group	Experimental	Healthy 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. Receives: Biological: C. difficile investigational vaccine based on the F2 antigen (GSK2904545A)
Placebo 18 - 45 Years Group	Placebo comparator	Healthy 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. Receives: Drug: Placebo
CDIFF Ag 50 - 70 Years Group	Experimental	Healthy 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. Receives: Biological: C. difficile investigational vaccine based on the F2 antigen (GSK2904545A)
CDIFF Ag + AS01B 50 - 70 Years Group	Experimental	Healthy 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. Receives: Biological: C. difficile investigational vaccine based on the F2 antigen (GSK2904545A) adjuvanted with AS01B
Placebo 50 - 70 Years Group	Placebo comparator	Healthy 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. Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Subjects With Any and Grade 3 Solicited Local Symptoms, After Each Vaccine Dose
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).
Measured: During the 7-day follow-up period (from the day of vaccination up to 6 subsequent days) after each vaccination
Number of Subjects With Any, Grade 3, Related and Grade 3 Related Solicited General Symptoms, After Each Vaccine Dose
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.
Measured: During the 7-day follow-up period (from the day of vaccination up to 6 subsequent days) after each vaccination
Number of Subjects With Any, Grade 3, Related, Grade 3 Related and Medically Attended Unsolicited Adverse Events (AEs)
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.
Measured: During the 30-day follow-up period (from the day of vaccination up to 29 subsequent days) after any vaccination
Number of Subjects With Serious Adverse Events (SAEs)
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.
Measured: From Day 1 up to and including Day 390 (Epoch 001)
Number of Subjects With Potential Immune-mediated Diseases (pIMDs)
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.
Measured: 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])
Number of Subjects With Hematological, Biochemical, and Urinary Laboratory Abnormalities at Screening
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.
Measured: 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])
Number of Subjects With Hematological and Biochemical Laboratory Abnormalities 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.
Measured: At Day 8
Number of Subjects With Hematological and Biochemical Laboratory Abnormalities 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.
Measured: At Day 31
Number of Subjects With Hematological and Biochemical Laboratory Abnormalities 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.
Measured: At Day 38
Number of Subjects With Hematological and Biochemical Laboratory Abnormalities 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.
Measured: At Day 180
Number of Subjects With Hematological and Biochemical Laboratory Abnormalities 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.
Measured: At Day 390
Number of Subjects With Hematological and Biochemical Laboratory Abnormalities 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.
Measured: At Day 476
Number of Subjects With Hematological and Biochemical Laboratory Abnormalities 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.
Measured: At Day 491
Number of Subjects With Hematological and Biochemical Laboratory Abnormalities 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.
Measured: At Day 670

Secondary outcomes (1)

Serum Neutralizing Anti-Toxin A and Anti-Toxin B Antibody Titers, as Measured by Toxin Neutralization Assay (TNA)
Serum neutralizing anti-Toxin A and anti-Toxin B antibody titers are presented as Geometric Mean Titers (GMTs), as measured by TNA.
Measured: At Day 1, Day 31, Day 61, Day 180, Day 390, Day 491, Day 521 and Day 670

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

5 Aug 201910 May 2022

First posted19 Jul 2019
Study start5 Aug 2019
Primary completion10 May 2022
Study completion10 May 2022

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Clostridium InfectionsStudies of the same condition, open and under way.
More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Prevention
Allocation: Randomised
Intervention model: Sequential
Model description: A 4-step staggered design will be used to ensure maximum safety of the participating subjects: Step 1: Vaccination of approximately 20 subjects aged 18-45 years. Step 2: Vaccination of approximately 20 subjects aged 50-70 years. Step 3: Vaccination of approximately 30 subjects aged 50-70 years. An iSRC will review all accumulating safety data after Dose 1 and 2 in Steps 1 to 3. If considered appropriate to proceed, the next step will start. Step 4: Vaccination of approximately 70 subjects aged 50-70 years. An iSRC will review all accumulating safety data 3 weeks after the start of vaccination in Step 4 and then about every 3 weeks until all subjects have received Dose 1. In addition, the iSRC will review all safety data after Dose 2 and after that a subcohort of subjects will receive the third dose. If there are any safety concerns observed during SRT reviews post Dose 3, an ad hoc iSRC meeting will take place to review the unblinded safety data.
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 140 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04026009
Sponsor's protocol ID: 208109
Other IDs: 2018-002304-14, 2018
Status last verified: May 2024
First submitted: 16 Jul 2019
Last updated: 23 Sep 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: Yes: IPD for this study will be made available via the Clinical Study Data Request site.

Publications

Leroux-Roels I, Alhatemi A, Caubet M, De Boever F, de Wergifosse B, El Idrissi M, Ferreira GS, Jacobs B, Lambert A, Morel S, Servais C, Yarzabal JP. Safety and Immunogenicity of an Adjuvanted Clostridioides difficile Vaccine Candidate in Healthy Adults: A Randomized Placebo-Controlled Phase 1 Study. J Infect Dis. 2025 Mar 17;231(3):e511-e520. doi: 10.1093/infdis/jiae466.
PubMed 39447053

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 23 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase I, Single-center, Randomized, Observer-blind, Placebo-controlled Study to Evaluate Safety, Reactogenicity and Immunogenicity of GSK's Clostridium Difficile Investigational Vaccine Based on the F2 Antigen With or Without AS01B Adjuvant, When Administered Intramuscularly According to a 0, 1-month Schedule to Healthy Adults Aged Between 18-45 Years and Between 50-70 Years, Followed by an Additional Dose Administered in a Partial Blind Manner Within an Interval of Approximately 15 Months After Dose 2, in a Subcohort of Subjects Aged 50-70 Years
ClinicalTrials.gov ID: NCT04026009
Acronym / sponsor ID: 208109
Conditions: Clostridium Infections
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 140 participants (actual)
Lead sponsor: GlaxoSmithKlineIndustry (pharma, biotech, devices)
Study start: 5 Aug 2019 (actual)
Primary completion: 10 May 2022 (actual)
Study completion: 10 May 2022 (actual)
First posted: 19 Jul 2019 (actual)
Results: Posted 23 Sep 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Sequential
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 5
Model description: A 4-step staggered design will be used to ensure maximum safety of the participating subjects: Step 1: Vaccination of approximately 20 subjects aged 18-45 years. Step 2: Vaccination of approximately 20 subjects aged 50-70 years. Step 3: Vaccination of approximately 30 subjects aged 50-70 years. An iSRC will review all accumulating safety data after Dose 1 and 2 in Steps 1 to 3. If considered appropriate to proceed, the next step will start. Step 4: Vaccination of approximately 70 subjects aged 50-70 years. An iSRC will review all accumulating safety data 3 weeks after the start of vaccination in Step 4 and then about every 3 weeks until all subjects have received Dose 1. In addition, the iSRC will review all safety data after Dose 2 and after that a subcohort of subjects will receive the third dose. If there are any safety concerns observed during SRT reviews post Dose 3, an ad hoc iSRC meeting will take place to review the unblinded safety data.

Arm	Type	Receives
CDIFF Ag 18 - 45 Years Group	Experimental	Biological: C. difficile investigational vaccine based on the F2 antigen (GSK2904545A)Healthy 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 Group	Placebo comparator	Drug: PlaceboHealthy 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 Group	Experimental	Biological: C. difficile investigational vaccine based on the F2 antigen (GSK2904545A)Healthy 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 Group	Experimental	Biological: C. difficile investigational vaccine based on the F2 antigen (GSK2904545A) adjuvanted with AS01BHealthy 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 Group	Placebo comparator	Drug: PlaceboHealthy 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.

Who may qualify

Ages: 18 to 70 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (12 listed)

Subjects who, in the opinion of the Investigator, can and will comply with the requirements of the protocol.
Written or witnessed/thumb print informed consent obtained from the subject prior to performance of any study specific procedure.
For Step 1 only: A male or female between, and including, 18-45 years of age at the time of the first vaccination.
For Steps 2, 3, and 4: A male or female between, and including, 50-70 years of age at the time of the first vaccination.
Healthy subjects as established by medical history and clinical examination before entering into the study.

Key exclusion criteria (32 listed)

Health condition that, in the opinion of the Investigator, may interfere with optimal participation in the study or place the volunteer at increased risk of AEs. Study clinicians, in consultation with the Principal Investigator will use clinical judgment on a case by case basis to assess safety risks under this criterion. The Principal Investigator will consult with the Medical Monitor as appropriate.
Use of any investigational or nonregistered product other than the study vaccine(s) during the period starting 30 days before the first dose of study vaccine(s) (Day 29 to Day 1), or planned use during the study period.
Any medical condition that in the judgment of the Investigator would make IM injection unsafe and subjects under treatment with anticoagulant therapy.
Chronic administration of immunosuppressants or other immune modifying drugs during the period starting 3 months prior to the first vaccination. For corticosteroids, this will mean prednisone ≥ 5 milligrams per day (mg/day) (for adult subjects), or equivalent. Inhaled and topical steroids are allowed.
Administration of long acting immune modifying drugs at any time during the study period.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
C. difficile investigational vaccine based on the F2 antigen (GSK2904545A)Also: CDIFF AgSubjects 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.	Biological	CDIFF Ag 18 - 45 Years Group, CDIFF Ag 50 - 70 Years Group
C. difficile investigational vaccine based on the F2 antigen (GSK2904545A) adjuvanted with AS01BAlso: CDIFF Ag + AS01BSubjects 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.	Biological	CDIFF Ag + AS01B 50 - 70 Years Group
PlaceboSubjects will receive 2 doses (0.5 mL each) of Placebo, administered intramuscularly in the deltoid, at a 0, 1-month dose interval.	Drug	Placebo 18 - 45 Years Group, Placebo 50 - 70 Years Group

Primary outcome

Number of Subjects With Any and Grade 3 Solicited Local Symptoms, After Each Vaccine Dose
Time frame: 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
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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.

1 secondary outcome

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

Results and safety

Results posted to the registry on 23 Sep 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
CDIFF Ag 18 - 45 Years Group	10	10
Placebo 18 - 45 Years Group	10	10
CDIFF Ag 50 - 70 Years Group	45	45
CDIFF Ag + AS01B 50 - 70 Years Group	45	44
Placebo 50 - 70 Years Group	30	29

Primary outcome: Number of Subjects With Any and Grade 3 Solicited Local Symptoms, After Each Vaccine Dose

Time frame: During the 7-day follow-up period (from the day of vaccination up to 6 subsequent days) after each vaccination. Count of participants. Unit: Participants

Measure	Placebo 18 - 45 Years Group n = 10	CDIFF Ag + AS01B 50 - 70 Years Group n = 45	Placebo 50 - 70 Years Group n = 30
Any Erythema, after Dose 1	0	8	0
Grade 3 Erythema, after Dose 1	0	0	0
Any Pain, after Dose 1	1	40	1
Grade 3 Pain, after Dose 1	0	1	0
Any Swelling, after Dose 1	0	3	0
Grade 3 Swelling, after Dose 1	0	0	0
Any Erythema, after Dose 2	0	19	0
Grade 3 Erythema, after Dose 2	0	4	0

Population analysed: The analysis is performed on the Solicited Safety Set, which included all subjects who received at least one dose of the study vaccine and for whom solicited safety data were available.

Primary outcome: Number of Subjects With Any, Grade 3, Related and Grade 3 Related Solicited General Symptoms, After Each Vaccine Dose

Time frame: During the 7-day follow-up period (from the day of vaccination up to 6 subsequent days) after each vaccination. Count of participants. Unit: Participants

Measure	CDIFF Ag 18 - 45 Years Group n = 10	Placebo 18 - 45 Years Group n = 10	CDIFF Ag 50 - 70 Years Group n = 45	CDIFF Ag + AS01B 50 - 70 Years Group n = 45	Placebo 50 - 70 Years Group n = 30
Any Arthralgia, after dose 1	0	0	0	5	3
Grade 3 Arthralgia, after dose 1	0	0	0	0	0
Related Arthralgia, after dose 1	0	0	0	4	3
Grade 3 related Arthralgia, after dose 1	0	0	0	0	0
Any Fatigue, after dose 1	4	2	9	20	7
Grade 3 Fatigue, after dose 1	0	0	0	0	1
Related Fatigue, after dose 1	2	1	8	19	7
Grade 3 related Fatigue, after dose 1	0	0	0	0	1

Primary outcome: Number of Subjects With Any, Grade 3, Related, Grade 3 Related and Medically Attended Unsolicited Adverse Events (AEs)

Time frame: During the 30-day follow-up period (from the day of vaccination up to 29 subsequent days) after any vaccination. Count of participants. Unit: Participants

Measure	CDIFF Ag 18 - 45 Years Group n = 10	Placebo 18 - 45 Years Group n = 10	CDIFF Ag 50 - 70 Years Group n = 45	CDIFF Ag + AS01B 50 - 70 Years Group n = 45	Placebo 50 - 70 Years Group n = 30
Any unsolicited AEs	3	2	22	27	11
Grade 3 unsolicited AEs	1	0	2	3	1
Related unsolicited AEs	0	0	0	8	0
Grade 3 related unsolicited AEs	0	0	0	0	0
Medically attended unsolicited AEs	1	0	8	14	3

Population analysed: The analysis is performed on the Exposed Set, which included all subjects who received at least one dose of the study vaccine and for whom safety data were available.

Primary outcome: Number of Subjects With Serious Adverse Events (SAEs)

Time frame: From Day 1 up to and including Day 390 (Epoch 001). Count of participants. Unit: Participants

Measure	CDIFF Ag 18 - 45 Years Group n = 10	Placebo 18 - 45 Years Group n = 10	CDIFF Ag 50 - 70 Years Group n = 45	CDIFF Ag + AS01B 50 - 70 Years Group n = 45	Placebo 50 - 70 Years Group n = 30
Value	0	1	3	3	0

Population analysed: The analysis is performed on the Exposed Set, which included all subjects who received at least one dose of the study vaccine and for whom safety data were available.

1 secondary outcome is reported in the full results.

Adverse events

Time frame: Solicited local and systemic AEs were collected during the 7-day (Days 1-7) follow-up period after vaccination. Unsolicited AEs were collected during the 30-day (Day 1-30) follow-up period after vaccination. SAEs were collected from first vaccine dose (Day 1) up to study end (Day 670).. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
CDIFF Ag 18 - 45 Years Group	0 of 10 (0%)	8 of 10 (80%)	0 of 10
Placebo 18 - 45 Years Group	1 of 10 (10%)	6 of 10 (60%)	0 of 10
CDIFF Ag + AS01B 50 - 70 Years Group	3 of 45 (6.7%)	45 of 45 (100%)	0 of 45
CDIFF Ag 50 - 70 Years Group	3 of 45 (6.7%)	32 of 45 (71.1%)	0 of 45
Placebo 50 - 70 Years Group	0 of 30 (0%)	23 of 30 (76.7%)	0 of 30

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 23 Sep 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 39447053Leroux-Roels I, Alhatemi A, Caubet M, De Boever F, de Wergifosse B, El Idrissi M, Ferreira GS, Jacobs B, Lambert A, Morel S, Servais C, Yarzabal JP. Safety and Immunogenicity of an Adjuvanted Clostridioides difficile Vaccine Candidate in Healthy Adults: A Randomized Placebo-Controlled Phase 1 Study. J Infect Dis. 2025 Mar 17;231(3):e511-e520. doi: 10.1093/infdis/jiae466.
Individual participant dataSharing planned: Yes. IPD for this study will be made available via the Clinical Study Data Request site.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

GSK Clinical Trials study director

GlaxoSmithKline

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 23 Sep 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Subjects With Any and Grade 3 Solicited Local Symptoms, After Each Vaccine Dose (time frame: During the 7-day follow-up period (from the day of vaccination up to 6 subsequent days) after each vaccination). The study lists 14 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04026009, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Sep 2024.