Clinical Trials List
Protocol NumberH-030-014
NCT Number(ClinicalTrials.gov Identfier)NCT01887912
2013-11-01 - 2021-12-31
Phase III
Terminated7
ICD-10J18.9
Pneumonia, unspecified organism
Efficacy, Immunogenicity, and Safety Study of Clostridium difficile Toxoid Vaccine in Subjects at Risk for C. difficile Infection
-
Trial Applicant
Pharmaceutical Research Associates Taiwan Inc.
-
Sponsor
Sanofi Pasteur Inc.
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- 王孝為 Division of Infectious Disease
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Wei-Ting Chang Division of Infectious Disease
- Yin-Ching Chuang Division of Infectious Disease
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- 林伯昌 Division of Infectious Disease
- 何承懋 Division of Infectious Disease
- Ho Mao-Wang Division of Infectious Disease
- Horng-Chaung Hsu Division of Infectious Disease
The Actual Total Number of Participants Enrolled
0 Terminated
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Min-Chi Lu Division of Infectious Disease
- 陳丹霞 Division of Infectious Disease
- 王耀東 Division of Infectious Disease
- 林俊哲 Division of Infectious Disease
- 李原地 Division of Infectious Disease
- 張明輝 Division of Infectious Disease
- 許倍豪 Division of Infectious Disease
- 楊宜瑱 Division of Infectious Disease
- 林敬斌 Division of Infectious Disease
The Actual Total Number of Participants Enrolled
0 Terminated
Condition/Disease
C. difficile Infection
Objectives
To assess the efficacy of the C. difficile vaccine in preventing the onset of symptomatic primary CDI confirmed by polymerase chain reaction (PCR) in adult subjects aged ≥ 50 years who are at risk for CDI and have received at least 1 injection
Test Drug
C. difficile Toxoid Vaccine
Active Ingredient
formaldehyde (pH 7.5)
Sodium citrate
sucrose
toxoids (A and B)
Sodium citrate
sucrose
toxoids (A and B)
Dosage Form
Vaccine
Dosage
0.00008
0.04
20
466
0.04
20
466
Endpoints
Symptomatic PCR-confirmed primary CDI cases, defined as:
• Presence of both of the following clinical symptoms:
• ≥ 3 loose stools in ≤ 24-hours
• loose stools lasting ≥ 24 hours
Notes:
- Timing of 24-hour period will start from the first episode of loose stools
- Loose stool is defined as type 6 (fluffy pieces with ragged edges, a mushy stool) or type 7 (watery, no solid pieces; entirely liquid) according to the Bristol Stool Chart (1).
and
• Stool sample positive for C. difficile by PCR
Note: Only results from the PCR testing performed by the central laboratory will be used for analyses.
or
• Confirmatory test of pseudomembranous colitis diagnosed through colonoscopy, and, if available, provision of a stool sample for PCRtesting
Efficacy:
• To assess prevention of symptomatic PCR-confirmed primary CDI cases after 3 injections administered at 0, 7, and 30 days
• To assess prevention of symptomatic PCR-confirmed primary CDI cases after completion of at least 2 injections
• To assess durability of prevention of symptomatic PCR-confirmed primary CDI cases up to 3.0 years in Stage 1 or 2.5 years in Stage 2 after the third injection
• To assess prevention of severe primary CDI cases in subjects with PCR-confirmed primary CDI
• To assess the effect of the vaccine on reduction of loose stool frequency in subjects who are symptomatic primary PCR-confirmed CDI cases
• To assess the effect of the vaccine on reduction of CDI episode/illness duration in subjects who are symptomatic primary PCR-confirmed CDI cases
Immunogenicity:
• To describe the immunogenicity to toxin A and toxin B:
• in the subset (1,500 out of 15,000) of subjects and in subjects with CDI (250) at Day 0 and Day 60 (± 14 days) and
• in the subset (1,500 out of 15,000) of subjects at Day 14 (+3 days), Day 30 (-3 days to +7 days), and every 6 months up to 3.0 years in Stage 1 or 2.5 years in Stage 2 (± 14 days) after the third injection
Safety:
• To describe the safety profile of all subjects who receive at least 1 injection
• Presence of both of the following clinical symptoms:
• ≥ 3 loose stools in ≤ 24-hours
• loose stools lasting ≥ 24 hours
Notes:
- Timing of 24-hour period will start from the first episode of loose stools
- Loose stool is defined as type 6 (fluffy pieces with ragged edges, a mushy stool) or type 7 (watery, no solid pieces; entirely liquid) according to the Bristol Stool Chart (1).
and
• Stool sample positive for C. difficile by PCR
Note: Only results from the PCR testing performed by the central laboratory will be used for analyses.
or
• Confirmatory test of pseudomembranous colitis diagnosed through colonoscopy, and, if available, provision of a stool sample for PCRtesting
Efficacy:
• To assess prevention of symptomatic PCR-confirmed primary CDI cases after 3 injections administered at 0, 7, and 30 days
• To assess prevention of symptomatic PCR-confirmed primary CDI cases after completion of at least 2 injections
• To assess durability of prevention of symptomatic PCR-confirmed primary CDI cases up to 3.0 years in Stage 1 or 2.5 years in Stage 2 after the third injection
• To assess prevention of severe primary CDI cases in subjects with PCR-confirmed primary CDI
• To assess the effect of the vaccine on reduction of loose stool frequency in subjects who are symptomatic primary PCR-confirmed CDI cases
• To assess the effect of the vaccine on reduction of CDI episode/illness duration in subjects who are symptomatic primary PCR-confirmed CDI cases
Immunogenicity:
• To describe the immunogenicity to toxin A and toxin B:
• in the subset (1,500 out of 15,000) of subjects and in subjects with CDI (250) at Day 0 and Day 60 (± 14 days) and
• in the subset (1,500 out of 15,000) of subjects at Day 14 (+3 days), Day 30 (-3 days to +7 days), and every 6 months up to 3.0 years in Stage 1 or 2.5 years in Stage 2 (± 14 days) after the third injection
Safety:
• To describe the safety profile of all subjects who receive at least 1 injection
Inclution Criteria
An individual must fulfill all of the following criteria in order to be eligible for trial enrollment:
1) Aged ≥ 50 years on the day of inclusiona
2) Informed consent form has been signed and dated
3) Able to attend all scheduled visits and to comply with all trial procedures
4) Covered by health insurance (only valid for specific countries)
5) Must fulfill at least 1 of the following criteria*
Risk Stratum 1:
• Has had at least 2 hospital stays, each lasting at least ≥ 72 hours, in the 12 months before enrollment
and
• Has received systemic (not topical) antibiotics in the 12 months before enrollment
or
Risk Stratum 2:
• Is anticipated to have an in-patient hospitalization for a planned surgical procedure within 60 days of enrollment. The impending hospital stay is planned to be ≥ 72 hours for a surgery involving 1 of the following:
• Kidney/bladder/urinary system
• Musculoskeletal system
• Respiratory system
• Circulatory system
• Central nervous system
• If an individual is either an in-patient in the hospital or had a previous hospitalization, the enrollment date must be at least 30 days from hospital discharge.
1) Aged ≥ 50 years on the day of inclusiona
2) Informed consent form has been signed and dated
3) Able to attend all scheduled visits and to comply with all trial procedures
4) Covered by health insurance (only valid for specific countries)
5) Must fulfill at least 1 of the following criteria*
Risk Stratum 1:
• Has had at least 2 hospital stays, each lasting at least ≥ 72 hours, in the 12 months before enrollment
and
• Has received systemic (not topical) antibiotics in the 12 months before enrollment
or
Risk Stratum 2:
• Is anticipated to have an in-patient hospitalization for a planned surgical procedure within 60 days of enrollment. The impending hospital stay is planned to be ≥ 72 hours for a surgery involving 1 of the following:
• Kidney/bladder/urinary system
• Musculoskeletal system
• Respiratory system
• Circulatory system
• Central nervous system
• If an individual is either an in-patient in the hospital or had a previous hospitalization, the enrollment date must be at least 30 days from hospital discharge.
Exclusion Criteria
An individual fulfilling any of the following criteria is to be excluded from trial enrollment:
1) Subject is pregnant, or lactating, or of childbearing potential (to be considered of nonchildbearing potential, a female must be post-menopausal for at least 1 year, surgically sterile, or using an effective method of contraceptiona or abstinence from at least 4 weeks prior to the first vaccination and until at least 4 weeks after the last vaccination)
2) Participation in the 4 weeks preceding the first trial vaccination or participation during the present trial period in another clinical trial investigating a vaccine, drug, medical device, or medical procedure
3) Receipt of any vaccine in the 4 weeks preceding the first trial vaccination except for influenza (seasonal or pandemic) and pneumococcal vaccines. This exception includes monovalent pandemic influenza vaccines and multivalent influenza vaccines.
4) Previous vaccination against C. difficile with either the trial vaccine, another vaccine, or
monoclonal antibodies
5) Diarrhea on day of enrollment
6) Self-reported current or prior CDI episode
7) Anticipated or current receipt of kidney dialysis treatment
8) History of gastrointestinal surgery for gastrointestinal malignancy (Note: Colonoscopy,
polypectomy, and appendectomy are not exclusion criteria.)
9) History of inflammatory bowel disease, irritable bowel syndrome, colostomy, or small or large intestine bowel surgery where resection was performed
10) Receiving enteral feeding (e.g., nasogastric, gastrostomy, and jejunostomy tube feeding)
11) Known or suspected congenital or acquired immunodeficiency; or receipt of
immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy, within the preceding 6 months; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months)
12) Known systemic hypersensitivity to any of the vaccine components, or history of a lifethreatening reaction to the vaccine used in the trial or to a vaccine containing any of the same substancesb
13) Self-reported thrombocytopenia, contraindicating IM vaccination
14) Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily
15) Current alcohol abuse or drug addiction that might interfere with the ability to comply with trial procedures in the opinion of the Investigator
16) Chronic illness that, in the opinion of the investigator, is at a stage where it might interfere with trial conduct or completiona
17) Moderate or severe acute illness/infection (according to investigator judgment) on the day of vaccination or febrile illness (temperature ≥ 38.0°C [≥ 100.4°F]). A prospective subject should not be included in the study until the condition has resolved or the febrile event has
subsided.
18) Identified as an Investigator or employee of the Investigator or study center with direct involvement in the proposed study, or identified as an immediate family member (i.e., parent, spouse, natural or adopted child) of the Investigator or employee with direct involvement in the proposed study If required by local regulations, if the subject has a primary physician who is not the Investigator, the site should contact this physician to inform him / her of the subject’s participation in the study.
In addition, the site should ask this primary physician to verify exclusion criteria relating to previous therapies, such as receipt of blood products or previous vaccines.
1) Subject is pregnant, or lactating, or of childbearing potential (to be considered of nonchildbearing potential, a female must be post-menopausal for at least 1 year, surgically sterile, or using an effective method of contraceptiona or abstinence from at least 4 weeks prior to the first vaccination and until at least 4 weeks after the last vaccination)
2) Participation in the 4 weeks preceding the first trial vaccination or participation during the present trial period in another clinical trial investigating a vaccine, drug, medical device, or medical procedure
3) Receipt of any vaccine in the 4 weeks preceding the first trial vaccination except for influenza (seasonal or pandemic) and pneumococcal vaccines. This exception includes monovalent pandemic influenza vaccines and multivalent influenza vaccines.
4) Previous vaccination against C. difficile with either the trial vaccine, another vaccine, or
monoclonal antibodies
5) Diarrhea on day of enrollment
6) Self-reported current or prior CDI episode
7) Anticipated or current receipt of kidney dialysis treatment
8) History of gastrointestinal surgery for gastrointestinal malignancy (Note: Colonoscopy,
polypectomy, and appendectomy are not exclusion criteria.)
9) History of inflammatory bowel disease, irritable bowel syndrome, colostomy, or small or large intestine bowel surgery where resection was performed
10) Receiving enteral feeding (e.g., nasogastric, gastrostomy, and jejunostomy tube feeding)
11) Known or suspected congenital or acquired immunodeficiency; or receipt of
immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy, within the preceding 6 months; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months)
12) Known systemic hypersensitivity to any of the vaccine components, or history of a lifethreatening reaction to the vaccine used in the trial or to a vaccine containing any of the same substancesb
13) Self-reported thrombocytopenia, contraindicating IM vaccination
14) Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily
15) Current alcohol abuse or drug addiction that might interfere with the ability to comply with trial procedures in the opinion of the Investigator
16) Chronic illness that, in the opinion of the investigator, is at a stage where it might interfere with trial conduct or completiona
17) Moderate or severe acute illness/infection (according to investigator judgment) on the day of vaccination or febrile illness (temperature ≥ 38.0°C [≥ 100.4°F]). A prospective subject should not be included in the study until the condition has resolved or the febrile event has
subsided.
18) Identified as an Investigator or employee of the Investigator or study center with direct involvement in the proposed study, or identified as an immediate family member (i.e., parent, spouse, natural or adopted child) of the Investigator or employee with direct involvement in the proposed study If required by local regulations, if the subject has a primary physician who is not the Investigator, the site should contact this physician to inform him / her of the subject’s participation in the study.
In addition, the site should ask this primary physician to verify exclusion criteria relating to previous therapies, such as receipt of blood products or previous vaccines.
The Estimated Number of Participants
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Taiwan
375 participants
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Global
16500 participants
