Study of a Candidate Clostridium Difficile Toxoid Vaccine in Subjects at Risk for C. Difficile Infection
This study is currently recruiting participants.
Verified September 2017 by Sanofi ( Sanofi Pasteur, a Sanofi Company )
Information provided by (Responsible Party):
Sanofi ( Sanofi Pasteur, a Sanofi Company )
First received: June 20, 2013
Last updated: September 1, 2017
Last verified: September 2017
The aim of this study is to evaluate the efficacy of the candidate Clostridium difficile vaccine to prevent primary symptomatic C. difficile infection (CDI) in subjects a risk for CDI where there is a substantial unmet medical need.
- 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.
- 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 describe the immunogenicity to toxin A and toxin B in the subset of subjects at specific time points.
- To describe the safety profile of all subjects who receive at least 1 injection.
Clostridium Difficile Infection
Biological: C. difficile Toxoid Vaccine
Biological: Placebo: 0.9% normal saline
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Prevention
||Efficacy, Immunogenicity, and Safety Study of Clostridium Difficile Toxoid Vaccine in Subjects at Risk for C. Difficile Infection (Cdiffense™)
Primary Outcome Measures:
- Number of symptomatic PCR-confirmed primary CDI cases after at least one injection [ Time Frame: Up to 3 years post-vaccination 1 ]
Presence of ≥ 3 loose stools for ≤ 24 hours and loose stools lasting ≥ 24 hours, and stool sample positive for C. difficile PCR, or confirmatory test of pseudomembranous colitis diagnosed through colonoscopy, and, if available, provision of a stool sample for PCR-testing
Secondary Outcome Measures:
- Number of symptomatic PCR-confirmed primary CDI cases after 3 injections [ Time Frame: Up to 3 years post-vaccination 3 ]
- Number of symptomatic PCR-confirmed primary CDI cases after at least 2 injections [ Time Frame: Up to 3 years post-vaccination 2 ]
- Number of symptomatic PCR-confirmed primary CDI cases after 3 injections since enrollment and within 3 years after the third injection [ Time Frame: Up to 3 years post-vaccination 3 ]
- Number of severe PCR-confirmed primary CDI cases [ Time Frame: Up to 3 years post-vaccination 3 ]
A severe case is defined when a subject has one or more of the following; fever ≥38.5°C, WBC count ≥ 15,000 cells/mm3 (if available), ileus, pseudomembranous colitis, serum albumin <3 g/dl, abdominal distension, abdominal tenderness, or admission to the intensive care unit within 7 days of CDI diagnosis
- Maximum number of loose stools per day associated with a symptomatic PCR-confirmed primary CDI case [ Time Frame: Up to 3 years post-vaccination 3 ]
Effect of the vaccine on reduction of loose stool frequency
- CDI episode/illness duration associated with a symptomatic PCR-confirmed primary CDI case [ Time Frame: Up to 3 years post-vaccination 3 ]
Duration is calculated as (clinical cure date - clinical case date + 1)
- Immunogenicity to toxins A and toxin B [ Time Frame: Day 0 to Day and every 6 months up to 3 years ]
Antibody concentrations against toxins A and B measured by ELISA and antibody titers measured by toxin neutralization assay in subsets of subjects
- Number of participants reporting solicited injection site and systemic reactions [ Time Frame: Day 0 to Day 6 after each injection ]
Solicited injection site reactions: Pain, Erythema, and Swelling. Solicited systemic reactions: Fever (temperature), Headache, Malaise, Myalgia, and Arthralgia.
| Estimated Enrollment:
| Study Start Date:
| Estimated Study Completion Date:
| Estimated Primary Completion Date:
||October 2019 (Final data collection date for primary outcome measure)
Experimental: C. difficile Vaccine Group
Participants will receive 1 injection of the C. difficile toxoid vaccine at Days 0, 7, and 30, respectively.
Biological: C. difficile Toxoid Vaccine
0.5 mL, Intramuscular
Placebo Comparator: Placebo Vaccine Group
Participants will receive 1 injection of placebo (0.9% normal saline) at Days 0, 7, and 30, respectively.
Biological: Placebo: 0.9% normal saline
0.5 mL, Intramuscular
The study is designed as an event-driven group sequential protocol with 4 interim analyses at defined information milestones and a final analysis when a specific number of clinical endpoints are reached.
Subjects will be randomly assigned to receive either the candidate vaccine or a placebo that will be administered in a 3-dose schedule.
|Ages Eligible for Study:
||50 Years and older (Adult, Senior)
|Sexes Eligible for Study:
|Accepts Healthy Volunteers:
- Aged ≥ 50 years on the day of inclusion
- Informed consent form has been signed and dated
- Able to attend all scheduled visits and to comply with all trial procedures
- Covered by health insurance (if required)
- Must fulfill at least 1 of the following criteria
Risk Stratum 1:
- Has had at least 2 hospital stays, each lasting at least ≥ 24 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.
- Subject is pregnant, or lactating, or of childbearing potential (to be considered of non-childbearing potential, a female must be post-menopausal for at least 1 year, surgically sterile, or using an effective method of contraception or abstinence from at least 4 weeks prior to the first vaccination and until at least 4 weeks after the last vaccination)
- 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
- 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
- Previous vaccination against C. difficile with either the trial vaccine, another vaccine, or monoclonal antibodies
- Diarrhea on day of enrollment
- Self-reported current or prior CDI episode
- Anticipated or current receipt of kidney dialysis treatment
- History of gastrointestinal surgery for gastrointestinal malignancy (Note: Colonoscopy, polypectomy, and appendectomy are not exclusion criteria.)
- History of inflammatory bowel disease, irritable bowel syndrome (must include diarrhea as a symptom), colostomy, or small or large intestine bowel surgery where resection was performed
- Receiving enteral feeding (e.g., nasogastric, gastrostomy, and jejunostomy tube feeding)
- 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)
- Known systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to the vaccine used in the trial or to a vaccine containing any of the same substances
- Self-reported thrombocytopenia, contraindicating intramuscular vaccination
- Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily
- Current alcohol abuse or drug addiction that might interfere with the ability to comply with trial procedures in the opinion of the Investigator
- Chronic illness that, in the opinion of the investigator, is at a stage where it might interfere with trial conduct or completion
- 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
- 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.
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To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01887912
Sanofi Pasteur, a Sanofi Company
||Sanofi Pasteur Inc.
||Sanofi Pasteur, a Sanofi Company
History of Changes
|Other Study ID Numbers:
2013-000775-32 ( EudraCT Number )
U1111-1127-7162 ( Other Identifier: WHO )
|Study First Received:
||June 20, 2013
||September 1, 2017
|Individual Participant Data (IPD) Sharing Statement:
|Plan to Share IPD:
||Individual participant data (IPD) and supporting clinical documents are available for request at clinicalstudydatarequest.com. While making information available, Sanofi continues to protect the privacy of the participants in clinical trials and to remove commercially confidential information (CCI). Details on Data Sharing criteria and process for requesting access can be found at this web address: clinicalstudydatarequest.com
|Studies a U.S. FDA-regulated Drug Product:
|Studies a U.S. FDA-regulated Device Product:
Keywords provided by Sanofi ( Sanofi Pasteur, a Sanofi Company ):
Clostridium difficile Toxoid Vaccine
Clostridium difficile infection
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on September 25, 2017
Physiological Effects of Drugs