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Trial record 1 of 1 for:    Efficacy, Immunogenicity, and Safety Study of Clostridium difficile Toxoid Vaccine in Subjects at Risk for C. difficile Infection
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Study of a Candidate Clostridium Difficile Toxoid Vaccine in Subjects at Risk for C. Difficile Infection

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01887912
First Posted: June 27, 2013
Last Update Posted: December 6, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Sanofi ( Sanofi Pasteur, a Sanofi Company )
  Purpose

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.

Primary objective:

  • 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.

Secondary Objectives:

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.

Immunogenicity:

  • To describe the immunogenicity to toxin A and toxin B in the subset of subjects at specific time points.

Safety:

  • To describe the safety profile of all subjects who receive at least 1 injection.

Condition Intervention Phase
Clostridium Difficile Infection Biological: C. difficile Toxoid Vaccine Biological: Placebo: 0.9% normal saline Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Efficacy, Immunogenicity, and Safety Study of Clostridium Difficile Toxoid Vaccine in Subjects at Risk for C. Difficile Infection (Cdiffense™)

Further study details as provided by Sanofi ( Sanofi Pasteur, a Sanofi Company ):

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: 16500
Study Start Date: July 2013
Estimated Study Completion Date: October 2019
Estimated Primary Completion Date: October 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

Detailed Description:

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.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   50 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01887912


  Show 335 Study Locations
Sponsors and Collaborators
Sanofi Pasteur, a Sanofi Company
Investigators
Study Director: Medical Director Sanofi Pasteur Inc.
  More Information

Additional Information:
Responsible Party: Sanofi Pasteur, a Sanofi Company
ClinicalTrials.gov Identifier: NCT01887912     History of Changes
Other Study ID Numbers: H-030-014
2013-000775-32 ( EudraCT Number )
U1111-1127-7162 ( Other Identifier: WHO )
First Submitted: June 20, 2013
First Posted: June 27, 2013
Last Update Posted: December 6, 2017
Last Verified: December 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: 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: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Sanofi ( Sanofi Pasteur, a Sanofi Company ):
Clostridium difficile Toxoid Vaccine
Clostridium difficile infection
Cdiffense

Additional relevant MeSH terms:
Infection
Communicable Diseases
Vaccines
Immunologic Factors
Physiological Effects of Drugs