Study of Different Formulations of a Clostridium Difficile Toxoid Vaccine Given at Three Different Schedules in Adults

NCT ID: NCT01230957

Last Updated: 2018-07-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

650 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-10-31

Study Completion Date

2013-03-31

Brief Summary

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This study will further evaluate the ACAM-CDIFF™ vaccine in a population of middle-aged to elderly individuals at risk of exposure to Clostridium difficile because of impending hospitalization or residence in a care facility.

Primary Objectives:

* To describe the safety profile of subjects in each of the study groups.
* To describe the immune responses elicited by toxoid A and toxoid B of subjects in each of the study groups.

Observational Objective:

* To describe the occurrence of first-time Clostridium difficile infection (CDI) episodes.

Detailed Description

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Participants will receive 3 doses of either one of 4 different formulations of ACAM-CDIFF™ vaccine or placebo, on one of 3 different schedules. The trial will have 2 stages. Stage I will test 4 different formulations of ACAM-CDIFF™ vaccine. Stage II will explore different vaccination schedules using one of these formulations.

Participants will be followed up for safety and immunogenicity; stool samples will also be provided in case of diarrhea.

Conditions

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Clostridium Difficile Infection Diarrhea

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Group 1

Participants will receive a dose Low-dose ACAM-CDIFF™ vaccine with adjuvant on Day 0, 7, and 30, respectively.

Group Type EXPERIMENTAL

Clostridium difficile toxoids A and B (Low-dose with adjuvant)

Intervention Type BIOLOGICAL

0.5 mL, Intramuscular on Days 0, 7, and 30

Group 2

Participants will receive a dose Low-dose ACAM-CDIFF™ vaccine without adjuvant on Day 0, 7, and 30, respectively.

Group Type EXPERIMENTAL

Clostridium difficile toxoids A and B (Low-dose without adjuvant)

Intervention Type BIOLOGICAL

0.5 mL, Intramuscular on Days 0, 7, and 30

Group 3

Participants will receive a dose High-dose ACAM-CDIFF™ vaccine with adjuvant on Day 0, 7, and 30, respectively.

Group Type EXPERIMENTAL

Clostridium difficile toxoids A and B (high-dose with adjuvant)

Intervention Type BIOLOGICAL

0.5 mL, Intramuscular on Days 0, 7, and 30

Group 4

Participants will receive a dose High-dose ACAM-CDIFF™ vaccine without adjuvant on Day 0, 7, and 30, respectively.

Group Type EXPERIMENTAL

Clostridium difficile toxoids A and B (high-dose without adjuvant)

Intervention Type BIOLOGICAL

0.5 mL, Intramuscular on Days 0, 7, and 30

Group 5

Participants will receive a dose Placebo (0.9% normal saline) on Day 0, 7, and 30, respectively.

Group Type PLACEBO_COMPARATOR

Placebo: 0.9% normal saline

Intervention Type BIOLOGICAL

0.5 mL, Intramuscular on Days 0, 7, and 30

Group 6

Participants will receive a dose of High-dose ACAM-CDIFF™ vaccine with adjuvant on Day 0, 7, and 180, respectively.

Group Type EXPERIMENTAL

Clostridium difficile toxoids A and B (high-dose with adjuvant)

Intervention Type BIOLOGICAL

0.5 mL, Intramuscular on Days 0, 7, and 180

Group 7

Participants will receive a dose of High-dose ACAM-CDIFF™ vaccine with adjuvant on Day 0, 30, and 180, respectively.

Group Type EXPERIMENTAL

Clostridium difficile toxoids A and B (high-dose with adjuvant)

Intervention Type BIOLOGICAL

0.5 mL, Intramuscular on Days 0, 30, and 180

Interventions

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Clostridium difficile toxoids A and B (Low-dose with adjuvant)

0.5 mL, Intramuscular on Days 0, 7, and 30

Intervention Type BIOLOGICAL

Clostridium difficile toxoids A and B (Low-dose without adjuvant)

0.5 mL, Intramuscular on Days 0, 7, and 30

Intervention Type BIOLOGICAL

Clostridium difficile toxoids A and B (high-dose with adjuvant)

0.5 mL, Intramuscular on Days 0, 7, and 30

Intervention Type BIOLOGICAL

Clostridium difficile toxoids A and B (high-dose without adjuvant)

0.5 mL, Intramuscular on Days 0, 7, and 30

Intervention Type BIOLOGICAL

Placebo: 0.9% normal saline

0.5 mL, Intramuscular on Days 0, 7, and 30

Intervention Type BIOLOGICAL

Clostridium difficile toxoids A and B (high-dose with adjuvant)

0.5 mL, Intramuscular on Days 0, 7, and 180

Intervention Type BIOLOGICAL

Clostridium difficile toxoids A and B (high-dose with adjuvant)

0.5 mL, Intramuscular on Days 0, 30, and 180

Intervention Type BIOLOGICAL

Other Intervention Names

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ACAM-CDIFF™ vaccine ACAM-CDIFF™ vaccine ACAM-CDIFF™ vaccine ACAM-CDIFF™ vaccine 0.9% normal saline ACAM-CDIFF™ vaccine ACAM-CDIFF™ vaccine

Eligibility Criteria

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Inclusion Criteria

* Aged 40 to 75 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
* For a woman of childbearing potential, use of an effective method of contraception or abstinence from at least 4 weeks prior to the first vaccination until at least 4 weeks after the last vaccination
* At risk for developing Clostridium difficile infection during the trial because of impending elective surgery or hospitalization within 60 days of enrollment, or current or impending residence in a long-term care facility or rehabilitation facility.

Exclusion Criteria

* Known pregnancy, or a positive urine pregnancy test
* Currently breastfeeding a child
* Participation in another clinical trial investigating a vaccine, drug, medical device, or medical procedure in the 4 weeks preceding the first trial vaccination
* Planned participation in another clinical trial during the present trial period
* Receipt of any vaccine in the 4 weeks preceding the first trial vaccination, except for influenza (seasonal or pandemic) and pneumococcal vaccine
* Planned receipt of any vaccine in the 4 weeks following any trial vaccination, except for influenza (seasonal or pandemic) and pneumococcal vaccines
* Previous vaccination against Clostridium difficile with either the trial vaccine or another vaccine
* Current or prior Clostridium difficile infection (CDI) episode
* Receipt of blood or blood-derived products in the past 3 months, which might interfere with assessment of the immune response
* 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)
* Self-reported seropositivity for Human Immunodeficiency Virus (HIV), hepatitis B, or hepatitis C
* Anticipated or current receipt of kidney dialysis treatment
* Known systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to a vaccine containing any of the same substances
* Self-reported thrombocytopenia, contraindicating intramuscular (IM) vaccination
* Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating IM 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
* Chronic illness that, in the opinion of the investigator, is at a stage where it might interfere with trial conduct or completion
* Identified as a study site employee who is involved in the protocol and may have direct access to trial-related data
* Subjects who have any history of intestinal diverticular bleeding
* Subjects who have had surgery within the past three months for gastrointestinal (GI) malignancy.
Minimum Eligible Age

40 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Sanofi Pasteur, a Sanofi Company

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Director

Role: STUDY_DIRECTOR

Sanofi Pasteur Inc.

Locations

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Redding, California, United States

Site Status

Bristol, Connecticut, United States

Site Status

Stamford, Connecticut, United States

Site Status

Clearwater, Florida, United States

Site Status

Coral Gables, Florida, United States

Site Status

Port Orange, Florida, United States

Site Status

St. Petersburg, Florida, United States

Site Status

Tampa, Florida, United States

Site Status

Atlanta, Georgia, United States

Site Status

Idaho Falls, Idaho, United States

Site Status

Newton, Kansas, United States

Site Status

Brockton, Massachusetts, United States

Site Status

Troy, Michigan, United States

Site Status

Neptune City, New Jersey, United States

Site Status

Binghamton, New York, United States

Site Status

Endwell, New York, United States

Site Status

Cary, North Carolina, United States

Site Status

Hickory, North Carolina, United States

Site Status

Raleigh, North Carolina, United States

Site Status

Centerville, Ohio, United States

Site Status

Pittsburgh, Pennsylvania, United States

Site Status

Uniontown, Pennsylvania, United States

Site Status

Mt. Pleasant, South Carolina, United States

Site Status

Bristol, Tennessee, United States

Site Status

Salt Lake City, Utah, United States

Site Status

Salt Lake City, Utah, United States

Site Status

Salt Lake City, Utah, United States

Site Status

Richmond, Virginia, United States

Site Status

Williamsburg, Virginia, United States

Site Status

Marshfield, Wisconsin, United States

Site Status

Countries

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United States

References

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de Bruyn G, Saleh J, Workman D, Pollak R, Elinoff V, Fraser NJ, Lefebvre G, Martens M, Mills RE, Nathan R, Trevino M, van Cleeff M, Foglia G, Ozol-Godfrey A, Patel DM, Pietrobon PJ, Gesser R; H-030-012 Clinical Investigator Study Team. Defining the optimal formulation and schedule of a candidate toxoid vaccine against Clostridium difficile infection: A randomized Phase 2 clinical trial. Vaccine. 2016 Apr 27;34(19):2170-8. doi: 10.1016/j.vaccine.2016.03.028. Epub 2016 Mar 21.

Reference Type RESULT
PMID: 27013431 (View on PubMed)

Small RD, Ozol-Godfrey A, Yan L. On the use of nonparametric tests for comparing immunological Reverse Cumulative distribution curves (RCDCs). Vaccine. 2019 Oct 16;37(44):6737-6742. doi: 10.1016/j.vaccine.2019.09.007. Epub 2019 Sep 16.

Reference Type DERIVED
PMID: 31537446 (View on PubMed)

Other Identifiers

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UTN: U1111-1114-3917

Identifier Type: OTHER

Identifier Source: secondary_id

H-030-012

Identifier Type: -

Identifier Source: org_study_id

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