Safety, Tolerability, and Immunogenicity of a Clostridium Difficile Toxoid Vaccine in Healthy Elderly Volunteers

NCT ID: NCT00214461

Last Updated: 2012-04-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 48 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-11-30
• Study Completion Date: 2006-02-28

Brief Summary

The purpose of this study is to determine the safety and tolerability of a modified C. difficile vaccine at 3 dose levels compared with a placebo control administered via intramuscular injection in healthy elderly subjects aged > or = 65 years. This is the companion study to H-030-008, in which healthy younger adults have already been dosed.

Detailed Description

Clostridium difficile is the leading infectious cause of nosocomial diarrhea in developed countries. Hospital outbreaks of Clostridium difficile-associated diarrhea (CDAD) are associated with substantial patient morbidity and mortality. Conventional therapy with antibiotics often results in secondary infection with resistant organisms or clinical relapse after discontinuation of the antimicrobial course. New strategies are needed to limit the impact of this opportunistic pathogen. Considerable evidence exists that immunity against C. difficile toxins may be effective in controlling CDAD. 48 subjects will be enrolled to receive one of three dose levels of modified C difficile vaccine or placebo administered on a 3-dose schedule. The study consists of a 30-day screening period, a 70-day treatment period, one follow-up phone interview 2 months after the last vaccination, and one follow-up clinic visit 6 months after the last vaccination.

Conditions

Clostridium Infections

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo Vaccine Group

Participants will receive a dose of vaccine diluent (placebo) on Days 0, 28 and 56, respectively.

Group Type: PLACEBO_COMPARATOR

Vaccine diluent buffer (Placebo)

Intervention Type: BIOLOGICAL

0.5 mL, Intramuscular on Day 0, Day 28, and Day 56, respectively.

Low Dose Vaccine Group

Participants will receive a dose of vaccine containing of 2 µg Clostridium Difficile toxoid on Days 0, 28 and 56, respectively.

Group Type: EXPERIMENTAL

C. difficile toxoid vaccine (2 µg)

Intervention Type: BIOLOGICAL

0.5 mL, Intramuscular on Day 0, Day 28, and Day 56, respectively.

Medium dose vaccine group

Participants will receive a dose of vaccine containing of 10 µg Clostridium Difficile toxoid on Days 0, 28 and 56, respectively.

Group Type: EXPERIMENTAL

C. difficile toxoid vaccine (10 µg)

Intervention Type: BIOLOGICAL

0.5 mL, Intramuscular on Day 0, Day 28 and Day 56, respectively.

High dose vaccine group

Participants will receive a dose of vaccine containing of 50 µg Clostridium Difficile toxoid on Days 0, 28 and 56, respectively.

Group Type: EXPERIMENTAL

C. difficile toxoid vaccine (50 µg)

Intervention Type: BIOLOGICAL

0.5 mL, Intramuscular on Day 0, Day 28, and Day 56, respectively.

Interventions

Vaccine diluent buffer (Placebo)

0.5 mL, Intramuscular on Day 0, Day 28, and Day 56, respectively.

Intervention Type: BIOLOGICAL

C. difficile toxoid vaccine (2 µg)

0.5 mL, Intramuscular on Day 0, Day 28, and Day 56, respectively.

Intervention Type: BIOLOGICAL

C. difficile toxoid vaccine (10 µg)

0.5 mL, Intramuscular on Day 0, Day 28 and Day 56, respectively.

Intervention Type: BIOLOGICAL

C. difficile toxoid vaccine (50 µg)

0.5 mL, Intramuscular on Day 0, Day 28, and Day 56, respectively.

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• Adult males or females, > or = 65 years
• In good general health
• Clinical lab tests within normal range
• Females must be post-menopausal
• Able and willing to participate for duration of study and must not participate in any other experimental study for at least 60 days after receiving the last dose of study vaccine

Exclusion Criteria

• Evidence of C. difficile infection
• Evidence of any previous antibiotic-associated diarrhea
• Active or inactive inflammatory bowel disease, irritable colon syndrome, chronic abdominal pain or other chronic diarrhea
• History of malignancy within 5 years
• History of anaphylaxis, asthma or severe vaccine or severe allergic drug reaction
• Known or suspected history of immunodeficiency
• Active or inactive immune-mediated or inflammatory disease
• History of drug or alcohol abuse disorders;
• Serology positive for HIV, hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV)
• Receipt of antibiotic therapy or an investigational drug within prior 30 days
• Blood or organ donation within prior 30 days.

• Minimum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Sanofi

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Thomas P Marbury, MD

Role: PRINCIPAL_INVESTIGATOR

Orlando Clinical Research Center

Richard Greenberg, MD

Role: PRINCIPAL_INVESTIGATOR

University of Kentucky

Locations

Orlando Clinical Research Center

Orlando, Florida, United States

University of Kentucky

Lexington, Kentucky, United States

Countries

United States

References

Greenberg RN, Marbury TC, Foglia G, Warny M. Phase I dose finding studies of an adjuvanted Clostridium difficile toxoid vaccine. Vaccine. 2012 Mar 16;30(13):2245-9. doi: 10.1016/j.vaccine.2012.01.065. Epub 2012 Feb 2.

Reference Type: DERIVED

PMID: 22306375 (View on PubMed)

Other Identifiers

H-030-009

Identifier Type: -

Identifier Source: org_study_id