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

Study Overview
=================
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 adults aged 18-55 years of age.

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.

Official Title
-----------------
A Phase I Randomized, Placebo-Controlled, Double-Blind, Dose-Ranging Study of the Safety, Tolerability and Immunogenicity of a Clostridium Difficile Toxoid Vaccine, Alum Adsorbed, in Healthy Adult Volunteers (18-55 Years)

Conditions
-----------------
Clostridium Infections

Intervention / Treatment
-----------------
* Biological: Placebo (vaccine diluent)
* Biological: Clostridium difficile vaccine
* Biological: Clostridium difficile vaccine
* Biological: Clostridium difficile vaccine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adult males or females, 18-55 years (inclusive) In good general health Clinical lab tests within normal range Non-pregnant female subjects 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; Pregnant or lactating female subjects; 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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Participants will receive a dose of vaccine diluent (placebo) on Days 0, 28, and 56, respectively. | Biological: Placebo (vaccine diluent)<br>* 0.5 mL, intramuscular (IM) on Days 0, 28, and 56, respectively.<br>|
| Experimental: Low dose vaccine<br>Participants will receive a 2 μg dose of C. difficile toxoid vaccine on Days 0, 28, and 56, respectively. | Biological: Clostridium difficile vaccine<br>* 0.5 mL, intramuscular on Days 0, 28, and 56, respectively.<br>|
| Experimental: Medium dose vaccine<br>Participants will receive a 10 μg dose of C. difficile toxoid vaccine on Days 0, 28, and 56, respectively | Biological: Clostridium difficile vaccine<br>* 0.5 mL, intramuscular on Days 0, 28, and 56, respectively.<br>|
| Experimental: High dose vaccine<br>Participants will receive a 50 μg dose of C. difficile toxoid vaccine on Days 0, 28, and 56, respectively | Biological: Clostridium difficile vaccine<br>* 0.5 mL, intramuscular on Days 0, 28, and 56, respectively.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Reporting Solicited Injection Site Erythema and Tenderness Post-vaccination With Either One of Three Formulations of Clostridium Difficile Vaccines or a Placebo Vaccine. |  | Day 0 and up to 7 days post each vaccination | 
| Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. |  | Day 0 to up to 70 days post-first vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Seroconversion for Toxin A and Toxin B Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Seroconversion was defined as a ≥4-fold increase in antibody levels from Baseline. For values below the limit of quantification (LLQ) for the assay, the LLQ was used. Serum anti-toxin IgG levels were determined by enzyme linked immunosorbent assay (ELISA). | Days 28, 56, 70, and 236 Post First Vaccination | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Clostridium difficile