Title

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

    Phase 1
  • Study Type

    Interventional
  • Study Participants

    50
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.
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.
Study Started
Jul 31
2005
Primary Completion
Jan 31
2006
Study Completion
Mar 31
2006
Results Posted
May 21
2012
Estimate
Last Update
Sep 14
2012
Estimate

Biological Placebo (vaccine diluent)

0.5 mL, intramuscular (IM) on Days 0, 28, and 56, respectively.

Biological Clostridium difficile vaccine

0.5 mL, intramuscular on Days 0, 28, and 56, respectively.

Biological Clostridium difficile vaccine

0.5 mL, intramuscular on Days 0, 28, and 56, respectively.

Biological Clostridium difficile vaccine

0.5 mL, intramuscular on Days 0, 28, and 56, respectively.

Placebo Placebo Comparator

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

Low dose vaccine Experimental

Participants will receive a 2 μg dose of C. difficile toxoid vaccine on Days 0, 28, and 56, respectively.

Medium dose vaccine Experimental

Participants will receive a 10 μg dose of C. difficile toxoid vaccine on Days 0, 28, and 56, respectively

High dose vaccine Experimental

Participants will receive a 50 μg dose of C. difficile toxoid vaccine on Days 0, 28, and 56, respectively

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

Summary

Placebo Group

Low Dose Vaccine Group

Medium Dose Vaccine Group

High Dose Vaccine Group

All Events

Event Type Organ System Event Term Placebo Group Low Dose Vaccine Group Medium Dose Vaccine Group High Dose Vaccine Group

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.

Placebo Group

Erythema Day 0

2.0
Participants

Erythema Day 28

Erythema Day 56

2.0
Participants

Tenderness Day 0

Tenderness Day 28

Tenderness Day 56

Low Dose Vaccine Group

Erythema Day 0

Erythema Day 28

3.0
Participants

Erythema Day 56

2.0
Participants

Tenderness Day 0

Tenderness Day 28

1.0
Participants

Tenderness Day 56

2.0
Participants

Medium Dose Vaccine Group

Erythema Day 0

1.0
Participants

Erythema Day 28

3.0
Participants

Erythema Day 56

3.0
Participants

Tenderness Day 0

3.0
Participants

Tenderness Day 28

Tenderness Day 56

1.0
Participants

High Dose Vaccine Group

Erythema Day 0

2.0
Participants

Erythema Day 28

2.0
Participants

Erythema Day 56

3.0
Participants

Tenderness Day 0

1.0
Participants

Tenderness Day 28

2.0
Participants

Tenderness Day 56

1.0
Participants

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.

Placebo Group

Abdominal pain

1.0
Participants

Blood potassium increased

3.0
Participants

Blood urea increased

Diarrhoea

3.0
Participants

Eosinophil count increased

1.0
Participants

Fatigue

2.0
Participants

Headache

4.0
Participants

Injection site erythema

2.0
Participants

Injection site induration

Injection site irritation

2.0
Participants

Injection site pain

8.0
Participants

Injection site paraesthesia

2.0
Participants

Injection site pruritus

Injection site swelling

1.0
Participants

Injection site warmth

1.0
Participants

Myalgia

2.0
Participants

Pain in extremity

5.0
Participants

Protein urine present

2.0
Participants

Red blood cells urine positive

2.0
Participants

Sensation of heaviness

Sinus headache

Upper respiratory tract infection

2.0
Participants

White blood cell count decreased

White blood cell count increased

White blood cells urine positive

3.0
Participants

Low Dose Vaccine Group

Abdominal pain

Blood potassium increased

1.0
Participants

Blood urea increased

1.0
Participants

Diarrhoea

2.0
Participants

Eosinophil count increased

2.0
Participants

Fatigue

1.0
Participants

Headache

4.0
Participants

Injection site erythema

6.0
Participants

Injection site induration

1.0
Participants

Injection site irritation

Injection site pain

11.0
Participants

Injection site paraesthesia

Injection site pruritus

Injection site swelling

2.0
Participants

Injection site warmth

1.0
Participants

Myalgia

1.0
Participants

Pain in extremity

Protein urine present

6.0
Participants

Red blood cells urine positive

5.0
Participants

Sensation of heaviness

Sinus headache

2.0
Participants

Upper respiratory tract infection

3.0
Participants

White blood cell count decreased

White blood cell count increased

2.0
Participants

White blood cells urine positive

1.0
Participants

Medium Dose Vaccine Group

Abdominal pain

1.0
Participants

Blood potassium increased

Blood urea increased

4.0
Participants

Diarrhoea

Eosinophil count increased

5.0
Participants

Fatigue

1.0
Participants

Headache

3.0
Participants

Injection site erythema

5.0
Participants

Injection site induration

4.0
Participants

Injection site irritation

1.0
Participants

Injection site pain

11.0
Participants

Injection site paraesthesia

Injection site pruritus

1.0
Participants

Injection site swelling

3.0
Participants

Injection site warmth

1.0
Participants

Myalgia

1.0
Participants

Pain in extremity

1.0
Participants

Protein urine present

4.0
Participants

Red blood cells urine positive

6.0
Participants

Sensation of heaviness

1.0
Participants

Sinus headache

Upper respiratory tract infection

2.0
Participants

White blood cell count decreased

2.0
Participants

White blood cell count increased

White blood cells urine positive

3.0
Participants

High Dose Vaccine Group

Abdominal pain

4.0
Participants

Blood potassium increased

Blood urea increased

2.0
Participants

Diarrhoea

3.0
Participants

Eosinophil count increased

3.0
Participants

Fatigue

2.0
Participants

Headache

Injection site erythema

6.0
Participants

Injection site induration

2.0
Participants

Injection site irritation

Injection site pain

12.0
Participants

Injection site paraesthesia

Injection site pruritus

3.0
Participants

Injection site swelling

3.0
Participants

Injection site warmth

3.0
Participants

Myalgia

1.0
Participants

Pain in extremity

3.0
Participants

Protein urine present

5.0
Participants

Red blood cells urine positive

5.0
Participants

Sensation of heaviness

2.0
Participants

Sinus headache

Upper respiratory tract infection

3.0
Participants

White blood cell count decreased

2.0
Participants

White blood cell count increased

White blood cells urine positive

3.0
Participants

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).

Placebo Group

Toxin A Day 236

Toxin A Day 28

Toxin A Day 56

Toxin A Day 70

Toxin B Day 236

Toxin B Day 28

Toxin B Day 56

Toxin B Day 70

Low Dose Vaccine Group

Toxin A Day 236

12.0
Participants

Toxin A Day 28

6.0
Participants

Toxin A Day 56

13.0
Participants

Toxin A Day 70

13.0
Participants

Toxin B Day 236

2.0
Participants

Toxin B Day 28

2.0
Participants

Toxin B Day 56

3.0
Participants

Toxin B Day 70

6.0
Participants

Medium Dose Vaccine Group

Toxin A Day 236

12.0
Participants

Toxin A Day 28

5.0
Participants

Toxin A Day 56

12.0
Participants

Toxin A Day 70

12.0
Participants

Toxin B Day 236

4.0
Participants

Toxin B Day 28

5.0
Participants

Toxin B Day 56

6.0
Participants

Toxin B Day 70

7.0
Participants

High Dose Vaccine Group

Toxin A Day 236

10.0
Participants

Toxin A Day 28

10.0
Participants

Toxin A Day 56

11.0
Participants

Toxin A Day 70

11.0
Participants

Toxin B Day 236

6.0
Participants

Toxin B Day 28

7.0
Participants

Toxin B Day 56

7.0
Participants

Toxin B Day 70

8.0
Participants

Total

50
Participants

Age Continuous

31.9
Years (Mean)
Standard Deviation: 10.28

Age, Categorical

Region of Enrollment

Sex: Female, Male

Overall Study

Placebo Group

Low Dose Vaccine Group

Medium Dose Vaccine Group

High Dose Vaccine Group

Drop/Withdrawal Reasons

Placebo Group

High Dose Vaccine Group