Phase I Randomized, Placebo-Controlled, Double-Blind, Dose Ranging Study, Safety, Tolerability and Immunogenicity

• ClinicalTrials.gov Identifier: NCT00772954
• Recruitment Status: Terminated
• First Posted: October 15, 2008
• Results First Posted: May 21, 2012
• Last Update Posted: May 21, 2012
• Sponsor: Sanofi
• Information provided by (Responsible Party): Sanofi

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
• Conditions: Clostridium Difficile Infection; Clostridium Difficile Diarrhea
• Interventions: Biological: Vaccine diluent buffer; Biological: Clostridium difficile toxoid vaccine (50 μg); Biological: Clostridium difficile toxoid vaccine (100 μg)
• Enrollment: 36

Participant Flow

Recruitment Details	Participants were enrolled on 28 March 2006 in 2 clinical centers in the US.
Pre-assignment Details	A total of 36 participants who met the inclusion, but no exclusion criteria were enrolled and vaccinated.

Arm/Group Title	Placebo Vaccine Group	Clostridium Difficile Toxoid Vaccine Group 1	Clostridium Difficile Toxoid Vaccine Group 2
Arm/Group Description	Participants received a dose of placebo (vaccine diluent) on Day 0 and Day 28.	Participants received a dose of 50 μg Clostridium difficile toxoid vaccine on Day 0 and Day 28.	Participants received a dose of 100 μg Clostridium difficile toxoid vaccine on Day 0 and Day 28.
Period Title: Overall Study
Started	12	12	12
Completed	12	12	11
Not Completed	0	0	1
Reason Not Completed
Adverse Event	0	0	1

Baseline Characteristics

Arm/Group Title		Placebo Vaccine Group	Clostridium Difficile Toxoid Vaccine Group 1	Clostridium Difficile Toxoid Vaccine Group 2	Total
Arm/Group Description		Participants received a dose of placebo (vaccine diluent) on Day 0 and Day 28.	Participants received a dose of 50 μg Clostridium difficile toxoid vaccine on Day 0 and Day 28.	Participants received a dose of 100 μg Clostridium difficile toxoid vaccine on Day 0 and Day 28.	Total of all reporting groups
Overall Number of Baseline Participants		12	12	12	36
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	12 participants	12 participants	12 participants	36 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	12 100.0%	12 100.0%	12 100.0%	36 100.0%
	>=65 years	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Age Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	12 participants	12 participants	12 participants	36 participants
		38.3 (12.98)	36.9 (12.67)	30.0 (8.57)	35.1 (11.84)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	12 participants	12 participants	12 participants	36 participants
	Female	7 58.3%	11 91.7%	5 41.7%	23 63.9%
	Male	5 41.7%	1 8.3%	7 58.3%	13 36.1%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	12 participants	12 participants	12 participants	36 participants
		12	12	12	36

Outcome Measures

1. Primary Outcome

Title	Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With One of Two Formulations of Clostridium Difficile Toxoid Vaccine or a Placebo Vaccine.
Description	[Not Specified]
Time Frame	Day 0 up to 70 days post first vaccination

Outcome Measure Data

Analysis Population Description

Safety assessments were on the safety population.

Arm/Group Title	Placebo Vaccine Group	Clostridium Difficile Toxoid Vaccine Group 1	Clostridium Difficile Toxoid Vaccine Group 2
Arm/Group Description:	Participants received a dose of placebo (vaccine diluent) on Day 0 and Day 28.	Participants received a dose of 50 μg Clostridium difficile toxoid vaccine on Day 0 and Day 28.	Participants received a dose of 100 μg Clostridium difficile toxoid vaccine on Day 0 and Day 28.
Overall Number of Participants Analyzed	12	12	12
Measure Type: Number; Unit of Measure: Participants
Injection site pain	7	12	9
Headache	5	4	5
Blood potassium decreased	1	4	3
Protein urine present	1	4	3
White blood cell count increased	1	4	3
Diarrhoea	3	3	2
Fatigue	3	3	2
Myalgia	1	5	1
White blood cells urine positive	2	2	3
Eosinophil count increased	3	1	3
Abdominal pain	2	1	3
Injection site erythema	2	3	1
Red blood cells urine positive	2	2	2
Injection site swelling	0	4	1
Injection site warmth	0	2	2
Malaise	0	3	0
Blood urea increased	2	1	0
Sinus congestion	2	0	1
Urine ketone body present	0	0	2

Adverse Events

Time Frame	Adverse events data were collected from the day of vaccination 1 (Day 0) to up to 8 months post-vaccination.
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Placebo Vaccine Group	Clostridium Difficile Toxoid Vaccine Group 1	Clostridium Difficile Toxoid Vaccine Group 2
Arm/Group Description	Participants received a dose of placebo (vaccine diluent) on Day 0 and Day 28.	Participants received a dose of 50 μg Clostridium difficile toxoid vaccine on Day 0 and Day 28.	Participants received a dose of 100 μg Clostridium difficile toxoid vaccine on Day 0 and Day 28.
All-Cause Mortality
	Placebo Vaccine Group	Clostridium Difficile Toxoid Vaccine Group 1	Clostridium Difficile Toxoid Vaccine Group 2
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--	--/--
Serious Adverse Events
	Placebo Vaccine Group	Clostridium Difficile Toxoid Vaccine Group 1	Clostridium Difficile Toxoid Vaccine Group 2
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/12 (0.00%)	0/12 (0.00%)	0/12 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Placebo Vaccine Group	Clostridium Difficile Toxoid Vaccine Group 1	Clostridium Difficile Toxoid Vaccine Group 2
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	11/12 (91.67%)	12/12 (100.00%)	12/12 (100.00%)
Gastrointestinal disorders
Diarrhoea * 1	3/12 (25.00%)	3/12 (25.00%)	2/12 (16.67%)
Abdominal pain * 1	2/12 (16.67%)	1/12 (8.33%)	3/12 (25.00%)
Abdominal pain lower * 2	2/12 (16.67%)	1/12 (8.33%)	3/12 (25.00%)
Nausea * 2	1/12 (8.33%)	0/12 (0.00%)	1/12 (8.33%)
Toothache * 2	1/12 (8.33%)	0/12 (0.00%)	0/12 (0.00%)
General disorders
Injection site pain * 1	7/12 (58.33%)	12/12 (100.00%)	9/12 (75.00%)
Fatigue * 1	3/12 (25.00%)	3/12 (25.00%)	2/12 (16.67%)
Injection site erythema * 1	2/12 (16.67%)	3/12 (25.00%)	1/12 (8.33%)
Injection site swelling * 1	0/12 (0.00%)	4/12 (33.33%)	1/12 (8.33%)
Injection site warmth * 1	0/12 (0.00%)	2/12 (16.67%)	2/12 (16.67%)
Malaise * 1	0/12 (0.00%)	3/12 (25.00%)	0/12 (0.00%)
Injection site hemorrhage * 2	0/12 (0.00%)	1/12 (8.33%)	0/12 (0.00%)
Injection site induration * 2	0/12 (0.00%)	0/12 (0.00%)	1/12 (8.33%)
Injection site pruritus * 2	0/12 (0.00%)	1/12 (8.33%)	1/12 (8.33%)
Pyrexia * 2	1/12 (8.33%)	1/12 (8.33%)	0/12 (0.00%)
Infections and infestations
Nasopharyngitis * 2	0/12 (0.00%)	0/12 (0.00%)	1/12 (8.33%)
Sinusitis * 2	1/12 (8.33%)	0/12 (0.00%)	1/12 (8.33%)
Injury, poisoning and procedural complications
Procedural pain * 2	0/12 (0.00%)	1/12 (8.33%)	0/12 (0.00%)
Investigations
Blood potassium decreased * 1	1/12 (8.33%)	4/12 (33.33%)	3/12 (25.00%)
Protein urine present * 1	1/12 (8.33%)	4/12 (33.33%)	3/12 (25.00%)
White blood cell count increased * 1	1/12 (8.33%)	4/12 (33.33%)	3/12 (25.00%)
White blood cells urine positive * 1	2/12 (16.67%)	2/12 (16.67%)	3/12 (25.00%)
Eosinophil count increased * 1	3/12 (25.00%)	1/12 (8.33%)	3/12 (25.00%)
Red blood cells urine positive * 1	2/12 (16.67%)	2/12 (16.67%)	2/12 (16.67%)
Blood urea increased * 1	2/12 (16.67%)	1/12 (8.33%)	0/12 (0.00%)
Urine ketone body present * 1	0/12 (0.00%)	0/12 (0.00%)	2/12 (16.67%)
Blood bilirubin increased * 2	1/12 (8.33%)	0/12 (0.00%)	0/12 (0.00%)
Blood calcium decreased * 2	1/12 (8.33%)	0/12 (0.00%)	0/12 (0.00%)
Haematocrit decreased * 2	1/12 (8.33%)	0/12 (0.00%)	1/12 (8.33%)
Monocyte count increased * 2	1/12 (8.33%)	0/12 (0.00%)	1/12 (8.33%)
White blood cell count decreased * 2	1/12 (8.33%)	0/12 (0.00%)	0/12 (0.00%)
Metabolism and nutrition disorders
Anorexia * 2	1/12 (8.33%)	1/12 (8.33%)	0/12 (0.00%)
Musculoskeletal and connective tissue disorders
Myalgia * 1	1/12 (8.33%)	5/12 (41.67%)	1/12 (8.33%)
Arthralgia * 2	0/12 (0.00%)	1/12 (8.33%)	1/12 (8.33%)
Back pain * 2	0/12 (0.00%)	1/12 (8.33%)	0/12 (0.00%)
Pain in extremity * 2	1/12 (8.33%)	0/12 (0.00%)	0/12 (0.00%)
Pain in jaw * 2	0/12 (0.00%)	0/12 (0.00%)	1/12 (8.33%)
Shoulder pain * 2	0/12 (0.00%)	1/12 (8.33%)	0/12 (0.00%)
Musculoskeletal stiffness * 2	0/12 (0.00%)	0/12 (0.00%)	1/12 (8.33%)
Nervous system disorders
Headache * 1	5/12 (41.67%)	4/12 (33.33%)	5/12 (41.67%)
Psychiatric disorders
Restlessness * 2	0/12 (0.00%)	0/12 (0.00%)	1/12 (8.33%)
Reproductive system and breast disorders
Cervical dysplasia * 2	1/12 (8.33%)	0/12 (0.00%)	0/12 (0.00%)
Dysmenorrhoea * 2	1/12 (8.33%)	0/12 (0.00%)	1/12 (8.33%)
Respiratory, thoracic and mediastinal disorders
Sinus congestion * 1	2/12 (16.67%)	0/12 (0.00%)	1/12 (8.33%)
Pharyngolaryngeal pain * 2	1/12 (8.33%)	0/12 (0.00%)	0/12 (0.00%)
Rhinitis allergic * 2	0/12 (0.00%)	1/12 (8.33%)	0/12 (0.00%)
Skin and subcutaneous tissue disorders
Dermatitis contact * 2	1/12 (8.33%)	0/12 (0.00%)	0/12 (0.00%)
Hyperhidrosis * 2	1/12 (8.33%)	0/12 (0.00%)	0/12 (0.00%)
Rosacea * 2	0/12 (0.00%)	0/12 (0.00%)	1/12 (8.33%)
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA 8.1; 2 Term from vocabulary, MedDRA 8.0

Limitations and Caveats

This study was terminated early in light of issues with CTM stability. All other study procedures and visits were performed per protocol.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Sponsor must have the opportunity to review at least 60 days prior to submission for publication or presentation. If review indicates that potentially patentable subject matter would be disclosed, publication or public disclosure may be delayed for a maximum of an additional 60 days to allow for filing the necessary patent applications

Results Point of Contact

• Name/Title: Medical Director
• Organization: Sanofi Pasteur Inc.
• EMail: RegistryContactUs@sanofipasteur.com

• Responsible Party: Sanofi
• ClinicalTrials.gov Identifier: NCT00772954
• Other Study ID Numbers: H-030-010
• First Submitted: October 10, 2008
• First Posted: October 15, 2008
• Results First Submitted: March 13, 2012
• Results First Posted: May 21, 2012
• Last Update Posted: May 21, 2012