Safety and Immunogenicity of Three Formulations of Vi-CRM197 Vaccine Against S. Typhi in Adults (18-40 Years Old)

• ClinicalTrials.gov Identifier: NCT01193907
• Recruitment Status: Completed
• First Posted: September 2, 2010
• Results First Posted: April 3, 2012
• Last Update Posted: January 17, 2014
• Sponsor: Novartis
• Information provided by (Responsible Party): Novartis

Study Description

Brief Summary:

This trial is aimed to evaluate the safety and immunogenicity profiles of three formulations of Vi-CRM197 conjugate vaccine against S. Typhi in healthy human adults in comparison with the currently licensed Vi polysaccharide vaccine

Condition or disease	Intervention/treatment	Phase
Typhoid Fever	Biological: NVGH Vi-CRM197 12.5 mcg; Biological: NVGH Vi-CRM197 5.0 mcg; Biological: NVGH Vi-CRM197 1.25 mcg; Biological: Vi-polysaccharide vaccine	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 88 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Prevention
• Official Title: A Phase 2, Randomized, Observer-blind, Controlled, Single Center Study to Evaluate the Safety and Immunogenicity of Three Formulations of the Novartis Vaccines Institute for Global Health (NVGH) Glycoconjugate Vaccine Against S. Typhi in Adult Subjects 18 to 40 Years of Age
• Study Start Date: October 2010
• Actual Primary Completion Date: November 2010
• Actual Study Completion Date: November 2010

Arms and Interventions

Arm	Intervention/treatment
Experimental: NVGH Vi-CRM197 conjugate vaccine 12.5 mcg; 1 dose of 0.5 mL containing 12.5 mcg of Vi-CRM	Biological: NVGH Vi-CRM197 12.5 mcg; 1 dose of 0.5 mL
Experimental: NVGH Vi-CRM197 conjugate vaccine 5 mcg; 1 dose of 0.5 mL containing 5 mcg of Vi-CRM	Biological: NVGH Vi-CRM197 5.0 mcg; 1 dose of 0.5 mL
Experimental: NVGH Vi-CRM197 conjugate vaccine 1.25 mcg; 1 dose of 0.5 mL containing 1.25 mcg of Vi-CRM	Biological: NVGH Vi-CRM197 1.25 mcg; 1 dose of 0.5 mL
Active Comparator: Typherix; 1 dose of 0.5 mL containing 25 mcg of Vi-polysaccharide	Biological: Vi-polysaccharide vaccine; 1 dose of 0.5 mL containing 25 mcg of Vi polysaccharide

Outcome Measures

Primary Outcome Measures :

1. Number of Subjects Reporting Any Post Immunization Reactions [ Time Frame: During the 7-day period after vaccination ]
   Solicited reactions collected during the 7-day period after vaccination are pain, erythema, induration, chills, malaise, myalgia, headache, arthralgia and fatigue
2. Number of Subjects Reporting Adverse Events [ Time Frame: During the 28-day period after vaccination ]
3. Anti-Vi ELISA (Enzyme Linked Immunosorbent Assay) Geometric Mean Concentration (GMC) [ Time Frame: At 28 days after vaccination ]
4. Percentage of Subjects With at Least 4-fold Increase in Anti-Vi ELISA Titer [ Time Frame: At 28 days after vaccination ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 40 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

1. Males and females of age ≥18 to ≤40 years.
2. Individuals who, after the nature of the study have been explained to them, have given written consent according to local regulatory requirements.
3. Individuals in good health as determined by the outcome of medical history, physical examination and clinical judgment of the investigator.
4. Individuals with negative urine screening tests for drug addition (Opiate, Cocaine, Amph/Metamphetamine, Cannabinoides )
5. If women, use of birth control one month before study start, a negative pregnancy test and willingness to use birth control measures for the entire study duration.

Exclusion Criteria:

1. Individuals with behavioral or cognitive impairment or psychiatric disease that, in the opinion of the investigator, may interfere with the subject's ability to participate in the study.
2. Individuals with any progressive or severe neurological disorder, seizure disorder or Guillain-Barré syndrome.
3. Individuals who are not able to understand and to follow all required study procedures for the whole period of the study.
4. Individuals with history of any illness that, in the opinion of the investigator, might interfere with the results of the study or pose additional risk to the subjects due to participation in the study.
5. Individuals with known or suspected HIV infection or HIV related disease, with history of an autoimmune disorder or any other known or suspected impairment /alteration of the immune system, or under immunosuppressive therapy including use of systemic corticosteroids or chronic use of inhaled high-potency corticosteroids within the previous 30 days, or were in chemotherapy treatment within the past 6 months.
6. Individuals with a known bleeding diathesis, or any condition that may be associated with a prolonged bleeding time.
7. Individuals with any serious chronic or progressive disease according to judgment of the investigator (e.g., neoplasm, insulin dependent diabetes, cardiac, renal or hepatic disease).
8. Individuals who have any malignancy or lymphoproliferative disorder.
9. Individuals with history of allergy to vaccine components.
10. Individuals participating in any clinical trial with another investigational product 30 days prior to first study visit or intent to participate in another clinical study at any time during the conduct of this study.
11. Individuals who have previously received any vaccines against typhoid fever (either oral live attenuated or injectable vaccines).
12. Individuals who received any other vaccines within 4 weeks prior to enrolment in this study or who are planning to receive any vaccine within 4 weeks from the study vaccine.
13. Individuals who have received blood, blood products and/or plasma derivatives including parenteral immunoglobulin preparations in the past 12 weeks.
14. Individuals who are part of study personnel or close family members to the personnel conducting this study.
15. Individuals with body temperature > 38.0 degrees Celsius within 3 days of intended study immunization.
16. BMI > 35 kg/m2.
17. Individuals with history of substance or alcohol abuse within the past 2 years.
18. Women who are pregnant or breast-feeding or of childbearing age who have not used any birth control measure one month prior to study start or do not plan to use acceptable birth control measures, for the duration of the study.
19. Females with history of stillbirth, neonatal loss, or previous infant with anomaly.
20. Individuals who have a previously ascertained or suspected disease caused by S. Typhi.
21. Individuals who have had household contact with/and or intimate exposure to an individual with laboratory confirmed S. Typhi.
22. Any condition which, in the opinion of the investigator may interfere with the evaluation of the study objectives.

Contacts and Locations

Locations

Belgium

Center for the Evaluation of Vaccination (CEV)

Antwerp, Wilrijk (Antwerp), Belgium, 2610

Sponsors and Collaborators

Novartis

More Information

Publications of Results:

van Damme P, Kafeja F, Anemona A, Basile V, Hilbert AK, De Coster I, Rondini S, Micoli F, Qasim Khan RM, Marchetti E, Di Cioccio V, Saul A, Martin LB, Podda A. Safety, immunogenicity and dose ranging of a new Vi-CRM₁₉₇ conjugate vaccine against typhoid fever: randomized clinical testing in healthy adults. PLoS One. 2011;6(9):e25398. doi: 10.1371/journal.pone.0025398. Epub 2011 Sep 30.

• Responsible Party: Novartis
• ClinicalTrials.gov Identifier: NCT01193907 History of Changes
• Other Study ID Numbers: H01_04TP; 2010-021874-12 ( EudraCT Number )
• First Posted: September 2, 2010
• Results First Posted: April 3, 2012
• Last Update Posted: January 17, 2014
• Last Verified: December 2013

Keywords provided by Novartis:

Typhoid fever; Glycoconjugate vaccine; Vi polysaccharide; Immunogenicity

Additional relevant MeSH terms:

Typhoid Fever; Salmonella Infections; Enterobacteriaceae Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Vaccines; Immunologic Factors; Physiological Effects of Drugs