Extension Study of H01_04TP to Evaluate the Booster Response Induced by Vi-CRM197 in Adults

A Phase 2, Open-label, Single-center, Extension Study to Evaluate the Booster Response Induced by Vi-CRM197 After Priming With Either Vi-CRM197 or Typherix Administered in Adult Subjects in H01_04TP Study (NCT01193907)

The purpose of this study is to evaluate the immunogenicity and the kinetics of the anti-Vi antibody response following secondary vaccination with the Novartis Vaccines Institute for Global Health (NVGH) Vi-CRM197 vaccine in healthy adults previously vaccinated with either the NVGH Vi-CRM197 or Vi-polysaccharide (Typherix) in the H01_04TP study (NCT01193907) and the immunogenicity and the kinetics of the anti-Vi antibody response following primary vaccination with the NVGH Vi-CRM197 vaccine in naïve healthy adults.

Study Overview

• Status: Completed
• Conditions: Typhoid Fever
• Intervention / Treatment: Biological: NVGH Vi-CRM197

• Study Type: Interventional
• Enrollment (Actual): 51
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Wilrijk
    • Antwerp, Wilrijk, Belgium, 2610
      • Centre for the Evaluation of Vaccination (CEV)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 42 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria

All Subjects:

1. Males and females of age ≥18 to ≤42 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. 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.

   H01_04TP subjects only:

5. Individuals who previously participated in the H01_04TP study and were vaccinated with either NVGH Vi-CRM197 (5μg) or with the licensed Vi-PS.
6. Individuals who have received no Vi vaccination subsequent to the one received in the H01_04TP study.

Inclusion criteria

All subjects:

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, 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 received any 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
12. Individuals who have received blood, blood products and/or plasma derivatives including parenteral immunoglobulin preparations in the past 12 weeks.
13. Individuals who are part of study personnel or close family members to the personnel conducting this study.
14. Individuals with body temperature > 38.0 degrees Celsius within 3 days of intended study immunization.
15. BMI > 35 kg/m2.
16. Individuals with history of substance or alcohol abuse within the past 2 years.
17. 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.
18. Females with history of stillbirth, neonatal loss, or previous infant with anomaly.
19. Individuals who have a previously ascertained or suspected disease caused by S. Typhi.
20. Individuals who have had household contact with/and or intimate exposure to an individual with laboratory confirmed S. Typhi.

21. Any condition which, in the opinion of the investigator may interfere with the evaluation of the study objectives.

    Naïve subjects only:

22. Individuals who have previously received any vaccine against typhoid fever (either oral live attenuated or injectable vaccines)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NVGH Vi-CRM/NVGH Vi-CRM; One 0.5 mL dose of NVGH Vi-CRM197 5.0 mcg in adults who received 1 dose of NVGH Vi-CRM197 5.0 mcg in H01_04TP study	Biological: NVGH Vi-CRM197; Vi-CRM197 glycoconjugated vaccine
Experimental: Vi-PS/NVGH Vi-CRM; One 0.5 mL dose of NVGH Vi-CRM197 5.0 mcg in adults who received 1 dose of Vi-polysaccharide (PS) in H01_04TP study	Biological: NVGH Vi-CRM197; Vi-CRM197 glycoconjugated vaccine
Experimental: NVGH Vi-CRM; One 0.5 mL dose of NVGH Vi-CRM197 5.0 mcg in naive adults	Biological: NVGH Vi-CRM197; Vi-CRM197 glycoconjugated vaccine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anti-Vi ELISA Geometric Mean Concentration (GMC)	To evaluate the immunogenicity and the kinetics of the immune response induced by one dose of NVGH Vi-CRM197 at study day 3 after vaccination as as measured by enzyme-linked immunosorbent assay (ELISA)	At 3 days after vaccination
Anti-Vi ELISA GMC	To evaluate the immunogenicity and the kinetics of the immune response induced by one dose of NVGH Vi-CRM197 at study day 7 after vaccination as as measured by ELISA	At 7 days after vaccination
Anti-Vi ELISA GMC	To evaluate the immunogenicity and the kinetics of the immune response induced by one dose of NVGH Vi-CRM197 at study day 28 after vaccination as as measured by ELISA	At 28 days after vaccination
Percentage of Subjects With at Least 4-fold Increase in Anti-Vi ELISA Titers		At 3 days after vaccination as compared to baseline
Percentage of Subjects With at Least 4-fold Increase in Anti-Vi ELISA Titers		At 7 days after vaccination as compared to baseline
Percentage of Subjects With at Least 4-fold Increase in Anti-Vi ELISA Titers		At 28 days after vaccination as compared to baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects Reporting Any (Local, Systemic and Other) Post Vaccination Reaction	Solicited reactions collected during the 7-day period after vaccination are pain, erythema, induration, chills, malaise, myalgia, headache, arthralgia, fatigue and fever.	During the 7-day period after vaccination
Number of Subjects Reporting AE	AE during 28 days after vaccination(including solicited reactions during 7 days after vaccination)	During the 28-day period after vaccination
Number of Subjects Reporting Serious Adverse Events (SAEs)		During the 28-day period after vaccination

Collaborators and Investigators

• Sponsor: Novartis
• Investigators: Principal Investigator: Pierre van Damme, MD, Universiteit Antwerpen

Study record dates

Study Major Dates

• Study Start: October 1, 2011
• Primary Completion (Actual): December 1, 2011
• Study Completion (Actual): December 1, 2011

Study Registration Dates

• First Submitted: September 19, 2011
• First Submitted That Met QC Criteria: September 21, 2011
• First Posted (Estimate): September 22, 2011

Study Record Updates

• Last Update Posted (Estimate): March 24, 2014
• Last Update Submitted That Met QC Criteria: February 4, 2014
• Last Verified: February 1, 2014

More Information

Terms related to this study

• Keywords: Immunogenicity; Typhoid fever; Glycoconjugate vaccine; Vi polysaccharide
• Additional Relevant MeSH Terms: Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Enterobacteriaceae Infections; Salmonella Infections; Typhoid Fever
• Other Study ID Numbers: H01_04E1TP