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

Study Overview
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Brief Summary
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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.

Official Title
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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)

Conditions
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Typhoid Fever

Intervention / Treatment
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* Biological: NVGH Vi-CRM197


Participation Criteria
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Eligibility Criteria
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Inclusion criteria All Subjects: Males and females of age ≥18 to ≤42 years. Individuals, who, after the nature of the study have been explained to them, have given written consent according to local regulatory requirements. Individuals in good health as determined by the outcome of medical history, physical examination and clinical judgment of the investigator. 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: Individuals who previously participated in the H01_04TP study and were vaccinated with either NVGH Vi-CRM197 (5μg) or with the licensed Vi-PS. Individuals who have received no Vi vaccination subsequent to the one received in the H01_04TP study. Inclusion criteria All subjects: 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. Individuals with any progressive or severe neurological disorder, seizure disorder or Guillain-Barré syndrome. Individuals who are not able to understand and to follow all required study procedures for the whole period of the study. 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. 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. Individuals with a known bleeding diathesis, or any condition that may be associated with a prolonged bleeding time. 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). Individuals who have any malignancy or lymphoproliferative disorder. Individuals with history of allergy to vaccine components. 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. 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 Individuals who have received blood, blood products and/or plasma derivatives including parenteral immunoglobulin preparations in the past 12 weeks. Individuals who are part of study personnel or close family members to the personnel conducting this study. Individuals with body temperature > 38.0 degrees Celsius within 3 days of intended study immunization. BMI > 35 kg/m2. Individuals with history of substance or alcohol abuse within the past 2 years. 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. Females with history of stillbirth, neonatal loss, or previous infant with anomaly. Individuals who have a previously ascertained or suspected disease caused by S. Typhi. Individuals who have had household contact with/and or intimate exposure to an individual with laboratory confirmed S. Typhi. Any condition which, in the opinion of the investigator may interfere with the evaluation of the study objectives. Naïve subjects only: Individuals who have previously received any vaccine against typhoid fever (either oral live attenuated or injectable vaccines)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 42 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NVGH Vi-CRM/NVGH Vi-CRM<br>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<br>* Vi-CRM197 glycoconjugated vaccine<br>|
| Experimental: Vi-PS/NVGH Vi-CRM<br>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<br>* Vi-CRM197 glycoconjugated vaccine<br>|
| Experimental: NVGH Vi-CRM<br>One 0.5 mL dose of NVGH Vi-CRM197 5.0 mcg in naive adults | Biological: NVGH Vi-CRM197<br>* Vi-CRM197 glycoconjugated vaccine<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Typhoid fever, Glycoconjugate vaccine, Vi polysaccharide, Immunogenicity