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

Study Overview
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Brief Summary
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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

Official Title
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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

Conditions
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Typhoid Fever

Intervention / Treatment
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* 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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females of age ≥18 to ≤40 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. Individuals with negative urine screening tests for drug addition (Opiate, Cocaine, Amph/Metamphetamine, Cannabinoides ) 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: 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, might interfere with the results of the study or 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 have previously received any vaccines against typhoid fever (either oral live attenuated or injectable vaccines). 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. 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 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: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NVGH Vi-CRM197 conjugate vaccine 12.5 mcg<br>1 dose of 0.5 mL containing 12.5 mcg of Vi-CRM | Biological: NVGH Vi-CRM197 12.5 mcg<br>* 1 dose of 0.5 mL<br>|
| Experimental: NVGH Vi-CRM197 conjugate vaccine 5 mcg<br>1 dose of 0.5 mL containing 5 mcg of Vi-CRM | Biological: NVGH Vi-CRM197 5.0 mcg<br>* 1 dose of 0.5 mL<br>|
| Experimental: NVGH Vi-CRM197 conjugate vaccine 1.25 mcg<br>1 dose of 0.5 mL containing 1.25 mcg of Vi-CRM | Biological: NVGH Vi-CRM197 1.25 mcg<br>* 1 dose of 0.5 mL<br>|
| Active Comparator: Typherix<br>1 dose of 0.5 mL containing 25 mcg of Vi-polysaccharide | Biological: Vi-polysaccharide vaccine<br>* 1 dose of 0.5 mL containing 25 mcg of Vi polysaccharide<br>|

What is the study measuring?
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Primary Outcome Measures

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