Safety and Immunogenicity of Typhax, a Typhoid Vaccine

Study Overview
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Brief Summary
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This was a randomized, double-blind, ascending dose study conducted at a single clinical research center.

Detailed Description
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Healthy adult subjects aged 18 to 55 years were assigned to 3 ascending dose cohorts of Typhax (0.5, 2.5 or 10 mcg Vi antigen). Groups of 15 subjects in each dose cohort were randomized to receive Typhax, Typhim Vi (25 mcg Vi antigen) or placebo (saline) in a ratio of 3:1:1, respectively. Typhax and placebo (saline) was administered as two dose regimen (Days 0 and 28), and Typhim Vi was given as a single dose (Day 0) with matching placebo on Day 28. All doses were administered by a unblinded third-party as 0.5 mL by intramuscular (IM) injection. Safety and reactogenicity endpoints was assessed at 14 and 28 days after the first Typhax vaccination and 14 days after the second vaccination. Immunogenicity was assessed using an enzyme-linked immunosorbent assay (ELISA) to measure anti-Vi antibody serum titers on days 0, 14, 28, 42 and 180. A positive immune response (seroconversion) by ELISA is defined as at least a 4-fold increase over baseline in the Vi-specific ELISA.

Official Title
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A Phase 1, Randomized, Double-Blind, Placebo-Controlled Dose Escalation Trial to Determine the Safety and Immunogenicity of Typhax Delivered IM

Conditions
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Typhoid Fever

Intervention / Treatment
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* Biological: Typhax (investigational typhoid fever candidate vaccine)
* Biological: Placebo
* Biological: Active Comparator Typhim Vi


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy adult men or women who are not pregnant or planning to become pregnant during study duration aged 18 to 55 years. Clinical laboratory parameters within normal laboratory limits or not found to be clinically significant by the PI Exclusion Criteria: Relevant history of physical or psychiatric illness or medical disorder that required treatment. Known or suspected hypersensitivity to investigational product Immunocompromised subjects Previous Typhoid vaccination or elevated anti-Vi antibodies at screening Known history of Typhoid infection in the previous 6 months Positive HIV, HBsAg, or HCV screen Any other condition or abnormality that, in the opinion of the Investigator, may compromise the safety of the patients

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: Sequential Assignment
Interventional Model Description: Randomized, Ascending Dose
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Typhax 0.5 mcg<br>Vaccine was administered IM on Days 0 and 28 (n=9). | Biological: Typhax (investigational typhoid fever candidate vaccine)<br> <br> |
| Experimental: Typhax 2.5 mcg<br>Vaccine was administered IM on Days 0 and 28 (n=9). | Biological: Typhax (investigational typhoid fever candidate vaccine)<br> <br> |
| Experimental: Typhax 10 mcg<br>Vaccine was administered IM on Days 0 and 28 (n=9). | Biological: Typhax (investigational typhoid fever candidate vaccine)<br> <br> |
| Active Comparator: Typhim Vi 25 mcg<br>Vaccine was administered IM Day 0 (n=9) followed by placebo control on Day 28 | Biological: Placebo<br>* Placebo is administered to the control group on Day 0 and 28<br>Biological: Active Comparator Typhim Vi<br>* A single dose of commercial typhoid fever vaccine Typhim Vi is administered on Day 0, followed by placebo control on Day 28<br>|
| Placebo Comparator: Placebo (saline)<br>Placebo control was administered IM Days 0 and 28 ( n=9) | Biological: Placebo<br>* Placebo is administered to the control group on Day 0 and 28<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants reporting solicited injection site and systemic events and unsolicited adverse events following vaccination with Typhax | Solicited Injection Site reactions: Pain, Tenderness, Erythema, Induration; Solicited Systemic Reactions Fever, Headache, Joint Pain, Joint Swelling, Fatigue, Myalgia, Nausea, Vomiting, Diarrhea | Days 0 up to Day 56 (= 28 Days post second vaccination) | 
| Number of participants reporting adverse events following vaccination with Typhax | Adverse events are assessed at study visits by PI for seriousness, relationship to investigational product , severity and other possible etiologies | Days 0 up to Day 210 | 
| Anti-Vi IgG antibody seroconversion and geometric mean antibody titers | The immunogenicity will be measured by ELISA for anti-Vi percent seroconversion and GMTs before and at day 14 after vaccination. | Day 0 - Day 14 | 
| Anti-Vi IgG antibody seroconversion and geometric mean antibody titers | The immunogenicity will be measured by ELISA for anti-Vi percent seroconversion and GMTs before and at day 28 after vaccination. | Day 0 - Day 28 | 
| Anti-Vi IgG antibody seroconversion and geometric mean antibody titers | The immunogenicity will be measured by ELISA for anti-Vi percent seroconversion and GMTs before and at day 42. | Day 0 - Day 42 | 
| Anti-Vi IgG antibody seroconversion and geometric mean antibody titers | The immunogenicity will be measured by ELISA for anti-Vi percent seroconversion and GMTs before and at day 180. | Day 0 - Day 180. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vi-specific B-cell ELISPOT responses | Immunogenicity was evaluated by comparing the number of Vi-specific B-cells by ELISPOT in PBMC samples | Days 0 through 38 |