Safety and Immunogenicity of Typhax, a Typhoid Vaccine
Primary Purpose
Typhoid Fever
Status
Completed
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Typhax (investigational typhoid fever candidate vaccine)
Placebo
Active Comparator Typhim Vi
Sponsored by
About this trial
This is an interventional prevention trial for Typhoid Fever
Eligibility Criteria
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Experimental
Experimental
Experimental
Active Comparator
Placebo Comparator
Arm Label
Typhax 0.5 mcg
Typhax 2.5 mcg
Typhax 10 mcg
Typhim Vi 25 mcg
Placebo (saline)
Arm Description
Vaccine was administered IM on Days 0 and 28 (n=9).
Vaccine was administered IM on Days 0 and 28 (n=9).
Vaccine was administered IM on Days 0 and 28 (n=9).
Vaccine was administered IM Day 0 (n=9) followed by placebo control on Day 28
Placebo control was administered IM Days 0 and 28 ( n=9)
Outcomes
Primary Outcome Measures
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
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
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.
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.
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.
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.
Secondary Outcome Measures
Vi-specific B-cell ELISPOT responses
Immunogenicity was evaluated by comparing the number of Vi-specific B-cells by ELISPOT in PBMC samples
Full Information
NCT ID
NCT03926455
First Posted
April 16, 2019
Last Updated
April 23, 2019
Sponsor
Matrivax Research and Development Corporation
1. Study Identification
Unique Protocol Identification Number
NCT03926455
Brief Title
Safety and Immunogenicity of Typhax, a Typhoid Vaccine
Official Title
A Phase 1, Randomized, Double-Blind, Placebo-Controlled Dose Escalation Trial to Determine the Safety and Immunogenicity of Typhax Delivered IM
Study Type
Interventional
2. Study Status
Record Verification Date
April 2019
Overall Recruitment Status
Completed
Study Start Date
March 28, 2016 (Actual)
Primary Completion Date
February 15, 2017 (Actual)
Study Completion Date
February 15, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Matrivax Research and Development Corporation
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This was a randomized, double-blind, ascending dose study conducted at a single clinical research center.
Detailed Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Typhoid Fever
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Model Description
Randomized, Ascending Dose
Masking
ParticipantInvestigator
Masking Description
Study vaccine will be administered by an unblinded staff member at the clinic
Allocation
Randomized
Enrollment
45 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Typhax 0.5 mcg
Arm Type
Experimental
Arm Description
Vaccine was administered IM on Days 0 and 28 (n=9).
Arm Title
Typhax 2.5 mcg
Arm Type
Experimental
Arm Description
Vaccine was administered IM on Days 0 and 28 (n=9).
Arm Title
Typhax 10 mcg
Arm Type
Experimental
Arm Description
Vaccine was administered IM on Days 0 and 28 (n=9).
Arm Title
Typhim Vi 25 mcg
Arm Type
Active Comparator
Arm Description
Vaccine was administered IM Day 0 (n=9) followed by placebo control on Day 28
Arm Title
Placebo (saline)
Arm Type
Placebo Comparator
Arm Description
Placebo control was administered IM Days 0 and 28 ( n=9)
Intervention Type
Biological
Intervention Name(s)
Typhax (investigational typhoid fever candidate vaccine)
Intervention Type
Biological
Intervention Name(s)
Placebo
Intervention Description
Placebo is administered to the control group on Day 0 and 28
Intervention Type
Biological
Intervention Name(s)
Active Comparator Typhim Vi
Intervention Description
A single dose of commercial typhoid fever vaccine Typhim Vi is administered on Day 0, followed by placebo control on Day 28
Primary Outcome Measure Information:
Title
Number of participants reporting solicited injection site and systemic events and unsolicited adverse events following vaccination with Typhax
Description
Solicited Injection Site reactions: Pain, Tenderness, Erythema, Induration; Solicited Systemic Reactions Fever, Headache, Joint Pain, Joint Swelling, Fatigue, Myalgia, Nausea, Vomiting, Diarrhea
Time Frame
Days 0 up to Day 56 (= 28 Days post second vaccination)
Title
Number of participants reporting adverse events following vaccination with Typhax
Description
Adverse events are assessed at study visits by PI for seriousness, relationship to investigational product , severity and other possible etiologies
Time Frame
Days 0 up to Day 210
Title
Anti-Vi IgG antibody seroconversion and geometric mean antibody titers
Description
The immunogenicity will be measured by ELISA for anti-Vi percent seroconversion and GMTs before and at day 14 after vaccination.
Time Frame
Day 0 - Day 14
Title
Anti-Vi IgG antibody seroconversion and geometric mean antibody titers
Description
The immunogenicity will be measured by ELISA for anti-Vi percent seroconversion and GMTs before and at day 28 after vaccination.
Time Frame
Day 0 - Day 28
Title
Anti-Vi IgG antibody seroconversion and geometric mean antibody titers
Description
The immunogenicity will be measured by ELISA for anti-Vi percent seroconversion and GMTs before and at day 42.
Time Frame
Day 0 - Day 42
Title
Anti-Vi IgG antibody seroconversion and geometric mean antibody titers
Description
The immunogenicity will be measured by ELISA for anti-Vi percent seroconversion and GMTs before and at day 180.
Time Frame
Day 0 - Day 180.
Secondary Outcome Measure Information:
Title
Vi-specific B-cell ELISPOT responses
Description
Immunogenicity was evaluated by comparing the number of Vi-specific B-cells by ELISPOT in PBMC samples
Time Frame
Days 0 through 38
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
31905228
Citation
Cartee RT, Thanawastien A, Griffin Iv TJ, Mekalanos JJ, Bart S, Killeen KP. A phase 1 randomized safety, reactogenicity, and immunogenicity study of Typhax: A novel protein capsular matrix vaccine candidate for the prevention of typhoid fever. PLoS Negl Trop Dis. 2020 Jan 6;14(1):e0007912. doi: 10.1371/journal.pntd.0007912. eCollection 2020 Jan.
Results Reference
derived
Learn more about this trial
Safety and Immunogenicity of Typhax, a Typhoid Vaccine
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