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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
Matrivax Research and Development Corporation
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Typhoid Fever

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

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

    First Posted
    April 16, 2019
    Last Updated
    April 23, 2019
    Sponsor
    Matrivax Research and Development Corporation
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    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

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    Safety and Immunogenicity of Typhax, a Typhoid Vaccine

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