Safety and Immunogenicity of Typhax, a Typhoid Vaccine

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

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

Study Overview

• Status: Completed
• Conditions: Typhoid Fever
• Intervention / Treatment: Biological: Typhax (investigational typhoid fever candidate vaccine); Biological: Placebo; Biological: Active Comparator Typhim Vi

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.

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Matrivax Research and Development Corporation

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): March 28, 2016
• Primary Completion (Actual): February 15, 2017
• Study Completion (Actual): February 15, 2017

Study Registration Dates

• First Submitted: April 16, 2019
• First Submitted That Met QC Criteria: April 23, 2019
• First Posted (Actual): April 24, 2019

Study Record Updates

• Last Update Posted (Actual): April 24, 2019
• Last Update Submitted That Met QC Criteria: April 23, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Enterobacteriaceae Infections; Salmonella Infections; Typhoid Fever
• Other Study ID Numbers: Typhax-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No