Safety and Immunogenicity of Typhax, a Typhoid Vaccine

Phase 1

Completed

• Conditions: Typhoid Fever

• Registration Number: NCT03926455
• Lead Sponsor: Matrivax Research and Development Corporation

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.

Study Timeline

• Study Start: 2016-03-28
• Primary Completion: 2017-02-15
• Study Completion: 2017-02-15
• Status Verified: 2019-04
• Study First Submitted: 2019-04-16
• Study First Submitted QC: 2019-04-23
• Last Update Submitted: 2019-04-23
• Study First Posted: 2019-04-24
• Last Update Posted: 2019-04-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 45

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Vi-specific B-cell ELISPOT responses	Days 0 through 38	Immunogenicity was evaluated by comparing the number of Vi-specific B-cells by ELISPOT in PBMC samples