Clinical trial NCT03926455: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Typhoid Fever
Lead sponsor: Matrivax Research and Development Corporation
Sponsor class: INDUSTRY
First posted: 2019-04-24
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Randomized, Ascending Dose
Primary purpose: PREVENTION

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.

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

Primary outcomes:
measure: Number of participants reporting solicited injection site and systemic events and unsolicited adverse events following vaccination with Typhax
timeFrame: Days 0 up to Day 56 (= 28 Days post second vaccination)
measure: Number of participants reporting adverse events following vaccination with Typhax
timeFrame: Days 0 up to Day 210
measure: Anti-Vi IgG antibody seroconversion and geometric mean antibody titers
timeFrame: Day 0 - Day 14
measure: Anti-Vi IgG antibody seroconversion and geometric mean antibody titers
timeFrame: Day 0 - Day 28
measure: Anti-Vi IgG antibody seroconversion and geometric mean antibody titers
timeFrame: Day 0 - Day 42
measure: Anti-Vi IgG antibody seroconversion and geometric mean antibody titers
timeFrame: Day 0 - Day 180.
Secondary outcomes:
measure: Vi-specific B-cell ELISPOT responses
timeFrame: Days 0 through 38
Other outcomes:
Locations:
Study officials:
References:
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.