Safety and Immunogenicity of Typhax, a Typhoid Vaccine

• ClinicalTrials.gov Identifier: NCT03926455
• Recruitment Status: Completed
• First Posted: April 24, 2019
• Last Update Posted: April 24, 2019
• Sponsor: Matrivax Research and Development Corporation
• Information provided by (Responsible Party): Matrivax Research and Development Corporation

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Typhoid Fever	Biological: Typhax (investigational typhoid fever candidate vaccine); Biological: Placebo; Biological: Active Comparator Typhim Vi	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 45 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment
• Intervention Model Description: Randomized, Ascending Dose
• Masking: Double (Participant, Investigator)
• Masking Description: Study vaccine will be administered by an unblinded staff member at the clinic
• Primary Purpose: Prevention
• Official Title: A Phase 1, Randomized, Double-Blind, Placebo-Controlled Dose Escalation Trial to Determine the Safety and Immunogenicity of Typhax Delivered IM
• Actual Study Start Date: March 28, 2016
• Actual Primary Completion Date: February 15, 2017
• Actual Study Completion Date: February 15, 2017

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Number of participants reporting solicited injection site and systemic events and unsolicited adverse events following vaccination with Typhax [ Time Frame: 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
2. Number of participants reporting adverse events following vaccination with Typhax [ Time Frame: 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
3. Anti-Vi IgG antibody seroconversion and geometric mean antibody titers [ Time Frame: Day 0 - Day 14 ]
   The immunogenicity will be measured by ELISA for anti-Vi percent seroconversion and GMTs before and at day 14 after vaccination.
4. Anti-Vi IgG antibody seroconversion and geometric mean antibody titers [ Time Frame: Day 0 - Day 28 ]
   The immunogenicity will be measured by ELISA for anti-Vi percent seroconversion and GMTs before and at day 28 after vaccination.
5. Anti-Vi IgG antibody seroconversion and geometric mean antibody titers [ Time Frame: Day 0 - Day 42 ]
   The immunogenicity will be measured by ELISA for anti-Vi percent seroconversion and GMTs before and at day 42.
6. Anti-Vi IgG antibody seroconversion and geometric mean antibody titers [ Time Frame: Day 0 - Day 180. ]
   The immunogenicity will be measured by ELISA for anti-Vi percent seroconversion and GMTs before and at day 180.

Secondary Outcome Measures :

1. Vi-specific B-cell ELISPOT responses [ Time Frame: Days 0 through 38 ]
   Immunogenicity was evaluated by comparing the number of Vi-specific B-cells by ELISPOT in PBMC samples

Eligibility Criteria

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

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

Contacts and Locations

No Contacts or Locations Provided

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Matrivax Research and Development Corporation
• ClinicalTrials.gov Identifier: NCT03926455
• Other Study ID Numbers: Typhax-101
• First Posted: April 24, 2019
• Last Update Posted: April 24, 2019
• Last Verified: April 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Typhoid Fever; Salmonella Infections; Enterobacteriaceae Infections; Gram-Negative Bacterial Infections; Bacterial Infections