Typhoid FeverPhase 1NCT03926455
Safety and Immunogenicity of Typhax, a Typhoid Vaccine
A Phase 1 study testing Typhax (investigational typhoid fever candidate vaccine) and Active Comparator Typhim Vi in people with Typhoid Fever, run by Matrivax Research and Development Corporation.
Trial summary
This was a randomized, double-blind, ascending dose study conducted at a single clinical research center. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Typhoid Fever
- What is being tested?
- Typhax (investigational typhoid fever candidate vaccine) and Active Comparator Typhim Vi
- Type of treatment
- Vaccines
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 45 participants
- Where
- No sites listed yet
- Study dates
- 28 Mar 2016to 15 Feb 2017
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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
About this study
Official title: 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.
Read the 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.
- Conditions
- Typhoid Fever
- Being tested
- Typhax (investigational typhoid fever candidate vaccine), Placebo, Active Comparator Typhim Vi
- Medical subject headings
- Typhoid Fever
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Typhax (investigational typhoid fever candidate vaccine)Biological
PlaceboBiological
Placebo is administered to the control group on Day 0 and 28
Active Comparator Typhim ViBiological
A single dose of commercial typhoid fever vaccine Typhim Vi is administered on Day 0, followed by placebo control on Day 28
| Study group | Role | What they receive |
|---|---|---|
| Typhax 0.5 mcg | Experimental | Vaccine was administered IM on Days 0 and 28 (n=9). Receives: Biological: Typhax (investigational typhoid fever candidate vaccine) |
| Typhax 2.5 mcg | Experimental | Vaccine was administered IM on Days 0 and 28 (n=9). Receives: Biological: Typhax (investigational typhoid fever candidate vaccine) |
| Typhax 10 mcg | Experimental | Vaccine was administered IM on Days 0 and 28 (n=9). Receives: Biological: Typhax (investigational typhoid fever candidate vaccine) |
| Typhim Vi 25 mcg | Active comparator | Vaccine was administered IM Day 0 (n=9) followed by placebo control on Day 28 Receives: Biological: Placebo; Biological: Active Comparator Typhim Vi |
| Placebo (saline) | Placebo comparator | Placebo control was administered IM Days 0 and 28 ( n=9) Receives: Biological: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Day 0 - Day 180.
Secondary outcomes (1)
Vi-specific B-cell ELISPOT responses
Immunogenicity was evaluated by comparing the number of Vi-specific B-cells by ELISPOT in PBMC samples
Measured: Days 0 through 38
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Apr 2019
- Study start28 Mar 2016
- Primary completion15 Feb 2017
- Study completion15 Feb 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Typhoid FeverStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Sequential
- Model description
- Randomized, Ascending Dose
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- Matrivax Research and Development Corporation
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03926455
- Sponsor's protocol ID
- Typhax-101
- Status last verified
- Apr 2019
- First submitted
- 16 Apr 2019
- Last updated
- 24 Apr 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
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.
PubMed 31905228
Study at a glance
From the registry record, last updated by the sponsor on 24 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Randomized, Double-Blind, Placebo-Controlled Dose Escalation Trial to Determine the Safety and Immunogenicity of Typhax Delivered IM
- ClinicalTrials.gov ID
- NCT03926455
- Acronym / sponsor ID
- Typhax-101
- Conditions
- Typhoid Fever
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 45 participants (actual)
- Lead sponsor
- Matrivax Research and Development CorporationIndustry (pharma, biotech, devices)
- Study start
- 28 Mar 2016 (actual)
- Primary completion
- 15 Feb 2017 (actual)
- Study completion
- 15 Feb 2017 (actual)
- First posted
- 24 Apr 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Double blind (participant, investigator)
- Number of arms
- 5
- Model description
- Randomized, Ascending Dose
| Arm | Type | Receives |
|---|---|---|
| Typhax 0.5 mcg | Experimental | Biological: Typhax (investigational typhoid fever candidate vaccine)Vaccine was administered IM on Days 0 and 28 (n=9). |
| Typhax 2.5 mcg | Experimental | Biological: Typhax (investigational typhoid fever candidate vaccine)Vaccine was administered IM on Days 0 and 28 (n=9). |
| Typhax 10 mcg | Experimental | Biological: Typhax (investigational typhoid fever candidate vaccine)Vaccine was administered IM on Days 0 and 28 (n=9). |
| Typhim Vi 25 mcg | Active comparator | Biological: Placebo, Biological: Active Comparator Typhim ViVaccine was administered IM Day 0 (n=9) followed by placebo control on Day 28 |
| Placebo (saline) | Placebo comparator | Biological: PlaceboPlacebo control was administered IM Days 0 and 28 ( n=9) |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Typhax (investigational typhoid fever candidate vaccine) | Biological | Typhax 0.5 mcg, Typhax 10 mcg, Typhax 2.5 mcg |
| PlaceboPlacebo is administered to the control group on Day 0 and 28 | Biological | Placebo (saline), Typhim Vi 25 mcg |
| Active Comparator Typhim ViA single dose of commercial typhoid fever vaccine Typhim Vi is administered on Day 0, followed by placebo control on Day 28 | Biological | Typhim Vi 25 mcg |
Primary outcome
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
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
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.
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.
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.
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.
1 secondary outcome
Vi-specific B-cell ELISPOT responses
Time frame: Days 0 through 38
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Apr 2019.
- Derived from this study: PubMed 31905228Cartee 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Typhax (investigational typhoid fever candidate vaccine) and Active Comparator Typhim Vi in people with Typhoid Fever, run by Matrivax Research and Development Corporation.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03926455, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Apr 2019.