PolioPhase 1NCT03922061
Evaluation of Safety, Reactogenicity and Immunogenicity of Fractional-dose Inactivated Polio Vaccine (fIPV) Given Intradermally With Double Mutant Enterotoxigenic Escherichia Coli Heat Labile Toxin (dmLT) Adjuvant
A Phase 1 study testing dmLT and fIPV in people with Polio, run by University of Vermont at 1 site in United States.
Trial summary
Polio is a serious disease that can cause paralysis and death. It is caused by a virus and can be prevented by vaccine. The World Health Organization's (WHO) Global Polio Eradication Initiative is trying to get rid of all polio disease around the world. Researchers want to help by testing a new vaccine. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Polio
- What is being tested?
- dmLT and fIPV
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 29 participants
- Where
- 1 siteUnited States
- Study dates
- 19 Mar 2019to 4 Jun 2020
- 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 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Adult male or female age 18-45 years, inclusive
- Signed informed consent form prior to initiation of any study activity
- Good general health as determined by review of medical history and physical exam
- Agrees to complete all study visits and procedures for the duration of the study
- Receipt of childhood vaccine series of Inactivated Polio Vaccine with verification of immunization record. American College of Immunization Practices (AICP) required that OPV use be discontinued by January 2000. Therefore, polio vaccines given after January 2000 in the U.S. are known to be IPV. If the documentation is unclear of the type of polio vaccine given between 1998 and 2000, additional confirmation of the type should be attempted to determine eligibility.
- Agrees to storage of specimens for future research
- Females of child bearing potential only: willing to use effective contraception from the following reliable methods through the first 28 days of the study: hormonal birth control, condoms with spermicide, diaphragm with spermicide, surgical sterilization, and intrauterine device. All female subjects will be considered as having childbearing potential except for those who have had a hysterectomy or tubal ligation or have no internal female organs. Transgender men who have internal female organs will be considered of childbearing potential and should be willing to use effective contraception during the trial. Exception: females who have sex with females (exclusively) and have no intention of conceiving a child during the study will not be required to use contraception.
Who cannot join
- History of receipt of any oral polio vaccine. Subjects will be required to present their childhood immunization record during the screening process. Subjects will be excluded if the immunization record indicates receipt of any dose of oral polio vaccine or if only 'polio vaccine' is listed on the record without specifying whether oral or inactivated polio vaccine was administered.
- Currently lactating, breastfeeding or pregnant.
- Clinical laboratory values ≥ Grade 2 on hematology or comprehensive metabolic panel, as defined in this protocol.
- Febrile illness (≥38.0°C (100.4°F) or acute gastroenteritis within 48 hours prior to administration of IP
- History of antimicrobial treatment in the 2 weeks before administration of IP
- Receipt of a live vaccine within 28 days or a killed vaccine within 14 days prior to inoculation, or anticipated receipt of any vaccine during the 28 days following inoculation.
Show all 18Show fewer
- History of a severe allergic reaction or anaphylaxis
- History of Guillian-Barre Syndrome
- Known history of hypersensitivity to any component of IPV to include: 2-phenoxyethanol, formaldehyde, neomycin, streptomycin, and polymyxin B
- Self-reported or suspected immunodeficiency, or receipt of immunosuppressive therapy within the preceding 6 months, or long-term systemic corticosteroid therapy. An immunosuppressive dose of corticosteroids (excluding topical or nasal) is defined as >10 mg of prednisone equivalent per day for >14 days.
- Asplenia
- Receipt of blood products within the past 6 months, including transfusions or immunoglobulin, or anticipated receipt of any blood products or immunoglobulins during the 28 days following inoculation
- Anticipated receipt of any investigational agent in the 28 days before or after receipt of investigational product
- Abnormal routine bowel habits as defined by fewer than three stools per week in the past 6 months
- Regular use (weekly or more often) of laxatives, anti-diarrheal, anti-constipation, or antacid therapy
- Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, rheumatologic, autoimmune, or renal disease based on history and physical exam. This includes any chronic medical condition (examples include diabetes mellitus, hypertension, autoimmune disorders, cardiovascular and renal diseases).
- Behavioral, cognitive, or psychiatric disease that, in the opinion of the investigator, affects the subject's ability to understand and cooperative with the requirements of the study protocol.
- Any other condition that, in the opinion of the study clinician, would jeopardize the safety or rights of a subject participating
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase I Evaluation of the Safety, Reactogenicity and Immunogenicity of Fractional-dose Inactivated Polio Vaccine (fIPV) Given Intradermally With Double Mutant [LT(R192G/L211A)] Enterotoxigenic Escherichia Coli Heat Labile Toxin (dmLT) Adjuvant
Polio is a serious disease that can cause paralysis and death. It is caused by a virus and can be prevented by vaccine. The World Health Organization's (WHO) Global Polio Eradication Initiative is trying to get rid of all polio disease around the world. Researchers want to help by testing a new vaccine.
In many countries, people are vaccinated with oral polio vaccine (OPV) given by mouth during childhood. OPV is good at giving immunity (protection from polio) in the body and the gastrointestinal (GI) tract. Immunity in the GI tract is called mucosal immunity. The downsides of using OPV are that it can be shed into the environment in people's feces after vaccination where it can infect people who are not vaccinated, and it can cause paralysis in 2-4 of every one million children vaccinated with OPV. The United States (U.S.) stopped giving any OPV to people for vaccinations in the 1990's. Since then, a polio vaccine called inactivated polio vaccine (IPV) is given as an injection for routine childhood immunizations in the U.S. You cannot get polio infection from IPV and it will not be shed into the environment.
Read more
In 2016, the WHO started a plan to help other countries gradually get rid of OPV. The downside of using IPV by itself is that, unlike OPV, it doesn't give enough mucosal immunity to protect people living in places where there is still polio. There are also supply shortages of IPV, which is a problem if there are outbreaks of polio. For the supply of IPV to help more people, it is safe and effective to use a tiny dose of IPV injected under the top layer of skin (intradermal or ID injection) rather than getting the full dose in the muscle. This is called a fractional dose of IPV, or fIPV.
To help stop using OPV globally, a better fIPV vaccine is needed. fIPV vaccine needs a substance to help stimulate a mucosal immune response. dmLT is a substance that has been shown to stimulate a mucosal immune response. It has been shown to be safe and effective in both humans and animals, both by itself and when given with other vaccines.
This study will test a mixture of fIPV-dmLT given intradermally (under the outer layer of the skin). This is the first study done in humans to give this combination intradermally. The IPV vaccine has already been approved by the FDA. The fIPV-dmLT vaccine has not been approved by the FDA.
Read the detailed description
This single site study conducted at The University of Vermont will enroll 30 healthy male and female adult volunteers aged 18-45 years with no history of oral polio vaccination for a Phase I randomized controlled double-blind trial evaluating the safety, reactogenicity and immunogenicity of a single dose of fIPV-dMLT versus a single dose of fIPV administered intradermally. Study volunteers will be screened with eligible volunteers enrolled who will randomized to receive a single dose of fIPV-dmLT or fIPV (2:1) on study day 0. The primary study objective is to determine the safety and reactogenicity of a single dose of adjuvanted fIPV-dmLT vaccine in healthy adults, as assessed by the frequency of systemic and local injection site adverse reactions (ARs) defined as vaccine-related adverse events (AEs), graded by severity, occurring within 28 days of dosing. Secondary objectives are to determine the safety of a single dose of adjuvanted fIPV-dmLT vaccine in healthy adults, as assessed by the percentage of subjects with at least one vaccine-related serious adverse event (SAE) occurring within 28 days of dosing. In addition, the systemic immune response to a single dose of vaccine in healthy adults, as assessed by poliovirus-specific serum neutralizing antibody responses in fIPV-dmLT recipients versus fIPV only recipients will be examined.
- Conditions
- Polio
- Being tested
- dmLT, fIPV
- Keywords
- inactivated polio vaccine (IPV), fractional-dose inactivated polio vaccine (fIPV), double mutant [LT(R192G/L211A)] Enterotoxigenic E coli heat toxin (dmLT)
- Medical subject headings
- Poliomyelitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
dmLTBiological
double mutant [LT(R192G/L211A)] Enterotoxigenic Escherichia coli heat labile toxin (dmLT)
fIPVBiological
fractional-dose inactived polio vaccine
| Study group | Role | What they receive |
|---|---|---|
| fIPV-dmLT | Experimental | fractional-dose inactivated polio vaccine (fIPV) given intradermally with double mutant [LT(R192G/L211A)] Enterotoxigenic Escherichia coli heat labile toxin (dmLT) adjuvant Receives: Biological: dmLT; Biological: fIPV |
| fIPV | Active comparator | fractional-dose inactivated polio vaccine (fIPV) given intradermally Receives: Biological: fIPV |
What is being measured
The primary outcome is the main question the study is designed to answer.
frequency of systemic and local injection (safety and reactogenicity)
frequency of systemic and local injection site adverse reactions (ARs) defined as vaccine-related adverse events (AEs), graded by severity
Measured: Events occuring within 28 days of dosing
Secondary outcomes (2)
percentage of subjects with at least one serious adverse event (secondary-safety)
percentage of subjects with at least one serious adverse event (SAE) occurring within 28 days of dosing will be summarized with severity, relationship to vaccine, and outcome
Measured: Events occuring within 28 days of dosing
Systemic immunogenicity
Proportion of participants showing at least a 4-fold boost in polio-specific serum neutralizing antibodies compared to baseline (Day 0) in fIPV-dmLT recipients vs. fIPV alone
Measured: Any timepoint up to day 28 post-vaccination
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Apr 2019
- Study start19 Mar 2019
- Primary completion18 Jul 2019
- Study completion4 Jun 2020
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 PolioStudies 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
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 29 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Vermont
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Kelly Cowan, University of Vermont
- Investigators
- Kelly Cowan, M.D., Principal investigator, University of VermontBeth Kirkpatrick, M.D., Principal investigator, University of Vermont
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03922061
- Sponsor's protocol ID
- CHRMS 19-0048
- Status last verified
- Aug 2020
- First submitted
- 16 Apr 2019
- Last updated
- 5 Aug 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Crothers JW, Ross Colgate E, Cowan KJ, Dickson DM, Walsh M, Carmolli M, Wright PF, Norton EB, Kirkpatrick BD. Intradermal fractional-dose inactivated polio vaccine (fIPV) adjuvanted with double mutant Enterotoxigenic Escherichia coli heat labile toxin (dmLT) is well-tolerated and augments a systemic immune response to all three poliovirus serotypes in a randomized placebo-controlled trial. Vaccine. 2022 Apr 26;40(19):2705-2713. doi: 10.1016/j.vaccine.2022.03.056. Epub 2022 Mar 30.
PubMed 35367069
Study at a glance
From the registry record, last updated by the sponsor on 5 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Evaluation of the Safety, Reactogenicity and Immunogenicity of Fractional-dose Inactivated Polio Vaccine (fIPV) Given Intradermally With Double Mutant [LT(R192G/L211A)] Enterotoxigenic Escherichia Coli Heat Labile Toxin (dmLT) Adjuvant
- ClinicalTrials.gov ID
- NCT03922061
- Acronym / sponsor ID
- CHRMS 19-0048
- Conditions
- Polio
- Keywords
- inactivated polio vaccine (IPV), fractional-dose inactivated polio vaccine (fIPV), double mutant [LT(R192G/L211A)] Enterotoxigenic E coli heat toxin (dmLT)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 29 participants (actual)
- Lead sponsor
- University of VermontUniversity, hospital or other
- Study start
- 19 Mar 2019 (actual)
- Primary completion
- 18 Jul 2019 (actual)
- Study completion
- 4 Jun 2020 (actual)
- First posted
- 19 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.
Polio is a serious disease that can cause paralysis and death. It is caused by a virus and can be prevented by vaccine. The World Health Organization's (WHO) Global Polio Eradication Initiative is trying to get rid of all polio disease around the world. Researchers want to help by testing a new vaccine.
In many countries, people are vaccinated with oral polio vaccine (OPV) given by mouth during childhood. OPV is good at giving immunity (protection from polio) in the body and the gastrointestinal (GI) tract. Immunity in the GI tract is called mucosal immunity. The downsides of using OPV are that it can be shed into the environment in people's feces after vaccination where it can infect people who are not vaccinated, and it can cause paralysis in 2-4 of every one million children vaccinated with OPV. The United States (U.S.) stopped giving any OPV to people for vaccinations in the 1990's. Since then, a polio vaccine called inactivated polio vaccine (IPV) is given as an injection for routine childhood immunizations in the U.S. You cannot get polio infection from IPV and it will not be shed into the environment.
In 2016, the WHO started a plan to help other countries gradually get rid of OPV. The downside of using IPV by itself is that, unlike OPV, it doesn't give enough mucosal immunity to protect people living in places where there is still polio. There are also supply shortages of IPV, which is a problem if there are outbreaks of polio. For the supply of IPV to help more people, it is safe and effective to use a tiny dose of IPV injected under the top layer of skin (intradermal or ID injection) rather than getting the full dose in the muscle. This is called a fractional dose of IPV, or fIPV.
To help stop using OPV globally, a better fIPV vaccine is needed. fIPV vaccine needs a substance to help stimulate a mucosal immune response. dmLT is a substance that has been shown to stimulate a mucosal immune response. It has been shown to be safe and effective in both humans and animals, both by itself and when given with other vaccines.
This study will test a mixture of fIPV-dmLT given intradermally (under the outer layer of the skin). This is the first study done in humans to give this combination intradermally. The IPV vaccine has already been approved by the FDA. The fIPV-dmLT vaccine has not been approved by the FDA.
Detailed description
This single site study conducted at The University of Vermont will enroll 30 healthy male and female adult volunteers aged 18-45 years with no history of oral polio vaccination for a Phase I randomized controlled double-blind trial evaluating the safety, reactogenicity and immunogenicity of a single dose of fIPV-dMLT versus a single dose of fIPV administered intradermally. Study volunteers will be screened with eligible volunteers enrolled who will randomized to receive a single dose of fIPV-dmLT or fIPV (2:1) on study day 0. The primary study objective is to determine the safety and reactogenicity of a single dose of adjuvanted fIPV-dmLT vaccine in healthy adults, as assessed by the frequency of systemic and local injection site adverse reactions (ARs) defined as vaccine-related adverse events (AEs), graded by severity, occurring within 28 days of dosing. Secondary objectives are to determine the safety of a single dose of adjuvanted fIPV-dmLT vaccine in healthy adults, as assessed by the percentage of subjects with at least one vaccine-related serious adverse event (SAE) occurring within 28 days of dosing. In addition, the systemic immune response to a single dose of vaccine in healthy adults, as assessed by poliovirus-specific serum neutralizing antibody responses in fIPV-dmLT recipients versus fIPV only recipients will be examined.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| fIPV-dmLT | Experimental | Biological: dmLT, Biological: fIPVfractional-dose inactivated polio vaccine (fIPV) given intradermally with double mutant [LT(R192G/L211A)] Enterotoxigenic Escherichia coli heat labile toxin (dmLT) adjuvant |
| fIPV | Active comparator | Biological: fIPVfractional-dose inactivated polio vaccine (fIPV) given intradermally |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Adult male or female age 18-45 years, inclusive
- Signed informed consent form prior to initiation of any study activity
- Good general health as determined by review of medical history and physical exam
- Agrees to complete all study visits and procedures for the duration of the study
- Receipt of childhood vaccine series of Inactivated Polio Vaccine with verification of immunization record. American College of Immunization Practices (AICP) required that OPV use be discontinued by January 2000. Therefore, polio vaccines given after January 2000 in the U.S. are known to be IPV. If the documentation is unclear of the type of polio vaccine given between 1998 and 2000, additional confirmation of the type should be attempted to determine eligibility.
Key exclusion criteria (18 listed)
- History of receipt of any oral polio vaccine. Subjects will be required to present their childhood immunization record during the screening process. Subjects will be excluded if the immunization record indicates receipt of any dose of oral polio vaccine or if only 'polio vaccine' is listed on the record without specifying whether oral or inactivated polio vaccine was administered.
- Currently lactating, breastfeeding or pregnant.
- Clinical laboratory values ≥ Grade 2 on hematology or comprehensive metabolic panel, as defined in this protocol.
- Febrile illness (≥38.0°C (100.4°F) or acute gastroenteritis within 48 hours prior to administration of IP
- History of antimicrobial treatment in the 2 weeks before administration of IP
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 |
|---|---|---|
| dmLTdouble mutant [LT(R192G/L211A)] Enterotoxigenic Escherichia coli heat labile toxin (dmLT) | Biological | fIPV-dmLT |
| fIPVfractional-dose inactived polio vaccine | Biological | fIPV, fIPV-dmLT |
Primary outcome
frequency of systemic and local injection (safety and reactogenicity)
Time frame: Events occuring within 28 days of dosing
frequency of systemic and local injection site adverse reactions (ARs) defined as vaccine-related adverse events (AEs), graded by severity
2 secondary outcomes
percentage of subjects with at least one serious adverse event (secondary-safety)
Time frame: Events occuring within 28 days of dosing
Systemic immunogenicity
Time frame: Any timepoint up to day 28 post-vaccination
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 5 Aug 2020.
- Derived from this study: PubMed 35367069Crothers JW, Ross Colgate E, Cowan KJ, Dickson DM, Walsh M, Carmolli M, Wright PF, Norton EB, Kirkpatrick BD. Intradermal fractional-dose inactivated polio vaccine (fIPV) adjuvanted with double mutant Enterotoxigenic Escherichia coli heat labile toxin (dmLT) is well-tolerated and augments a systemic immune response to all three poliovirus serotypes in a randomized placebo-controlled trial. Vaccine. 2022 Apr 26;40(19):2705-2713. doi: 10.1016/j.vaccine.2022.03.056. Epub 2022 Mar 30.
- 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.
Kelly Cowan, M.D. principal investigator
University of Vermont
Beth Kirkpatrick, M.D. principal investigator
University of Vermont
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing dmLT and fIPV in people with Polio, run by University of Vermont at 1 site in United States.
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 7 inclusion and 18 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 5 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. 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?
frequency of systemic and local injection (safety and reactogenicity) (time frame: Events occuring within 28 days of dosing). 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 NCT03922061, 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 5 Aug 2020.