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

NCT03922061 | Completed Phase 1 FDA Drug

• 1 other identifier: CHRMS 19-0048
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Polio

Keywords

inactivated polio vaccine (IPV); fractional-dose inactivated polio vaccine (fIPV); double mutant [LT(R192G/L211A)] Enterotoxigenic E coli heat toxin (dmLT)

Outcome Measures

Primary Outcomes (1)

• 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

  Events occuring within 28 days of dosing

Secondary Outcomes (2)

• percentage of subjects with at least one serious adverse event (secondary-safety)

  Events occuring within 28 days of dosing

• Systemic immunogenicity

  Any timepoint up to day 28 post-vaccination

Study Arms (2)

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

Biological: dmLT; Biological: fIPV

fIPV

ACTIVE COMPARATOR

fractional-dose inactivated polio vaccine (fIPV) given intradermally

Biological: fIPV

Interventions

dmLT BIOLOGICAL

double mutant \[LT(R192G/L211A)\] Enterotoxigenic Escherichia coli heat labile toxin (dmLT)

fIPV-dmLT

fIPV BIOLOGICAL

fractional-dose inactived polio vaccine

fIPV; fIPV-dmLT

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• University of Vermont: lead

Study Sites (1)

University of Vermont

Burlington, Vermont, 05405, United States

Location

Related Publications (1)

• 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.

  PMID: 35367069 DERIVED

MeSH Terms

Conditions

Poliomyelitis

Condition Hierarchy (Ancestors)

Myelitis; Central Nervous System Infections; Infections; Enterovirus Infections; Picornaviridae Infections; RNA Virus Infections; Virus Diseases; Central Nervous System Diseases; Nervous System Diseases; Spinal Cord Diseases; Neuroinflammatory Diseases; Neuromuscular Diseases

Study Officials

• Kelly Cowan, M.D.

  University of Vermont

  PRINCIPAL INVESTIGATOR

• Beth Kirkpatrick, M.D.

  University of Vermont

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Pediatrics

Study Record Dates

• First Submitted: April 16, 2019
• First Posted: April 19, 2019
• Study Start: March 19, 2019
• Primary Completion: July 18, 2019
• Study Completion: June 4, 2020
• Last Updated: August 5, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)