Safety and Immunogenicity Study of an Inactivated Vaccine Against Hand, Foot and Mouth Disease Caused by Enterovirus 71

• ClinicalTrials.gov Identifier: NCT01376479
• Recruitment Status: Completed
• First Posted: June 20, 2011
• Last Update Posted: May 6, 2015
• Sponsor: Inviragen Inc.
• Information provided by (Responsible Party): Takeda ( Inviragen Inc. )

Study Description

Brief Summary:

The purpose of this study is to evaluate the safety and immune response of an inactivated vaccine to prevent hand, foot and mouth disease (HFMD) caused by Enterovirus 71 (EV71).

Condition or disease	Intervention/treatment	Phase
Hand, Foot and Mouth Disease	Biological: INV21 Low Dose; Biological: INV21 High Dose; Biological: Placebo	Phase 1

Detailed Description:

Hand, foot and mouth disease (HFMD) caused by Enterovirus 71 (EV71) can be severely debilitating for some children with a risk of paralysis and death. The most susceptible age group is the 1 to 5 year olds, and the disease is spread via the oral-fecal route. Currently, there is no antiviral therapy nor there is a vaccine available to prevent HFMD. In this study, an inactivated vaccine (INV21) based on the EV71 antigen will be evaluated in terms of safety and immune response that is generated after two doses of the vaccine are given to healthy adults. Safety assessments include the frequency and severity of systemic adverse events as well as local reactions. Immune response will be assessed by measurement of EV71 neutralizing antibody levels at specified time points throughout the study.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 36 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Phase I, Double Blind, Randomized, Placebo-controlled, Dose Escalation Study to Assess the Safety and Immunogenicity of a Prophylactic Vaccine Against Enterovirus Infection in Healthy Adults
• Study Start Date: August 2011
• Actual Primary Completion Date: November 2011
• Actual Study Completion Date: April 2012

Arms and Interventions

Arm	Intervention/treatment
Experimental: INV21 Low Dose	Biological: INV21 Low Dose; Inactivated EV71 vaccine containing whole viral particles of EV71 formulated with aluminum hydroxide.; Other Name: INV21; Biological: Placebo; Phosphate Buffered Saline (PBS)
Experimental: INV21 High Dose	Biological: INV21 High Dose; Inactivated EV71 vaccine consisting of whole viral particles of EV71 formulated with aluminum hydroxide.; Other Name: INV21; Biological: Placebo; Phosphate Buffered Saline (PBS)

Outcome Measures

Primary Outcome Measures :

1. Frequency of systemic adverse events and local reactions in healthy adults following two doses of INV21 given 28 days apart [ Time Frame: 56 days ]
   Frequency and severity of systemic adverse events up to 56 days post first dose. Frequency and severity of local reactions up to 14 days post each dose.

Secondary Outcome Measures :

1. Immunogenicity of INV21 vaccine in healthy adults following two doses given 28 days apart [ Time Frame: 8 months ]
   Geometric mean titers based on neutralizing antibody titers. Measurement of fold-increase over baseline of neutralizing titers against EV71. Durability of immune response at 2 months and 6 months after the last dose.

Eligibility Criteria

• Ages Eligible for Study: 21 Years to 45 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Male or female aged 21 to 45 years, inclusive, at time of screening
• In good health as determined by medical history and physical examination.
• Normal clinical safety laboratory examinations.
• Body mass index (BMI) in the range 19-28 kg/m2.
• Documented negative serology for HIV, Hepatitis C antibody, and Hepatitis B surface antigen.
• Females of child bearing potential must have a negative urine pregnancy test result during screening and a negative urine pregnancy test immediately prior to vaccination.
• Willing and able to give written informed consent to participate.
• Willing and able to communicate with the Investigator and understand the requirements of the study.
• Low levels of EV71 neutralizing antibody.

Exclusion Criteria:

• Any medical, psychiatric, social condition, occupational reason or other responsibility that, in the judgment of the investigator, is a contraindication to protocol participation or impairs a volunteer's ability to give informed consent
• Clinically significant hematological (including bleeding disorders), renal, hepatic, pulmonary (including asthma), central nervous system (including epilepsy, seizures, convulsions, or chronic migraines), cardiovascular, or gastrointestinal disorders, according to Investigator's judgment.
• Ongoing rash or other dermatologic disease.
• Abnormal ECG as assessed by the Investigator.
• History of diabetes mellitus.
• Hypersensitivity to any vaccine.
• History of severe HFMD with CNS involvement.
• Receipt of any vaccine in the 4 weeks preceding the first trial vaccination.
• Planned receipt of any vaccine in the 4 weeks following each of the vaccinations in this study.
• History of thymic pathology, thymectomy, myasthenia or any immunodeficiency.
• History of recurring migraines or on prescription medication for treatment of recurring headaches or migraines.
• Positive urine test for drugs of abuse.
• Females who are pregnant or lactating

Contacts and Locations

Locations

Singapore

Investigational Medicine Unit, National University Hospital

Singapore, Singapore, 119074

Sponsors and Collaborators

Inviragen Inc.

Investigators

• Principal Investigator: Paul A Tambyah, MBBS; Department of Medicine, National University Hospital

More Information

• Responsible Party: Inviragen Inc.
• ClinicalTrials.gov Identifier: NCT01376479
• Other Study ID Numbers: INV-EVR-101
• First Posted: June 20, 2011
• Last Update Posted: May 6, 2015
• Last Verified: May 2015

Keywords provided by Takeda ( Inviragen Inc. ):

HFMD; EV71; Enterovirus; INV21; Encephalitis

Additional relevant MeSH terms:

Enterovirus Infections; Foot-and-Mouth Disease; Hand, Foot and Mouth Disease; Mouth Diseases; Picornaviridae Infections; RNA Virus Infections; Virus Diseases; Stomatognathic Diseases; Coxsackievirus Infections