A Safety and Efficacy Study of the Hepatitis E Vaccine in Nepal.

May 8, 2019 updated by: U.S. Army Medical Research and Development Command

A Phase II, Prospective, Randomized, Double-blind, Placebo Controlled, Field Efficacy Trial of a Candidate Hepatitis E Vaccine in Nepal.

The purpose of this study is to determine if a hepatitis E vaccine is safe and able to prevent symptomatic liver disease due to the hepatitis E virus.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This is a prospective, randomized, double-blind, placebo-controlled with 2 study groups (vaccine and placebo). Three doses of the study vaccine are given according to a 0, 1, 6 month schedule. Vaccine efficacy will be assessed by maintaining active surveillance for clinical hepatitis every 2 weeks and hospital based surveillance for the full duration of the trial. Total planned study population is 2000 eligible subjects (1000 in the vaccine group and 1000 in the placebo group). Total vaccinated cohort for the analysis of reactogenicity is 200 (100 in the vaccine group and 100 in the placebo group).

Volunteers who enroll will be followed for evidence of symptomatic liver disease for approximately 2 years, and those who become ill will be admitted to hospital for care.

To evaluate safety, a randomly designated subset will be monitored for 7 days after each vaccination to solicit specific symptoms at the injection site and generally. Additionally, all adverse events will be collected for 30 days after each vaccine dose and all serious adverse events will be collected throughout the trial.

Study Type

Interventional

Enrollment (Actual)

2000

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Nepal
      • Kathmandu, Nepal
        • Shree Birendra Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • A male or female 18 years of age or older at the time of the first vaccination.
  • Written or oral witnessed (if the subject was illiterate) informed consent obtained from the subject
  • Free of obvious health problems as established by medical history before entering into the study
  • If the subject was female, she must have a negative serum pregnancy test within 48 hours prior to each vaccination and must agree to avoid becoming pregnant during the course of vaccination and until 30 days after the last dose of vaccine.

Exclusion Criteria:

  • Use of any investigational or non-registered drug or vaccine other than the study vaccine(s) within 30 days preceding the first dose of study vaccine, or planned use during the study period.
  • Administration of chronic (defined as more than 14 days) immunosuppressants or other immune modifying drugs within six months of vaccination. For corticosteroids, this will mean prednisone, or equivalent, * 0.5 mg/kg/day. Inhaled and topical steroids are allowed.
  • Any chronic drug therapy to be continued during the study period with the exception of contraceptive agents, homeopathic remedies, vitamins, minerals and any other dietary supplements or other drug therapy at the discretion of the investigator.
  • Planned administration/administration of a vaccine not foreseen by the study protocol within 30 days of the first dose of study vaccine, excluding tetanus toxoid or rabies vaccine.
  • Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection, as reported by the volunteer (testing for HIV will not be performed).
  • History of allergic disease or reactions likely to be exacerbated by any component of the vaccine.
  • Major congenital defects or serious chronic illness.
  • History of any neurologic disorders or seizures.
  • Acute disease at the time of enrollment. Acute disease was defined as the presence of a moderate or severe illness with or without fever. All vaccines could be administered to persons with a minor illness such as diarrhea, mild upper respiratory infection with or without low-grade febrile illness, i.e., oral temperature < 38.0°C (100.4°F).
  • Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by history.
  • Administration of immunoglobulins and/or any blood products within the three months preceding the first dose of study vaccine or planned administration during the study period.
  • Pregnant female.
  • History of chronic alcohol consumption (defined as the consumption of the equivalent of 4 or more 12 ounce beers 4 or more times a week) and/or intravenous drug abuse.
  • Antibodies to rHEV (* 20 WR U/mL).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 20mcg Recombinant HEV
20mcg of recombinant HEV antigen administered intramuscularly in the deltoid according to a 0, 1 and 6 month schedule
Biological: Hepatitis E vaccine, recombinant (Sar 56 kDa)
20mcg or rhE Sar 56 kDa/dose of 0.5 mL, aluminium hydroxide (0.5 mg/dose) and phenoxyethanol (2.5 mg/dose)
Placebo Comparator: Placebo
PBS buffer placebo containing alum was administered intramuscularly in the deltoid according to a 0, 1 and 6 month schedule.
Other: Placebo
PBS buffer placebo containing alum

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percent of Participants of Definite Hepatitis E by Category and Immunological Markers (Anti HEV) During the Follow-up Period
Time Frame: 14 days after dose 3 at 6 months

Percent of participants of definite hepatitis E by category and immunological markers (anti HEV) during the follow-up period.

  • Illness for at least 3 days comprised of at least 3 of the following symptoms: fatigue, loss of appetite, abdominal discomfort, right upper quadrant pain, nausea, vomiting
  • Peak of Alanine Aminotransferase (ALT) greater then 2.5 times the upper limit of normal (2.5 x 42 =105)
  • Percent of Participants = n x 100 / N
14 days after dose 3 at 6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percent of Participants of Definite Hepatitis E Disease by Category During the Follow-up Period
Time Frame: 14 days after dose 2 until 14 days after dose 3

Percent of participants of definite hepatitis E and vaccine efficacy by category during the follow-up period

  • Illness for at least 3 days comprised of at least 3 of the following symptoms: fatigue, loss of appetite, abdominal discomfort, right upper quadrant pain, nausea, vomiting
  • Peak of Alanine Aminotransferase (ALT) greater then 2.5 times the upper limit of normal (2.5 x 42 =105)
  • Percent of participants = n x 100 / N
14 days after dose 2 until 14 days after dose 3
Number of Suspected, Definite, Probable and Not Confirmed Hepatitis E Disease Cases
Time Frame: before dose 1 thru 14 days after dose 3
Number of suspected, definite, probable and not confirmed hepatitis E disease cases during surveillance period
before dose 1 thru 14 days after dose 3

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

U.S. Army Medical Research and Development Command

Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)
GlaxoSmithKline

Investigators

  • Principal Investigator: Mrigendra P Shrestha, MD, Armed Forces Research Institute of Medical Sciences, Thailand
  • Principal Investigator: Robert M Scott, MD, Walter Reed Army Institute of Research (WRAIR)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 9, 2001

Primary Completion (Actual)

January 19, 2004

Study Completion (Actual)

January 1, 2005

Study Registration Dates

First Submitted

February 2, 2006

First Submitted That Met QC Criteria

February 2, 2006

First Posted (Estimate)

February 6, 2006

Study Record Updates

Last Update Posted (Actual)

May 29, 2019

Last Update Submitted That Met QC Criteria

May 8, 2019

Last Verified

May 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • WRAIR 749
  • HSRRB A-9117.1
  • GSK 304558/003 (HEV-003)
  • IND 7815 (Other Identifier: FDA)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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