Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00287469
Recruitment Status : Completed
First Posted : February 6, 2006
Results First Posted : May 29, 2019
Last Update Posted : May 29, 2019
Sponsor:
Collaborators:
GlaxoSmithKline
National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by (Responsible Party):
U.S. Army Medical Research and Development Command

Tracking Information
First Submitted Date  ICMJE February 2, 2006
First Posted Date  ICMJE February 6, 2006
Results First Submitted Date  ICMJE October 9, 2018
Results First Posted Date  ICMJE May 29, 2019
Last Update Posted Date May 29, 2019
Actual Study Start Date  ICMJE July 9, 2001
Actual Primary Completion Date January 19, 2004   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 8, 2019)
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
Original Primary Outcome Measures  ICMJE
 (submitted: February 2, 2006)
definite hepatitis E disease with onset at least two weeks after vaccine/placebo dose 3.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 8, 2019)
  • 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
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: February 2, 2006)
  • definite and probable hepatitis E disease with onset at least two weeks post vaccine/placebo dose 3
  • definite hepatitis E disease with onset at least two weeks post vaccine/placebo dose and before two weeks after vaccine/placebo dose 3.
  • hepatitis E disease severity.
  • vaccine safety
  • level of total immunoglobulin to HEV capsid
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Safety and Efficacy Study of the Hepatitis E Vaccine in Nepal.
Official Title  ICMJE A Phase II, Prospective, Randomized, Double-blind, Placebo Controlled, Field Efficacy Trial of a Candidate Hepatitis E Vaccine in Nepal.
Brief Summary 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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
Condition  ICMJE Hepatitis
Intervention  ICMJE
  • 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)
  • Other: Placebo
    PBS buffer placebo containing alum
Study Arms  ICMJE
  • Experimental: 20mcg Recombinant HEV
    20mcg of recombinant HEV antigen administered intramuscularly in the deltoid according to a 0, 1 and 6 month schedule
    Intervention: Biological: Hepatitis E vaccine, recombinant (Sar 56 kDa)
  • Placebo Comparator: Placebo
    PBS buffer placebo containing alum was administered intramuscularly in the deltoid according to a 0, 1 and 6 month schedule.
    Intervention: Other: Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 2, 2006)
2000
Original Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE January 2005
Actual Primary Completion Date January 19, 2004   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Nepal
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00287469
Other Study ID Numbers  ICMJE WRAIR 749
HSRRB A-9117.1
GSK 304558/003 (HEV-003)
IND 7815 ( Other Identifier: FDA )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party U.S. Army Medical Research and Development Command
Study Sponsor  ICMJE U.S. Army Medical Research and Development Command
Collaborators  ICMJE
  • GlaxoSmithKline
  • National Institute of Allergy and Infectious Diseases (NIAID)
Investigators  ICMJE
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)
PRS Account U.S. Army Medical Research and Development Command
Verification Date May 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP