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

Phase 2

Completed

Conditions: Hepatitis

Interventions: Other: Placebo
Biological: Hepatitis E vaccine, recombinant (Sar 56 kDa)

Registration Number: NCT00287469

Lead Sponsor: U.S. Army Medical Research and Development Command

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 2000

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	PBS buffer placebo containing alum was administered intramuscularly in the deltoid according to a 0, 1 and 6 month schedule.
20mcg Recombinant HEV	Hepatitis E vaccine, recombinant (Sar 56 kDa)	20mcg of recombinant HEV antigen administered intramuscularly in the deltoid according to a 0, 1 and 6 month schedule

Primary Outcome Measures

Name	Time	Method
Percent of Participants of Definite Hepatitis E by Category and Immunological Markers (Anti HEV) During the Follow-up Period	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

Secondary Outcome Measures

Name	Time	Method
Number of Suspected, Definite, Probable and Not Confirmed Hepatitis E Disease Cases	before dose 1 thru 14 days after dose 3	Number of suspected, definite, probable and not confirmed hepatitis E disease cases during surveillance period
Percent of Participants of Definite Hepatitis E Disease by Category During the Follow-up Period	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