Hepatitis
Conditions
Keywords
Hepatitis E, clinical hepatitis, vaccine, efficacy, 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.
Interventions
BIOLOGICALHepatitis 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)
OTHERPlacebo
PBS buffer placebo containing alum
Sponsors
GlaxoSmithKline
National Institute of Allergy and Infectious Diseases (NIAID)
U.S. Army Medical Research and Development Command
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
Countries
Nepal
Participant flow
Recruitment details
2000 subject were recruited by Royal Nepalese Army investigators at the Shree Birendra Hospital, Kathmandu from a well characterized population of Royal Nepalese Army military personnel stationed in the Kathmandu Valley and their family members and up to 5 US citizens residing in the Nepal.
Participants by arm
| Arm | Count |
|---|---|
| Placebo PBS buffer placebo containing alum was administered intramuscularly in the deltoid according to a 0, 1 and 6 month schedule.
Placebo: PBS buffer placebo containing alum | 1,000 |
| 20mcg Recombinant HEV 20mcg of recombinant HEV antigen administered intramuscularly in the deltoid according to a 0, 1 and 6 month schedule
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) | 1,000 |
| Total | 2,000 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 |
| Overall Study | Lost to Follow-up | 74 | 69 |
| Overall Study | moved from area | 144 | 138 |
| Overall Study | serious adverse event | 1 | 6 |
Baseline characteristics
| Characteristic | Placebo | 20mcg Recombinant HEV | Total |
|---|---|---|---|
| Age, Continuous Female | 31.3 Years STANDARD_DEVIATION 12.69 | 28.0 Years STANDARD_DEVIATION 8.29 | 29.6 Years STANDARD_DEVIATION 10.07 |
| Age, Continuous Male | 25.1 Years STANDARD_DEVIATION 6.12 | 25.2 Years STANDARD_DEVIATION 6.34 | 25.2 Years STANDARD_DEVIATION 6.23 |
| Region of Enrollment Nepal | 1000 participants | 1000 participants | 2000 participants |
| Sex: Female, Male Female | 4 Participants | 4 Participants | 8 Participants |
| Sex: Female, Male Male | 996 Participants | 996 Participants | 1992 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 1,000 | 6 / 1,000 |
| other Total, other adverse events | 226 / 1,000 | 229 / 1,000 |
| serious Total, serious adverse events | 200 / 1,000 | 143 / 1,000 |
Outcome results
Primary
Percent of Participants of Definite Hepatitis E by Category and Immunological Markers (Anti HEV) During the Follow-up Period
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
Time frame: 14 days after dose 3 at 6 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 20mcg Recombinant HEV | Percent of Participants of Definite Hepatitis E by Category and Immunological Markers (Anti HEV) During the Follow-up Period | Jaundice; IgM≥100 WR U/mL or total lg≥2500 WR U/mL | 0.3 Percent of Participants |
| 20mcg Recombinant HEV | Percent of Participants of Definite Hepatitis E by Category and Immunological Markers (Anti HEV) During the Follow-up Period | Illness; total lg ≥ 2500 WR U/mL | 0.0 Percent of Participants |
| 20mcg Recombinant HEV | Percent of Participants of Definite Hepatitis E by Category and Immunological Markers (Anti HEV) During the Follow-up Period | Jaundice; total lg ≥ 2500 WR U/mL | 0.3 Percent of Participants |
| 20mcg Recombinant HEV | Percent of Participants of Definite Hepatitis E by Category and Immunological Markers (Anti HEV) During the Follow-up Period | Illness; IgM≥100 WR U/mL or total lg≥2500 WR U/mL | 0.0 Percent of Participants |
| 20mcg Recombinant HEV | Percent of Participants of Definite Hepatitis E by Category and Immunological Markers (Anti HEV) During the Follow-up Period | Illness; IgM ≥ 100 WR U/mL | 0.0 Percent of Participants |
| 20mcg Recombinant HEV | Percent of Participants of Definite Hepatitis E by Category and Immunological Markers (Anti HEV) During the Follow-up Period | Jaun/Ill; IgM≥100 WR U/mL or total lg≥2500 WR U/mL | 0.3 Percent of Participants |
| 20mcg Recombinant HEV | Percent of Participants of Definite Hepatitis E by Category and Immunological Markers (Anti HEV) During the Follow-up Period | Jaundice; IgM ≥ 100 WR U/mL | 0.0 Percent of Participants |
| Placebo | Percent of Participants of Definite Hepatitis E by Category and Immunological Markers (Anti HEV) During the Follow-up Period | Jaun/Ill; IgM≥100 WR U/mL or total lg≥2500 WR U/mL | 7.4 Percent of Participants |
| Placebo | Percent of Participants of Definite Hepatitis E by Category and Immunological Markers (Anti HEV) During the Follow-up Period | Jaundice; IgM ≥ 100 WR U/mL | 6.9 Percent of Participants |
| Placebo | Percent of Participants of Definite Hepatitis E by Category and Immunological Markers (Anti HEV) During the Follow-up Period | Jaundice; total lg ≥ 2500 WR U/mL | 0.1 Percent of Participants |
| Placebo | Percent of Participants of Definite Hepatitis E by Category and Immunological Markers (Anti HEV) During the Follow-up Period | Jaundice; IgM≥100 WR U/mL or total lg≥2500 WR U/mL | 7.0 Percent of Participants |
| Placebo | Percent of Participants of Definite Hepatitis E by Category and Immunological Markers (Anti HEV) During the Follow-up Period | Illness; IgM ≥ 100 WR U/mL | 0.3 Percent of Participants |
| Placebo | Percent of Participants of Definite Hepatitis E by Category and Immunological Markers (Anti HEV) During the Follow-up Period | Illness; total lg ≥ 2500 WR U/mL | 0.0 Percent of Participants |
| Placebo | Percent of Participants of Definite Hepatitis E by Category and Immunological Markers (Anti HEV) During the Follow-up Period | Illness; IgM≥100 WR U/mL or total lg≥2500 WR U/mL | 0.3 Percent of Participants |
Secondary
Number of Suspected, Definite, Probable and Not Confirmed Hepatitis E Disease Cases
Number of suspected, definite, probable and not confirmed hepatitis E disease cases during surveillance period
Time frame: before dose 1 thru 14 days after dose 3
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 20mcg Recombinant HEV | Number of Suspected, Definite, Probable and Not Confirmed Hepatitis E Disease Cases | Any hep cases: between 14 days after dose 1 and 2 | 5 Number of Hepatitis E Cases |
| 20mcg Recombinant HEV | Number of Suspected, Definite, Probable and Not Confirmed Hepatitis E Disease Cases | Definite hepE cases: within 14 days after dose 3 | 1 Number of Hepatitis E Cases |
| 20mcg Recombinant HEV | Number of Suspected, Definite, Probable and Not Confirmed Hepatitis E Disease Cases | Any hep cases: Total | 92 Number of Hepatitis E Cases |
| 20mcg Recombinant HEV | Number of Suspected, Definite, Probable and Not Confirmed Hepatitis E Disease Cases | Definite hepE cases: from 14 days after dose 3 | 66 Number of Hepatitis E Cases |
| 20mcg Recombinant HEV | Number of Suspected, Definite, Probable and Not Confirmed Hepatitis E Disease Cases | Any hep cases: between 14 days after dose 2 and 3 | 7 Number of Hepatitis E Cases |
| 20mcg Recombinant HEV | Number of Suspected, Definite, Probable and Not Confirmed Hepatitis E Disease Cases | Definate hepE cases: Total | 78 Number of Hepatitis E Cases |
| 20mcg Recombinant HEV | Number of Suspected, Definite, Probable and Not Confirmed Hepatitis E Disease Cases | Definite hepE cases: before dose 1 | 0 Number of Hepatitis E Cases |
| 20mcg Recombinant HEV | Number of Suspected, Definite, Probable and Not Confirmed Hepatitis E Disease Cases | Probable hepE cases | 0 Number of Hepatitis E Cases |
| 20mcg Recombinant HEV | Number of Suspected, Definite, Probable and Not Confirmed Hepatitis E Disease Cases | Any hep cases: within 14 days after dose 1 | 1 Number of Hepatitis E Cases |
| 20mcg Recombinant HEV | Number of Suspected, Definite, Probable and Not Confirmed Hepatitis E Disease Cases | Not confirmed hepE: before dose 1 | 0 Number of Hepatitis E Cases |
| 20mcg Recombinant HEV | Number of Suspected, Definite, Probable and Not Confirmed Hepatitis E Disease Cases | Definite hepE cases: within 14 days after dose 1 | 1 Number of Hepatitis E Cases |
| 20mcg Recombinant HEV | Number of Suspected, Definite, Probable and Not Confirmed Hepatitis E Disease Cases | Not confirmed hepE: within 14 days after dose 1 | 0 Number of Hepatitis E Cases |
| 20mcg Recombinant HEV | Number of Suspected, Definite, Probable and Not Confirmed Hepatitis E Disease Cases | Any hep cases: within 14 days after dose 3 | 1 Number of Hepatitis E Cases |
| 20mcg Recombinant HEV | Number of Suspected, Definite, Probable and Not Confirmed Hepatitis E Disease Cases | Not confirmed hepE: btwn 14dys after dose 1 and 2 | 2 Number of Hepatitis E Cases |
| 20mcg Recombinant HEV | Number of Suspected, Definite, Probable and Not Confirmed Hepatitis E Disease Cases | Definite hepE cases: btwn 14dys after dose 1 and 2 | 3 Number of Hepatitis E Cases |
| 20mcg Recombinant HEV | Number of Suspected, Definite, Probable and Not Confirmed Hepatitis E Disease Cases | Not confirmed hepE: within 14 days after dose 2 | 0 Number of Hepatitis E Cases |
| 20mcg Recombinant HEV | Number of Suspected, Definite, Probable and Not Confirmed Hepatitis E Disease Cases | Any hep cases: within 14 days after dose 2 | 0 Number of Hepatitis E Cases |
| 20mcg Recombinant HEV | Number of Suspected, Definite, Probable and Not Confirmed Hepatitis E Disease Cases | Not confirmed hepE: btwn 14dys after dose 2 and 3 | 0 Number of Hepatitis E Cases |
| 20mcg Recombinant HEV | Number of Suspected, Definite, Probable and Not Confirmed Hepatitis E Disease Cases | Definite hepE cases: within 14 days after dose 2 | 0 Number of Hepatitis E Cases |
| 20mcg Recombinant HEV | Number of Suspected, Definite, Probable and Not Confirmed Hepatitis E Disease Cases | Not confirmed hepE: within 14 days after dose 3 | 0 Number of Hepatitis E Cases |
| 20mcg Recombinant HEV | Number of Suspected, Definite, Probable and Not Confirmed Hepatitis E Disease Cases | Any hep cases: from 14 days after dose 3 | 78 Number of Hepatitis E Cases |
| 20mcg Recombinant HEV | Number of Suspected, Definite, Probable and Not Confirmed Hepatitis E Disease Cases | Not confirmed hepE: from 14 days after dose 3 | 12 Number of Hepatitis E Cases |
| 20mcg Recombinant HEV | Number of Suspected, Definite, Probable and Not Confirmed Hepatitis E Disease Cases | Definite hepE cases: btwn 14dys after dose 2 and 3 | 7 Number of Hepatitis E Cases |
| 20mcg Recombinant HEV | Number of Suspected, Definite, Probable and Not Confirmed Hepatitis E Disease Cases | Not confirmed hepE: total | 14 Number of Hepatitis E Cases |
| 20mcg Recombinant HEV | Number of Suspected, Definite, Probable and Not Confirmed Hepatitis E Disease Cases | Any acute hep cases: before dose 1 | 0 Number of Hepatitis E Cases |
| Placebo | Number of Suspected, Definite, Probable and Not Confirmed Hepatitis E Disease Cases | Not confirmed hepE: total | 10 Number of Hepatitis E Cases |
| Placebo | Number of Suspected, Definite, Probable and Not Confirmed Hepatitis E Disease Cases | Any acute hep cases: before dose 1 | 1 Number of Hepatitis E Cases |
| Placebo | Number of Suspected, Definite, Probable and Not Confirmed Hepatitis E Disease Cases | Any hep cases: within 14 days after dose 1 | 3 Number of Hepatitis E Cases |
| Placebo | Number of Suspected, Definite, Probable and Not Confirmed Hepatitis E Disease Cases | Any hep cases: between 14 days after dose 1 and 2 | 2 Number of Hepatitis E Cases |
| Placebo | Number of Suspected, Definite, Probable and Not Confirmed Hepatitis E Disease Cases | Any hep cases: within 14 days after dose 2 | 0 Number of Hepatitis E Cases |
| Placebo | Number of Suspected, Definite, Probable and Not Confirmed Hepatitis E Disease Cases | Any hep cases: between 14 days after dose 2 and 3 | 4 Number of Hepatitis E Cases |
| Placebo | Number of Suspected, Definite, Probable and Not Confirmed Hepatitis E Disease Cases | Any hep cases: within 14 days after dose 3 | 0 Number of Hepatitis E Cases |
| Placebo | Number of Suspected, Definite, Probable and Not Confirmed Hepatitis E Disease Cases | Any hep cases: from 14 days after dose 3 | 9 Number of Hepatitis E Cases |
| Placebo | Number of Suspected, Definite, Probable and Not Confirmed Hepatitis E Disease Cases | Any hep cases: Total | 19 Number of Hepatitis E Cases |
| Placebo | Number of Suspected, Definite, Probable and Not Confirmed Hepatitis E Disease Cases | Definite hepE cases: before dose 1 | 0 Number of Hepatitis E Cases |
| Placebo | Number of Suspected, Definite, Probable and Not Confirmed Hepatitis E Disease Cases | Definite hepE cases: within 14 days after dose 1 | 3 Number of Hepatitis E Cases |
| Placebo | Number of Suspected, Definite, Probable and Not Confirmed Hepatitis E Disease Cases | Definite hepE cases: btwn 14dys after dose 1 and 2 | 2 Number of Hepatitis E Cases |
| Placebo | Number of Suspected, Definite, Probable and Not Confirmed Hepatitis E Disease Cases | Definite hepE cases: within 14 days after dose 2 | 0 Number of Hepatitis E Cases |
| Placebo | Number of Suspected, Definite, Probable and Not Confirmed Hepatitis E Disease Cases | Definite hepE cases: btwn 14dys after dose 2 and 3 | 1 Number of Hepatitis E Cases |
| Placebo | Number of Suspected, Definite, Probable and Not Confirmed Hepatitis E Disease Cases | Definite hepE cases: within 14 days after dose 3 | 0 Number of Hepatitis E Cases |
| Placebo | Number of Suspected, Definite, Probable and Not Confirmed Hepatitis E Disease Cases | Definite hepE cases: from 14 days after dose 3 | 3 Number of Hepatitis E Cases |
| Placebo | Number of Suspected, Definite, Probable and Not Confirmed Hepatitis E Disease Cases | Definate hepE cases: Total | 9 Number of Hepatitis E Cases |
| Placebo | Number of Suspected, Definite, Probable and Not Confirmed Hepatitis E Disease Cases | Probable hepE cases | 0 Number of Hepatitis E Cases |
| Placebo | Number of Suspected, Definite, Probable and Not Confirmed Hepatitis E Disease Cases | Not confirmed hepE: before dose 1 | 1 Number of Hepatitis E Cases |
| Placebo | Number of Suspected, Definite, Probable and Not Confirmed Hepatitis E Disease Cases | Not confirmed hepE: within 14 days after dose 1 | 0 Number of Hepatitis E Cases |
| Placebo | Number of Suspected, Definite, Probable and Not Confirmed Hepatitis E Disease Cases | Not confirmed hepE: btwn 14dys after dose 1 and 2 | 0 Number of Hepatitis E Cases |
| Placebo | Number of Suspected, Definite, Probable and Not Confirmed Hepatitis E Disease Cases | Not confirmed hepE: within 14 days after dose 2 | 0 Number of Hepatitis E Cases |
| Placebo | Number of Suspected, Definite, Probable and Not Confirmed Hepatitis E Disease Cases | Not confirmed hepE: btwn 14dys after dose 2 and 3 | 3 Number of Hepatitis E Cases |
| Placebo | Number of Suspected, Definite, Probable and Not Confirmed Hepatitis E Disease Cases | Not confirmed hepE: within 14 days after dose 3 | 0 Number of Hepatitis E Cases |
| Placebo | Number of Suspected, Definite, Probable and Not Confirmed Hepatitis E Disease Cases | Not confirmed hepE: from 14 days after dose 3 | 6 Number of Hepatitis E Cases |
Secondary
Percent of Participants of Definite Hepatitis E Disease by Category During the Follow-up Period
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
Time frame: 14 days after dose 2 until 14 days after dose 3
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 20mcg Recombinant HEV | Percent of Participants of Definite Hepatitis E Disease by Category During the Follow-up Period | Jaundice; IgM ≥ 100 WR U/ml | 0.1 Percent of Participants |
| 20mcg Recombinant HEV | Percent of Participants of Definite Hepatitis E Disease by Category During the Follow-up Period | Jaundice; total Ig ≥ 2500 WR U/ml | 0.0 Percent of Participants |
| 20mcg Recombinant HEV | Percent of Participants of Definite Hepatitis E Disease by Category During the Follow-up Period | Jaundice; IgM≥100 WR U/mL or total lg≥2500 WR U/mL | 0.1 Percent of Participants |
| 20mcg Recombinant HEV | Percent of Participants of Definite Hepatitis E Disease by Category During the Follow-up Period | Illness; ImG ≥ 100 WR U/ml | 0.0 Percent of Participants |
| 20mcg Recombinant HEV | Percent of Participants of Definite Hepatitis E Disease by Category During the Follow-up Period | Illness; total Ig ≥ 2500 WR U/ml | 0.0 Percent of Participants |
| 20mcg Recombinant HEV | Percent of Participants of Definite Hepatitis E Disease by Category During the Follow-up Period | Jaun/Ill; IgM≥100 WR U/mL or total lg≥2500 WR U/mL | 0.1 Percent of Participants |
| Placebo | Percent of Participants of Definite Hepatitis E Disease by Category During the Follow-up Period | Illness; total Ig ≥ 2500 WR U/ml | 0.0 Percent of Participants |
| Placebo | Percent of Participants of Definite Hepatitis E Disease by Category During the Follow-up Period | Jaundice; IgM ≥ 100 WR U/ml | 0.8 Percent of Participants |
| Placebo | Percent of Participants of Definite Hepatitis E Disease by Category During the Follow-up Period | Illness; ImG ≥ 100 WR U/ml | 0.0 Percent of Participants |
| Placebo | Percent of Participants of Definite Hepatitis E Disease by Category During the Follow-up Period | Jaundice; total Ig ≥ 2500 WR U/ml | 0.0 Percent of Participants |
| Placebo | Percent of Participants of Definite Hepatitis E Disease by Category During the Follow-up Period | Jaun/Ill; IgM≥100 WR U/mL or total lg≥2500 WR U/mL | 0.8 Percent of Participants |
| Placebo | Percent of Participants of Definite Hepatitis E Disease by Category During the Follow-up Period | Jaundice; IgM≥100 WR U/mL or total lg≥2500 WR U/mL | 0.8 Percent of Participants |