HepatitisPhase 2NCT00287469
A Safety and Efficacy Study of the Hepatitis E Vaccine in Nepal.
A Phase 2 study testing Hepatitis E vaccine, recombinant (Sar 56 kDa) in people with Hepatitis, run by U.S. Army Medical Research and Development Command at 1 site in Nepal.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Hepatitis
- What is being tested?
- Hepatitis E vaccine, recombinant (Sar 56 kDa)
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 2,000 participants
- Where
- 1 siteNepal
- Study dates
- 9 Jul 2001to Jan 2005
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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.
- Conditions
- Hepatitis
- Being tested
- Hepatitis E vaccine, recombinant (Sar 56 kDa), Placebo
- Keywords
- Hepatitis E, clinical hepatitis, vaccine, efficacy, Nepal
- Medical subject headings
- Hepatitis, Hepatitis E
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hepatitis E vaccine, recombinant (Sar 56 kDa)Biological
20mcg or rhE Sar 56 kDa/dose of 0.5 mL, aluminium hydroxide (0.5 mg/dose) and phenoxyethanol (2.5 mg/dose)
PlaceboOther
PBS buffer placebo containing alum
| Study group | Role | What they receive |
|---|---|---|
| 20mcg Recombinant HEV | Experimental | 20mcg of recombinant HEV antigen administered intramuscularly in the deltoid according to a 0, 1 and 6 month schedule Receives: Biological: Hepatitis E vaccine, recombinant (Sar 56 kDa) |
| Placebo | Placebo comparator | PBS buffer placebo containing alum was administered intramuscularly in the deltoid according to a 0, 1 and 6 month schedule. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 14 days after dose 3 at 6 months
Secondary outcomes (2)
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
Measured: 14 days after dose 2 until 14 days after dose 3
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
Measured: before dose 1 thru 14 days after dose 3
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Feb 2006 (estimated)
- Study start9 Jul 2001
- Primary completion19 Jan 2004
- Study completionJan 2005
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for HepatitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 2,000 participants (actual)
Sponsor and investigators
- Lead sponsor
- U.S. Army Medical Research and Development Command
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Mrigendra P Shrestha, MD, Principal investigator, Armed Forces Research Institute of Medical Sciences, ThailandRobert M Scott, MD, Principal investigator, Walter Reed Army Institute of Research (WRAIR)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00287469
- Sponsor's protocol ID
- WRAIR 749
- Other IDs
- HSRRB A-9117.1, GSK 304558/003 (HEV-003), IND 7815
- Status last verified
- May 2019
- First submitted
- 2 Feb 2006
- Last updated
- 29 May 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Worm HC, Schlauder GG, Brandstatter G. Hepatitis E and its emergence in non-endemic areas. Wien Klin Wochenschr. 2002 Aug 30;114(15-16):663-70.
PubMed 12602109Worm HC, van der Poel WH, Brandstatter G. Hepatitis E: an overview. Microbes Infect. 2002 May;4(6):657-66. doi: 10.1016/s1286-4579(02)01584-8.
PubMed 12048035Emerson SU, Purcell RH. Running like water--the omnipresence of hepatitis E. N Engl J Med. 2004 Dec 2;351(23):2367-8. doi: 10.1056/NEJMp048285. No abstract available.
PubMed 15575050Purcell RH. Hepatitis viruses: changing patterns of human disease. Proc Natl Acad Sci U S A. 1994 Mar 29;91(7):2401-6. doi: 10.1073/pnas.91.7.2401.
PubMed 8146130Worm HC, Wirnsberger G. Hepatitis E vaccines: progress and prospects. Drugs. 2004;64(14):1517-31. doi: 10.2165/00003495-200464140-00002.
PubMed 15233590Shrestha MP, Scott RM, Joshi DM, Mammen MP Jr, Thapa GB, Thapa N, Myint KS, Fourneau M, Kuschner RA, Shrestha SK, David MP, Seriwatana J, Vaughn DW, Safary A, Endy TP, Innis BL. Safety and efficacy of a recombinant hepatitis E vaccine. N Engl J Med. 2007 Mar 1;356(9):895-903. doi: 10.1056/NEJMoa061847.
PubMed 17329696
Study at a glance
From the registry record, last updated by the sponsor on 29 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II, Prospective, Randomized, Double-blind, Placebo Controlled, Field Efficacy Trial of a Candidate Hepatitis E Vaccine in Nepal.
- ClinicalTrials.gov ID
- NCT00287469
- Acronym / sponsor ID
- WRAIR 749
- Conditions
- Hepatitis
- Keywords
- Hepatitis E, clinical hepatitis, vaccine, efficacy, Nepal
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 2,000 participants (actual)
- Lead sponsor
- U.S. Army Medical Research and Development CommandUS federal agency
- Collaborators
- GlaxoSmithKline, National Institute of Allergy and Infectious Diseases (NIAID)
- Study start
- 9 Jul 2001 (actual)
- Primary completion
- 19 Jan 2004 (actual)
- Study completion
- Jan 2005 (actual)
- First posted
- 6 Feb 2006 (estimated)
- Results
- Posted 29 May 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 20mcg Recombinant HEV | Experimental | Biological: 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 |
| Placebo | Placebo comparator | Other: PlaceboPBS buffer placebo containing alum was administered intramuscularly in the deltoid according to a 0, 1 and 6 month schedule. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (14 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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) | Biological | 20mcg Recombinant HEV |
| PlaceboPBS buffer placebo containing alum | Other | Placebo |
Primary outcome
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
2 secondary outcomes
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
Number of Suspected, Definite, Probable and Not Confirmed Hepatitis E Disease Cases
Time frame: before dose 1 thru 14 days after dose 3
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 May 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 12602109Worm HC, Schlauder GG, Brandstatter G. Hepatitis E and its emergence in non-endemic areas. Wien Klin Wochenschr. 2002 Aug 30;114(15-16):663-70.
- Background: PubMed 12048035Worm HC, van der Poel WH, Brandstatter G. Hepatitis E: an overview. Microbes Infect. 2002 May;4(6):657-66. doi: 10.1016/s1286-4579(02)01584-8.
- Background: PubMed 15575050Emerson SU, Purcell RH. Running like water--the omnipresence of hepatitis E. N Engl J Med. 2004 Dec 2;351(23):2367-8. doi: 10.1056/NEJMp048285. No abstract available.
- Background: PubMed 8146130Purcell RH. Hepatitis viruses: changing patterns of human disease. Proc Natl Acad Sci U S A. 1994 Mar 29;91(7):2401-6. doi: 10.1073/pnas.91.7.2401.
- Background: PubMed 15233590Worm HC, Wirnsberger G. Hepatitis E vaccines: progress and prospects. Drugs. 2004;64(14):1517-31. doi: 10.2165/00003495-200464140-00002.
- Derived from this study: PubMed 17329696Shrestha MP, Scott RM, Joshi DM, Mammen MP Jr, Thapa GB, Thapa N, Myint KS, Fourneau M, Kuschner RA, Shrestha SK, David MP, Seriwatana J, Vaughn DW, Safary A, Endy TP, Innis BL. Safety and efficacy of a recombinant hepatitis E vaccine. N Engl J Med. 2007 Mar 1;356(9):895-903. doi: 10.1056/NEJMoa061847.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mrigendra P Shrestha, MD principal investigator
Armed Forces Research Institute of Medical Sciences, Thailand
Robert M Scott, MD principal investigator
Walter Reed Army Institute of Research (WRAIR)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Hepatitis E vaccine, recombinant (Sar 56 kDa) in people with Hepatitis, run by U.S. Army Medical Research and Development Command at 1 site in Nepal.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 May 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Nepal. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 May 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00287469, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 May 2019.