A Phase 2 interventional study of Hepatitis E vaccine, recombinant (Sar 56 kDa) and Placebo in Hepatitis, sponsored by U.S. Army Medical Research and Development Command. Completed at 1 site in Nepal. Open to participants aged 18 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2019-05-29.
Sponsored by U.S. Army Medical Research and Development Command · Phase 2, Interventional, and Prevention
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.
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.
37 studies on the registry are indexed under Hepatitis E; 9 are open to participants now.
This study's enrollment of 2,000 is above the median of 330 across 26 interventional studies indexed under Hepatitis E.
Browse Hepatitis E studies →U.S. Army Medical Research and Development Command is the lead sponsor of 153 studies on the registry; 8 are open to participants now.
Of its 23 completed or terminated interventional studies of FDA-regulated products, 16 (70%) have results posted.
Compared within Hepatitis E, this study's primary condition as ClinicalTrials.gg classifies it; the registry's first condition term is Hepatitis. The counts are of registry records indexed under each term, refreshed daily. How we classify →
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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)
PBS buffer placebo containing alum was administered intramuscularly in the deltoid according to a 0, 1 and 6 month schedule.
Other: Placebo
20mcg or rhE Sar 56 kDa/dose of 0.5 mL, aluminium hydroxide (0.5 mg/dose) and phenoxyethanol (2.5 mg/dose)
PBS buffer placebo containing alum
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
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
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
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.
| Milestone | Placebo | 20mcg Recombinant HEV |
|---|---|---|
| Started | 1000 | 1000 |
| Completed | 780 | 786 |
| Not completed | 220 | 214 |
| Withdrew: Serious adverse event | 1 | 6 |
| Withdrew: Adverse event | 1 | 1 |
| Withdrew: Moved from area | 144 | 138 |
| Withdrew: Lost to follow-up | 74 | 69 |
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
| Percent of Participants | 20mcg Recombinant HEV | Placebo |
|---|---|---|
| Jaundice; IgM ≥ 100 WR U/mL | 0.0 (0.0 to 0.4) | 6.9 (5.3 to 8.8) |
| Jaundice; total lg ≥ 2500 WR U/mL | 0.3 (0.1 to 1.0) | 0.1 (0.0 to 0.6) |
| Jaundice; IgM≥100 WR U/mL or total lg≥2500 WR U/mL | 0.3 (0.1 to 1.0) | 7.0 (5.4 to 8.9) |
| Illness; IgM ≥ 100 WR U/mL | 0.0 (0.0 to 0.4) | 0.3 (0.1 to 1.0) |
| Illness; total lg ≥ 2500 WR U/mL | 0.0 (0.0 to 0.4) | 0.0 (0.0 to 0.4) |
| Illness; IgM≥100 WR U/mL or total lg≥2500 WR U/mL | 0.0 (0.0 to 0.4) | 0.3 (0.1 to 1.0) |
| Jaun/Ill; IgM≥100 WR U/mL or total lg≥2500 WR U/mL | 0.3 (0.1 to 1.0) | 7.4 (5.7 to 9.3) |
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
| Percent of Participants | 20mcg Recombinant HEV | Placebo |
|---|---|---|
| Jaundice; IgM ≥ 100 WR U/ml | 0.1 (0.0 to 0.6) | 0.8 (0.4 to 1.6) |
| Jaundice; total Ig ≥ 2500 WR U/ml | 0.0 (0.0 to 0.4) | 0.0 (0.0 to 0.4) |
| Jaundice; IgM≥100 WR U/mL or total lg≥2500 WR U/mL | 0.1 (0.0 to 0.6) | 0.8 (0.4 to 1.6) |
| Illness; ImG ≥ 100 WR U/ml | 0.0 (0.0 to 0.4) | 0.0 (0.0 to 0.4) |
| Illness; total Ig ≥ 2500 WR U/ml | 0.0 (0.0 to 0.4) | 0.0 (0.0 to 0.4) |
| Jaun/Ill; IgM≥100 WR U/mL or total lg≥2500 WR U/mL | 0.1 (0.0 to 0.6) | 0.8 (0.4 to 1.6) |
Number of suspected, definite, probable and not confirmed hepatitis E disease cases during surveillance period
| Number of Hepatitis E Cases | Placebo | 20mcg Recombinant HEV |
|---|---|---|
| Any acute hep cases: before dose 1 | 0 | 1 |
| Any hep cases: within 14 days after dose 1 | 1 | 3 |
| Any hep cases: between 14 days after dose 1 and 2 | 5 | 2 |
| Any hep cases: within 14 days after dose 2 | 0 | 0 |
| Any hep cases: between 14 days after dose 2 and 3 | 7 | 4 |
| Any hep cases: within 14 days after dose 3 | 1 | 0 |
| Any hep cases: from 14 days after dose 3 | 78 | 9 |
| Any hep cases: Total | 92 | 19 |
| Definite hepE cases: before dose 1 | 0 | 0 |
| Definite hepE cases: within 14 days after dose 1 | 1 | 3 |
| Definite hepE cases: btwn 14dys after dose 1 and 2 | 3 | 2 |
| Definite hepE cases: within 14 days after dose 2 | 0 | 0 |
| Definite hepE cases: btwn 14dys after dose 2 and 3 | 7 | 1 |
| Definite hepE cases: within 14 days after dose 3 | 1 | 0 |
| Definite hepE cases: from 14 days after dose 3 | 66 | 3 |
| Definate hepE cases: Total | 78 | 9 |
| Probable hepE cases | 0 | 0 |
| Not confirmed hepE: before dose 1 | 0 | 1 |
| Not confirmed hepE: within 14 days after dose 1 | 0 | 0 |
| Not confirmed hepE: btwn 14dys after dose 1 and 2 | 2 | 0 |
| Not confirmed hepE: within 14 days after dose 2 | 0 | 0 |
| Not confirmed hepE: btwn 14dys after dose 2 and 3 | 0 | 3 |
| Not confirmed hepE: within 14 days after dose 3 | 0 | 0 |
| Not confirmed hepE: from 14 days after dose 3 | 12 | 6 |
| Not confirmed hepE: total | 14 | 10 |
Collected over Within 31 days (days 0-30) post-vaccination. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Placebo | 1/1,000 (0.1%) | 200/1,000 (20%) | 226/1,000 (22.6%) |
| 20mcg Recombinant HEV | 6/1,000 (0.6%) | 143/1,000 (14.3%) | 229/1,000 (22.9%) |
| Event | Placebo | 20mcg Recombinant HEV |
|---|---|---|
| Hepatitis EInfections and infestations | 81/1000 | 10/1000 |
| Typhoid feverInfections and infestations | 24/1000 | 30/1000 |
| LeptospirosisInfections and infestations | 12/1000 | 2/1000 |
| Viral infectionInfections and infestations | 9/1000 | 5/1000 |
| Gun shot woundInjury, poisoning and procedural complications | 3/1000 | 9/1000 |
| Paratyphoid feverInfections and infestations | 7/1000 | 8/1000 |
| Salmonella bacteraemiaInfections and infestations | 3/1000 | 7/1000 |
| PyrexiaGeneral disorders | 6/1000 | 1/1000 |
| GiardiasisInfections and infestations | 3/1000 | 6/1000 |
| Upper respiratory tract infectionInfections and infestations | 4/1000 | 6/1000 |
| Event | Placebo | 20mcg Recombinant HEV |
|---|---|---|
| HeadacheNervous system disorders | 43/1000 | 36/1000 |
| PyrexiaGeneral disorders | 31/1000 | 29/1000 |
| DiarrhoeaGastrointestinal disorders | 22/1000 | 22/1000 |
| NasopharyngitisInfections and infestations | 20/1000 | 22/1000 |
| Abdominal painGastrointestinal disorders | 10/1000 | 15/1000 |
| Upper respiratory tract infectionInfections and infestations | 15/1000 | 9/1000 |
| TonsillitisInfections and infestations | 11/1000 | 8/1000 |
| DizzinessNervous system disorders | 10/1000 | 4/1000 |
| DyspepsiaGastrointestinal disorders | 7/1000 | 9/1000 |
| CoughRespiratory, thoracic and mediastinal disorders | 8/1000 | 8/1000 |
| Age, Continuous(Years) | Placebo | 20mcg Recombinant HEV | Total |
|---|---|---|---|
| Female | 31.3 ± 12.69 | 28.0 ± 8.29 | 29.6 ± 10.07 |
| Male | 25.1 ± 6.12 | 25.2 ± 6.34 | 25.2 ± 6.23 |
| Sex: Female, Male(Participants) | Placebo | 20mcg Recombinant HEV | Total |
|---|---|---|---|
| Female | 4 | 4 | 8 |
| Male | 996 | 996 | 1992 |
| Region of Enrollment(participants) | Placebo | 20mcg Recombinant HEV | Total |
|---|---|---|---|
| Nepal | 1000 | 1000 | 2000 |
Ran from Jul 2001 to primary completion in Jan 2004, 30 months.
Results were first posted in May 2019, 15 years 4 months after primary completion.
How these figures are worked out, and which studies are left out of them.
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