Dengue Hemorrhagic FeverPhase 1NCT00458120
Safety of and Immune Response to Two Different Dengue Virus Vaccines in Individuals Previously Immunized Against Dengue Virus
A Phase 1 study testing rDEN1delta30 and rDEN2/4delta30(ME) in people with Dengue Hemorrhagic Fever, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial summary
Dengue fever, which is caused by dengue viruses, is a major health problem in subtropical regions of the world. There are four different forms (serotypes) of dengue virus that can cause dengue fever. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Dengue Hemorrhagic Fever
- What is being tested?
- rDEN1delta30 and rDEN2/4delta30(ME)
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 36 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2007to Aug 2008
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Previous vaccination with rDEN1delta30, rDEN2/4delta30(ME), OR rDEN4delta30 vaccine
- General good health
- Available for the duration of the study
- Willing to use accepted forms of contraception
Who cannot join
- Clinically significant neurologic, heart, lung, liver, rheumatologic, autoimmune, or kidney disease by history, physical examination, or laboratory studies including urinalysis
- Behavioral, cognitive, or psychiatric disease that, in the opinion of the investigator, may interfere with the study
- Certain abnormal laboratory values
- Medical, work, or family problems as a result of alcohol or illegal drug use within 12 months of study entry
- History of severe allergy or anaphylaxis
- Severe asthma requiring an emergency room visit or hospitalization within 6 months of study entry
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- HIV infected
- Hepatitis C virus infected
- Hepatitis B surface antibody positive
- Known immunodeficiency syndrome
- Use of corticosteroids or immunosuppressive drugs 30 days prior to study entry. Participants who have used topical or nasal corticosteroids are not excluded.
- Receipt of live vaccine within 4 weeks of study entry
- Receipt of killed vaccine within 2 weeks of study entry
- Absence of spleen
- Plan to travel to an area where dengue virus is common
- Any investigational product within 30 days of study entry
- Other condition that, in the opinion of the investigator, would interfere with the study
- Pregnancy or breastfeeding
Trial locations and contacts
1 site in 1 country.
United States1 site
Center for Immunization Research
Baltimore, Maryland, 21205
About this study
Official title: Evaluation of the Safety and Immunogenicity of Heterologous Dengue Vaccine Administration in Dengue Immune Individuals
Dengue fever, which is caused by dengue viruses, is a major health problem in subtropical regions of the world. There are four different forms (serotypes) of dengue virus that can cause dengue fever. The purpose of this study is to determine the safety and immune response to a vaccine containing a particular dengue serotype when an individual has been previously vaccinated with a different dengue serotype.
Read the detailed description
The World Health Organization estimates that dengue virus causes more than 50 million cases of dengue fever a year. Dengue virus infection is the leading cause of hospitalization and death in children of most tropical Asian countries. There are four different serotypes of dengue virus. Most cases of dengue hemorrhagic fever/dengue shock syndrome are caused by secondary infection with a dengue serotype different from the first serotype the individual was infected with. A vaccine that would be effective in preventing infection by multiple dengue serotypes is desirable. The purpose of this study is to determine the safety of and immune response to two different dengue virus vaccines in individuals who have been previously vaccinated against a different serotype.
This study will last at least 42 days. Participants will be recruited from a database of previous dengue vaccine recipients and will be stratified by the type of vaccine previously received. Participants assigned to Cohort 1 and Cohort 2 will have already been vaccinated with the rDEN4delta30 vaccine. Participants assigned to Cohort 3 will have already been vaccinated with the rDEN2/4delta30(ME) vaccine. Participants in Cohort 4 will have already been vaccinated with the rDEN1delta30 vaccine. Participants in Cohorts 1 and 3 will be randomly assigned to receive either the rDEN1delta30 vaccine or placebo. Participants in Cohorts 2 and 4 will be randomly assigned to receive either the rDEN2/4delta30(ME) vaccine or placebo.
Participants will receive their assigned vaccination on Day 0. Study visits will occur every other day until Day 16, and then at Days 21, 28, and 42. At each visit, blood collection, vital signs measurement, and a physical exam will occur. In addition, participants will be asked to monitor their temperature daily, 3 times a day, from Day 0 to Day 16. Patients will also be asked to enroll in an optional skin biopsy sub-study.
- Conditions
- Dengue Hemorrhagic Fever
- Being tested
- rDEN1delta30, rDEN2/4delta30(ME), Placebo to rDEN1delta30 or rDEN2/4delta30(ME)
- Keywords
- Dengue Fever, Dengue Hemorrhagic Fever, Dengue Vaccination
- Medical subject headings
- Severe Dengue, Dengue
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rDEN1delta30Biological
Live attenuated 10^3 dose of rDEN1delta30 vaccine. Participants must have been previously vaccinated with rDEN4delta30 or rDEN2/4delta30(ME) vaccines.
rDEN2/4delta30(ME)Biological
Live attenuated 10^3 dose of rDEN2/4delta30(ME) vaccine. Participants must have been previously vaccinated with rDEN4delta30 or rDEN1delta30 vaccines.
Placebo to rDEN1delta30 or rDEN2/4delta30(ME)Biological
Placebo vaccines for rDEN1delta30 and rDEN2/4delta30(ME)
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Participants previously vaccinated with rDEN4delta30 will receive one subcutaneous vaccination (10^3 dose of vaccine) of rDEN1delta30 vaccine into the deltoid region of either arm. Receives: Biological: rDEN1delta30 |
| 2 | Experimental | Participants previously vaccinated with rDEN4delta30 will receive one subcutaneous vaccination (10^3 dose of vaccine) of rDEN2/4delta30(ME) into the deltoid region of either arm. Receives: Biological: rDEN2/4delta30(ME) |
| 3 | Experimental | Participants previously vaccinated with rDEN2/4delta30(ME) will receive one subcutaneous vaccination (10^3 dose of vaccine) of rDEN1delta30 vaccine into the deltoid region of either arm. Receives: Biological: rDEN1delta30 |
| 4 | Experimental | Participants previously vaccinated with rDEN1delta30 will receive one subcutaneous vaccination (10^3 dose of vaccine) of rDEN2/4delta30(ME) vaccine into the deltoid region of either arm. Receives: Biological: rDEN2/4delta30(ME) |
| 5 | Placebo comparator | One subcutaneous vaccination with placebo into the deltoid region of either arm. Receives: Biological: Placebo to rDEN1delta30 or rDEN2/4delta30(ME) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number, severity, and seriousness of vaccine-related adverse events observed through active and passive surveillance
Measured: Throughout study
Neutralizing antibody to all four dengue serotypes
Measured: At Days 0, 28, and 42
Secondary outcomes (5)
Assess the frequency, quantity, and duration of viremia in each vaccine cohort studied
Measured: Throughout study
To determine if cellular targets of vaccine infection, including peripheral blood mononuclear cells and skin, are different after heterologous infection of a second dengue virus vaccine of a different serotype
Measured: Throughout study
Compare the safety and immunogenicity between each heterologous dengue vaccine virus cohort
Measured: At study completion
Evaluate the immunopathological mechanism of heterologous vaccine virus associated rash in those volunteers who are willing to undergo skin biopsy
Measured: Throughout study
Characterize the antibody response after heterolouous vaccine infection
Measured: Throughout study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Apr 2007 (estimated)
- Study startMar 2007
- Primary completionAug 2008
- Study completionAug 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Dengue Hemorrhagic FeverStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- 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 1
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- Johns Hopkins Bloomberg School of Public Health
- Investigators
- Anna Durbin, MD, Principal investigator, Center for Immunization Research, Johns Hopkins School of Public Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00458120
- Sponsor's protocol ID
- CIR 227
- Other IDs
- WIRB Protocol Number 20070409
- Status last verified
- Dec 2010
- First submitted
- 6 Apr 2007
- Last updated
- 14 Dec 2010
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Durbin AP, Whitehead SS, McArthur J, Perreault JR, Blaney JE Jr, Thumar B, Murphy BR, Karron RA. rDEN4delta30, a live attenuated dengue virus type 4 vaccine candidate, is safe, immunogenic, and highly infectious in healthy adult volunteers. J Infect Dis. 2005 Mar 1;191(5):710-8. doi: 10.1086/427780. Epub 2005 Jan 27.
PubMed 15688284Chaturvedi UC, Shrivastava R, Nagar R. Dengue vaccines: problems and prospects. Indian J Med Res. 2005 May;121(5):639-52.
PubMed 15937367Guzman MG, Mune M, Kouri G. Dengue vaccine: priorities and progress. Expert Rev Anti Infect Ther. 2004 Dec;2(6):895-911. doi: 10.1586/14789072.2.6.895.
PubMed 15566333Durbin AP, Schmidt A, Elwood D, Wanionek KA, Lovchik J, Thumar B, Murphy BR, Whitehead SS. Heterotypic dengue infection with live attenuated monotypic dengue virus vaccines: implications for vaccination of populations in areas where dengue is endemic. J Infect Dis. 2011 Feb 1;203(3):327-34. doi: 10.1093/infdis/jiq059. Epub 2010 Dec 14.
PubMed 21208923
Study at a glance
From the registry record, last updated by the sponsor on 14 Dec 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of the Safety and Immunogenicity of Heterologous Dengue Vaccine Administration in Dengue Immune Individuals
- ClinicalTrials.gov ID
- NCT00458120
- Acronym / sponsor ID
- CIR 227
- Conditions
- Dengue Hemorrhagic Fever
- Keywords
- Dengue Fever, Dengue Hemorrhagic Fever, Dengue Vaccination
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Collaborators
- Johns Hopkins Bloomberg School of Public Health
- Study start
- Mar 2007
- Primary completion
- Aug 2008 (actual)
- Study completion
- Aug 2008 (actual)
- First posted
- 9 Apr 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Dengue fever, which is caused by dengue viruses, is a major health problem in subtropical regions of the world. There are four different forms (serotypes) of dengue virus that can cause dengue fever. The purpose of this study is to determine the safety and immune response to a vaccine containing a particular dengue serotype when an individual has been previously vaccinated with a different dengue serotype.
Detailed description
The World Health Organization estimates that dengue virus causes more than 50 million cases of dengue fever a year. Dengue virus infection is the leading cause of hospitalization and death in children of most tropical Asian countries. There are four different serotypes of dengue virus. Most cases of dengue hemorrhagic fever/dengue shock syndrome are caused by secondary infection with a dengue serotype different from the first serotype the individual was infected with. A vaccine that would be effective in preventing infection by multiple dengue serotypes is desirable. The purpose of this study is to determine the safety of and immune response to two different dengue virus vaccines in individuals who have been previously vaccinated against a different serotype.
This study will last at least 42 days. Participants will be recruited from a database of previous dengue vaccine recipients and will be stratified by the type of vaccine previously received. Participants assigned to Cohort 1 and Cohort 2 will have already been vaccinated with the rDEN4delta30 vaccine. Participants assigned to Cohort 3 will have already been vaccinated with the rDEN2/4delta30(ME) vaccine. Participants in Cohort 4 will have already been vaccinated with the rDEN1delta30 vaccine. Participants in Cohorts 1 and 3 will be randomly assigned to receive either the rDEN1delta30 vaccine or placebo. Participants in Cohorts 2 and 4 will be randomly assigned to receive either the rDEN2/4delta30(ME) vaccine or placebo.
Participants will receive their assigned vaccination on Day 0. Study visits will occur every other day until Day 16, and then at Days 21, 28, and 42. At each visit, blood collection, vital signs measurement, and a physical exam will occur. In addition, participants will be asked to monitor their temperature daily, 3 times a day, from Day 0 to Day 16. Patients will also be asked to enroll in an optional skin biopsy sub-study.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Biological: rDEN1delta30Participants previously vaccinated with rDEN4delta30 will receive one subcutaneous vaccination (10^3 dose of vaccine) of rDEN1delta30 vaccine into the deltoid region of either arm. |
| 2 | Experimental | Biological: rDEN2/4delta30(ME)Participants previously vaccinated with rDEN4delta30 will receive one subcutaneous vaccination (10^3 dose of vaccine) of rDEN2/4delta30(ME) into the deltoid region of either arm. |
| 3 | Experimental | Biological: rDEN1delta30Participants previously vaccinated with rDEN2/4delta30(ME) will receive one subcutaneous vaccination (10^3 dose of vaccine) of rDEN1delta30 vaccine into the deltoid region of either arm. |
| 4 | Experimental | Biological: rDEN2/4delta30(ME)Participants previously vaccinated with rDEN1delta30 will receive one subcutaneous vaccination (10^3 dose of vaccine) of rDEN2/4delta30(ME) vaccine into the deltoid region of either arm. |
| 5 | Placebo comparator | Biological: Placebo to rDEN1delta30 or rDEN2/4delta30(ME)One subcutaneous vaccination with placebo into the deltoid region of either arm. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Previous vaccination with rDEN1delta30, rDEN2/4delta30(ME), OR rDEN4delta30 vaccine
- General good health
- Available for the duration of the study
- Willing to use accepted forms of contraception
Key exclusion criteria (18 listed)
- Clinically significant neurologic, heart, lung, liver, rheumatologic, autoimmune, or kidney disease by history, physical examination, or laboratory studies including urinalysis
- Behavioral, cognitive, or psychiatric disease that, in the opinion of the investigator, may interfere with the study
- Certain abnormal laboratory values
- Medical, work, or family problems as a result of alcohol or illegal drug use within 12 months of study entry
- History of severe allergy or anaphylaxis
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 |
|---|---|---|
| rDEN1delta30Live attenuated 10^3 dose of rDEN1delta30 vaccine. Participants must have been previously vaccinated with rDEN4delta30 or rDEN2/4delta30(ME) vaccines. | Biological | 1, 3 |
| rDEN2/4delta30(ME)Live attenuated 10^3 dose of rDEN2/4delta30(ME) vaccine. Participants must have been previously vaccinated with rDEN4delta30 or rDEN1delta30 vaccines. | Biological | 2, 4 |
| Placebo to rDEN1delta30 or rDEN2/4delta30(ME)Placebo vaccines for rDEN1delta30 and rDEN2/4delta30(ME) | Biological | 5 |
Primary outcome
Number, severity, and seriousness of vaccine-related adverse events observed through active and passive surveillance
Time frame: Throughout study
Neutralizing antibody to all four dengue serotypes
Time frame: At Days 0, 28, and 42
5 secondary outcomes
Assess the frequency, quantity, and duration of viremia in each vaccine cohort studied
Time frame: Throughout study
To determine if cellular targets of vaccine infection, including peripheral blood mononuclear cells and skin, are different after heterologous infection of a second dengue virus vaccine of a different serotype
Time frame: Throughout study
Compare the safety and immunogenicity between each heterologous dengue vaccine virus cohort
Time frame: At study completion
Evaluate the immunopathological mechanism of heterologous vaccine virus associated rash in those volunteers who are willing to undergo skin biopsy
Time frame: Throughout study
Characterize the antibody response after heterolouous vaccine infection
Time frame: Throughout study
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Dec 2010.
- Background: PubMed 15688284Durbin AP, Whitehead SS, McArthur J, Perreault JR, Blaney JE Jr, Thumar B, Murphy BR, Karron RA. rDEN4delta30, a live attenuated dengue virus type 4 vaccine candidate, is safe, immunogenic, and highly infectious in healthy adult volunteers. J Infect Dis. 2005 Mar 1;191(5):710-8. doi: 10.1086/427780. Epub 2005 Jan 27.
- Background: PubMed 15937367Chaturvedi UC, Shrivastava R, Nagar R. Dengue vaccines: problems and prospects. Indian J Med Res. 2005 May;121(5):639-52.
- Background: PubMed 15566333Guzman MG, Mune M, Kouri G. Dengue vaccine: priorities and progress. Expert Rev Anti Infect Ther. 2004 Dec;2(6):895-911. doi: 10.1586/14789072.2.6.895.
- Derived from this study: PubMed 21208923Durbin AP, Schmidt A, Elwood D, Wanionek KA, Lovchik J, Thumar B, Murphy BR, Whitehead SS. Heterotypic dengue infection with live attenuated monotypic dengue virus vaccines: implications for vaccination of populations in areas where dengue is endemic. J Infect Dis. 2011 Feb 1;203(3):327-34. doi: 10.1093/infdis/jiq059. Epub 2010 Dec 14.
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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.
Anna Durbin, MD principal investigator
Center for Immunization Research, Johns Hopkins School of Public Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing rDEN1delta30 and rDEN2/4delta30(ME) in people with Dengue Hemorrhagic Fever, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
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 18 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 14 Dec 2010. 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 United States. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Number, severity, and seriousness of vaccine-related adverse events observed through active and passive surveillance (time frame: Throughout study). The study lists 2 primary outcomes in all. 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 NCT00458120, which also lists 4 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 14 Dec 2010.