DenguePhase 1NCT00375726
Safety of and Immune Response to a Dengue Virus Vaccine (rDEN3/4delta30[ME]) in Healthy Adults
A Phase 1 study testing rDEN3/4delta30(ME) in people with Dengue, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial summary
Dengue fever, caused by dengue viruses, is a major health problem in the tropical and subtropical regions of the world. The purpose of this study is to test the safety of and immune response to a new dengue virus vaccine in healthy adults. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Dengue
- What is being tested?
- rDEN3/4delta30(ME)
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 58 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2006to Sep 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
- Good general health
- Available for the duration of the study
- Willing to use acceptable forms of contraception for the duration of the study
Who cannot join
- Significant neurologic, heart, lung, liver, rheumatologic, autoimmune, or kidney disease
- Behavioral, cognitive, or psychiatric disease that, in the opinion of the investigator, may interfere with the study
- Significant laboratory abnormalities
- Medical, work, or family problems as a result of alcohol or illegal drug use within 12 months prior to study entry
- History of severe allergic reaction or anaphylaxis
- Emergency room visit or hospitalization for severe asthma within 6 months prior to study entry
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- HIV-1 infected
- Hepatitis C virus (HCV) infected
- Hepatitis B surface antigen positive
- Immunodeficiency syndrome
- Use of corticosteroids or immunosuppressive medications within 30 days prior to study entry. Participants using topical or nasal corticosteroids are not excluded.
- Live vaccine within 4 weeks prior to study entry
- Killed vaccine within 2 weeks prior to study entry
- Absence of spleen
- Blood products within 6 months prior to study entry
- Previous dengue virus or other flavivirus (e.g., yellow fever virus, St. Louis encephalitis, West Nile virus) infection
- Previously received yellow fever or dengue vaccine
- Plans to travel to an area where dengue infection is common
- Received an investigational agent within 30 days prior to 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: Phase 1 Study of the Safety and Immunogenicity of rDEN3/4delta30(ME), a Live Attenuated Virus Vaccine Candidate for the Prevention of Dengue Serotype 3
Dengue fever, caused by dengue viruses, is a major health problem in the tropical and subtropical regions of the world. The purpose of this study is to test the safety of and immune response to a new dengue virus vaccine in healthy adults.
Read the detailed description
Dengue viruses, which cause dengue fever and dengue shock syndrome, are a major cause of morbidity and mortality in several of the world's tropical and subtropical regions. The rDEN3/4delta30(ME) vaccine is a live attenuated dengue virus vaccine that may be protective against dengue virus serotype 3 (DEN3). The purpose of this study is to evaluate the safety and immunogenicity of the rDEN3/4delta30(ME) vaccine in healthy adults.
This study will last 40 weeks. Participants will be randomly assigned to receive one of three doses of rDEN3/4delta30(ME) or placebo. Participants in Group 1 will receive the middle dose of rDEN3/4delta30(ME) or placebo at study entry. Group 2a will begin enrollment after the immunogenicity review of all participants in Group 1. Participants in Group 2a will receive the highest dose of rDEN4delta30(ME) or placebo at study entry. Group 2b will begin enrollment after the immunogenicity review of all participants in Group 2a. Participants in Group 2b will receive the lowest dose of rDEN4delta30(ME) or placebo.
After vaccination, participants in all groups will be followed closely every other day for the first 16 days of the study. Participants will take their temperature three times a day through Day 16 and record each measurement in a diary. After Day 16, participants will have study visits on Days 21, 28, 42, and 180; a physical exam and blood collection will occur at all visits. Some participants may be asked to join a skin biopsy substudy.
- Conditions
- Dengue
- Being tested
- rDEN3/4delta30(ME), Placebo
- Keywords
- Dengue Fever, Dengue Vaccine, Dengue Virus, Dengue Hemorrhagic Fever, Dengue Shock Syndrome
- Medical subject headings
- Dengue, Severe Dengue
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rDEN3/4delta30(ME)Biological
Live attenuated rDEN3/4delta30(ME) vaccine (one of three doses)
PlaceboBiological
Placebo for rDEN3/4delta30(ME)
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | One subcutaneous vaccination with rDEN3/4delta30(ME) vaccine (10^3 PFU dose) into the deltoid region of either arm. Receives: Biological: rDEN3/4delta30(ME) |
| 2 | Experimental | One subcutaneous vaccination with rDEN3/4delta30(ME) vaccine (10^5 PFU dose) into the deltoid region of either arm. This arm may enroll after Arm 1 depending on the immunological response of Arm 1. Receives: Biological: rDEN3/4delta30(ME) |
| 3 | Experimental | One subcutaneous vaccination with rDEN3/4delta30(ME) vaccine (10^1 PFU dose) into the deltoid region of either arm. This arm may enroll after Arm 1 depending on the immunological response of Arm 1. Receives: Biological: rDEN3/4delta30(ME) |
| 4 | Placebo comparator | One subcutaneous vaccination with placebo into the deltoid region of either arm. Receives: Biological: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety, as defined by frequency of vaccine-related adverse events, as classified by both intensity and severity through active and passive surveillance
Measured: Throughout study
Immunogenicity, as determined by anti-DEN3 neutralizing antibody measured on Days 0, 21, 28, 42, and 180
Measured: Throughout study
Secondary outcomes (5)
Assess the frequency, quantity, and duration of viremia in each dose cohort studied
Measured: Throughout study
Determine the number of vaccinees infected with rDEN3/4delta30(ME)
Measured: Throughout study
Determine cellular targets of vaccine infection, including peripheral blood mononuclear cells (PBMCs) and skin from participants who are willing to undergo skin biopsy
Measured: Throughout study
Compare the infectivity rates, safety, and immunogenicity between dose groups
Measured: At study completion
Evaluate the immunopathological mechanism of vaccine-associated rash in those volunteers who are willing to undergo skin biopsy
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 posted13 Sep 2006 (estimated)
- Study startOct 2006
- Primary completionSep 2008
- Study completionSep 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 DengueStudies 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
- 58 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
- NCT00375726
- Sponsor's protocol ID
- CIR 228
- Other IDs
- WIRB Protocol Number 20061667
- Status last verified
- Dec 2010
- First submitted
- 12 Sep 2006
- Last updated
- 14 Dec 2010
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Blaney JE Jr, Durbin AP, Murphy BR, Whitehead SS. Development of a live attenuated dengue virus vaccine using reverse genetics. Viral Immunol. 2006 Spring;19(1):10-32. doi: 10.1089/vim.2006.19.10.
PubMed 16553547Blaney JE Jr, Hanson CT, Firestone CY, Hanley KA, Murphy BR, Whitehead SS. Genetically modified, live attenuated dengue virus type 3 vaccine candidates. Am J Trop Med Hyg. 2004 Dec;71(6):811-21.
PubMed 15642976Blaney JE Jr, Matro JM, Murphy BR, Whitehead SS. Recombinant, live-attenuated tetravalent dengue virus vaccine formulations induce a balanced, broad, and protective neutralizing antibody response against each of the four serotypes in rhesus monkeys. J Virol. 2005 May;79(9):5516-28. doi: 10.1128/JVI.79.9.5516-5528.2005.
PubMed 15827166Durbin 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 15688284
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
- Phase 1 Study of the Safety and Immunogenicity of rDEN3/4delta30(ME), a Live Attenuated Virus Vaccine Candidate for the Prevention of Dengue Serotype 3
- ClinicalTrials.gov ID
- NCT00375726
- Acronym / sponsor ID
- CIR 228
- Conditions
- Dengue
- Keywords
- Dengue Fever, Dengue Vaccine, Dengue Virus, Dengue Hemorrhagic Fever, Dengue Shock Syndrome
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 58 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
- Oct 2006
- Primary completion
- Sep 2008 (actual)
- Study completion
- Sep 2008 (actual)
- First posted
- 13 Sep 2006 (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, caused by dengue viruses, is a major health problem in the tropical and subtropical regions of the world. The purpose of this study is to test the safety of and immune response to a new dengue virus vaccine in healthy adults.
Detailed description
Dengue viruses, which cause dengue fever and dengue shock syndrome, are a major cause of morbidity and mortality in several of the world's tropical and subtropical regions. The rDEN3/4delta30(ME) vaccine is a live attenuated dengue virus vaccine that may be protective against dengue virus serotype 3 (DEN3). The purpose of this study is to evaluate the safety and immunogenicity of the rDEN3/4delta30(ME) vaccine in healthy adults.
This study will last 40 weeks. Participants will be randomly assigned to receive one of three doses of rDEN3/4delta30(ME) or placebo. Participants in Group 1 will receive the middle dose of rDEN3/4delta30(ME) or placebo at study entry. Group 2a will begin enrollment after the immunogenicity review of all participants in Group 1. Participants in Group 2a will receive the highest dose of rDEN4delta30(ME) or placebo at study entry. Group 2b will begin enrollment after the immunogenicity review of all participants in Group 2a. Participants in Group 2b will receive the lowest dose of rDEN4delta30(ME) or placebo.
After vaccination, participants in all groups will be followed closely every other day for the first 16 days of the study. Participants will take their temperature three times a day through Day 16 and record each measurement in a diary. After Day 16, participants will have study visits on Days 21, 28, 42, and 180; a physical exam and blood collection will occur at all visits. Some participants may be asked to join a skin biopsy substudy.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Biological: rDEN3/4delta30(ME)One subcutaneous vaccination with rDEN3/4delta30(ME) vaccine (10^3 PFU dose) into the deltoid region of either arm. |
| 2 | Experimental | Biological: rDEN3/4delta30(ME)One subcutaneous vaccination with rDEN3/4delta30(ME) vaccine (10^5 PFU dose) into the deltoid region of either arm. This arm may enroll after Arm 1 depending on the immunological response of Arm 1. |
| 3 | Experimental | Biological: rDEN3/4delta30(ME)One subcutaneous vaccination with rDEN3/4delta30(ME) vaccine (10^1 PFU dose) into the deltoid region of either arm. This arm may enroll after Arm 1 depending on the immunological response of Arm 1. |
| 4 | Placebo comparator | Biological: PlaceboOne 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 (3 listed)
- Good general health
- Available for the duration of the study
- Willing to use acceptable forms of contraception for the duration of the study
Key exclusion criteria (21 listed)
- Significant neurologic, heart, lung, liver, rheumatologic, autoimmune, or kidney disease
- Behavioral, cognitive, or psychiatric disease that, in the opinion of the investigator, may interfere with the study
- Significant laboratory abnormalities
- Medical, work, or family problems as a result of alcohol or illegal drug use within 12 months prior to study entry
- History of severe allergic reaction 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 |
|---|---|---|
| rDEN3/4delta30(ME)Live attenuated rDEN3/4delta30(ME) vaccine (one of three doses) | Biological | 1, 2, 3 |
| PlaceboPlacebo for rDEN3/4delta30(ME) | Biological | 4 |
Primary outcome
Safety, as defined by frequency of vaccine-related adverse events, as classified by both intensity and severity through active and passive surveillance
Time frame: Throughout study
Immunogenicity, as determined by anti-DEN3 neutralizing antibody measured on Days 0, 21, 28, 42, and 180
Time frame: Throughout study
5 secondary outcomes
Assess the frequency, quantity, and duration of viremia in each dose cohort studied
Time frame: Throughout study
Determine the number of vaccinees infected with rDEN3/4delta30(ME)
Time frame: Throughout study
Determine cellular targets of vaccine infection, including peripheral blood mononuclear cells (PBMCs) and skin from participants who are willing to undergo skin biopsy
Time frame: Throughout study
Compare the infectivity rates, safety, and immunogenicity between dose groups
Time frame: At study completion
Evaluate the immunopathological mechanism of vaccine-associated rash in those volunteers who are willing to undergo skin biopsy
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 16553547Blaney JE Jr, Durbin AP, Murphy BR, Whitehead SS. Development of a live attenuated dengue virus vaccine using reverse genetics. Viral Immunol. 2006 Spring;19(1):10-32. doi: 10.1089/vim.2006.19.10.
- Background: PubMed 15642976Blaney JE Jr, Hanson CT, Firestone CY, Hanley KA, Murphy BR, Whitehead SS. Genetically modified, live attenuated dengue virus type 3 vaccine candidates. Am J Trop Med Hyg. 2004 Dec;71(6):811-21.
- Background: PubMed 15827166Blaney JE Jr, Matro JM, Murphy BR, Whitehead SS. Recombinant, live-attenuated tetravalent dengue virus vaccine formulations induce a balanced, broad, and protective neutralizing antibody response against each of the four serotypes in rhesus monkeys. J Virol. 2005 May;79(9):5516-28. doi: 10.1128/JVI.79.9.5516-5528.2005.
- 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.
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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 rDEN3/4delta30(ME) in people with Dengue, 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 3 inclusion and 21 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?
Safety, as defined by frequency of vaccine-related adverse events, as classified by both intensity and severity 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 NCT00375726, 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.