DenguePhase 1NCT00322946
Safety of and Immune Response to a Dengue Virus Vaccine (rDEN4delta30-4995) in Healthy Adults
A Phase 1 study testing rDEN4delta30-4995 in people with Dengue, 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 tropical and subtropical regions of the world. The purpose of this study is to evaluate the safety and immune response to the dengue vaccine DEN4delta30-4995 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?
- rDEN4delta30-4995
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 84 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2007to Aug 2009
- 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
- Adult males and non-pregnant females between 18 and 50 years of age
- Good general health
- Available for the duration of the study
- Willing to use acceptable methods of contraception for the duration of the study
Who cannot join
- Significant neurologic, cardiac, 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
- Severe asthma
Show all 21Show fewer
- HIV-1 serotype infected
- Hepatitis C virus (HCV) infected
- Hepatitis B surface antigen positive
- Immunodeficiency syndrome
- Use of corticosteroids or immunosuppressive medications within 2 weeks prior to study entry. Individuals 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
- Prior receipt of yellow fever or dengue vaccine (licensed or experimental)
- 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 affect participation in the study
- Pregnant or breastfeeding
Trial locations and contacts
1 site in 1 country.
United States1 site
Vanderbilt University School of Medicine
Nashville, Tennessee, 37232-2581
About this study
Official title: Phase 1 Study of the Safety and Immunogenicity of rDEN4delta30-4995, a Live Attenuated Virus Vaccine Candidate for the Prevention of Dengue Serotype 4
Dengue fever, which is caused by dengue viruses, is a major health problem in tropical and subtropical regions of the world. The purpose of this study is to evaluate the safety and immune response to the dengue vaccine DEN4delta30-4995 in healthy adults.
Read the detailed description
Dengue viruses account for more than 50 million cases of dengue fever and a half million cases of the more severe disease, dengue hemorrhagic fever/dengue shock syndrome. Infection with dengue viruses is the leading cause of hospitalization and death in children in at least eight Asian countries. The goal of producing a vaccine against dengue fever is to induce a long-lived antibody response against all four dengue serotypes. The rDEN4delta30-4995 vaccine candidate is a live attenuated recombinant virus derived from rDEN4delta30 for protection against dengue virus serotype 4. The purpose of this study is to evaluate the safety, reactogenicity, and immunogenicity of rDEN4delta30-4995 in healthy adults.
This study will last 180 days (6 months). Participants in Cohort 1 will be randomly assigned to receive the highest dose of rDEN4delta30 or placebo at study entry. Participants in Cohort 2 will be randomly assigned to receive a lower dose of rDEN4delta30 or placebo. Participants in Cohort 3 will be randomly assigned to receive the lowest dose of rDEN4delta30 or placebo. Cohorts 2 and 3 will begin after a safety review of all participants in the previous cohort.
After initial vaccination, participants in Cohort 1 will be followed every other day for the first 16 days of the study, monitoring their temperature three times a day through Day 16 and recording these measurements in a diary. After Day 16, study visits will occur on Days 21, 28, 42, and 180 and will include a physical exam and blood collection. Some participants will also be asked to undergo a skin biopsy or additional blood collection at selected visits.
- Conditions
- Dengue
- Being tested
- rDEN4delta30-4995, 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.
rDEN4delta30-4995Biological
Live attenuated rDEN4delta30-4995 vaccine (one of three doses)
PlaceboBiological
Placebo for rDEN4delta30-4995
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | One subcutaneous vaccination with rDEN4delta30-4995 vaccine (10^5 PFU dose) into the deltoid region of either arm. Receives: Biological: rDEN4delta30-4995 |
| 2 | Experimental | One subcutaneous vaccination with rDEN4delta30-4995 vaccine (10^3 PFU dose) into the deltoid region of either arm. This arm will enroll after Arm 1. Receives: Biological: rDEN4delta30-4995 |
| 3 | Experimental | One subcutaneous vaccination with rDEN4delta30-4995 vaccine (10^1 PFU dose) into the deltoid region of either arm. This arm will enroll after Arms 1 and 2. Receives: Biological: rDEN4delta30-4995 |
| 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.
Frequency of vaccine-related adverse events, graded by severity for each dose
Measured: Throughout study
Immunogenicity of the rDEN4delta30-4995 vaccine against DEN4 virus by measurement of plaque reduction neutralization titers (PRNT)
Measured: At Days 28 and 42
Secondary outcomes (3)
Durability of antibody responses to DEN4 virus
Measured: At Month 6
Frequency, quantity, and duration of viremia in each dose cohort studied based on the mean peak viremia, mean day onset of viremia, and mean duration of viremia of each dose cohort
Measured: Throughout study
Number of vaccinees infected with the rDEN4delta30-4995 chimeric vaccine
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 posted8 May 2006 (estimated)
- Study startJan 2007
- Primary completionAug 2009
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
- 84 participants (estimated)
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 (CIR), Johns Hopkins School of Public Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00322946
- Sponsor's protocol ID
- CIR 221
- Other IDs
- WIRB Protocol Number 20061807
- Status last verified
- Nov 2008
- First submitted
- 4 May 2006
- Last updated
- 7 Aug 2009
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Bhamarapravati N, Sutee Y. Live attenuated tetravalent dengue vaccine. Vaccine. 2000 May 26;18 Suppl 2:44-7. doi: 10.1016/s0264-410x(00)00040-2.
PubMed 10821973Blaney 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 16553547Durbin 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 15688284Durbin AP, Karron RA, Sun W, Vaughn DW, Reynolds MJ, Perreault JR, Thumar B, Men R, Lai CJ, Elkins WR, Chanock RM, Murphy BR, Whitehead SS. Attenuation and immunogenicity in humans of a live dengue virus type-4 vaccine candidate with a 30 nucleotide deletion in its 3'-untranslated region. Am J Trop Med Hyg. 2001 Nov;65(5):405-13. doi: 10.4269/ajtmh.2001.65.405.
PubMed 11716091
Study at a glance
From the registry record, last updated by the sponsor on 7 Aug 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1 Study of the Safety and Immunogenicity of rDEN4delta30-4995, a Live Attenuated Virus Vaccine Candidate for the Prevention of Dengue Serotype 4
- ClinicalTrials.gov ID
- NCT00322946
- Acronym / sponsor ID
- CIR 221
- 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
- 84 participants (estimated)
- 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
- Jan 2007
- Primary completion
- Aug 2009 (actual)
- First posted
- 8 May 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, which is caused by dengue viruses, is a major health problem in tropical and subtropical regions of the world. The purpose of this study is to evaluate the safety and immune response to the dengue vaccine DEN4delta30-4995 in healthy adults.
Detailed description
Dengue viruses account for more than 50 million cases of dengue fever and a half million cases of the more severe disease, dengue hemorrhagic fever/dengue shock syndrome. Infection with dengue viruses is the leading cause of hospitalization and death in children in at least eight Asian countries. The goal of producing a vaccine against dengue fever is to induce a long-lived antibody response against all four dengue serotypes. The rDEN4delta30-4995 vaccine candidate is a live attenuated recombinant virus derived from rDEN4delta30 for protection against dengue virus serotype 4. The purpose of this study is to evaluate the safety, reactogenicity, and immunogenicity of rDEN4delta30-4995 in healthy adults.
This study will last 180 days (6 months). Participants in Cohort 1 will be randomly assigned to receive the highest dose of rDEN4delta30 or placebo at study entry. Participants in Cohort 2 will be randomly assigned to receive a lower dose of rDEN4delta30 or placebo. Participants in Cohort 3 will be randomly assigned to receive the lowest dose of rDEN4delta30 or placebo. Cohorts 2 and 3 will begin after a safety review of all participants in the previous cohort.
After initial vaccination, participants in Cohort 1 will be followed every other day for the first 16 days of the study, monitoring their temperature three times a day through Day 16 and recording these measurements in a diary. After Day 16, study visits will occur on Days 21, 28, 42, and 180 and will include a physical exam and blood collection. Some participants will also be asked to undergo a skin biopsy or additional blood collection at selected visits.
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: rDEN4delta30-4995One subcutaneous vaccination with rDEN4delta30-4995 vaccine (10^5 PFU dose) into the deltoid region of either arm. |
| 2 | Experimental | Biological: rDEN4delta30-4995One subcutaneous vaccination with rDEN4delta30-4995 vaccine (10^3 PFU dose) into the deltoid region of either arm. This arm will enroll after Arm 1. |
| 3 | Experimental | Biological: rDEN4delta30-4995One subcutaneous vaccination with rDEN4delta30-4995 vaccine (10^1 PFU dose) into the deltoid region of either arm. This arm will enroll after Arms 1 and 2. |
| 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 (4 listed)
- Adult males and non-pregnant females between 18 and 50 years of age
- Good general health
- Available for the duration of the study
- Willing to use acceptable methods of contraception for the duration of the study
Key exclusion criteria (21 listed)
- Significant neurologic, cardiac, 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 |
|---|---|---|
| rDEN4delta30-4995Live attenuated rDEN4delta30-4995 vaccine (one of three doses) | Biological | 1, 2, 3 |
| PlaceboPlacebo for rDEN4delta30-4995 | Biological | 4 |
Primary outcome
Frequency of vaccine-related adverse events, graded by severity for each dose
Time frame: Throughout study
Immunogenicity of the rDEN4delta30-4995 vaccine against DEN4 virus by measurement of plaque reduction neutralization titers (PRNT)
Time frame: At Days 28 and 42
3 secondary outcomes
Durability of antibody responses to DEN4 virus
Time frame: At Month 6
Frequency, quantity, and duration of viremia in each dose cohort studied based on the mean peak viremia, mean day onset of viremia, and mean duration of viremia of each dose cohort
Time frame: Throughout study
Number of vaccinees infected with the rDEN4delta30-4995 chimeric vaccine
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 7 Aug 2009.
- Background: PubMed 10821973Bhamarapravati N, Sutee Y. Live attenuated tetravalent dengue vaccine. Vaccine. 2000 May 26;18 Suppl 2:44-7. doi: 10.1016/s0264-410x(00)00040-2.
- 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 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 11716091Durbin AP, Karron RA, Sun W, Vaughn DW, Reynolds MJ, Perreault JR, Thumar B, Men R, Lai CJ, Elkins WR, Chanock RM, Murphy BR, Whitehead SS. Attenuation and immunogenicity in humans of a live dengue virus type-4 vaccine candidate with a 30 nucleotide deletion in its 3'-untranslated region. Am J Trop Med Hyg. 2001 Nov;65(5):405-13. doi: 10.4269/ajtmh.2001.65.405.
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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 (CIR), 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 rDEN4delta30-4995 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 4 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 7 Aug 2009. 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?
Frequency of vaccine-related adverse events, graded by severity for each dose (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 NCT00322946, 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 7 Aug 2009.