Dengue Shock SyndromePhase 1NCT00919178
Safety of and Immune Response to DEN4 Vaccine Component Candidate for Dengue Virus
A Phase 1 study testing DEN4 Vaccine Candidate in people with Dengue Shock Syndrome and Dengue Hemorrhagic Fever, run by National Institute of Allergy and Infectious Diseases (NIAID) at 2 sites in United States.
Trial summary
Infection with dengue viruses is one of the leading causes of hospitalization and death in children in several tropical Asian counties. The World Health Organization (WHO) estimates that these viruses are responsible for more than 50 million cases of dengue fever (DF) and approximately 0.5 million cases of the more… Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Dengue Shock Syndrome, Dengue Hemorrhagic Fever
- What is being tested?
- DEN4 Vaccine Candidate
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 70 participants
- Where
- 2 sitesUnited States
- Study dates
- Jul 2009to May 2010
- 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
- Willing and able to provide informed consent
- Good general health as determined by physical examination, laboratory screening, and review of medical history
- Available for the duration of the study, approximately 26 weeks postvaccination
- Willing to use acceptable forms of birth control. More information on this criterion can be found in the study protocol.
Who cannot join
- Currently breast-feeding, or pregnant
- Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, rheumatologic, autoimmune, or renal disease by history, physical examination, and/or laboratory studies
- Behavioral, cognitive, or psychiatric disease that in the opinion of the Investigator affects the ability of the volunteer to understand and cooperate with the requirements of the study protocol
- Screening laboratory values of Grade 1 or above for absolute neutrophil count(ANC), ALT, and serum creatinine, as defined in this protocol
- Any other condition that in the opinion of the Investigator would jeopardize the safety or rights of a volunteer participating in the trial or would render the volunteer unable to comply with the protocol
- Any significant alcohol or drug abuse in the past 12 months which has caused medical, occupational, or family problems, as indicated by volunteer history
Show all 21Show fewer
- History of a severe allergic reaction or anaphylaxis
- Severe asthma (emergency room visit or hospitalization within the last 6 months)
- Positive HIV-1 serology by screening and confirmatory assays
- Positive for hepatitis C virus (HCV) by screening and confirmatory assays
- Positive for hepatitis B virus (HBV) by hepatitis B surface antigen (HBsAg) screening
- Any known immunodeficiency syndrome
- Use of anticoagulant medications
- Use of corticosteroids (excluding topical or nasal) or immunosuppressive drugs within 42 days prior to or following vaccination. Immunosuppressive dose of corticosteroids is defined as 10 mg or more prednisone equivalent per day for 14 or more days.
- Receipt of a live vaccine within 28 days or a killed vaccine within the 14 days prior to vaccination or anticipated receipt of any vaccine during the 42 days following vaccination
- History of a surgical splenectomy
- Receipt of blood products within the past 6 months, including transfusions or immunoglobulin or anticipated receipt of any blood products or immunoglobulin during the 42 days following vaccination
- History or serologic evidence of previous dengue virus infection or other flavivirus infection (e.g., yellow fever virus, St. Louis encephalitis, West Nile virus)
- Previous receipt of a flavivirus vaccine (licensed or experimental)
- Receipt of any investigational agent in the 42 days before or after vaccination
- Volunteer has definite plans to travel to a dengue endemic area during the study
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Center for Immunization Research, Johns Hopkins School of Public Health
Baltimore, Maryland
University of Vermont Vaccine Testing Center
Burlington, Vermont
About this study
Official title: Phase I Evaluation of the Safety and Immunogenicity of rDEN4delta30 Lot# 109A, a Live Attenuated DEN4 Vaccine, in Healthy Flavivirus-naïve Adult Volunteers.
Infection with dengue viruses is one of the leading causes of hospitalization and death in children in several tropical Asian counties. The World Health Organization (WHO) estimates that these viruses are responsible for more than 50 million cases of dengue fever (DF) and approximately 0.5 million cases of the more severe disease, dengue hemorrhagic fever/ shock syndrome (DHF/DSS) annually. Because dengue viruses are endemic in most tropical and subtropical regions, keeping more than 2 billion persons at risk for acquiring dengue, the WHO has made development of a dengue vaccine a top priority.
The purpose of this study is to evaluate the safety and effectiveness of a candidate DEN4 vaccine aimed at preventing infection with dengue virus serotype 4.
Read the detailed description
Dengue viruses are endemic in most tropical and subtropical regions of the world with more than 2 billion persons at risk for acquiring dengue. There are four serotypes of dengue virus (DEN 1, DEN 2, DEN 3, and DEN 4) each capable of causing dengue illness ranging from mild, self-limited febrile illness to life-threatening disease. Because previous infection with one dengue serotype can increase the risk for DHF/DSS following infection with a different serotype, immunization would ideally provide immunity against all four dengue viral serotypes.
Several live, attenuated dengue vaccines have been tested in Phase I and/or Phase II clinical trials. Although some have appeared promising in early trials, none have been able to meet the requirements for a safe and effective vaccine. Meeting these requirements has been particularly difficult when testing vaccines containing all four serotypes. The vaccine candidate in this study is live-attenuated rDEN4delta30, which will target the DEN4 serotype, it is a potential component for a future tetravalent dengue vaccine.
This is a double-blind, random assignment, placebo-controlled study in healthy, adult volunteers. The purpose of this study is to evaluate the safety and effectiveness of a single dose of DEN4 vaccine. Some participants will be receiving placebo as a comparative measure, to better assess vaccine-associated versus non vaccine-associated adverse events.
To qualify for participation in the study, volunteers will undergo an eligibility screening which will include medical history, physical exam, hematology testing, liver and renal function testing, coagulation studies, human immunodeficiency virus (HIV) and hepatitis B and C screening, urinalysis, and screening for pervious flavivirus infection. Urine pregnancy testing will also be required for female volunteers.
Duration of individual participation in the study is approximately 26 weeks following vaccination on Study Day 0. Volunteers will be randomly assigned to receive either rDEN4delta30 or placebo; 50 participants will receive the vaccine, 20 will receive placebo. On the day of vaccination, all volunteers will be reassessed by study personnel to ensure continued eligibility, vital signs will be taken, and a physical exam will be performed. Female participants will also have a pregnancy test and review of acceptable pregnancy prevention methods. Eligible participants will receive a vaccination of Study Day 0, followed by a 30 minute post vaccination assessment for adverse events. After vaccination, volunteers will be evaluated in the clinic approximately every other day for the first 16 days if study.
During the course of study, volunteers will have blood drawn and clinical evaluations performed on Study Days 21, 28, 42, and 180 post-vaccination. All participants will be asked to record oral temperatures 3 times a day for the first 16 days post-vaccination.
- Conditions
- Dengue Shock Syndrome, Dengue Hemorrhagic Fever
- Being tested
- DEN4 Vaccine Candidate, DEN4 Vaccine Placebo
- Keywords
- Dengue virus, Vaccine, DEN4, Dengue
- 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.
DEN4 Vaccine CandidateBiological
DEN4 Vaccine Candidate
Participants will receive a single immunization on Study Day 0. Vaccine will be delivered by subcutaneous injection in the upper arm, at a volume of 0.5 mL.
DEN4 Vaccine PlaceboBiological
DEN4 Vaccine Placebo
Participants will receive a single immunization on Study Day 0. Placebo will be delivered by subcutaneous injection in the upper arm, at a volume of 0.5 mL.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Participants will receive a single immunization for Dengue virus serotype 4 (DEN4) Receives: Biological: DEN4 Vaccine Candidate |
| 2 | Placebo comparator | Participants will receive a single immunization in the form of placebo resembling vaccine for DEN 4 Receives: Biological: DEN4 Vaccine Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Immunogenicity of vaccine candidate, as assessed by neutralizing antibody titers to DEN4
Measured: At Weeks 4 and 6 following vaccination
Safety of vaccine candidate, as assessed by the frequency of vaccine-related adverse events, graded by severity
Measured: Throughout study
Secondary outcomes (7)
Frequency, quantity, and duration of viremia following vaccination
Measured: Throughout study
Number of vaccinees infected with vaccine virus
Measured: Throughout study
Infectivity rates, safety, and immunogenicity of a single dose of candidate vaccine compared with previous rates from a previous lot of similar vaccine
Measured: Throughout study
Durability of antibody response
Measured: At 26 Weeks following vaccination
Phenotype of peripheral blood mononuclear cells at primary infection with the rDEN4delta30 vaccine
Measured: Throughout study
Immunopathological mechanism of vaccine-associated rash in those volunteers who are willing to undergo skin biopsy
Measured: Throughout study
Cellular immune response to primary infection with the rDEN4delta30 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 posted12 Jun 2009 (estimated)
- Study startJul 2009
- Primary completionMay 2010
- Study completionMay 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Dengue Shock SyndromeStudies 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
- 70 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Anna Durbin, MD, Principal investigator, Johns Hopkins Bloomberg School of Public HealthBeth Kirkpatrick, MD, Principal investigator, University of Vermont Vaccine Testing Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00919178
- Sponsor's protocol ID
- CIR 256
- Status last verified
- Dec 2012
- First submitted
- 11 Jun 2009
- Last updated
- 3 Jan 2013
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Swaminathan S, Khanna N. Dengue: recent advances in biology and current status of translational research. Curr Mol Med. 2009 Mar;9(2):152-73. doi: 10.2174/156652409787581592.
PubMed 19275624Tan GK, Alonso S. Pathogenesis and prevention of dengue virus infection: state-of-the-art. Curr Opin Infect Dis. 2009 Jun;22(3):302-8. doi: 10.1097/QCO.0b013e328329ae32.
PubMed 19262377Wiwanitkit V. Dengue vaccines: a new hope? Hum Vaccin. 2009 Aug;5(8):566-7. doi: 10.4161/hv.5.8.8481. Epub 2009 Aug 18.
PubMed 19337028
Study at a glance
From the registry record, last updated by the sponsor on 3 Jan 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Evaluation of the Safety and Immunogenicity of rDEN4delta30 Lot# 109A, a Live Attenuated DEN4 Vaccine, in Healthy Flavivirus-naïve Adult Volunteers.
- ClinicalTrials.gov ID
- NCT00919178
- Acronym / sponsor ID
- CIR 256
- Conditions
- Dengue Shock Syndrome, Dengue Hemorrhagic Fever
- Keywords
- Dengue virus, Vaccine, DEN4, Dengue
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 70 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- Jul 2009
- Primary completion
- May 2010 (actual)
- Study completion
- May 2010 (actual)
- First posted
- 12 Jun 2009 (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.
Infection with dengue viruses is one of the leading causes of hospitalization and death in children in several tropical Asian counties. The World Health Organization (WHO) estimates that these viruses are responsible for more than 50 million cases of dengue fever (DF) and approximately 0.5 million cases of the more severe disease, dengue hemorrhagic fever/ shock syndrome (DHF/DSS) annually. Because dengue viruses are endemic in most tropical and subtropical regions, keeping more than 2 billion persons at risk for acquiring dengue, the WHO has made development of a dengue vaccine a top priority.
The purpose of this study is to evaluate the safety and effectiveness of a candidate DEN4 vaccine aimed at preventing infection with dengue virus serotype 4.
Detailed description
Dengue viruses are endemic in most tropical and subtropical regions of the world with more than 2 billion persons at risk for acquiring dengue. There are four serotypes of dengue virus (DEN 1, DEN 2, DEN 3, and DEN 4) each capable of causing dengue illness ranging from mild, self-limited febrile illness to life-threatening disease. Because previous infection with one dengue serotype can increase the risk for DHF/DSS following infection with a different serotype, immunization would ideally provide immunity against all four dengue viral serotypes.
Several live, attenuated dengue vaccines have been tested in Phase I and/or Phase II clinical trials. Although some have appeared promising in early trials, none have been able to meet the requirements for a safe and effective vaccine. Meeting these requirements has been particularly difficult when testing vaccines containing all four serotypes. The vaccine candidate in this study is live-attenuated rDEN4delta30, which will target the DEN4 serotype, it is a potential component for a future tetravalent dengue vaccine.
This is a double-blind, random assignment, placebo-controlled study in healthy, adult volunteers. The purpose of this study is to evaluate the safety and effectiveness of a single dose of DEN4 vaccine. Some participants will be receiving placebo as a comparative measure, to better assess vaccine-associated versus non vaccine-associated adverse events.
To qualify for participation in the study, volunteers will undergo an eligibility screening which will include medical history, physical exam, hematology testing, liver and renal function testing, coagulation studies, human immunodeficiency virus (HIV) and hepatitis B and C screening, urinalysis, and screening for pervious flavivirus infection. Urine pregnancy testing will also be required for female volunteers.
Duration of individual participation in the study is approximately 26 weeks following vaccination on Study Day 0. Volunteers will be randomly assigned to receive either rDEN4delta30 or placebo; 50 participants will receive the vaccine, 20 will receive placebo. On the day of vaccination, all volunteers will be reassessed by study personnel to ensure continued eligibility, vital signs will be taken, and a physical exam will be performed. Female participants will also have a pregnancy test and review of acceptable pregnancy prevention methods. Eligible participants will receive a vaccination of Study Day 0, followed by a 30 minute post vaccination assessment for adverse events. After vaccination, volunteers will be evaluated in the clinic approximately every other day for the first 16 days if study.
During the course of study, volunteers will have blood drawn and clinical evaluations performed on Study Days 21, 28, 42, and 180 post-vaccination. All participants will be asked to record oral temperatures 3 times a day for the first 16 days post-vaccination.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Biological: DEN4 Vaccine CandidateParticipants will receive a single immunization for Dengue virus serotype 4 (DEN4) |
| 2 | Placebo comparator | Biological: DEN4 Vaccine PlaceboParticipants will receive a single immunization in the form of placebo resembling vaccine for DEN 4 |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Willing and able to provide informed consent
- Good general health as determined by physical examination, laboratory screening, and review of medical history
- Available for the duration of the study, approximately 26 weeks postvaccination
- Willing to use acceptable forms of birth control. More information on this criterion can be found in the study protocol.
Key exclusion criteria (21 listed)
- Currently breast-feeding, or pregnant
- Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, rheumatologic, autoimmune, or renal disease by history, physical examination, and/or laboratory studies
- Behavioral, cognitive, or psychiatric disease that in the opinion of the Investigator affects the ability of the volunteer to understand and cooperate with the requirements of the study protocol
- Screening laboratory values of Grade 1 or above for absolute neutrophil count(ANC), ALT, and serum creatinine, as defined in this protocol
- Any other condition that in the opinion of the Investigator would jeopardize the safety or rights of a volunteer participating in the trial or would render the volunteer unable to comply with the protocol
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 |
|---|---|---|
| DEN4 Vaccine CandidateDEN4 Vaccine Candidate Participants will receive a single immunization on Study Day 0. Vaccine will be delivered by subcutaneous injection in the upper arm, at a volume of 0.5 mL. | Biological | 1 |
| DEN4 Vaccine PlaceboDEN4 Vaccine Placebo Participants will receive a single immunization on Study Day 0. Placebo will be delivered by subcutaneous injection in the upper arm, at a volume of 0.5 mL. | Biological | 2 |
Primary outcome
Immunogenicity of vaccine candidate, as assessed by neutralizing antibody titers to DEN4
Time frame: At Weeks 4 and 6 following vaccination
Safety of vaccine candidate, as assessed by the frequency of vaccine-related adverse events, graded by severity
Time frame: Throughout study
7 secondary outcomes
Frequency, quantity, and duration of viremia following vaccination
Time frame: Throughout study
Number of vaccinees infected with vaccine virus
Time frame: Throughout study
Infectivity rates, safety, and immunogenicity of a single dose of candidate vaccine compared with previous rates from a previous lot of similar vaccine
Time frame: Throughout study
Durability of antibody response
Time frame: At 26 Weeks following vaccination
Phenotype of peripheral blood mononuclear cells at primary infection with the rDEN4delta30 vaccine
Time frame: Throughout study
Immunopathological mechanism of vaccine-associated rash in those volunteers who are willing to undergo skin biopsy
Time frame: Throughout study
Cellular immune response to primary infection with the rDEN4delta30 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 3 Jan 2013.
- Background: PubMed 19275624Swaminathan S, Khanna N. Dengue: recent advances in biology and current status of translational research. Curr Mol Med. 2009 Mar;9(2):152-73. doi: 10.2174/156652409787581592.
- Background: PubMed 19262377Tan GK, Alonso S. Pathogenesis and prevention of dengue virus infection: state-of-the-art. Curr Opin Infect Dis. 2009 Jun;22(3):302-8. doi: 10.1097/QCO.0b013e328329ae32.
- Background: PubMed 19337028Wiwanitkit V. Dengue vaccines: a new hope? Hum Vaccin. 2009 Aug;5(8):566-7. doi: 10.4161/hv.5.8.8481. Epub 2009 Aug 18.
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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
Johns Hopkins Bloomberg School of Public Health
Beth Kirkpatrick, MD principal investigator
University of Vermont Vaccine Testing Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing DEN4 Vaccine Candidate in people with Dengue Shock Syndrome and Dengue Hemorrhagic Fever, run by National Institute of Allergy and Infectious Diseases (NIAID) at 2 sites 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 3 Jan 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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?
Immunogenicity of vaccine candidate, as assessed by neutralizing antibody titers to DEN4 (time frame: At Weeks 4 and 6 following vaccination). 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 NCT00919178, which also lists 3 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 3 Jan 2013.