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DenguePhase 1NCT01072786

Evaluation of the Safety and Immune Response of Five Admixtures of a Tetravalent Dengue Virus Vaccine

A Phase 1 study testing TetraVax-DV Vaccine-Admixture 1, TetraVax-DV Vaccine-Admixture 2 and TetraVax-DV Vaccine-Admixture 3 in people with Dengue, run by National Institute of Allergy and Infectious Diseases (NIAID) at 4 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

Dengue viruses can cause dengue fever and other serious health conditions, primarily affecting people living in tropical regions of the world. This study will evaluate the safety and immune responses of five formulations of a tetravalent 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?
TetraVax-DV Vaccine-Admixture 1, TetraVax-DV Vaccine-Admixture 2 and TetraVax-DV Vaccine-Admixture 3
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
141 participants
Where
4 sitesUnited States
Study dates
Jul 2010to Jun 2012
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

  • In 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 post-vaccination
  • Willing to participate in the study as evidenced by signing the informed consent document
  • Female participants of childbearing potential must be willing to use effective contraception for the duration of the trial. More information on this criterion can be found in the protocol.
  • Receipt of vaccine at first vaccination
  • In good general health, as determined by physical examination and review of medical history
Show all 9Show fewer
  • Available for the duration of the study, approximately 6 months post-vaccination
  • Willing to participate in the study as evidenced by signing the informed consent document
  • Female participants of childbearing potential must be willing to use effective contraception for the duration of the trial. More information on this criterion can be found in the protocol.

Who cannot join

  • Pregnant or breastfeeding
  • 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 person's ability to understand and cooperate with the requirements of the study
  • Screening laboratory values of Grade 1 or above for absolute neutrophil count (ANC), alanine aminotransferase (ALT), and serum creatinine, as defined in the protocol
  • Any other condition that in the opinion of the investigator would jeopardize the safety or rights of a person participating in the study or would render the person unable to comply with the study
  • Any significant alcohol or drug abuse in the 12 months before study entry which has caused medical, occupational, or family problems, as indicated by medical history
Show all 41Show fewer
  • History of a severe allergic reaction or anaphylaxis
  • Severe asthma (emergency room visit or hospitalization in the 6 months before study entry)
  • HIV infection, by screening and confirmatory assays
  • Hepatitis C virus (HCV) infection, by screening and confirmatory assays
  • Hepatitis B virus (HBV) infection, 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 of prednisone equivalent per day for 14 days or longer
  • 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
  • Absence of spleen
  • Receipt of blood products in the 6 months before study entry, 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)
  • Anticipated receipt of any investigational agent in the 42 days before or after vaccination
  • Has definite plans to travel to a dengue endemic area during the study
  • Refusal to allow storage of specimens for future research
  • Pregnant or breastfeeding
  • 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 person's ability to understand and cooperate with the requirements of the study
  • Any other condition that in the opinion of the investigator would jeopardize the safety or rights of a person participating in the study or would render the person unable to comply with the study
  • Any significant alcohol or drug abuse in the past 12 months which has caused medical, occupational, or family problems, as indicated by medical history
  • History of a severe allergic reaction or anaphylaxis
  • Severe asthma (emergency room visit or hospitalization within the last 6 months)
  • HIV infection, by screening and confirmatory assays
  • Hepatitis C virus (HCV) infection, by screening and confirmatory assays
  • Hepatitis B virus (HBV) infection, 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 of prednisone equivalent per day for 14 days or longer
  • 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
  • Absence of spleen
  • 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
  • Anticipated receipt of any other investigational agent in the 42 days before or after vaccination
  • Has definite plans to travel to a dengue endemic area during the study
  • Refusal to allow storage of specimens for future research

Trial locations and contacts

4 sites in 1 country.

United States4 sites

  • Center for Immunization Research, Johns Hopkins School of Public Health

    Baltimore, Maryland, 21205

  • Fletcher Allen Health Care (FAHC), General Clinical Research Center (GCRC)

    Burlington, Vermont, 05401

  • University of Vermont Vaccine Testing Center

    Burlington, Vermont, 05401

  • Center for Immunization Research, Johns Hopkins School of Public Health

    Washington D.C., District of Columbia, 20037

Other trials in United States

About this study

Official title: A Phase 1 Evaluation of the Safety and Immunogenicity of Five Admixtures of TetraVax-DV, a Recombinant Live Attenuated Tetravalent Dengue Virus Vaccine, in Healthy Flavivirus-naïve Adult Subjects

Dengue viruses can cause dengue fever and other serious health conditions, primarily affecting people living in tropical regions of the world. This study will evaluate the safety and immune responses of five formulations of a tetravalent dengue virus vaccine in healthy adults.

Read the detailed description

Dengue viruses cause dengue fever and the more severe condition, dengue hemorrhagic fever/shock syndrome. Dengue viruses are common in most tropical and subtropical regions of the world and infection with dengue viruses is the leading cause of hospitalization and death in children in many tropical Asian countries. For these reasons, the World Health Organization (WHO) has made the development of a dengue virus vaccine a top priority. This study will evaluate the safety and immunogenicity of five versions of a live, attenuated, tetravalent dengue virus vaccine called TetraVax-DV.

This study will enroll healthy adults 18-50 years old. Participants will be randomly assigned to receive one of the five versions of TetraVax-DV or placebo. At the vaccination study visit, participants will undergo a medical history review, physical examination, blood and urine collection, and vital sign measurements. Participants will then receive one injection of their assigned vaccine or placebo in the upper arm. After receiving the vaccine, participants will remain in the clinic for 30 minutes for observation. At home, participants will monitor and record their temperature three times a day for 16 days. Additional study visits will occur at Days 2, 4, 6, 8, 10, 12, 14, 16, 21, 28, 42, and 180 for physical exams, assessment of symptoms, and blood and urine collection. Some participants will attend an additional study visit at Day 60.

Participants who received one of the five versions of the vaccine will be asked to take part in an optional substudy that will evaluate the safety and immunogenicity of a second vaccination 6 months after the first vaccination. In the substudy, participants will be randomly assigned to receive either the same vaccine they received in the first part of the study or a placebo vaccine. For 6 months following the second vaccination, participants will attend study visits and take part in the same study procedures that occurred in the first part of the study.

Conditions
Dengue
Being tested
TetraVax-DV Vaccine-Admixture 1, TetraVax-DV Vaccine-Admixture 2, TetraVax-DV Vaccine-Admixture 3, TetraVax-DV Vaccine-Admixture 4, Placebo
Keywords
Dengue Virus, Dengue Fever, Dengue Vaccine, 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.

  • TetraVax-DV Vaccine-Admixture 1Biological

    One subcutaneous injection of a recombinant live attenuated TetraVax-DV vaccine, admixture 1 (10^3 PFU of rDEN1Δ30, 10^3 PFU of rDEN2/4Δ30[ME], 10^3 PFU of rDEN3-3´D4Δ30, 10^3 PFU of rDEN4Δ30)

  • TetraVax-DV Vaccine-Admixture 2Biological

    One subcutaneous injection of a recombinant live attenuated TetraVax-DV vaccine, admixture 2 (10^3 PFU of rDEN1Δ30, 10^3 PFU of rDEN2/4Δ30[ME], 10^3 PFU of rDEN3-3´D4Δ30, 10^3 PFU of rDEN4Δ30-200,201)

  • TetraVax-DV Vaccine-Admixture 3Biological

    One subcutaneous injection of a recombinant live attenuated TetraVax-DV vaccine, admixture 3 (10^3 PFU of rDEN1Δ30, 10^3 PFU of rDEN2/4Δ30[ME], 10^3 PFU of rDEN3Δ30/31-7164, 10^3 PFU of rDEN4Δ30)

  • TetraVax-DV Vaccine-Admixture 4Biological

    One subcutaneous injection of a recombinant live attenuated TetraVax-DV vaccine, admixture 4 (10^3 PFU of rDEN1Δ30, 10^3 PFU of rDEN2/4Δ30[ME], 10^3 PFU of rDEN3Δ30/31-7164, 10^3 PFU of rDEN4Δ30-200,201)

  • PlaceboBiological

    One subcutaneous injection of a placebo containing vaccine diluent but no actual vaccine

  • TetraVax-DV Vaccine-Admixture 5Biological

    One subcutaneous injection of a recombinant live attenuated TetraVax-DV vaccine, admixture 5 (10^3 PFU of rDEN1Δ30, 10^4 PFU of rDEN2/4Δ30(ME), 10^3 PFU of rDEN3Δ30/31-7164, and 10^3 PFU of rDEN4Δ30)

Study groups in NCT01072786
Study groupRoleWhat they receive
TetraVax-DV Vaccine-Admixture 1ExperimentalParticipants will receive the TetraVax-DV admixture 1 vaccine.
Receives: Biological: TetraVax-DV Vaccine-Admixture 1
TetraVax-DV Vaccine-Admixture 2ExperimentalParticipants will receive the TetraVax-DV admixture 2 vaccine.
Receives: Biological: TetraVax-DV Vaccine-Admixture 2
TetraVax-DV Vaccine-Admixture 3ExperimentalParticipants will receive the TetraVax-DV admixture 3 vaccine.
Receives: Biological: TetraVax-DV Vaccine-Admixture 3
TetraVax-DV Vaccine-Admixture 4ExperimentalParticipants will receive the TetraVax-DV admixture 4 vaccine.
Receives: Biological: TetraVax-DV Vaccine-Admixture 4
PlaceboPlacebo comparatorParticipants will receive the placebo.
Receives: Biological: Placebo
TetraVax-DV Vaccine-Admixture 5ExperimentalParticipants will receive the TetraVax-DV admixture 5 vaccine.
Receives: Biological: TetraVax-DV Vaccine-Admixture 5

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Safety of five TetraVax-DV admixtures, as assessed by the frequency of vaccine-related adverse events (AEs), graded by severity

    Measured: Measured out to Day 28

  2. Determination of the serum plaque reduction neutralization titer 60% (PRNT_60) to DEN1, DEN2, DEN3, and DEN4 viruses

    Measured: Measured at Days 0, 28, 42, and 180

  3. Monovalent, bivalent, trivalent, and tetravalent seropositivity and seroconversion rates

    Measured: Measured at 4 and 6 weeks after vaccination

  4. Seropositivity and seroconversion rates to greater than 60% in in the TetraVax-DV admixture 5 vaccine arm

    Measured: Measured by Day 42

Secondary outcomes (6)

  1. Frequency, quantity, and duration of viremia following vaccination

    Measured: Measured out to Day 21

  2. Number of vaccinees infected with DEN1, DEN2, DEN3, and DEN4

    Measured: Measured by Day 42

  3. Duration of the neutralizing antibody response

    Measured: Measured at Day 180

  4. Safety and immunogenicity of a second dose of vaccine given 6 months after the first dose (optional substudy)

    Measured: Measured at Day 222 (42 days after second dose)

  5. Seroconversion as assessed by a greater than or equal to 4-fold rise in DEN1, DEN2, DEN3, or DEN4 neutralizing antibody titers compared with the pre-vaccination antibody titer

    Measured: Measured by Day 42

  6. Seropositivity as assessed by PRNT_60 to DEN1, DEN2, DEN3, DEN4 greater than or equal to 1:10 compared with the pre-vaccination titer

    Measured: Measured by Day 42

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Feb 2010 (estimated)
  2. Study startJul 2010
  3. Primary completionJun 2012
  4. Study completionJun 2012

Resources

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, Investigator, Outcomes assessor
Enrolment
141 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01072786
Sponsor's protocol ID
CIR 268
Status last verified
Dec 2012
First submitted
19 Feb 2010
Last updated
3 Jan 2013
Results posted
No
Data monitoring committee
Yes

Publications

  • Durbin AP, McArthur J, Marron JA, Blaney JE Jr, Thumar B, Wanionek K, Murphy BR, Whitehead SS. The live attenuated dengue serotype 1 vaccine rDEN1Delta30 is safe and highly immunogenic in healthy adult volunteers. Hum Vaccin. 2006 Jul-Aug;2(4):167-73. doi: 10.4161/hv.2.4.2944. Epub 2006 Jul 24.

    PubMed 17012875

  • Blaney JE Jr, Durbin AP, Murphy BR, Whitehead SS. Targeted mutagenesis as a rational approach to dengue virus vaccine development. Curr Top Microbiol Immunol. 2010;338:145-58. doi: 10.1007/978-3-642-02215-9_11.

    PubMed 19802584

  • Durbin AP, McArthur JH, Marron JA, Blaney JE, Thumar B, Wanionek K, Murphy BR, Whitehead SS. rDEN2/4Delta30(ME), a live attenuated chimeric dengue serotype 2 vaccine is safe and highly immunogenic in healthy dengue-naive adults. Hum Vaccin. 2006 Nov-Dec;2(6):255-60. doi: 10.4161/hv.2.6.3494. Epub 2006 Nov 5.

    PubMed 17106267

  • 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 15688284

  • McArthur JH, Durbin AP, Marron JA, Wanionek KA, Thumar B, Pierro DJ, Schmidt AC, Blaney JE Jr, Murphy BR, Whitehead SS. Phase I clinical evaluation of rDEN4Delta30-200,201: a live attenuated dengue 4 vaccine candidate designed for decreased hepatotoxicity. Am J Trop Med Hyg. 2008 Nov;79(5):678-84.

    PubMed 18981503

  • Kirkpatrick BD, Durbin AP, Pierce KK, Carmolli MP, Tibery CM, Grier PL, Hynes N, Diehl SA, Elwood D, Jarvis AP, Sabundayo BP, Lyon CE, Larsson CJ, Jo M, Lovchik JM, Luke CJ, Walsh MC, Fraser EA, Subbarao K, Whitehead SS. Robust and Balanced Immune Responses to All 4 Dengue Virus Serotypes Following Administration of a Single Dose of a Live Attenuated Tetravalent Dengue Vaccine to Healthy, Flavivirus-Naive Adults. J Infect Dis. 2015 Sep 1;212(5):702-10. doi: 10.1093/infdis/jiv082. Epub 2015 Mar 22.

    PubMed 25801652

  • Durbin AP, Kirkpatrick BD, Pierce KK, Elwood D, Larsson CJ, Lindow JC, Tibery C, Sabundayo BP, Shaffer D, Talaat KR, Hynes NA, Wanionek K, Carmolli MP, Luke CJ, Murphy BR, Subbarao K, Whitehead SS. A single dose of any of four different live attenuated tetravalent dengue vaccines is safe and immunogenic in flavivirus-naive adults: a randomized, double-blind clinical trial. J Infect Dis. 2013 Mar 15;207(6):957-65. doi: 10.1093/infdis/jis936. Epub 2013 Jan 17.

    PubMed 23329850

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing TetraVax-DV Vaccine-Admixture 1, TetraVax-DV Vaccine-Admixture 2 and TetraVax-DV Vaccine-Admixture 3 in people with Dengue, run by National Institute of Allergy and Infectious Diseases (NIAID) at 4 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 9 inclusion and 41 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 4 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?

Safety of five TetraVax-DV admixtures, as assessed by the frequency of vaccine-related adverse events (AEs), graded by severity (time frame: Measured out to Day 28). The study lists 4 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 NCT01072786, which also lists 7 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.

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