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DenguePhase 1NCT02317900

Evaluation of the Safety and Efficacy of a Single Dose of a Dengue Vaccine (TV005) in Healthy Adults

A Phase 1 study testing TV005 and rDEN2∆30-7169 in people with Dengue, run by National Institute of Allergy and Infectious Diseases (NIAID) at 2 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 are widespread in most tropical and subtropical regions of the world. This study will evaluate the safety and protective efficacy of a dengue vaccine (called TV005) against viremia and rash induced by a DENV-2 vaccine virus (called rDEN2∆30-7169) 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?
TV005 and rDEN2∆30-7169
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
48 participants
Where
2 sitesUnited States
Study dates
Dec 2014to Nov 2016
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 male or female between 18 and 50 years of age, inclusive
  • 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-second inoculation
  • Willingness to participate in the study as evidenced by signing the informed consent document
  • Females Only: Female participants of childbearing potential willing to use effective contraception. Reliable methods of contraception include: hormonal birth control, condoms with spermicide, diaphragm with spermicide, surgical sterilization, intrauterine device, and abstinence (6 months or longer since last sexual encounter). All female participants will be considered having childbearing potential except for those with hysterectomy, tubal ligation, tubal coil (at least 3 months prior to vaccination), or post-menopausal status documented as at least 1 year since last menstrual period.
  • Good general health as determined by physical examination and review of medical history
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  • Available for the duration of the study, approximately 26 weeks after the second dose
  • Willingness to participate in the study as evidenced by signing the informed consent document
  • Females Only: Female participants of childbearing potential willing to use effective contraception for the duration of the trial. Reliable methods of contraception include: hormonal birth control, condoms with spermicide, diaphragm with spermicide, surgical sterilization, intrauterine device, and abstinence (6 months or longer since last sexual encounter). All female participants will be considered having childbearing potential except for those with hysterectomy, tubal ligation, tubal coil (at least 3 months prior to vaccination), or post-menopausal status documented as at least 1 year since last menstrual period.

Who cannot join

  • Females Only: Currently pregnant, as determined by positive beta-human choriogonadotropin (HCG) test, 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 ability of the participant to understand and cooperate with the requirements of the study protocol
  • Screening laboratory values of Grade 1 or above for absolute neutrophil count (ANC), alanine aminotransferase (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 participant in the trial or would render the participant 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 participant history
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  • 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 28 days prior to or following vaccination. Immunosuppressive dose of corticosteroids is defined as greater than or equal to 10 mg prednisone equivalent per day for greater than or equal to 14 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 28 days following vaccination
  • Asplenia
  • Receipt of blood products within the past 6 months, including transfusions or immunoglobulin or anticipated receipt of any blood products or immunoglobulin during the 28 days following vaccination
  • History or serologic evidence of previous dengue virus infection or other flavivirus infection (e.g., yellow fever virus, St. Louis encephalitis virus, West Nile virus)
  • Previous receipt of a flavivirus vaccine (licensed or experimental)
  • Anticipated receipt of any investigational agent in the 28 days before or after vaccination
  • Participant has definite plans to travel to a dengue endemic area during the study
  • Refusal to allow storage of specimens for future research
  • Anaphylaxis or angioedema following the first dose of vaccine
  • Females Only: Currently pregnant, as determined by positive beta-HCG test, 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 ability of the participant to understand and cooperate with the requirements of the study protocol
  • Any other condition that in the opinion of the investigator would jeopardize the safety or rights of a participant in the trial or would render the participant 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 participant 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
  • HCV infection, by screening and confirmatory assays
  • HBV infection, by 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 greater than or equal to 10 mg prednisone equivalent per day for greater than or equal to 14 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 28 days following vaccination
  • Asplenia
  • Receipt of blood products within the past 6 months, including transfusions or immunoglobulin or anticipated receipt of any blood products or immunoglobulin during the 28 days following vaccination
  • Anticipated receipt of any other investigational agent in the 28 days before or after vaccination
  • Participant has definite plans to travel to a dengue endemic area during the study
  • Refusal to allow storage of specimens for future research
  • Other Treatments and Ongoing Exclusion Criteria:
  • The following criteria will be reviewed on Study Days 28 and 56 following each vaccination. If any become applicable during the study, the participant will not be included in further immunogenicity evaluations, as of the exclusionary visit. The participant will, however, be encouraged to remain in the study for safety evaluations for the duration of the study.
  • Use of any investigational drug or investigational vaccine other than the study vaccine during the 28-day period post-vaccination
  • Chronic administration (greater than or equal to 14 days) of steroids (defined as prednisone equivalent of greater than to equal to 10 mg per day), immunosuppressants, or other immune-modifying drugs initiated during the 28-day period post-vaccination (topical and nasal steroids are allowed)
  • Receipt of a licensed vaccine during the 28-day period post-vaccination
  • Receipt of immunoglobulins and/or any blood products during the 28-day period post-vaccination
  • Pregnancy

Trial locations and contacts

2 sites in 1 country.

United States2 sites

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

    Baltimore, Maryland, 21205

  • University of Vermont Vaccine Testing Center

    Burlington, Vermont, 05405

Other trials in United States

About this study

Official title: A Phase 1 Evaluation of the Safety and Protective Efficacy of a Single Dose of the Live Attenuated Tetravalent Dengue Vaccine TV005 to Protect Against Infection With Attenuated DENV-2, rDEN2∆30-7169

Dengue viruses are widespread in most tropical and subtropical regions of the world. This study will evaluate the safety and protective efficacy of a dengue vaccine (called TV005) against viremia and rash induced by a DENV-2 vaccine virus (called rDEN2∆30-7169) in healthy adults.

Read the detailed description

There are four types of dengue viruses (DENV-1, DENV-2, DENV-3, and DENV-4), each of which can cause mild to life-threatening illness. This study will evaluate the protective efficacy of TV005 (a dengue virus vaccine) administered at Day 0 against viremia and rash induced by rDEN2∆30-7169 (a live attenuated candidate DENV-2 vaccine) administered at Day 180. The safety and immunogenicity of the TV005 and rDEN2∆30-7169 vaccines will also be evaluated.

This study will enroll healthy adults with no history of previous infection with a dengue virus or a flavivirus. Participants will be randomly assigned to receive a single injection of TV005 or placebo at study entry (Day 0). All participants will receive a single injection of rDEN2∆30-7169 on Day 180. For at least 30 minutes after each vaccination, participants will remain in the study clinic to be monitored for any adverse effects of the vaccines. Participants will record their temperature three times a day for 16 days after the first and second vaccinations.

In addition to study visits at Day 0 and 180, participants will attend study visits at Day 4, 6, 8, 10, 12, 14, 16, 21, 28, 56, 90, 150, 184, 186, 188, 190, 192, 194, 196, 201, 208, 236, 270, and 360. At select study visits, participants will undergo a physical examination, medical history review, blood collection, and a pregnancy test for female participants.

Conditions
Dengue
Being tested
TV005, Placebo, rDEN2∆30-7169
Medical subject headings
Dengue

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TV005Biological

    TV005 is a live attenuated recombinant tetravalent dengue virus vaccine. It will be administered as a 0.5 mL dose containing 10^3 plaque forming units (PFUs) of each component (10^3.3 PFUs/mL of rDEN1∆30, 10^4.3 PFU/mL of rDEN2/4∆30(ME), 10^3.3 PFU/mL of rDEN3∆30/31-7164 and 10^3.3 PFU/mL of rDEN4∆30). It will be delivered by subcutaneous injection in the deltoid region of the upper arm.

  • PlaceboBiological

    The placebo vaccine will be administered as a 0.5 mL dose delivered by subcutaneous injection in the deltoid region of the upper arm.

  • rDEN2∆30-7169Biological

    rDEN2∆30-7169 is a live recombinant attenuated DENV-2 candidate vaccine virus. It will be administered as a 0.5 mL dose containing 10^3 PFUs of rDEN2∆30-7169. It will be delivered by subcutaneous injection in the deltoid region of the upper arm.

Study groups in NCT02317900
Study groupRoleWhat they receive
TV005 and rDEN2∆30-7169ExperimentalParticipants will receive one injection of TV005 at study entry (Day 0). On Day 180, participants will receive one injection of rDEN2∆30-7169.
Receives: Biological: TV005; Biological: rDEN2∆30-7169
Placebo and rDEN2∆30-7169Placebo comparatorParticipants will receive one injection of placebo at study entry (Day 0). On Day 180, participants will receive one injection of rDEN2∆30-7169.
Receives: Biological: Placebo; Biological: rDEN2∆30-7169

What is being measured

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

  1. Frequency of viremia in participants administered 10^3 PFU of rDEN2∆30-7169 at Study Day 180

    The incidence, magnitude, and duration of rDEN2∆30-7169 viremia following administration of rDEN2∆30-7169 at Study Day 180 in participants who received TV005 on Study Day 0 will be compared to those who received placebo on Study Day 0.

    Measured: Measured through Day 360

  2. Proportion of participants who received TV005 & develop rash and/or neutropenia following administration of rDEN2∆30-7169 compared to proportion of participants who received placebo & developed rash and/or neutropenia following receipt of rDEN2∆30-7169

    Measured: Measured through Day 360

Secondary outcomes (9)

  1. Frequency of vaccine-related adverse events (AEs), graded by severity

    The frequency of immediate, systemic, and local AEs following vaccination will be summarized.

    Measured: Measured through Day 28 after each vaccination

  2. Frequency of virus-related AEs, graded by severity, following primary inoculation (inoculation of those participants who received placebo at Study Day 0)

    The frequency of immediate, systemic, and local AEs following vaccination of prior placebo-recipients with rDEN2∆30-7169 will be summarized.

    Measured: Measured through Day 28 after each vaccination

  3. Frequency of viremia of rDEN1∆30, rDEN2/4∆30(ME), rDEN3∆30/31, and rDEN4∆30 following TV005 vaccination

    Quantity and duration of viremia will also be assessed

    Measured: Measured through Day 16

  4. Number of TV005 vaccinees infected with DENV-1, DENV-2, DENV-3, and DENV-4

    Infection is defined as recovery of vaccine virus from the blood or serum of a participant and/or by seropositivity to DENV (PRNT50 greater than or equal to 1:10).

    Measured: Measured through Day 360

  5. Evaluation of the immunogenicity of TV005, as assessed by PRNT50 to DENV-1, DENV-2, DENV-3, and DENV-4 at 28, 56, and 90 days after TV005 vaccination

    Monovalent, bivalent, trivalent, and tetravalent seropositivity rates will be determined at these time points.

    Measured: Measured through Day 360

  6. Evaluation of the immunogenicity of rDEN2∆30-7169 in flavivirus-naïve participants as assessed by the PRNT50 to DENV-2, for each participant at Study Day 0, 28, 56, and 90 post-vaccination with rDEN2∆30-7169

    This objective will be performed only for those participants who received placebo on Study Day 0 and rDEN2∆30-7169 on Study Day 180.

    Measured: Measured through Day 360

  7. Number of rDEN2∆30-7169 vaccine recipients who become infected with DENV-2 following primary rDEN2∆30-7169 vaccination (placebo recipients at Study Day 0)

    Infection is defined as recovery of vaccine virus from the blood or serum of a participant and/or by seropositivity to DENV-2 (PRNT50 greater than or equal to 1:10)

    Measured: Measured through Day 360

  8. Evaluation of if peak neutralizing antibody titer against DENV-2 following TV005 vaccination or neutralizing antibody titer against DENV-2 measured at Day 180 correlates with protection against viremia, rash, and/or neutropenia following inoculation

    Measured: Measured through Day 360

  9. Evaluation of if inoculation with rDEN2∆30-7169 at 6 months will boost neutralizing antibody titers to DENV-1, DENV-2, DENV-3, and DENV-4 in those participants who received TV005 on Study Day 0.

    Measured: Measured through Day 360

Timeline

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

  1. First posted17 Dec 2014 (estimated)
  2. Study startDec 2014
  3. Primary completionNov 2016

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
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
48 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02317900
Sponsor's protocol ID
CIR 299
Status last verified
Jan 2017
First submitted
15 Dec 2014
Last updated
1 Feb 2017
Results posted
No
Data monitoring committee
Yes

Publications

  • Pierce KK, Durbin AP, Walsh MR, Carmolli M, Sabundayo BP, Dickson DM, Diehl SA, Whitehead SS, Kirkpatrick BD. TV005 dengue vaccine protects against dengue serotypes 2 and 3 in two controlled human infection studies. J Clin Invest. 2024 Feb 1;134(3):e173328. doi: 10.1172/JCI173328.

    PubMed 37971871

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing TV005 and rDEN2∆30-7169 in people with Dengue, 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 9 inclusion and 49 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 1 Feb 2017. 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?

Frequency of viremia in participants administered 10^3 PFU of rDEN2∆30-7169 at Study Day 180 (time frame: Measured through Day 360). 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 NCT02317900, which also lists 1 linked publication.

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 1 Feb 2017.

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