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Evaluating the Safety and Immune Response to a Dengue Virus Vaccine in Healthy Adults

Primary Purpose

Dengue

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
rDEN2Δ30-7169 vaccine
Placebo
Sponsored by
National Institute of Allergy and Infectious Diseases (NIAID)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Dengue

Eligibility Criteria

18 Years - 50 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • 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
  • Willingness to participate in the study as evidenced by signing the informed consent document
  • Female participants of childbearing potential willing to use effective contraception for the duration of the trial. More information on this criterion can be found in the protocol.

Exclusion Criteria:

  • Currently pregnant, as determined by positive beta-human chorionic gonadotropin (HCG) test, 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 ability of the participant to understand and cooperate with the requirements of the study protocol
  • Confirmed screening laboratory values of Grade 1 or above for absolute neutrophil count (ANC), alanine aminotransferase (ALT), and serum creatinine, as defined in the protocol. Confirmation will be obtained by repeating the test to ensure the abnormal value was not due to aberrancy.
  • 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
  • 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
  • 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 Days 28 and 56 following 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.

Ongoing Exclusion Criteria:

  • 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 or 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

Sites / Locations

  • John Hopkins Bloomberg School of Public Health - Center for Immunization Research (CIR)

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

rDEN2Δ30-7169 vaccine

Placebo

Arm Description

Participants will receive a single injection of the rDEN2Δ30-7169 vaccine at study entry.

Participants will receive a single injection of placebo at study entry.

Outcomes

Primary Outcome Measures

Safety of rDEN2Δ30-7169 vaccine as assessed by the frequency of vaccine-related adverse events (AEs)
AEs are classified by both severity and seriousness, through active and passive surveillance.
Frequency, quantity, and duration of viremia following vaccination
Subjects will have samples assayed for vaccine virus on Study Days 0, 2, 4, 6, 8, 10, 12, 14, and 16. Serum will be serially diluted and the titer of vaccine virus determined.
Immune response of the vaccine at 4 and 8 weeks post-vaccination
Seropositivity to DENV-2 is defined as PRNT50 ≥ 1:10. Seroconversion is defined as a ≥ 4-fold rise in PRNT50 to wt DENV-2 Tonga/74 by Study Day 56.
Titer of virus vaccine
The peak titer, day of onset, and duration of viremia will be calculated for each subject within the vaccinated group.
Number of vaccinees who seroconvert to DENV-2 by study Day 56
Seroconversion will be defined as a ≥ 4-fold rise in PRNT50 to wt DENV-2 Tonga/74 by Study Day 56.

Secondary Outcome Measures

Number of vaccinees infected with rDEN2Δ30-7169 vaccine
Infection is defined as recovery of vaccine virus from the blood or serum of a subject and/or by seroconversion to DENV-2 defined as a ≥ 4-fold rise in DENV-2 neutralizing antibody titers by Study Day 56 when compared with Study Day 0.
Comparison of infectivity rates, safety, and immunogenicity of a single dose of rDEN2Δ30 vaccine with the reported infectivity and safety of rDEN2/4Δ30 from previous clinical trials
Durability of neutralizing antibody by measuring serum neutralizing antibody to DENV-2 out to 180 days after vaccination

Full Information

First Posted
August 26, 2013
Last Updated
December 14, 2015
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
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1. Study Identification

Unique Protocol Identification Number
NCT01931176
Brief Title
Evaluating the Safety and Immune Response to a Dengue Virus Vaccine in Healthy Adults
Official Title
A Phase 1 Evaluation of the Safety and Immunogenicity of rDEN2Δ30-7169, a Live Attenuated Monovalent Dengue Virus Vaccine
Study Type
Interventional

2. Study Status

Record Verification Date
December 2015
Overall Recruitment Status
Completed
Study Start Date
June 2013 (undefined)
Primary Completion Date
December 2014 (Actual)
Study Completion Date
May 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Dengue viruses can cause dengue fever and other more serious illnesses. The purpose of this study is to evaluate the safety and immune response to a dengue virus vaccine.
Detailed Description
Dengue viruses can cause dengue fever and the more severe disease, dengue hemorrhagic fever/shock syndrome (DHF/DSS). Infection with dengue viruses is the leading cause of hospitalization and death in children in at least 8 tropical Asian countries. There are 4 types of dengue virus (DENV-1, DENV-2, DENV-3, and DENV-4), each of which can cause dengue illness ranging from a mild illness to life-threatening disease. This study will evaluate the experimental rDEN2Δ30-7169 vaccine for the prevention of illness due to DENV-2. The purpose of this study is to evaluate the safety and immunogenicity of this vaccine in healthy adults with no history of previous flavivirus infection. At study entry, participants will be randomly assigned to receive either the dengue virus vaccine or placebo. They will remain in the clinic for 30 minutes after receiving the injection for monitoring. Study visits will occur at Days 2, 4, 6, 8, 10, 12, 14, 16, 21, 28, 56, and 180. All study visits will include a blood collection, and most study visits will include a physical examination. Female participants will have a pregnancy test at select visits. Participants will record their temperature at least 3 times a day for the first 16 days; study researchers will review these readings during the study visits.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Dengue

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
14 (Actual)

8. Arms, Groups, and Interventions

Arm Title
rDEN2Δ30-7169 vaccine
Arm Type
Experimental
Arm Description
Participants will receive a single injection of the rDEN2Δ30-7169 vaccine at study entry.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants will receive a single injection of placebo at study entry.
Intervention Type
Biological
Intervention Name(s)
rDEN2Δ30-7169 vaccine
Intervention Description
Administered at a dose of 10^3 plaque-forming units (PFU); delivered by subcutaneous injection in the deltoid region of the upper arm
Intervention Type
Biological
Intervention Name(s)
Placebo
Intervention Description
Delivered by subcutaneous injection in the deltoid region of the upper arm
Primary Outcome Measure Information:
Title
Safety of rDEN2Δ30-7169 vaccine as assessed by the frequency of vaccine-related adverse events (AEs)
Description
AEs are classified by both severity and seriousness, through active and passive surveillance.
Time Frame
Measured through participants' last study visit at Day 180
Title
Frequency, quantity, and duration of viremia following vaccination
Description
Subjects will have samples assayed for vaccine virus on Study Days 0, 2, 4, 6, 8, 10, 12, 14, and 16. Serum will be serially diluted and the titer of vaccine virus determined.
Time Frame
Measured through participants' last study visit at Day 180
Title
Immune response of the vaccine at 4 and 8 weeks post-vaccination
Description
Seropositivity to DENV-2 is defined as PRNT50 ≥ 1:10. Seroconversion is defined as a ≥ 4-fold rise in PRNT50 to wt DENV-2 Tonga/74 by Study Day 56.
Time Frame
Measured at 4 and 8 weeks post-vaccination
Title
Titer of virus vaccine
Description
The peak titer, day of onset, and duration of viremia will be calculated for each subject within the vaccinated group.
Time Frame
Measured through participants' last study visit at Day 180
Title
Number of vaccinees who seroconvert to DENV-2 by study Day 56
Description
Seroconversion will be defined as a ≥ 4-fold rise in PRNT50 to wt DENV-2 Tonga/74 by Study Day 56.
Time Frame
Measured through Day 56
Secondary Outcome Measure Information:
Title
Number of vaccinees infected with rDEN2Δ30-7169 vaccine
Description
Infection is defined as recovery of vaccine virus from the blood or serum of a subject and/or by seroconversion to DENV-2 defined as a ≥ 4-fold rise in DENV-2 neutralizing antibody titers by Study Day 56 when compared with Study Day 0.
Time Frame
Measured through participants' last study visit at Day 180
Title
Comparison of infectivity rates, safety, and immunogenicity of a single dose of rDEN2Δ30 vaccine with the reported infectivity and safety of rDEN2/4Δ30 from previous clinical trials
Time Frame
Measured through participants' last study visit at Day 180
Title
Durability of neutralizing antibody by measuring serum neutralizing antibody to DENV-2 out to 180 days after vaccination
Time Frame
Measured through participants' last study visit at Day 180

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: 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 Willingness to participate in the study as evidenced by signing the informed consent document Female participants of childbearing potential willing to use effective contraception for the duration of the trial. More information on this criterion can be found in the protocol. Exclusion Criteria: Currently pregnant, as determined by positive beta-human chorionic gonadotropin (HCG) test, 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 ability of the participant to understand and cooperate with the requirements of the study protocol Confirmed screening laboratory values of Grade 1 or above for absolute neutrophil count (ANC), alanine aminotransferase (ALT), and serum creatinine, as defined in the protocol. Confirmation will be obtained by repeating the test to ensure the abnormal value was not due to aberrancy. 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 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 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 Days 28 and 56 following 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. Ongoing Exclusion Criteria: 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 or 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Anna Durbin, MD
Organizational Affiliation
Center for Immunization Research (CIR), Johns Hopkins School of Public Health
Official's Role
Principal Investigator
Facility Information:
Facility Name
John Hopkins Bloomberg School of Public Health - Center for Immunization Research (CIR)
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21205
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
26424605
Citation
Larsen CP, Whitehead SS, Durbin AP. Dengue human infection models to advance dengue vaccine development. Vaccine. 2015 Dec 10;33(50):7075-82. doi: 10.1016/j.vaccine.2015.09.052. Epub 2015 Sep 28.
Results Reference
derived

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Evaluating the Safety and Immune Response to a Dengue Virus Vaccine in Healthy Adults

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