Dengue Controlled Human Infection Model in Dhaka, Bangladesh
Primary Purpose
Dengue
Status
Active
Phase
Phase 2
Locations
Bangladesh
Study Type
Interventional
Intervention
TV005
rDEN2Δ30-7169 attenuated virus strain
Sponsored by
About this trial
This is an interventional prevention trial for Dengue
Eligibility Criteria
Inclusion Criteria:
-
All of the following inclusion criteria must be met for a volunteer to be eligible for study participation:
- Adult male or female between 18 and 45 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 and willing to consent to a potential inpatient admission following receipt of the biotechnological synthetic attenuated virus strain.
- Willing to participate in the study as evidenced by signing the informed consent document.
- Females of childbearing potential only: Willing to use effective contraception for at least 30 days prior to and 28 days following receipt of the investigational product.
Exclusion Criteria:
-
A volunteer will not be eligible for study participation if any of the following criteria are met:
- Serologic evidence of previous wild-type dengue.
- Females Only: Currently lactating, breastfeeding or pregnant, as determined by positive urine human choriogonadotropin (CG) test.
- Positive test result on rapid point-of-care NS1 dengue test performed on study day 0.
- Interim history of fever without a known cause since screening visit.
- 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 subject 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, or platelets 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 them 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 subject history.
- History of a severe allergic reaction or anaphylaxis.
- Hepatitis C virus (HCV) infection, by screening and confirmatory assays
- Hepatitis B virus (HBV) infection, by Hepatitis B surface antigen (HBsAg) screening.
- Self-reported or suspected immunodeficiency, or receipt of immunosuppressive therapy within the preceding 6 months, or long-term systemic corticosteroid therapy.
- Current use of anticoagulant medications.
- Use of aspirin and/or non-steroidal anti-inflammatory medications within 7 days of vaccination or anticipated receipt within 14 days following vaccination.
- 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.
- Previous receipt of a licensed or experimental dengue vaccine.
- Asplenia.
- Receipt of blood products, including transfusions or immunoglobulin within 90 days prior to receipt of investigational product or anticipated receipt during the study period.
- Anticipated receipt of any investigational agent in the 28 days before or after receipt of investigational product.
Sites / Locations
- Icddr,B
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Intervention followed by challenge
Placebo followed by challenge
Arm Description
Participants receiving TV005 and then challenged with the rDEN2Δ30-7169 attenuated virus strain.
Participants receiving placebo and then challenged with the rDEN2Δ30-7169 attenuated virus strain.
Outcomes
Primary Outcome Measures
Frequency of viremia
Proportion of volunteers with viremia following treatment with the attenuated virus strain among those who received TV005 versus placebo at vaccination. Viremia will be measured by qRT-PCR.
Secondary Outcome Measures
Quantity of Viremia
Quantity of viremia following treatment with the attenuated virus strain. Quantity of viremia will be measured by qRT-PCR.
Duration of viremia
Number of days viremic following treatment with the attenuated virus strain.
Frequency of volunteers with adverse events
Proportion of volunteers in each arm experiencing adverse events.
Frequency of volunteers with adverse events
Proportion of volunteers in each arm experiencing adverse events.
Full Information
NCT ID
NCT05229354
First Posted
October 18, 2021
Last Updated
February 8, 2023
Sponsor
Beth Kirkpatrick
Collaborators
International Centre for Diarrhoeal Disease Research, Bangladesh
1. Study Identification
Unique Protocol Identification Number
NCT05229354
Brief Title
Dengue Controlled Human Infection Model in Dhaka, Bangladesh
Official Title
Phase II Evaluation of the Safety and Protective Efficacy of a Single Dose of the Live Attenuated Tetravalent Dengue Vaccine TetraVax-DV TV005 to Protect Against Infection With Live, Recombinant DENV-2 (rDEN2∆30-7169) Attenuated Strain in a Dengue Endemic Population in South Asia
Study Type
Interventional
2. Study Status
Record Verification Date
February 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
December 11, 2021 (Actual)
Primary Completion Date
February 2024 (Anticipated)
Study Completion Date
July 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Beth Kirkpatrick
Collaborators
International Centre for Diarrhoeal Disease Research, Bangladesh
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The primary objective is to determine, among dengue-naïve adults in an endemic population, the protective efficacy of TetraVax-DV TV005 vaccine against dengue infection induced by a live recombinant attenuated rDEN2∆30-7169 attenuated virus strain administered 6, 12, or 24 months after vaccination.
Secondary objectives are:
Determine the durability of protection of TetraVax-DV TV005.
Evaluate the safety of TetraVax-DV TV005 in dengue-naïve volunteers in a dengue endemic population.
Evaluate the safety of the rDEN2∆30-7169 attenuated virus strain in a dengue endemic population.
Detailed Description
This is a single center, Phase II, placebo-controlled, double-blind study to evaluate the ability of a single dose of TetraVax-DV TV005 vaccine to protect against infection induced by a live recombinant attenuated rDEN2∆30-7169 attenuated virus strain administered 6, 12, and 24 months after vaccination. TetraVax-DV TV005 will contain 103 PFU of rDEN1∆30, 104 PFU of rDEN2/4∆30(ME), 103 PFU of rDEN3∆30/31-7164 and 103 of rDEN4∆30. The dose of rDEN2∆30-7169 attenuated virus strain (DENV-2) will be 103 PFU. The placebo group will receive Plasma-Lyte A Injection pH 7.4.
The study population will be comprised of 192 healthy male and healthy non-pregnant, non-lactating female dengue-naïve adult volunteers aged 18-45 years, inclusive, from dengue-endemic Dhaka, Bangladesh. After providing written informed consent, volunteers will undergo eligibility screening, including medical history, physical examination, hematology testing, liver function testing, hepatitis B and C screening, and serology screening for previous dengue infection. Pregnancy testing will be performed on females with childbearing potential. All screening tests must be performed within 60 days prior to vaccination.
Eligible volunteers will be enrolled to receive TetraVax-DV TV005 or placebo (2:1) on an outpatient basis in one of three cohorts based on intended treatment with the attenuated virus strain timepoint (6, 12 or 24 months). The sequence of treatment assignments to either TV005 or placebo will be generated using block randomization. Randomization will occur sequentially at the time of study enrollment (vaccination) using a pre-generated list. All enrolled volunteers will be followed for 3 years post-vaccination for safety.
At 6, 12, and 24 months post-vaccination, volunteers will be re-screened for treatment with the attenuated virus strain with a live recombinant attenuated DENV-2 virus strain (rDEN2Δ30-7169). Volunteers will receive treatment with the attenuated virus strain in three separate treatment groups each consisting of 33 randomly-selected, eligible vaccine and placebo recipients (2:1) from the three independently vaccinated cohorts. Following treatment with the attenuated virus strain, designated study staff will make home visits to study participants to collect fever and AE information once per day up to day 16. A total of 66 vaccine and 33 placebo recipients (52% of enrolled population) will receive the attenuated virus strain.
Administration of the attenuated virus strain to volunteers at 12 and 24 months is contingent upon DSMB approval following review of all cumulative safety data from those volunteers treated with the attenuated virus strain at 6 months. Volunteers who receive placebo and are subsequently treated with the attenuated virus strain will be offered the TetraVax-DV TV005 vaccination 2 months after their attenuated virus strain dose. All volunteers who receive treatment with the attenuated virus strain will be followed for a minimum of one year post-treatment with the attenuated virus strain for safety (included in the overall 3 years of safety follow up).
Volunteers receiving treatment with the attenuated virus strain will be closely monitored following treatment with the attenuated virus strain and will be admitted to a local hospital for closer observation should they meet admission criteria. Administration of the attenuated virus strain to volunteers at 12 and 24 months is contingent upon DSMB approval following review of all cumulative safety data from those volunteers treated with the attenuated virus strain at 6 months. Volunteers who receive placebo and are subsequently treated with the attenuated virus strain will be offered the TetraVax-DV TV005 vaccination 2 months after their attenuated virus strain dose. All volunteers who receive treatment with the attenuated virus strain will be followed for a minimum of one year post-treatment with the attenuated virus strain for safety (included in the overall 3 years of safety follow up).
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 2
Interventional Study Model
Parallel Assignment
Model Description
Eligible volunteers will be enrolled to receive TetraVax-DV TV005 or placebo (2:1) on an outpatient basis in one of three cohorts based on intended treatment with the attenuated virus strain timepoint (6, 12 or 24 months). The sequence of treatment assignments to either TV005 or placebo will be generated using block randomization. Randomization will occur sequentially at the time of study enrollment (vaccination) using a pre-generated list. All enrolled volunteers will be followed for 3 years post-vaccination for safety.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
While clinical staff, all investigators, and study volunteers will remain blinded until each cohort's respective unblinding timepoint, the PI will assign an unblinded statistician to analyze the safety data. This designee will provide safety data to study staff as a summary report with blinding maintained.
Allocation
Randomized
Enrollment
192 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Intervention followed by challenge
Arm Type
Experimental
Arm Description
Participants receiving TV005 and then challenged with the rDEN2Δ30-7169 attenuated virus strain.
Arm Title
Placebo followed by challenge
Arm Type
Experimental
Arm Description
Participants receiving placebo and then challenged with the rDEN2Δ30-7169 attenuated virus strain.
Intervention Type
Biological
Intervention Name(s)
TV005
Intervention Description
The TV005 admixture is comprised of four monovalent dengue vaccine candidates representing each of the four DENV serotypes: rDEN1Δ30, rDEN2/4Δ30(ME), rDEN3Δ30/31, and rDEN4Δ30.
Intervention Type
Biological
Intervention Name(s)
rDEN2Δ30-7169 attenuated virus strain
Other Intervention Name(s)
rDEN2Δ30-7169 Lot DEN2#121A
Intervention Description
based on a cDNA derived DENV-2 virus (strain Tonga/74) in which the 3´ UTR of DENV-2 contains a 30 (nt) deletion (nt 173 - 143) homologous to the ∆30 deletion in the 3´ UTR of rDEN4Δ30 (named Δ30 for consistency). A plasmid was constructed to encode the entire genome of DENV-2 Tonga/74. The cDNA of the 3´ UTR of DENV-2 Tonga/74 was then modified to introduce a 31-nucleotide deletion homologous to the DEN4Δ30 deletion (∆30). Genome-length, capped, RNA transcripts were synthesized from the plasmid p2Δ30-7169 and purified
Primary Outcome Measure Information:
Title
Frequency of viremia
Description
Proportion of volunteers with viremia following treatment with the attenuated virus strain among those who received TV005 versus placebo at vaccination. Viremia will be measured by qRT-PCR.
Time Frame
28 days following challenge.
Secondary Outcome Measure Information:
Title
Quantity of Viremia
Description
Quantity of viremia following treatment with the attenuated virus strain. Quantity of viremia will be measured by qRT-PCR.
Time Frame
28 days following challenge
Title
Duration of viremia
Description
Number of days viremic following treatment with the attenuated virus strain.
Time Frame
28 days following challenge
Title
Frequency of volunteers with adverse events
Description
Proportion of volunteers in each arm experiencing adverse events.
Time Frame
28-days post receipt of TV005 or placebo
Title
Frequency of volunteers with adverse events
Description
Proportion of volunteers in each arm experiencing adverse events.
Time Frame
28-days post receipt of challenge
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
-
All of the following inclusion criteria must be met for a volunteer to be eligible for study participation:
Adult male or female between 18 and 45 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 and willing to consent to a potential inpatient admission following receipt of the attenuated virus strain.
Willing to participate in the study as evidenced by signing the informed consent document.
Females of childbearing potential only: Willing to use effective contraception for at least 30 days prior to and 28 days following receipt of the investigational product.
Exclusion Criteria:
-
A volunteer will not be eligible for study participation if any of the following criteria are met:
Serologic evidence of previous wild-type dengue.
Females Only: Currently lactating, breastfeeding or pregnant, as determined by positive urine human choriogonadotropin (CG) test.
Positive test result on rapid point-of-care NS1 dengue test performed on study day 0.
Interim history of fever without a known cause since screening visit.
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 subject 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, or platelets 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 them 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 subject history.
History of a severe allergic reaction or anaphylaxis.
Hepatitis C virus (HCV) infection, by screening and confirmatory assays
Hepatitis B virus (HBV) infection, by Hepatitis B surface antigen (HBsAg) screening.
Self-reported or suspected immunodeficiency, or receipt of immunosuppressive therapy within the preceding 6 months, or long-term systemic corticosteroid therapy.
Current use of anticoagulant medications.
Use of aspirin and/or non-steroidal anti-inflammatory medications within 7 days of vaccination or anticipated receipt within 14 days following vaccination.
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.
Previous receipt of a licensed or experimental dengue vaccine.
Asplenia.
Receipt of blood products, including transfusions or immunoglobulin within 90 days prior to receipt of investigational product or anticipated receipt during the study period.
Anticipated receipt of any investigational agent in the 28 days before or after receipt of investigational product.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Beth Kirkpatrick, MD
Organizational Affiliation
University of Vermont
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Rashidul Haque, MD
Organizational Affiliation
International Centre for Diarrhoeal Disease Research
Official's Role
Principal Investigator
Facility Information:
Facility Name
Icddr,B
City
Dhaka
Country
Bangladesh
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Dengue Controlled Human Infection Model in Dhaka, Bangladesh
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