Dengue Controlled Human Infection Model in Dhaka, Bangladesh

NCT05229354 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: PR-19099
• Study Type: interventional
• Target: 192
• Locations: 1 country
• Sites: 1

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:

1. 1.Determine the durability of protection of TetraVax-DV TV005.
2. 2.Evaluate the safety of TetraVax-DV TV005 in dengue-naïve volunteers in a dengue endemic population.
3. 3.Evaluate the safety of the rDEN2∆30-7169 attenuated virus strain in a dengue endemic population.

Conditions

Dengue

Outcome Measures

Primary Outcomes (1)

• 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.

  28 days following challenge.

Secondary Outcomes (4)

• Quantity of Viremia

  28 days following challenge

• Duration of viremia

  28 days following challenge

• Frequency of volunteers with adverse events

  28-days post receipt of TV005 or placebo

• Frequency of volunteers with adverse events

  28-days post receipt of challenge

Study Arms (2)

Intervention followed by challenge

EXPERIMENTAL

Participants receiving TV005 and then challenged with the rDEN2Δ30-7169 attenuated virus strain.

Biological: TV005; Biological: rDEN2Δ30-7169 attenuated virus strain

Placebo followed by challenge

EXPERIMENTAL

Participants receiving placebo and then challenged with the rDEN2Δ30-7169 attenuated virus strain.

Biological: rDEN2Δ30-7169 attenuated virus strain

Interventions

TV005 BIOLOGICAL

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 followed by challenge

rDEN2Δ30-7169 attenuated virus strain BIOLOGICAL

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

Also known as: rDEN2Δ30-7169 Lot DEN2#121A

Intervention followed by challenge; Placebo followed by challenge

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Beth Kirkpatrick: lead
• International Centre for Diarrhoeal Disease Research, Bangladesh: collaborator

Study Sites (1)

Icddr,B

Dhaka, Bangladesh

Location

MeSH Terms

Conditions

Dengue

Condition Hierarchy (Ancestors)

Mosquito-Borne Diseases; Vector Borne Diseases; Infections; Arbovirus Infections; Virus Diseases; Flavivirus Infections; Flaviviridae Infections; RNA Virus Infections; Hemorrhagic Fevers, Viral

Study Officials

• Beth Kirkpatrick, MD

  University of Vermont

  PRINCIPAL INVESTIGATOR

• Rashidul Haque, MD

  International Centre for Diarrhoeal Disease Research

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD, Professor of Medicine

Model Details: 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.

Study Record Dates

• First Submitted: October 18, 2021
• First Posted: February 8, 2022
• Study Start: December 11, 2021
• Primary Completion: November 20, 2023
• Study Completion: July 1, 2025
• Last Updated: July 17, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

BA (1)