Trial to Model Primary, Secondary, and Tertiary Dengue Using a Monovalent Vaccine

NCT05691530 | Active Not Recruiting Phase 1 Results FDA Drug

• 2 other identifiers: 10001078001078-I
• Study Type: interventional
• Target: 127
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Dengue is a disease caused by a virus transmitted by mosquitoes in tropical and subtropical regions. Dengue is a leading cause of hospital stays and death in parts of Asia and Latin America, and outbreaks have occurred in the US. Currently, dengue vaccines are limited and do not protect all people equally. One vaccine actually increased the risk of severe disease in some people and was taken off the market. Better vaccines are needed. Objectives: To test a potential new vaccine against dengue. To see if side effects and immune responses are different depending on a person's previous exposure to dengue. Eligibility: Healthy people aged 18 to 59 years. Design: Participants will visit the clinic 11 times in 7 months; 9 of those visits will be in the first 2 months. Two additional visits are optional. Participants will be screened. They will have a physical exam with urine and blood tests. They will complete a survey about their travel history. Participants may opt to have a lymph node aspiration before receiving the study vaccine. An area in the left armpit will be numbed. A needle will be inserted to remove some cells from a lymph node. The vaccine will be injected into the fat under the skin of the participant's upper left arm. Participants will return for a provider visit and blood draws every 3 days for about the first 2 weeks. Then they will return for a provider visit and blood draws after longer intervals up to 7 months. The lymph node aspiration may be repeated at later visits. Participants may opt to return for a last visit after 12 months.

Conditions

Response To Dengue Exposure

Keywords

Viremia; Geometric Mean Titer; Safety; Immunogenicity; Sequential Exposure; Lymph Node Aspirates

Outcome Measures

Primary Outcomes (8)

• Number of Participants With Local Adverse Events (AEs)

  Number of participants with at least one solicited local adverse events occurring within twenty-eight days of vaccine administration. Local reactogenicity included injection site pain, injection site tenderness, injection site bruising, injection site redness, injection site erythema, injection site swelling/induration, and injection site pruritus. Adverse events were captured by investigator examination and history from participants.

  Through day 28 after vaccine administration

• Number of Participants With Systemic Adverse Events (AEs)

  Number of participants with systemic adverse events occurring within twenty-eight days of vaccine administration. Systemic reactogenicity events included fever, headache, eye pain (retro-orbital pain), photophobia, nausea, fatigue, myalgia, arthralgia, and maculo-papular rash (dengue-like rash). Adverse events were captured by investigator examination and history from participants.

  Through day 28 after vaccine administration

• Severity of Local Adverse Events (AEs) by Grade

  The severity of local AEs was graded using the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Clinical Trials. Grade 1: Pain, Pruritis = does not interfere with activity; Tenderness = mild discomfort to touch; Erythema/Redness, Bruising = 2.5-5 cm; Induration/Swelling = 2.5-5 cm and does not interfere with activity. Grade 2: Pain, Pruritis = Some interference with activity or requires \>1 dose of medication; Tenderness= Discomfort with movement; Erythema/Redness, Bruising = 5.1-10 cm; Induration/Swelling = 5.1-10 cm or interferes with activity. Grade 3: Pain, Pruritis= Prevents daily activity and requires medical intervention; Tenderness = Significant discomfort at rest; Erythema/Redness, Bruising = \> 10 cm; Induration/Swelling = \> 10 cm or prevents daily activity. Grade 4: Pain, Tenderness = Hospitalization; Erythema/Redness, Induration/Swelling = Necrosis or exfoliative dermatitis; Bruising, Pruritus: Requiring medical attention

  Through day 28 after vaccine administration

• Severity of Systemic Adverse Events (AEs)

  The severity of systemic AEs was assessed using the grading scale below: Grade 1: Fever = 100.4-101.1\^oF; Fatigue, Retro-orbital pain, Photophobia, Nausea, Headache, Myalgia, Arthralgia = No interference with activity, may require one dose of medication/treatment; Dengue-like rash: Rash is present but asymptomatic. Grade 2: Fever = 101.2-102.0\^oF; Fatigue, Retro-orbital pain, Photophobia, Nausea, Headache, Myalgia, Arthralgia = Some interference with activity or requires \>1 dose of medication/treatment; Dengue-like rash: Rash is symptomatic but does not interfere with activity. Grade 3: Fever = 102.1-104\^oF; Fatigue, Retro-orbital pain, Photophobia, Nausea, Headache, Myalgia, Arthralgia = Prevents daily activity and requires medical intervention; Dengue-like rash: Rash is symptomatic and interferes with activity. Grade 4: Fever = \>104\^oF; Fatigue, Retro-orbital pain, Photophobia, Nausea, Headache, Myalgia, Arthralgia, Dengue-like rash: Hospitalization.

  Through day 28 after vaccine administration

• Number of Participants With Unexpected Adverse Events (AEs)

  Number of participants with unexpected adverse (AE) events occurring up to 28 days after vaccine administration of vaccine. Unexpected adverse event is defined as an AE that is not listed in the investigator's brochure at the frequency, AND specificity, AND severity that has been observed.

  Through day 28 after vaccine administration

• Number of Participants With Serious Adverse Events (AEs)

  Number of participants with serious adverse events defined as any grade 4 or higher local or systemic adverse events based on the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Clinical Trials. Local AEs: Grade 4: Pain, Tenderness = Hospitalization; Erythema/Redness, Induration/Swelling = Necrosis or exfoliative dermatitis requiring medical attention; Bruising: Hematoma requiring medical attention; Pruritis: Pruritis requiring medical attention Systemic AEs: Grade 4: Fever = \>104\^oF; Fatigue, Retro-orbital pain, Photophobia, Nausea, Headache, Myalgia, Arthralgia, Dengue-like rash: Hospitalization. Grade 5: Death

  Through day 180 after vaccine administration

• Mean Fold-change in Dengue virus1-4 Neutralizing Antibody Mean Titer Between Days 0 and 28

  The dengue virus (DENV) geometric mean titer (GMT) is a measure of average humoral immunity against all four dengue virus (DENV1-4) serotypes before and after vaccination obtained using plaque reduction neutralization tests (PRNT). The fold change in the DENV1-4 neutralizing antibody GMT between days 0 and 28 was analyzed as GMT Day 28/GMT Day 0.

  Day 28 and day 0

• Mean Peak Viremia

  The mean peak viremia was measured by viral quantitative reverse transcription polymerase chain reaction (qRT-PCR) for days 3, 6, 9, 12, and 15. Analysis was done as the average of the log mean of the peak value for each participant.

  Day 3 through day 15

Secondary Outcomes (3)

• Mean Fold-change in Dengue virus1-4 Neutralizing Antibody Mean Titer Between Days 0 and 57

  Day 57 and day 0

• Mean Titer for Dengue Virus Neutralizing Antibody

  Day 0, Day 28, and Day 57

• Percent Dengue-specific CD8+ T-cells

  Day 15

Study Arms (3)

Flavivirus naïve

EXPERIMENTAL

Participants were classified as flavivirus-naive if they met any of the following criteria: a 50% plaque reduction neutralization test (PRNT50) titer \<10 for all dengue serotypes, no history of flavivirus vaccination, or no travel history associated with an increased risk of other flavivirus infections. If there was any concern regarding prior flavivirus exposure, antibody testing was performed to confirm the absence of exposure. Participants received a single 0.5 mL subcutaneous injection of 10\^3.3 PFU/mL rDEN3Δ30/31-7164 vaccine formulated in Plasma-Lyte A (pH 7.4) diluent in the deltoid region on day 0.

Drug: rDEN3Δ30/31-7164

Polytypic dengue virus antibody profile

EXPERIMENTAL

Participants were considered dengue immune if they had a 50% plaque reduction neutralization test (PRNT50) titer of ≥10 against any dengue serotype. Among these participants, those whose highest PRNT50 titer was \<4-fold higher than the second-highest serotype were further categorized as follows: participants with PRNT50 titers ≥60 for at least two serotypes were classified as "polytypic", whereas those with PRNT50 titers between 10 and 60 were classified as "expanded polytypic". Participants received a single 0.5 mL subcutaneous injection of 10\^3.3 PFU/mL rDEN3Δ30/31-7164 vaccine formulated in Plasma-Lyte A (pH 7.4) diluent in the deltoid region on day 0.

Drug: rDEN3Δ30/31-7164

Primary Heterotypic dengue virus antibody profile

EXPERIMENTAL

Participants where the highest plaque reduction neutralization test (PRNT50) titer is ≥4-fold higher than the second highest serotype (or one serotype ≥10 and others \<10) were considered monotypic. Of these, participants with their highest titer to DENV3 were excluded, and all others were included in the heterotypic group. Participants received a single 0.5 mL subcutaneous injection of 10\^3.3 PFU/mL rDEN3Δ30/31-7164 vaccine formulated in Plasma-Lyte A (pH 7.4) diluent in the deltoid region on day 0.

Drug: rDEN3Δ30/31-7164

Interventions

rDEN3Δ30/31-7164 DRUG

The rDEN3Δ30/31-7164 vaccine is a live attenuated virus constructed by creating two deletions in the 3' untranslated region (UTR) of the DENV-3 Sleman/78 strain. The vaccine dose consists of 0.5 mL of 10\^3.3 PFU/mL of rDEN3Δ30/31-7164 plus Plasma-Lyte A pH 7.4 diluent delivered subcutaneously into the deltoid area on day 0.

Flavivirus naïve; Polytypic dengue virus antibody profile; Primary Heterotypic dengue virus antibody profile

Eligibility Criteria

• Age: 18 Years - 59 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• To be eligible to participate in this study, an individual must meet all the following criteria:
• Aged 18 to 59 years.
• In good general health as evidenced by medical history, physical examination, and laboratory screening results.
• Willing to allow storage of samples and data for future research.
• Willing to forgo receipt of any vaccine in the 28 days preceding the vaccine or in the 28 days following the dose of vaccine. For participants opting for lymph node (LN) fine needle aspiration (FNA) on day 57, they must be willing to forgo any vaccine through final LN FNA.
• For individuals who can become pregnant: use of at least one method of highly effective contraception from the invitation to participate in the trial through day 60 after vaccination.
• Able to provide informed consent.
• Willing to adhere to lifestyle considerations for the duration of the study.
• Willing to avoid travel to a dengue-endemic area as defined by the Centers for Disease Control and Prevention (CDC) from 1 month before vaccination through day 57
• Baseline absolute neutrophil count (ANC) \> 750 cells/microL.
• Baseline creatinine \< 1.5 mg/dL.
• Baseline ALT \< 1.25 x upper limit of normal.
• Serologic evidence of previous dengue virus infection indicative of either one previous DENV1, 2, or 4 infection or infection with at least two different serotypes.
• For the flavivirus-naïve group, they must have no history of flavivirus vaccination, medical illness concerning for a flavivirus infection, or travel history that increases the likelihood of other flavivirus infections. If there is uncertainty about a previous flavivirus exposure, then confirmatory antibody testing against the virus of interest must be negative.
• Agree to avoid participation in other clinical studies requiring investigational interventions for the duration of this study (180 days).

You may not qualify if:

• An individual who meets any of the following criteria will be excluded from participation in this study:
• Pregnant at screening.
• History of or positive test result for HIV, hepatitis B, or hepatitis C.
• History of previous dengue vaccine.
• Has any of the following:
• More than 10 days of systemic immunosuppressive medications (\>=10 mg prednisone dose or its equivalent) or cytotoxic medication within the 30 days prior to vaccination or immunomodulating therapy within 180 days prior to vaccination.
• Received blood products, including immunoglobulin products, within 120 days prior to vaccination.
• History of serious reactions to vaccines.
• Hereditary, acquired, or idiopathic forms of angioedema.
• Idiopathic urticaria within the past year.
• Asthma that is not well controlled or required emergency care, urgent care, hospitalization, or intubation during the past two years or that requires the use of oral or intravenous steroids.
• Type 1 or type 2 diabetes mellitus that is not well controlled (hemoglobin A1c \> 8).
• Clinically significant autoimmune disease or immunodeficiency.
• Blood pressure \>= 180/110 (stage 3 hypertension) on at least 2 measures.
• Documented diagnosis of a bleeding disorder (e.g., factor deficiency, coagulopathy, or platelet disorder requiring special precautions).

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): collaborator
• National Institutes of Health Clinical Center (CC): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (1)

• Odio CD, Lowman KE, Law M, Aogo RA, Hunsberger S, Wood BJ, Kassin M, Levy E, Callier V, Firdous S, Hasund CM, Voirin C, Kattappuram R, Yek C, Manning J, Durbin A, Whitehead SS, Katzelnick LC. Phase 1 trial to model primary, secondary, and tertiary dengue using a monovalent vaccine. BMC Infect Dis. 2023 May 23;23(1):345. doi: 10.1186/s12879-023-08299-5.

  PMID: 37221466 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Viremia

Condition Hierarchy (Ancestors)

Virus Diseases; Infections; Sepsis; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Dr. Camila Odio
• Organization: National Institute of Allergy and Infectious Diseases

camila.odio@nih.gov

+1 240 338 4945

Study Officials

• Camila D Odio, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 19, 2023
• First Posted: January 20, 2023
• Study Start: March 7, 2023
• Primary Completion: April 23, 2025
• Study Completion: May 1, 2026
• Last Updated: April 28, 2026
• Results First Posted: April 28, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, ANALYTIC CODE
• Time Frame: Data will be shared at the time of or shortly after publication.
• Access Criteria: Data associated with manuscripts will be publicly available. Additional data will be by request to investigator.

Locations

US (1)