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| ID | Type | Description | Link |
|---|---|---|---|
| 001078-I |
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| Name | Class |
|---|---|
| National Institute of Allergy and Infectious Diseases (NIAID) | NIH |
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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.
Study Description:
Phase 1 trial wherein healthy adults with no (naive), one (primary heterotypic), or more than one (polytypic) previous natural dengue virus (DENV) infection(s) will be immunized with the DENV3 monovalent vaccine rDEN3Δ30/31-7164. We aim to examine how pre-vaccine host immunity influences the safety and immunogenicity of monovalent DENV3 vaccination in a non-endemic population. We hypothesize that the vaccine will be safe and well tolerated, and all groups will have evidence of infection with the vaccine strain as indicated by a significant increase in the DENV neutralizing antibody geometric mean titer (GMT) between days 0 and 28. However, due to the immunity conferred by prior dengue exposure(s), the polytypic group will have the lowest and the heterotypic group will have the highest mean peak viremia, indicating protection and enhancement, respectively. Additionally, the polytypic group will have the strongest CD8+ T-cell responses at day 15 and will only have a transient rise in GMT with no difference in GMT between days 0 and 57. In contrast, the change in GMT will persist at day 57 in the heterotypic and naive groups. Finally, we expect that prior immunity will influence the vaccine response as evidenced by a significant association between the day 0 GMT and GMT at days 28 and 57.
Primary Objective:
Evaluate the safety of monovalent DENV3 vaccination in those with distinct natural DENV infection histories living in non-endemic areas, and how prior DENV immunity influences protection against vaccine strain infection evaluated by the change in GMT and mean peak viremia.
Secondary Objective:
Further evaluate how DENV infection history impacts the immunogenicity of the vaccine.
Primary Endpoints:
Secondary Endpoints:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
|
| 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Mean Fold-change in Dengue virus1-4 Neutralizing Antibody Mean Titer Between Days 0 and 57 | 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 57 was analyzed as GMT Day 57/GMT Day 0. |
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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.
Agree to avoid participation in other clinical studies requiring investigational interventions for the duration of this study (180 days).
Agree to avoid blood and plasma donation outside this study through day 28.
Contraceptive requirements: Participants who can get pregnant must agree to use highly effective contraception as outlined below from the invitation to participate in the study (approximately 2 weeks after screening) through day 60. Day 0 will be scheduled at least 28 days after the initiation of effective contraception. Participants who can get pregnant must have a negative pregnancy test on day 0 before receiving rDEN3Δ30/31-7164. If a participant becomes pregnant or suspects they are pregnant by day 60, then they should inform the study staff and their primary care physician immediately. Acceptable forms of contraception are:
Pregnancy after day 60 will not be exclusionary as this will not impact our primary or secondary endpoints. Although we may observe pregnancy-associated differences in the transcriptome, these endpoints are exploratory and we have chosen to prioritize safety and inclusivity for people who can become pregnant. Study blood draw volumes after day 28 are less than the recommended volumes for research blood in critically ill patients. Pregnant participants will be excluded from LN FNA due to the potential risks of anesthetics that may be used. Pregnancy testing will be performed on each LN FNA day, with a negative result required to proceed to aspiration.
EXCLUSION CRITERIA:
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:
Any medical, psychiatric, or social condition that, in the judgement of the investigator, is a contraindication to protocol participation.
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| Name | Affiliation | Role |
|---|---|---|
| Camila D Odio, M.D. | National Institute of Allergy and Infectious Diseases (NIAID) | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| National Institutes of Health Clinical Center | Bethesda | Maryland | 20892 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37221466 | Derived | 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. |
| Label | URL |
|---|---|
| NIH Clinical Center Detailed Web Page | View source |
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Human data generated in this study may be shared for future research as follows:
Data will be shared at the time of or shortly after publication.
Data associated with manuscripts will be publicly available. Additional data will be by request to investigator.
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127 participants consented to this study:
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| ID | Title | Description |
|---|---|---|
| FG000 | Flavivirus naïve | 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. |
| FG001 | Polytypic Dengue Virus Antibody Profile | 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. |
| FG002 | Primary Heterotypic Dengue Virus Antibody Profile | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Flavivirus naïve | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | The 'per protocol subset', which is based on participants assignment determined by day 0 dengue antibody profile. | Posted | Count of Participants | Participants | Through day 28 after vaccine administration |
|
Through day 180 for all participants and up to day 365 for participants who opt for long-term follow-up.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Flavivirus naïve | 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Skin infection | Infections and infestations | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Camila Odio | National Institute of Allergy and Infectious Diseases | +1 240 338 4945 | camila.odio@nih.gov |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jan 29, 2026 | Mar 10, 2026 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D014766 | Viremia |
| ID | Term |
|---|---|
| D014777 | Virus Diseases |
| D007239 | Infections |
| D018805 | Sepsis |
| D018746 | Systemic Inflammatory Response Syndrome |
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|
| 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 |
| Day 57 and day 0 |
| Mean Titer for Dengue Virus Neutralizing Antibody | The dengue virus (DENV) geometric mean titer (GMT) is a measure of average humoral immunity against all four dengue virus (DENV1-4) serotypes. GMT for the DENV1-4 neutralizing antibody titer was assessed for days 0, 28, and 57. | Day 0, Day 28, and Day 57 |
| Percent Dengue-specific CD8+ T-cells | Percent dengue virus (DENV)-specific CD8+ T-cells among total CD8+ T-cells at day 15 was measured through flow cytometric analyses using the Activation-Induced Marker (AIM) assays. | Day 15 |
| BG001 | Polytypic Dengue Virus Antibody Profile | 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. |
| BG002 | Primary Heterotypic Dengue Virus Antibody Profile | 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. |
| BG003 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| OG001 | Polytypic Dengue Virus Antibody Profile | 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. |
| OG002 | Primary Heterotypic Dengue Virus Antibody Profile | 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. |
|
|
| Primary | 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. | The 'per protocol subset', which is based on participants assignment determined by day 0 dengue antibody profile. | Posted | Count of Participants | Participants | Through day 28 after vaccine administration |
|
|
|
| Primary | 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 | The 'per protocol subset', which is based on participants assignment determined by day 0 dengue antibody profile. | Posted | Count of Participants | Participants | Through day 28 after vaccine administration |
|
|
|
| Primary | 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. | The 'per protocol subset', which is based on participants assignment determined by day 0 dengue antibody profile. | Posted | Count of Participants | Participants | Through day 28 after vaccine administration |
|
|
|
| Primary | 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. | The 'per protocol subset', which is based on participants assignment determined by day 0 dengue antibody profile. | Posted | Count of Participants | Participants | Through day 28 after vaccine administration |
|
|
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| Primary | 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 | The 'per protocol subset', which is based on participants assignment determined by day 0 dengue antibody profile. | Posted | Count of Participants | Participants | Through day 180 after vaccine administration |
|
|
|
| Primary | 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. | The 'per protocol subset', which is based on participants assignment determined by day 0 dengue antibody profile. | Posted | Geometric Mean | 95% Confidence Interval | Ratio | Day 28 and day 0 |
|
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| Primary | 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. | The 'per protocol subset', which is based on participants assignment determined by day 0 dengue antibody profile. | Posted | Mean | 95% Confidence Interval | log copies/mL | Day 3 through day 15 |
|
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| Secondary | Mean Fold-change in Dengue virus1-4 Neutralizing Antibody Mean Titer Between Days 0 and 57 | 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 57 was analyzed as GMT Day 57/GMT Day 0. | The 'per protocol subset', which is based on participants assignment determined by day 0 dengue antibody profile. | Posted | Geometric Mean | 95% Confidence Interval | Ratio | Day 57 and day 0 |
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| Secondary | Mean Titer for Dengue Virus Neutralizing Antibody | The dengue virus (DENV) geometric mean titer (GMT) is a measure of average humoral immunity against all four dengue virus (DENV1-4) serotypes. GMT for the DENV1-4 neutralizing antibody titer was assessed for days 0, 28, and 57. | The 'per protocol subset', which is based on participants assignment determined by day 0 dengue antibody profile. | Posted | Geometric Mean | 95% Confidence Interval | titer | Day 0, Day 28, and Day 57 |
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| Secondary | Percent Dengue-specific CD8+ T-cells | Percent dengue virus (DENV)-specific CD8+ T-cells among total CD8+ T-cells at day 15 was measured through flow cytometric analyses using the Activation-Induced Marker (AIM) assays. | The 'per protocol subset', which is based on participants assignment determined by day 0 dengue antibody profile. | Posted | Geometric Mean | 95% Confidence Interval | percentage of dengue-specific CD8+ cells | Day 15 |
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|
|
| 0 |
| 14 |
| 1 |
| 14 |
| 14 |
| 14 |
| EG001 | Polytypic Dengue Virus Antibody Profile | 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. | 0 | 13 | 0 | 13 | 13 | 13 |
| EG002 | Primary Heterotypic Dengue Virus Antibody Profile | 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. | 0 | 18 | 0 | 18 | 18 | 18 |
| Leukopenia | Blood and lymphatic system disorders | Systematic Assessment |
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| Lymphadenopathy | Blood and lymphatic system disorders | Systematic Assessment |
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| Lymphopenia | Blood and lymphatic system disorders | Systematic Assessment |
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| Neutropenia | Blood and lymphatic system disorders | Systematic Assessment |
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| Bradycardia | Cardiac disorders | Systematic Assessment |
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| Tachycardia | Cardiac disorders | Systematic Assessment |
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| Chalazion | Eye disorders | Systematic Assessment |
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| Dry eye | Eye disorders | Systematic Assessment |
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| Eye pain | Eye disorders | Systematic Assessment |
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| Periorbital oedema | Eye disorders | Systematic Assessment |
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| Photophobia | Eye disorders | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | Systematic Assessment |
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| Gastrooesophageal reflux disease | Gastrointestinal disorders | Systematic Assessment |
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| Large intestine polyp | Gastrointestinal disorders | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | Systematic Assessment |
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| Toothache | Gastrointestinal disorders | Systematic Assessment |
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| Chills | General disorders | Systematic Assessment |
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| Fatigue | General disorders | Systematic Assessment |
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| Injection site erythema | General disorders | Systematic Assessment |
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| Injection site pain | General disorders | Systematic Assessment |
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| Malaise | General disorders | Systematic Assessment |
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| Pain | General disorders | Systematic Assessment |
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| Pyrexia | General disorders | Systematic Assessment |
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| Tenderness | General disorders | Systematic Assessment |
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| Thirst | General disorders | Systematic Assessment |
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| Vessel puncture site bruise | General disorders | Systematic Assessment |
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| Vessel puncture site pain | General disorders | Systematic Assessment |
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| Hypersensitivity | Immune system disorders | Systematic Assessment |
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| Acute sinusitis | Infections and infestations | Systematic Assessment |
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| Bronchitis | Infections and infestations | Systematic Assessment |
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| COVID-19 | Infections and infestations | Systematic Assessment |
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| Gastroenteritis | Infections and infestations | Systematic Assessment |
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| Herpes simplex | Infections and infestations | Systematic Assessment |
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| Influenza | Infections and infestations | Systematic Assessment |
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| Lower respiratory tract infection | Infections and infestations | Systematic Assessment |
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| Oral herpes | Infections and infestations | Systematic Assessment |
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| Pneumonia | Infections and infestations | Systematic Assessment |
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| Rhinovirus infection | Infections and infestations | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | Systematic Assessment |
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| Urinary tract infection | Infections and infestations | Systematic Assessment |
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| Viral infection | Infections and infestations | Systematic Assessment |
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| Arthropod bite | Injury, poisoning and procedural complications | Systematic Assessment |
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| Contusion | Injury, poisoning and procedural complications | Systematic Assessment |
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| Epicondylitis | Injury, poisoning and procedural complications | Systematic Assessment |
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| Fall | Injury, poisoning and procedural complications | Systematic Assessment |
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| Injury | Injury, poisoning and procedural complications | Systematic Assessment |
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| Post procedural contusion | Injury, poisoning and procedural complications | Systematic Assessment |
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| Procedural pain | Injury, poisoning and procedural complications | Systematic Assessment |
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| Procedural site reaction | Injury, poisoning and procedural complications | Systematic Assessment |
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| Activated partial thromboplastin time prolonged | Investigations | Systematic Assessment |
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| Alanine aminotransferase increased | Investigations | Systematic Assessment |
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| Aspartate aminotransferase increased | Investigations | Systematic Assessment |
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| Blood bilirubin increased | Investigations | Systematic Assessment |
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| Blood creatine phosphokinase increased | Investigations | Systematic Assessment |
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| Blood fibrinogen decreased | Investigations | Systematic Assessment |
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| Blood fibrinogen increased | Investigations | Systematic Assessment |
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| Blood urea increased | Investigations | Systematic Assessment |
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| C-reactive protein increased | Investigations | Systematic Assessment |
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| Haemoglobin decreased | Investigations | Systematic Assessment |
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| Hepatic enzyme increased | Investigations | Systematic Assessment |
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| Respiratory rate | Investigations | Systematic Assessment |
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| Decreased appetite | Metabolism and nutrition disorders | Systematic Assessment |
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| Hyperglycaemia | Metabolism and nutrition disorders | Systematic Assessment |
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| Hyperkalaemia | Metabolism and nutrition disorders | Systematic Assessment |
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| Hypoglycaemia | Metabolism and nutrition disorders | Systematic Assessment |
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| Hypokalaemia | Metabolism and nutrition disorders | Systematic Assessment |
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| Hyponatraemia | Metabolism and nutrition disorders | Systematic Assessment |
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| Polydipsia | Metabolism and nutrition disorders | Systematic Assessment |
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| Vitamin D deficiency | Metabolism and nutrition disorders | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Pain in extremity | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Cluster headache | Nervous system disorders | Systematic Assessment |
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| Dizziness | Nervous system disorders | Systematic Assessment |
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| Headache | Nervous system disorders | Systematic Assessment |
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| Paraesthesia | Nervous system disorders | Systematic Assessment |
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| Presyncope | Nervous system disorders | Systematic Assessment |
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| Anxiety | Psychiatric disorders | Systematic Assessment |
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| Attention deficit hyperactivity disorder | Psychiatric disorders | Systematic Assessment |
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| Insomnia | Psychiatric disorders | Systematic Assessment |
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| Dysuria | Renal and urinary disorders | Systematic Assessment |
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| Pollakiuria | Renal and urinary disorders | Systematic Assessment |
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| Menorrhagia | Reproductive system and breast disorders | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Dysphonia | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Dyspnoea | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Nasal congestion | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Rhinitis allergic | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Sinus congestion | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Throat irritation | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Dermatitis contact | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Dry skin | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Hyperhidrosis | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Keloid scar | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Night sweats | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Pruritus | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Rash erythematous | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Rash maculo-papular | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Skin hyperpigmentation | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Diastolic hypertension | Vascular disorders | Systematic Assessment |
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| Hypotension | Vascular disorders | Systematic Assessment |
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| Systolic hypertension | Vascular disorders | Systematic Assessment |
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Not provided
Not provided
Not provided
| D007249 |
| Inflammation |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| Title | Measurements |
|---|---|
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| Eye pain (Retro-orbital pain) |
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| Photophobia |
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| Nausea |
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| Fatigue |
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| Myalgia |
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| Arthralgia |
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| Maculo-papular rash (Dengue-like rash) |
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| Title | Measurements |
|---|---|
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| Grade 3 |
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| Grade 4 |
|
| Title | Measurements |
|---|---|
|
| Grade 3 |
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| Grade 4 |
|
| Title | Measurements |
|---|---|
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| Day 57 |
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