Dengue
Conditions
Keywords
Safety, Immunogenicity, intradermal Qdenga
Brief summary
Official title: Immunogenicity of an intradermal Qdenga vaccine among healthy volunteers: A pilot study
Detailed description
As in the setting of low- to middle-income countries, to demonstrating that lower doses of vaccine via intradermal route can still elicit robust immune responses, thereby lowering the overall cost of vaccination might be particularly meaningful ,with possible extra benefit of experiencing fewer side effects or risk of allergy. This study goal is to explores the potential of intradermal administration of Qdenga, hypothesizing that a lower dose via this route could achieve adequate immunogenicity compared to the standard subcutaneous administration, thus offering a cost-effective alternative particularly in low-resource settings where dengue is most prevalent.
Interventions
BIOLOGICALVaccine
Subcutaneous route vs Intradermal route
Sponsors
Prince of Songkla University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
* Thai adult aged 18-60 years, who not previously received dengue vaccine. * The subjects are able to and willing to comply with the requirements of the clinical trial program and could complete the 3-month follow-up of the study. * Individuals who are in good health condition at the time of entry into the trial as determined by medical history, physical examination and clinical judgment of the investigator and meet the requirements of immunization * The subject can provide with informed consent and sign informed consent form
Exclusion criteria
* Have a medical history or family history of convulsion, epilepsy, encephalopathy and psychosis. * Be allergic to any component of the research vaccines or used to have a history of hypersensitivity or serious reactions to vaccination. * Women with positive urine pregnancy test, pregnant or breast-feeding, or have a pregnancy plan within six months. * Have acute infectious diseases, including dengue infection * Have severe chronic diseases or condition in progress cannot be controlled. For example, poor controlled DM and uncontrolled HT. * Have the history of urticaria 1 year before receiving the investigational vaccine. * Have known underlying diseases of thrombocytopenia or other coagulation disorders (which may cause contraindications for intramuscular injection). * Have needle sickness. * Have the history of immunosuppressive therapy, cytotoxic therapy or systemic corticosteroids * Have received blood products within 4 months before injection of investigational vaccines. * Under anti-tuberculosis treatment. * Not be able to follow the protocol, or not be able to understand the informed consent according to the researcher's judgment, due to various medical, psychological, social or other conditions.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dengue IgG Level | Day 0 (Baseline), Day 30 (30 days post 1st vaccination) and Day 120 (30 days post 2nd vaccination) | To measure Antibody level for dengue by ELISA on day 0, day 30 and day 120 after 1st vaccination |
| CD4 T Cell Responses | Day 0 (Baseline), Day 30 (30 days post 1st vaccination) and Day 120 (30 days post 2nd vaccination) | To measure T cell responses to dengue antigen by ELISpot on day 0, day 30 and day 120 after 1st vaccination. |
| CD8 T Cell Response | Day 0 (Baseline), Day 30 (30 days post 1st vaccination) and Day 120 (30 days post 2nd vaccination) | To measure T cell responses to dengue antigen by ELISpot on day 0, day 30 and day 120 after 1st vaccination. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Systemic Reactions | at day 7 and 30 post each vaccination | fever, chill, fatique, headache, myalgia |
| Pain at Vaccination Site, 7 Day Post 1st Vaccination | 7 day post 1st vaccination | Injection-site pain reported during the 7-day period following the first vaccine dose. |
| Erythema at Vaccination Site, 7 Day Post 1st Vaccination | 7 day post 1st vaccination | Erythema at vaccination site reported during the 7-day period following the first vaccine dose. |
| All-Cause Mortality | at day 7 and 30 post each vaccination | Death from any cause occurring from the first vaccination until the end of the 120-day follow-up period. |
| Headache, 7 Day Post 1st Vaccination | 7 day post 1st vaccination | Self-reported headache during the 7-day period following the first vaccine dose. |
| Erythema at Vaccination Site, 7 Day Post 2nd Vaccination | 7 day post 2nd vaccination | Erythema at vaccination site reported during the 7-day period following the second vaccine dose. |
| Malaise, 7 Day Post 1st Vaccination | 7 day post 1st vaccination | Self-reported malaise during the 7-day period following the first vaccine dose. |
| Serious Adverse Events | at day 7 and 30 post each vaccination | Any untoward medical occurrence during the study period that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, or is a congenital anomaly/birth defect, regardless of its relationship to the study vaccine. |
| Local Reactions | at day 7 and 30 post each vaccination | \- Include any reported pain, swelling, erythema or nodule at the vaccination site |
Countries
Thailand
Participant flow
Recruitment details
29 adult volunteers were assessed for eligibility; 24 eligible participants were randomized into 2 groups (n = 12 per group).
Pre-assignment details
5 were excluded (4 have negative baseline dengue IgG, 1 withdraw from the study after randomization because of acute febrile illness prior to first dose vaccination).
Participants by arm
| Arm | Count |
|---|---|
| SC ID subcutaneous Qdenga for 1st vaccination then intradermal Qdenga for 2nd vaccination | 12 |
| SC SC subcutaneous Qdenga for 1st vaccination then subcutaneous Qdenga for 2nd vaccination | 12 |
| Total | 24 |
Baseline characteristics
| Characteristic | SC SC | Total | SC ID |
|---|---|---|---|
| Age, Continuous | 39 year | 35.6 year | 32.2 year |
| Body Mass Index | 20.96 kg/m^2 | 21.05 kg/m^2 | 21.18 kg/m^2 |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Sex: Female, Male Female | 11 Participants | 21 Participants | 10 Participants |
| Sex: Female, Male Male | 1 Participants | 3 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 12 |
| other Total, other adverse events | 3 / 12 | 3 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 |
Outcome results
Primary
CD4 T Cell Responses
To measure T cell responses to dengue antigen by ELISpot on day 0, day 30 and day 120 after 1st vaccination.
Time frame: Day 0 (Baseline), Day 30 (30 days post 1st vaccination) and Day 120 (30 days post 2nd vaccination)
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| SC ID | CD4 T Cell Responses | Baseline | 22.0 SFCs per 10^6 PBMCs |
| SC ID | CD4 T Cell Responses | Day 30 | 137.5 SFCs per 10^6 PBMCs |
| SC ID | CD4 T Cell Responses | Day 120 | 98.5 SFCs per 10^6 PBMCs |
| SC SC | CD4 T Cell Responses | Baseline | 15.0 SFCs per 10^6 PBMCs |
| SC SC | CD4 T Cell Responses | Day 30 | 103.0 SFCs per 10^6 PBMCs |
| SC SC | CD4 T Cell Responses | Day 120 | 94.5 SFCs per 10^6 PBMCs |
Primary
CD8 T Cell Response
To measure T cell responses to dengue antigen by ELISpot on day 0, day 30 and day 120 after 1st vaccination.
Time frame: Day 0 (Baseline), Day 30 (30 days post 1st vaccination) and Day 120 (30 days post 2nd vaccination)
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| SC ID | CD8 T Cell Response | Baseline | 5.0 SFCs per 10^6 PBMCs |
| SC ID | CD8 T Cell Response | Day 30 | 62.0 SFCs per 10^6 PBMCs |
| SC ID | CD8 T Cell Response | Day 120 | 6.0 SFCs per 10^6 PBMCs |
| SC SC | CD8 T Cell Response | Baseline | 11.0 SFCs per 10^6 PBMCs |
| SC SC | CD8 T Cell Response | Day 30 | 11.0 SFCs per 10^6 PBMCs |
| SC SC | CD8 T Cell Response | Day 120 | 10.0 SFCs per 10^6 PBMCs |
Primary
Dengue IgG Level
To measure Antibody level for dengue by ELISA on day 0, day 30 and day 120 after 1st vaccination
Time frame: Day 0 (Baseline), Day 30 (30 days post 1st vaccination) and Day 120 (30 days post 2nd vaccination)
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| SC ID | Dengue IgG Level | Baseline | 108.9 RU/ml |
| SC ID | Dengue IgG Level | Day 30 | 158.5 RU/ml |
| SC ID | Dengue IgG Level | Day 120 | 148.6 RU/ml |
| SC SC | Dengue IgG Level | Baseline | 104.0 RU/ml |
| SC SC | Dengue IgG Level | Day 30 | 143.2 RU/ml |
| SC SC | Dengue IgG Level | Day 120 | 141.3 RU/ml |
Comparison: Kruskal-Wallis test followed by Dunn's multiple comparisons testp-value: <0.01Kruskal-Wallis
Secondary
All-Cause Mortality
Death from any cause occurring from the first vaccination until the end of the 120-day follow-up period.
Time frame: at day 7 and 30 post each vaccination
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SC ID | All-Cause Mortality | All-Cause mortality | 0 Participants |
| SC SC | All-Cause Mortality | All-Cause mortality | 0 Participants |
Secondary
Erythema at Vaccination Site, 7 Day Post 1st Vaccination
Erythema at vaccination site reported during the 7-day period following the first vaccine dose.
Time frame: 7 day post 1st vaccination
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SC ID | Erythema at Vaccination Site, 7 Day Post 1st Vaccination | 2 Participants |
| SC SC | Erythema at Vaccination Site, 7 Day Post 1st Vaccination | 0 Participants |
Secondary
Erythema at Vaccination Site, 7 Day Post 2nd Vaccination
Erythema at vaccination site reported during the 7-day period following the second vaccine dose.
Time frame: 7 day post 2nd vaccination
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SC ID | Erythema at Vaccination Site, 7 Day Post 2nd Vaccination | 2 Participants |
| SC SC | Erythema at Vaccination Site, 7 Day Post 2nd Vaccination | 0 Participants |
Secondary
Headache, 7 Day Post 1st Vaccination
Self-reported headache during the 7-day period following the first vaccine dose.
Time frame: 7 day post 1st vaccination
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SC ID | Headache, 7 Day Post 1st Vaccination | 0 Participants |
| SC SC | Headache, 7 Day Post 1st Vaccination | 1 Participants |
Secondary
Local Reactions
\- Include any reported pain, swelling, erythema or nodule at the vaccination site
Time frame: at day 7 and 30 post each vaccination
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SC ID | Local Reactions | 3 Participants |
| SC SC | Local Reactions | 1 Participants |
Secondary
Malaise, 7 Day Post 1st Vaccination
Self-reported malaise during the 7-day period following the first vaccine dose.
Time frame: 7 day post 1st vaccination
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SC ID | Malaise, 7 Day Post 1st Vaccination | 0 Participants |
| SC SC | Malaise, 7 Day Post 1st Vaccination | 1 Participants |
Secondary
Pain at Vaccination Site, 7 Day Post 1st Vaccination
Injection-site pain reported during the 7-day period following the first vaccine dose.
Time frame: 7 day post 1st vaccination
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SC ID | Pain at Vaccination Site, 7 Day Post 1st Vaccination | 2 Participants |
| SC SC | Pain at Vaccination Site, 7 Day Post 1st Vaccination | 1 Participants |
Secondary
Serious Adverse Events
Any untoward medical occurrence during the study period that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, or is a congenital anomaly/birth defect, regardless of its relationship to the study vaccine.
Time frame: at day 7 and 30 post each vaccination
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SC ID | Serious Adverse Events | 0 Participants |
| SC SC | Serious Adverse Events | 0 Participants |
Secondary
Systemic Reactions
fever, chill, fatique, headache, myalgia
Time frame: at day 7 and 30 post each vaccination
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SC ID | Systemic Reactions | 0 Participants |
| SC SC | Systemic Reactions | 2 Participants |