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| ID | Type | Description | Link |
|---|---|---|---|
| U1111-1181-8290 | Registry Identifier | WHO |
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The purpose of this study is to assess the safety of Takeda's Tetravalent Dengue Vaccine Candidate (TDV) (previously DENVax) in healthy adults when given as either a subcutaneous (SC) or intradermal (ID) injection at two dose levels (low and high). The vaccine will be given as two doses 90 days apart. Safety assessments include injection site evaluation and adverse events. The immune response generated after vaccination will be assessed up to 9 months after the first vaccination.
This is a single center, placebo-controlled, randomized study assessing the safety and tolerability of two dose levels (low and high) of TDV administered subcutaneously or intradermally in two doses separated by an interval of 90 days. Initial dosing of low dose cohort will be performed and Day 21 safety assessed prior to administration of second dose to low dose cohort on Day 90 and initial dosing of high dose cohort. Day 21 safety for the high dose cohort will be assessed prior to administration of second dose for this cohort. Safety (local injection site reactions and solicited and unsolicited adverse events) will be assessed through Day 120 post-first (1 month after the second dose). Immunogenicity will be assessed at specified time points up to Day 120 post-prime (1 month after the second dose) and again on Days 180 and 270 (6 and 9 months post-first).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group 1: Low Dose; SC | Experimental | TDV-1: 8 x 10^3 Plaque Forming Units (PFU), TDV-2: 5 x 10^3 PFU, TDV-3: 1 x 10^4 PFU, TDV-4: 2 x 10^5 PFU or placebo administered subcutaneously on Days 0 and 90. Dose volume is 0.5 mL. |
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| Group 2: Low Dose; ID | Experimental | TDV-1: 8 x 10^3 PFU, TDV-2: 5 x 10^3 PFU, TDV-3: 1 x 10^4 PFU, TDV-4: 2 x 10^5 PFU or placebo administered intradermally on Days 0 and 90. Dose volume is 0.1 mL. |
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| Group 3: High Dose; SC | Experimental | TDV-1: 2 x 10^4 PFU, TDV-2: 5 x 10^4 PFU, TDV-3: 1 x 10^5 PFU, TDV-4: 3 x 10^5 PFU or placebo administered subcutaneously on Days 0 and 90. Dose volume is 0.5 mL. |
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| Group 4: High Dose; ID | Experimental | TDV-1: 2 x 10^4 PFU, TDV-2: 5 x 10^4 PFU, TDV-3: 1 x 10^5 PFU, TDV-4: 3 x 10^5 PFU or placebo administered intradermally on Days 0 and 90. Dose volume is 0.1 mL. |
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| Placebo (SC) | Placebo Comparator | Phosphate buffered saline administered subcutaneously in a volume of 0.5 mL. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| TDV - Low Dose | Biological | TDV is a tetravalent dengue vaccine comprised of four recombinant, live attenuated dengue virus strains: TDV-1, TDV-2, TDV-3 and TDV-4. Low dose contains: TDV-1: 8 x 10^3 PFU, TDV-2: 5 x 10^3 PFU, TDV-3: 1 x 10^4 PFU, and TDV-4: 2 x 10^5 PFU, total virus per dose 2.2 x 10^5 PFU |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Local Injection Site Reaction by Severity | Solicited local reactions were reported using a participant diary. Pain was categorized as Mild (aware of pain but it does not interfere with daily activity and no pain medication is taken); Moderate (aware of pain; there is interference with daily activity or it requires use of pain medication); Severe (aware of pain and it prevents daily activity), redness was categorized as Mild (greater than [>] 15 millimeter [mm]); Moderate as (15-30 mm); Severe (>30 mm), swelling was categorized as Mild (<15 mm); Moderate (15-30 mm); Severe (>30 mm), and itching was categorized as Mild (slight itching at injection site); Moderate (moderate itching at injection extremity); Severe (itching over entire body). | Within 14 days after either of the vaccination given on Day 1 or 90 (Day 14 for first vaccination, Day 104 for second vaccination) |
| Number of Participants With Systemic Adverse Events (AEs) by Severity | Solicited systemic AEs were reported using a participant diary. Solicited systemic AEs included fever (>= 37.8°C), headache, muscle pain, joint pain, eye pain, photophobia, fatigue, body rash, nausea, vomiting and other (any other symptom not listed in the diary) and were categorized as Mild: transient symptoms, discomfort noticed but easily tolerated, no interference to normal daily activities; Moderate: marked symptoms, moderate interference with daily activities; Severe: considerable interference with daily activities. | Within 14 days after either of the vaccination given on Day 1 or 90 (Day 14 for first vaccination, Day 104 for second vaccination) |
| Number of Participants With Solicited Local and Systemic AEs | Within 14 days after either of the vaccination given on Day 1 or 90 (Day 14 for first vaccination, Day 104 for second vaccination) | |
| Number of Participants With Unsolicited Local and Systemic AEs | Baseline up to 30 days after second vaccination (Day 120) |
| Measure | Description | Time Frame |
|---|---|---|
| Geometric Mean Neutralizing Antibody Titers (GMTs) of All Four Dengue Serotypes After First Vaccination | GMT was assessed for the four dengue serotypes: Dengue TDV-1, TDV-2, TDV-3 and TDV-4. GMTs and 95 percent (%) confidence interval (CIs) were calculated by taking the anti-logs of the means and 95% CI of the log transformed titers. | Days 14, 30, 60 and 90 after first vaccination |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Ivan D Velez, MD, Ph.D. | PECET, Universidad the Antioquia, Medellin, Colombia | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Program For The Study and Control of Tropical Diseases | MedellÃn | Colombia |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25087476 | Derived | Osorio JE, Velez ID, Thomson C, Lopez L, Jimenez A, Haller AA, Silengo S, Scott J, Boroughs KL, Stovall JL, Luy BE, Arguello J, Beatty ME, Santangelo J, Gordon GS, Huang CY, Stinchcomb DT. Safety and immunogenicity of a recombinant live attenuated tetravalent dengue vaccine (DENVax) in flavivirus-naive healthy adults in Colombia: a randomised, placebo-controlled, phase 1 study. Lancet Infect Dis. 2014 Sep;14(9):830-8. doi: 10.1016/S1473-3099(14)70811-4. Epub 2014 Jul 23. |
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Healthy male and female participants were enrolled in 1 of the 8 treatment groups: Low Dose Subcutaneous:TDV, Low Dose Subcutaneous: Placebo, Low Dose Intradermal:TDV, Low Dose Intradermal:Placebo, High Dose Subcutaneous:TDV, High Dose Subcutaneous:Placebo, High Dose Intradermal:TDV, High Dose Intradermal:Placebo.
Participants took part in the study at 1 investigative site in Colombia from 11 October 2010 to 09 November 2011.
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| ID | Title | Description |
|---|---|---|
| FG000 | Low Dose Subcutaneous: TDV | TDV 0.5 milliliter (mL), injection, subcutaneously, once on Day 0 (first dose) and Day 90 (second dose). Takeda's Tetravalent Dengue Vaccine Candidate (TDV) (previously DENVax) comprised of 4 recombinant, live attenuated dengue virus strains: TDV-1, TDV-2, TDV-3 and TDV-4. Low dose contains: TDV-1: 8*10^3 plaque forming units (PFU), TDV-2: 5*10^3 PFU, TDV-3: 1*10^4 PFU, and TDV-4: 2*10^5 PFU, total virus per dose: 2.2*10^5 PFU. |
| FG001 | Low Dose Subcutaneous: Placebo | TDV placebo-matching 0.5 mL injection, subcutaneously, once on Day 0 (first dose) and Day 90 (second dose). |
| FG002 | Low Dose Intradermal: TDV | TDV 0.1 mL, injection, intradermally, once on Day 0 (first dose) and Day 90 (second dose). TDV is a tetravalent dengue vaccine comprised of 4 recombinant, live attenuated dengue virus strains: TDV-1, TDV-2, TDV-3 and TDV-4. Low dose contains: TDV-1: 8*10^3 PFU, TDV-2: 5*10^3 PFU, TDV-3: 1*10^4 PFU, and TDV-4: 2*10^5 PFU, total virus per dose: 2.2*10^5 PFU. |
| FG003 | Low Dose Intradermal: Placebo | TDV placebo-matching 0.1 mL injection, intradermally, once on Day 0 (first dose) and Day 90 (second dose). |
| FG004 | High Dose Subcutaneous: TDV | TDV 0.5 mL, injection, subcutaneously, once on Day 0 (first dose) and Day 90 (second dose). TDV is a tetravalent dengue vaccine comprised of 4 recombinant, live attenuated dengue virus strains: TDV-1, TDV-2, TDV-3 and TDV-4. High dose contains TDV-1: 2*10^4 PFU, TDV-2: 5*10^4 PFU, TDV-3: 1*10^5 PFU, and TDV-4: 3*10^5 PFU, total virus per dose: 4.7*10^5 PFU. |
| FG005 | High Dose Subcutaneous: Placebo | TDV placebo-matching 0.5 mL injection, subcutaneously, once on Day 0 (first dose) and Day 90 (second dose). |
| FG006 | High Dose Intradermal: TDV | TDV 0.1 mL, injection, intradermally, once on Day 0 (first dose) and Day 90 (second dose). TDV is a tetravalent dengue vaccine comprised of 4 recombinant, live attenuated dengue virus strains: TDV-1, TDV-2, TDV-3 and TDV-4. High dose contains TDV-1: 2*10^4 PFU, TDV-2: 5*10^4 PFU, TDV-3: 1*10^5 PFU, and TDV-4: 3*10^5 PFU, total virus per dose: 4.7*10^5 PFU. |
| FG007 | High Dose Intradermal: Placebo | TDV placebo-matching 0.1 mL injection, intradermally, once on Day 0 (first dose) and Day 90 (second dose). |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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The safety population included all randomized participants who received at least one dose of study vaccine and for whom post-dosing safety data was obtained.
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| ID | Title | Description |
|---|---|---|
| BG000 | Low Dose Subcutaneous: TDV | TDV 0.5 mL, injection, subcutaneously, once on Day 0 (first dose) and Day 90 (second dose). TDV is a tetravalent dengue vaccine comprised of 4 recombinant, live attenuated dengue virus strains: TDV-1, TDV-2, TDV-3 and TDV-4. Low dose contains: TDV-1: 8*10^3 PFU, TDV-2: 5*10^3 PFU, TDV-3: 1*10^4 PFU, and TDV-4: 2*10^5 PFU, total virus per dose: 2.2*10^5 PFU. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Number |
| 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 Injection Site Reaction by Severity | Solicited local reactions were reported using a participant diary. Pain was categorized as Mild (aware of pain but it does not interfere with daily activity and no pain medication is taken); Moderate (aware of pain; there is interference with daily activity or it requires use of pain medication); Severe (aware of pain and it prevents daily activity), redness was categorized as Mild (greater than [>] 15 millimeter [mm]); Moderate as (15-30 mm); Severe (>30 mm), swelling was categorized as Mild (<15 mm); Moderate (15-30 mm); Severe (>30 mm), and itching was categorized as Mild (slight itching at injection site); Moderate (moderate itching at injection extremity); Severe (itching over entire body). | The safety population included all randomized participants who received at least one dose of study vaccine and for whom post-dosing safety data was obtained. | Posted | Number | participants | Within 14 days after either of the vaccination given on Day 1 or 90 (Day 14 for first vaccination, Day 104 for second vaccination) |
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Adverse events are adverse events that started after the first dose of double-blind study vaccine and up to Day 120
A SAE is any untoward medical occurrence that at any dose was fatal, life-threatening, required hospitalization/prolongation of existing hospitalization, resulted in persistent/significant disability/incapacity, congenital anomaly/birth defect, medically significant or required intervention to prevent one or other of the outcomes listed here.
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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 | Low Dose Subcutaneous: TDV | TDV 0.5 mL, injection, subcutaneously, once on Day 0 (first dose) and Day 90 (second dose). TDV is a tetravalent dengue vaccine comprised of 4 recombinant, live attenuated dengue virus strains: TDV-1, TDV-2, TDV-3 and TDV-4. Low dose contains: TDV-1: 8*10^3 PFU, TDV-2: 5*10^3 PFU, TDV-3: 1*10^4 PFU, and TDV-4: 2*10^5 PFU, total virus per dose: 2.2*10^5 PFU. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Suicide attempt | Psychiatric disorders | MedDRA (13.1) | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| ANAEMIA | Blood and lymphatic system disorders | MedDRA (13.1) | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Director | Takeda | +1-877-825-3327 | trialdisclosures@takeda.com |
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| ID | Term |
|---|---|
| D003715 | Dengue |
| ID | Term |
|---|---|
| D000096724 | Mosquito-Borne Diseases |
| D000079426 | Vector Borne Diseases |
| D007239 | Infections |
| D001102 | Arbovirus Infections |
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| Placebo (ID) | Placebo Comparator | Phosphate buffered saline administered intradermally in a dose volume of 0.1 mL. |
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| TDV - High Dose | Biological | TDV is a tetravalent dengue vaccine comprised of four recombinant, live attenuated dengue virus strains: TDV-1, TDV-2, TDV-3 and TDV-4. High dose contains TDV-1: 2 x 10^4 PFU, TDV-2: 5 x 10^4 PFU, TDV-3: 1 x 10^5 PFU, and TDV-4: 3 x 10^5 PFU, total virus per dose : 4.7 x 10^5 PFU. TDV administered intradermally. |
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| Placebo | Biological | Phosphate Buffered Saline (PBS) |
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| GMTs of All Four Dengue Serotypes After Second Vaccination | GMT was assessed for the four dengue serotypes: TDV-1, TDV-2, TDV-3 and TDV-4. GMTs and 95% CIs were calculated by taking the anti-logs of the means and 95% CI of the log transformed titers. | Days 14 and 30 after second vaccination (Day 104 and 120 respectively) |
| Rate of Seroconversion to Each of Four Dengue Serotypes After the First Vaccination | Seroconversion was defined as a Plaque Reduction Neutralization Test (PRNT) titer resulting in 50% reduction in plaques (PRNT[50]) >=10 (if the pre-vaccination PRNT[50] value was <10, indicated as a value of 5 in the immunogenicity data collection sheet) OR a PRNT(50) value that was >=4-fold the pre-vaccination titer value (if the pre-vaccination PRNT[50] value was >=10). Seroconversion was assessed for the four dengue serotypes: TDV-1, TDV-2, TDV-3 and TDV-4. The 95% CIs for percentages are the exact CIs (%) based upon the binomial distribution. Percentages are based on the number of participants in the FAS with non-missing MN assay samples at each visit. | Days 14, 30, 60 and 90 after first vaccination |
| Rate of Seroconversion to Each of Four Dengue Serotypes After the Second Vaccination | Seroconversion was defined as a PRNT titer resulting in 50% reduction in plaques (PRNT[50]) >=10 (if the pre-vaccination PRNT[50] value was <10, indicated as a value of 5 in the immunogenicity data collection sheet) OR a PRNT(50) value that was >=4-fold the pre-vaccination titer value (if the pre-vaccination PRNT[50] value was >=10). Seroconversion was assessed for the four dengue serotypes: TDV-1, TDV-2, TDV-3 and TDV-4. The 95% CIs for percentages are the exact CIs (%) based upon the binomial distribution. Percentages are based on the number of participants in the FAS with non-missing MN assay samples at each visit (n). | Days 14 and 30 after second vaccination (Days 104 and 120 respectively) |
| Percentage of Participants With Durability of Immune Response | Immune response was considered durable if the participant had detectable neutralizing antibodies (seroconversion) to all 4 dengue serotypes at 90 and 180 days after the second dose (i.e. Days 180 and 270, respectively). Seroconversion is defined as post-vaccination PRNT(50) titer >=10 where pre-vaccination PRNT 50 titer <10, or post-vaccination PRNT(50) Titer >=4-fold the pre-vaccination PRNT(50) titer value where pre-vaccination PRNT(50) titer >=10. Percentage of participants with seroconversion on Days 180 and 270 are based on the number of participants in the FAS with non-missing MN assay samples at each visit. The 95% CIs for percentages are the exact CIs (%) based upon the binomial distribution. | Days 180 and 270 |
| Number of Participants Positive for Vaccine Viremia for Each of the Four Vaccine Strain Serotypes After the First and Second Vaccination | Serotype-specific vaccine viremia was assessed for the four vaccine strain serotypes: TDV-1, TDV-2, TDV-3 and TDV-4. Only those serotypes and time-points where at least 1 participant had serotype-specific vaccine viremia detection were reported. | Baseline and at multiple time points up to Day 14 after each vaccination |
| Duration of Vaccine Viremia | 14 Days after each vaccination |
| Titers of Vaccine Viremia | 14 Days after each vaccination |
| Adverse Event |
|
| BG001 | Low Dose Subcutaneous: Placebo | TDV placebo-matching 0.5 mL injection, subcutaneously, once on Day 0 (first dose) and Day 90 (second dose). |
| BG002 | Low Dose Intradermal: TDV | TDV 0.1 mL, injection, intradermally, once on Day 0 (first dose) and Day 90 (second dose). TDV is a tetravalent dengue vaccine comprised of 4 recombinant, live attenuated dengue virus strains: TDV-1, TDV-2, TDV-3 and TDV-4. Low dose contains: TDV-1: 8*10^3 PFU, TDV-2: 5*10^3 PFU, TDV-3: 1*10^4 PFU, and TDV-4: 2*10^5 PFU, total virus per dose: 2.2*10^5 PFU. |
| BG003 | Low Dose Intradermal: Placebo | TDV placebo-matching 0.1 mL injection, intradermally, once on Day 0 (first dose) and Day 90 (second dose). |
| BG004 | High Dose Subcutaneous: TDV | TDV 0.5 mL, injection, subcutaneously, once on Day 0 (first dose) and Day 90 (second dose). TDV is a tetravalent dengue vaccine comprised of 4 recombinant, live attenuated dengue virus strains: TDV-1, TDV-2, TDV-3 and TDV-4. High dose contains TDV-1: 2*10^4 PFU, TDV-2: 5*10^4 PFU, TDV-3: 1*10^5 PFU, and TDV-4: 3*10^5 PFU, total virus per dose: 4.7*10^5 PFU. |
| BG005 | High Dose Subcutaneous: Placebo | TDV placebo-matching 0.5 mL injection, subcutaneously, once on Day 0 (first dose) and Day 90 (second dose). |
| BG006 | High Dose Intradermal: TDV | TDV 0.1 mL, injection, intradermally, once on Day 0 (first dose) and Day 90 (second dose). TDV is a tetravalent dengue vaccine comprised of 4 recombinant, live attenuated dengue virus strains: TDV-1, TDV-2, TDV-3 and TDV-4. High dose contains TDV-1: 2*10^4 PFU, TDV-2: 5*10^4 PFU, TDV-3: 1*10^5 PFU, and TDV-4: 3*10^5 PFU, total virus per dose: 4.7*10^5 PFU. |
| BG007 | High Dose Intradermal: Placebo | TDV placebo-matching 0.1 mL injection, intradermally, once on Day 0 (first dose) and Day 90 (second dose). |
| BG008 | Total | Total of all reporting groups |
| participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | The baseline measure category "other" refers to mixed race. | Number | participants |
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| OG000 | Low Dose Subcutaneous: TDV | TDV 0.5 mL, injection, subcutaneously, once on Day 0 (first dose) and Day 90 (second dose). TDV is a tetravalent dengue vaccine comprised of 4 recombinant, live attenuated dengue virus strains: TDV-1, TDV-2, TDV-3 and TDV-4. Low dose contains: TDV-1: 8*10^3 PFU, TDV-2: 5*10^3 PFU, TDV-3: 1*10^4 PFU, and TDV-4: 2*10^5 PFU, total virus per dose: 2.2*10^5 PFU. |
| OG001 | Low Dose Subcutaneous: Placebo | TDV placebo-matching 0.5 mL injection, subcutaneously, once on Day 0 (first dose) and Day 90 (second dose). |
| OG002 | Low Dose Intradermal: TDV | TDV 0.1 mL, injection, intradermally, once on Day 0 (first dose) and Day 90 (second dose). TDV is a tetravalent dengue vaccine comprised of 4 recombinant, live attenuated dengue virus strains: TDV-1, TDV-2, TDV-3 and TDV-4. Low dose contains: TDV-1: 8*10^3 PFU, TDV-2: 5*10^3 PFU, TDV-3: 1*10^4 PFU, and TDV-4: 2*10^5 PFU, total virus per dose: 2.2*10^5 PFU. |
| OG003 | Low Dose Intradermal: Placebo | TDV placebo-matching 0.1 mL injection, intradermally, once on Day 0 (first dose) and Day 90 (second dose). |
| OG004 | High Dose Subcutaneous: TDV | TDV 0.5 mL, injection, subcutaneously, once on Day 0 (first dose) and Day 90 (second dose). TDV is a tetravalent dengue vaccine comprised of 4 recombinant, live attenuated dengue virus strains: TDV-1, TDV-2, TDV-3 and TDV-4. High dose contains TDV-1: 2*10^4 PFU, TDV-2: 5*10^4 PFU, TDV-3: 1*10^5 PFU, and TDV-4: 3*10^5 PFU, total virus per dose: 4.7*10^5 PFU. |
| OG005 | High Dose Subcutaneous: Placebo | TDV placebo-matching 0.5 mL injection, subcutaneously, once on Day 0 (first dose) and Day 90 (second dose). |
| OG006 | High Dose Intradermal: TDV | TDV 0.1 mL, injection, intradermally, once on Day 0 (first dose) and Day 90 (second dose). TDV is a tetravalent dengue vaccine comprised of 4 recombinant, live attenuated dengue virus strains: TDV-1, TDV-2, TDV-3 and TDV-4. High dose contains TDV-1: 2*10^4 PFU, TDV-2: 5*10^4 PFU, TDV-3: 1*10^5 PFU, and TDV-4: 3*10^5 PFU, total virus per dose: 4.7*10^5 PFU. |
| OG007 | High Dose Intradermal: Placebo | TDV placebo-matching 0.1 mL injection, intradermally, once on Day 0 (first dose) and Day 90 (second dose). |
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| Primary | Number of Participants With Systemic Adverse Events (AEs) by Severity | Solicited systemic AEs were reported using a participant diary. Solicited systemic AEs included fever (>= 37.8°C), headache, muscle pain, joint pain, eye pain, photophobia, fatigue, body rash, nausea, vomiting and other (any other symptom not listed in the diary) and were categorized as Mild: transient symptoms, discomfort noticed but easily tolerated, no interference to normal daily activities; Moderate: marked symptoms, moderate interference with daily activities; Severe: considerable interference with daily activities. | The safety population included all randomized participants who received at least one dose of study vaccine and for whom post-dosing safety data was obtained. | Posted | Number | participants | Within 14 days after either of the vaccination given on Day 1 or 90 (Day 14 for first vaccination, Day 104 for second vaccination) |
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| Primary | Number of Participants With Solicited Local and Systemic AEs | The safety population included all randomized participants who received at least one dose of study vaccine and for whom post-dosing safety data was obtained. | Posted | Number | participants | Within 14 days after either of the vaccination given on Day 1 or 90 (Day 14 for first vaccination, Day 104 for second vaccination) |
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| Primary | Number of Participants With Unsolicited Local and Systemic AEs | The safety population included all randomized participants who received at least one dose of study vaccine and for whom post-dosing safety data was obtained. | Posted | Number | participants | Baseline up to 30 days after second vaccination (Day 120) |
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| Secondary | Geometric Mean Neutralizing Antibody Titers (GMTs) of All Four Dengue Serotypes After First Vaccination | GMT was assessed for the four dengue serotypes: Dengue TDV-1, TDV-2, TDV-3 and TDV-4. GMTs and 95 percent (%) confidence interval (CIs) were calculated by taking the anti-logs of the means and 95% CI of the log transformed titers. | The full analysis set (FAS) included all randomized participants who received at least one dose of study vaccine and for whom valid pre- and post-dosing blood samples were received. Here 'n' is number of participants with non-missing microneutralization (MN) Assay samples. | Posted | Geometric Mean | 95% Confidence Interval | titer | Days 14, 30, 60 and 90 after first vaccination |
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| Secondary | GMTs of All Four Dengue Serotypes After Second Vaccination | GMT was assessed for the four dengue serotypes: TDV-1, TDV-2, TDV-3 and TDV-4. GMTs and 95% CIs were calculated by taking the anti-logs of the means and 95% CI of the log transformed titers. | The FAS included all randomized participants who received at least one dose of study vaccine and for whom valid pre- and post-dosing blood samples were received. Here 'n' is number of participants with non-missing MN Assay samples. | Posted | Geometric Mean | 95% Confidence Interval | titer | Days 14 and 30 after second vaccination (Day 104 and 120 respectively) |
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| Secondary | Rate of Seroconversion to Each of Four Dengue Serotypes After the First Vaccination | Seroconversion was defined as a Plaque Reduction Neutralization Test (PRNT) titer resulting in 50% reduction in plaques (PRNT[50]) >=10 (if the pre-vaccination PRNT[50] value was <10, indicated as a value of 5 in the immunogenicity data collection sheet) OR a PRNT(50) value that was >=4-fold the pre-vaccination titer value (if the pre-vaccination PRNT[50] value was >=10). Seroconversion was assessed for the four dengue serotypes: TDV-1, TDV-2, TDV-3 and TDV-4. The 95% CIs for percentages are the exact CIs (%) based upon the binomial distribution. Percentages are based on the number of participants in the FAS with non-missing MN assay samples at each visit. | The FAS included all randomized participants who received at least one dose of study vaccine and for whom valid pre- and post-dosing blood samples were received. | Posted | Number | 95% Confidence Interval | percentage of participants | Days 14, 30, 60 and 90 after first vaccination |
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| Secondary | Rate of Seroconversion to Each of Four Dengue Serotypes After the Second Vaccination | Seroconversion was defined as a PRNT titer resulting in 50% reduction in plaques (PRNT[50]) >=10 (if the pre-vaccination PRNT[50] value was <10, indicated as a value of 5 in the immunogenicity data collection sheet) OR a PRNT(50) value that was >=4-fold the pre-vaccination titer value (if the pre-vaccination PRNT[50] value was >=10). Seroconversion was assessed for the four dengue serotypes: TDV-1, TDV-2, TDV-3 and TDV-4. The 95% CIs for percentages are the exact CIs (%) based upon the binomial distribution. Percentages are based on the number of participants in the FAS with non-missing MN assay samples at each visit (n). | The FAS included all randomized participants who received at least one dose of study vaccine and for whom valid pre- and post-dosing blood samples were received. | Posted | Number | 95% Confidence Interval | percentage of participants | Days 14 and 30 after second vaccination (Days 104 and 120 respectively) |
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| Secondary | Percentage of Participants With Durability of Immune Response | Immune response was considered durable if the participant had detectable neutralizing antibodies (seroconversion) to all 4 dengue serotypes at 90 and 180 days after the second dose (i.e. Days 180 and 270, respectively). Seroconversion is defined as post-vaccination PRNT(50) titer >=10 where pre-vaccination PRNT 50 titer <10, or post-vaccination PRNT(50) Titer >=4-fold the pre-vaccination PRNT(50) titer value where pre-vaccination PRNT(50) titer >=10. Percentage of participants with seroconversion on Days 180 and 270 are based on the number of participants in the FAS with non-missing MN assay samples at each visit. The 95% CIs for percentages are the exact CIs (%) based upon the binomial distribution. | The FAS included all randomized participants who received at least one dose of study vaccine and for whom valid pre- and post-dosing blood samples were received. | Posted | Number | 95% Confidence Interval | percentage of participants | Days 180 and 270 |
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|
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| Secondary | Number of Participants Positive for Vaccine Viremia for Each of the Four Vaccine Strain Serotypes After the First and Second Vaccination | Serotype-specific vaccine viremia was assessed for the four vaccine strain serotypes: TDV-1, TDV-2, TDV-3 and TDV-4. Only those serotypes and time-points where at least 1 participant had serotype-specific vaccine viremia detection were reported. | The FAS included all randomized participants who received at least one dose of study vaccine and for whom valid pre- and post-dosing blood samples were received. | Posted | Number | participants | Baseline and at multiple time points up to Day 14 after each vaccination |
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|
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| Secondary | Duration of Vaccine Viremia | Due to the low prevalence of vaccine viremia, estimates of average titer duration of viral RNA within study groups would not be meaningful. Therefore as per change in planned analysis only number of participants with positive vaccine viremia of all four vaccine strain serotypes after first and second vaccination was reported. | Posted | 14 Days after each vaccination |
|
|
| Secondary | Titers of Vaccine Viremia | Due to the low prevalence of vaccine viremia, estimates of average titer levels of viral RNA within study groups would not be meaningful. Therefore as per change in planned analysis only number of participants with positive vaccine viremia of all four vaccine strain serotypes after first and second vaccination was reported. | Posted | 14 Days after each vaccination |
|
|
| 0 |
| 19 |
| 12 |
| 19 |
| EG001 | Low Dose Subcutaneous: Placebo | TDV placebo-matching 0.5 mL injection, subcutaneously, once on Day 0 (first dose) and Day 90 (second dose). | 0 | 5 | 5 | 5 |
| EG002 | Low Dose Intradermal: TDV | TDV 0.1 mL, injection, intradermally, once on Day 0 (first dose) and Day 90 (second dose). TDV is a tetravalent dengue vaccine comprised of 4 recombinant, live attenuated dengue virus strains: TDV-1, TDV-2, TDV-3 and TDV-4. Low dose contains: TDV-1: 8*10^3 PFU, TDV-2: 5*10^3 PFU, TDV-3: 1*10^4 PFU, and TDV-4: 2*10^5 PFU, total virus per dose: 2.2*10^5 PFU. | 0 | 21 | 13 | 21 |
| EG003 | Low Dose Intradermal: Placebo | TDV placebo-matching 0.1 mL injection, intradermally, once on Day 0 (first dose) and Day 90 (second dose). | 1 | 3 | 3 | 3 |
| EG004 | High Dose Subcutaneous: TDV | TDV 0.5 mL, injection, subcutaneously, once on Day 0 (first dose) and Day 90 (second dose). TDV is a tetravalent dengue vaccine comprised of 4 recombinant, live attenuated dengue virus strains: TDV-1, TDV-2, TDV-3 and TDV-4. High dose contains TDV-1: 2*10^4 PFU, TDV-2: 5*10^4 PFU, TDV-3: 1*10^5 PFU, and TDV-4: 3*10^5 PFU, total virus per dose: 4.7*10^5 PFU. | 1 | 21 | 15 | 21 |
| EG005 | High Dose Subcutaneous: Placebo | TDV placebo-matching 0.5 mL injection, subcutaneously, once on Day 0 (first dose) and Day 90 (second dose). | 0 | 4 | 2 | 4 |
| EG006 | High Dose Intradermal: TDV | TDV 0.1 mL, injection, intradermally, once on Day 0 (first dose) and Day 90 (second dose). TDV is a tetravalent dengue vaccine comprised of 4 recombinant, live attenuated dengue virus strains: TDV-1, TDV-2, TDV-3 and TDV-4. High dose contains TDV-1: 2*10^4 PFU, TDV-2: 5*10^4 PFU, TDV-3: 1*10^5 PFU, and TDV-4: 3*10^5 PFU, total virus per dose: 4.7*10^5 PFU. | 0 | 18 | 13 | 18 |
| EG007 | High Dose Intradermal: Placebo | TDV placebo-matching 0.1 mL injection, intradermally, once on Day 0 (first dose) and Day 90 (second dose). | 0 | 5 | 3 | 5 |
| Ankle fracture | Injury, poisoning and procedural complications | MedDRA (13.1) | Non-systematic Assessment |
|
| LYMPHADENOPATHY | Blood and lymphatic system disorders | MedDRA (13.1) | Non-systematic Assessment |
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| THROMBOCYTOSIS | Blood and lymphatic system disorders | MedDRA (13.1) | Non-systematic Assessment |
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| EAR PAIN | Ear and labyrinth disorders | MedDRA (13.1) | Non-systematic Assessment |
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| EYE PAIN | Eye disorders | MedDRA (13.1) | Non-systematic Assessment |
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| PHOTOPHOBIA | Eye disorders | MedDRA (13.1) | Non-systematic Assessment |
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| ABDOMINAL PAIN LOWER | Gastrointestinal disorders | MedDRA (13.1) | Non-systematic Assessment |
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| ABDOMINAL PAIN UPPER | Gastrointestinal disorders | MedDRA (13.1) | Non-systematic Assessment |
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| NAUSEA | Gastrointestinal disorders | MedDRA (13.1) | Non-systematic Assessment |
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| CHEST PAIN | General disorders | MedDRA (13.1) | Non-systematic Assessment |
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| FATIGUE | General disorders | MedDRA (13.1) | Non-systematic Assessment |
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| INJECTION SITE ERYTHEMA | General disorders | MedDRA (13.1) | Non-systematic Assessment |
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| INJECTION SITE HAEMATOMA | General disorders | MedDRA (13.1) | Non-systematic Assessment |
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| PYERXIA | General disorders | MedDRA (13.1) | Non-systematic Assessment |
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| VACCINATION SITE HAEMATOMA | General disorders | MedDRA (13.1) | Non-systematic Assessment |
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| VACCINATION SITE SCAB | General disorders | MedDRA (13.1) | Non-systematic Assessment |
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| ASYMPTOMATIC BACTERIURIA | Infections and infestations | MedDRA (13.1) | Non-systematic Assessment |
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| GASTROENTERITIS | Infections and infestations | MedDRA (13.1) | Non-systematic Assessment |
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| NASOPHARYNGITIS | Infections and infestations | MedDRA (13.1) | Non-systematic Assessment |
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| ORAL HERPES | Infections and infestations | MedDRA (13.1) | Non-systematic Assessment |
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| OTITIS EXTERNA | Infections and infestations | MedDRA (13.1) | Non-systematic Assessment |
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| PHARYNGITIS | Infections and infestations | MedDRA (13.1) | Non-systematic Assessment |
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| RESPIRATORY TRACT INFECTION | Infections and infestations | MedDRA (13.1) | Non-systematic Assessment |
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| RHINITIS | Infections and infestations | MedDRA (13.1) | Non-systematic Assessment |
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| TONSILLITIS | Infections and infestations | MedDRA (13.1) | Non-systematic Assessment |
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| URINARY TRACT INFECTION | Infections and infestations | MedDRA (13.1) | Non-systematic Assessment |
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| VAGINITIS BACTERIAL | Infections and infestations | MedDRA (13.1) | Non-systematic Assessment |
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| TOXICITY TO VARIOUS AGENTS | Injury, poisoning and procedural complications | MedDRA (13.1) | Non-systematic Assessment |
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| ACTIVATED PARTIAL THROMBOPLASTIN TIME PROLONGED | Investigations | MedDRA (13.1) | Non-systematic Assessment |
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| BLOOD FIBRINOGEN INCREASED | Investigations | MedDRA (13.1) | Non-systematic Assessment |
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| BACK PAIN | Musculoskeletal and connective tissue disorders | MedDRA (13.1) | Non-systematic Assessment |
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| BURSITIS | Musculoskeletal and connective tissue disorders | MedDRA (13.1) | Non-systematic Assessment |
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| DIZZINESS | Nervous system disorders | MedDRA (13.1) | Non-systematic Assessment |
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| HEADACHE | Nervous system disorders | MedDRA (13.1) | Non-systematic Assessment |
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| COUGH | Respiratory, thoracic and mediastinal disorders | MedDRA (13.1) | Non-systematic Assessment |
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| OROPHARYNGEAL PAIN | Respiratory, thoracic and mediastinal disorders | MedDRA (13.1) | Non-systematic Assessment |
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| RHINORRHOEA | Respiratory, thoracic and mediastinal disorders | MedDRA (13.1) | Non-systematic Assessment |
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| ERYTHEMA | Skin and subcutaneous tissue disorders | MedDRA (13.1) | Non-systematic Assessment |
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| PRURITUS | Skin and subcutaneous tissue disorders | MedDRA (13.1) | Non-systematic Assessment |
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| RASH | Skin and subcutaneous tissue disorders | MedDRA (13.1) | Non-systematic Assessment |
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| URTICARIA | Skin and subcutaneous tissue disorders | MedDRA (13.1) | Non-systematic Assessment |
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| HAEMATOMA | Vascular disorders | MedDRA (13.1) | Non-systematic Assessment |
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| PERIPHERAL COLDNESS | Vascular disorders | MedDRA (13.1) | Non-systematic Assessment |
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No publication related to study results will be made without Sponsor's prior written approval. Any proposed publication or presentation will be submitted to Sponsor for review 60 days in advance of publication. Institution will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for an additional 60 days to preserve intellectual property.
| D014777 |
| Virus Diseases |
| D018177 | Flavivirus Infections |
| D018178 | Flaviviridae Infections |
| D012327 | RNA Virus Infections |
| D006482 | Hemorrhagic Fevers, Viral |
| Fever: Moderate |
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| Fever: Severe |
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| Headache: Mild |
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| Headache: Moderate |
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| Headache: Severe |
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| Muscle pain: Mild |
|
| Muscle pain: Moderate |
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| Muscle pain: Severe |
|
| Joint pain: Mild |
|
| Joint pain: Moderate |
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| Joint pain: Severe |
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| Eye pain: Mild |
|
| Eye pain: Moderate |
|
| Eye pain: Severe |
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| Photophobia: Mild |
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| Photophobia: Moderate |
|
| Photophobia: Severe |
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| Fatigue: Mild |
|
| Fatigue: Moderate |
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| Fatigue: Severe |
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| Body Rash: Mild |
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| Body Rash: Moderate |
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| Body Rash: Severe |
|
| Nausea: Mild |
|
| Nausea: Moderate |
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| Nausea: Severe |
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| Vomiting: Mild |
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| Vomiting: Moderate |
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| Vomiting: Severe |
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| Other: Mild |
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| Other: Moderate |
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| Other: Severe |
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| Systemic solicited AEs |
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| Systemic unsolicited AEs |
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| Day 14 TDV-2 (n=19, 5, 21, 3, 21, 4, 18, 5) |
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| Day 14 TDV-3 (n=19, 5, 21, 3, 21, 4, 18, 5) |
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| Day 14 TDV-4 (n=19, 5, 21, 3, 21, 4, 18, 5) |
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| Day 30 TDV-1(n=19, 5, 21, 3, 21, 4, 18, 5) |
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| Day 30 TDV-2 (n=19, 5, 21, 3, 21, 4, 18, 5) |
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| Day 30 TDV-3 (n=19, 5, 21, 3, 21, 4, 18, 5) |
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| Day 30 TDV-4 (n=19, 5, 21, 3, 21, 4, 18, 5) |
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| Day 60 TDV-1 (n=19, 5, 21, 3, 19, 4, 18, 5) |
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| Day 60 TDV-2 (n=19, 5, 21, 3, 19, 4, 18, 5) |
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| Day 60 TDV-3 (n=19, 5, 21, 3, 19, 4, 18, 5) |
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| Day 60 TDV-4 (n=19, 5, 21, 3, 19, 4, 18, 5) |
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| Day 90 TDV-1 (n=19, 5, 21, 3, 19, 4, 17, 3) |
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| Day 90 TDV-2 (n=19, 5, 21, 3, 19, 4, 17, 3) |
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| Day 90 TDV-3 (n=19, 5, 21, 3, 19, 4, 17, 3) |
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| Day 90 TDV-4 (n=19, 5, 21, 3, 19, 4, 17, 3) |
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| Day 104 TDV-2 (n=19, 5, 21, 3, 18, 4, 17, 3) |
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| Day 104 TDV-3 (n=19, 5, 21, 3, 18, 4, 17, 3) |
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| Day 104 TDV-4 (n=19, 5, 21, 3, 18, 4, 17, 3) |
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| Day 120 TDV-1(n=19, 5, 21, 3, 19, 4, 17, 3) |
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| Day 120 TDV-2 (n=19, 5, 21, 3, 19, 4, 17, 3) |
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| Day 120 TDV-3 (n=19, 5, 21, 3, 19, 4, 17, 3) |
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| Day 120 TDV-4 (n=19, 5, 21, 3, 19, 4, 17, 3) |
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| Day 14 TDV-2 (n=19, 5, 21, 3, 21, 4, 18, 5) |
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| Day 14 TDV-3 (n=19, 5, 21, 3, 21, 4, 18, 5) |
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| Day 14 TDV-4 (n=19, 5, 21, 3, 21, 4, 18, 5) |
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| Day 30 TDV-1 (n=19, 5, 21, 3, 21, 4, 18, 5) |
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| Day 30 TDV-2 (n=19, 5, 21, 3, 21, 4, 18, 5) |
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| Day 30 TDV-3 (n=19, 5, 21, 3, 21, 4, 18, 5) |
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| Day 30 TDV-4 (n=19, 5, 21, 3, 21, 4, 18, 5) |
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| Day 60 TDV-1 (n=19, 5, 21, 3, 19, 4, 18, 5) |
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| Day 60 TDV-2 (n=19, 5, 21, 3, 19, 4, 18, 5) |
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| Day 60 TDV-3 (n=19, 5, 21, 3, 19, 4, 18, 5) |
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| Day 60 TDV-4 (n=19, 5, 21, 3, 19, 4, 18, 5) |
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| Day 90 TDV-1 (n=19, 5, 21, 3, 19, 4, 17, 3) |
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| Day 90 TDV-2 (n=19, 5, 21, 3, 19, 4, 17, 3) |
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| Day 90 TDV-3 (n=19, 5, 21, 3, 19, 4, 17, 3) |
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| Day 90 TDV-4 (n=19, 5, 21, 3, 19, 4, 17, 3) |
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| Day 104 TDV-2 (n=19, 5, 21, 3, 18, 4, 17, 3) |
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| Day 104 TDV-3 (n=19, 5, 21, 3, 18, 4, 17, 3) |
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| Day 104 TDV-4 (n=19, 5, 21, 3, 18, 4, 17, 3) |
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| Day 120 TDV-1 (n=19, 5, 21, 3, 19, 4, 17, 3) |
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| Day 120 TDV-2 (n=19, 5, 21, 3, 19, 4, 17, 3) |
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| Day 120 TDV-3 (n=19, 5, 21, 3, 19, 4, 17, 3) |
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| Day 120 TDV-4 (n=19, 5, 21, 3, 19, 4, 17, 3) |
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| Day 180 TDV-2 |
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| Day 180 TDV-3 |
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| Day 180 TDV-4 |
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| Day 270 TDV-1 |
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| Day 270 TDV-2 |
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| Day 270 TDV-3 |
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| Day 270 TDV-4 |
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| Day 7 TDV-2 (n= 19, 5, 21, 3, 21, 4, 18, 5) |
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| Day 9 TDV-2 (n= 19, 5, 21, 3, 21, 4, 18, 5) |
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| Day 11 TDV-2 (n= 19, 5, 21, 3, 21, 4, 18, 5) |
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| Day 14 TDV-2 (n= 19, 5, 21, 3, 21, 4, 18, 5) |
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| Day 97 TDV-2 (n= 19, 5, 21, 3, 21, 3, 17, 3) |
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| Day 99 TDV-2 (n= 19, 5, 21, 3, 21, 3, 17, 3) |
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| Day 101 TDV-2 (n= 19, 5, 21, 3, 21, 3, 17, 3) |
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| Day 104 TDV-2 (n= 19, 5, 21, 3, 18, 4, 17, 3) |
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| Day 5 TDV-3 (n= 19, 5, 21, 3, 21, 4, 18, 5) |
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| Day 7 TDV-3 (n= 19, 5, 21, 3, 21, 4, 18, 5) |
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| Day 9 TDV-3 (n= 19, 5, 21, 3, 21, 4, 18, 5) |
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| Day 97 TDV-3 (n= 19, 5, 21, 3, 19, 4, 17, 3) |
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| Day 99 TDV-3 (n= 19, 5, 21, 3, 19, 4, 17, 3) |
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| Day 101 TDV-3 (n= 19, 5, 21, 3, 19, 4, 17, 3) |
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| Day 7 TDV-4 (n= 19, 5, 21, 3, 21, 4, 18, 5) |
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| Day 97 TDV-4 (n= 19, 5, 21, 3, 19, 4, 17, 3) |
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