Phase 1b Study Investigating Safety & Immunogenicity of TDV Given Intradermally by Needle or Needle-Free PharmaJet Injector

Study Overview
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Brief Summary
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The purpose of this study is to compare the safety, tolerability and immunogenicity of Takeda's Tetravalent Dengue Vaccine Candidate (TDV) [previously DENVax] when administered intradermally in varied dosing schedules and via different methods of administration (conventional needle/syringe versus needle-free PharmaJet® injector).

Detailed Description
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This is an exploratory trial to assess the safety, tolerability and immunogenicity of vaccination with a tetravalent dengue vaccine (TDV) in healthy adults delivered intradermally using the conventional needle/syringe or a needle-free PharmaJet® injector. Two (2) intradermal injections of either vaccine or placebo will be administered to qualified participants (one in each arm) on Day 0 of the study. A subsequent injection will also be given on Day 90 with either vaccine or placebo (in one arm only). Participants will be evaluated for safety and dengue neutralizing antibody to all four serotypes. All participants will also be evaluated for injection site reactions and have blood drawn for viremia, neutralizing antibodies, cell mediated immunity and innate immunity. Participants will be required to participate for approximately 10 months from recruitment and collection of data for primary outcomes (through Day 120) including collection of additional samples for measurement of longer term antibody titers (through Day 270). This project has been funded in whole or in part with Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under Contract No. HHSN272201000034C.

Official Title
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Phase 1b, Partial-Blind, Parallel Group, Randomized Study to Investigate the Safety and Immunogenicity of a Tetravalent Chimeric Dengue Vaccine (DENVax) Administered Intradermally Using Needle or a Needle-Free PharmaJet® Injector in Healthy Adults

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Biological: TDV
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: In good health as determined by medical history and physical examination (including blood pressure and heart rate). Negative for human immunodeficiency virus-1 (HIV-1) antibodies, Hepatitis C antibodies & Hepatitis B surface antigen. Females negative by urine pregnancy test at screening and immediately prior to injection, and were willing to use reliable means of contraception. Body Mass Index (BMI) ≤ 35 kg/m^2. Exclusion Criteria: Any Grade 2 or above abnormality in the screening laboratory tests. History of Dengue Fever, Japanese Encephalitis, West Nile or Yellow Fever disease. Seropositivity to dengue or West Nile virus. Extensive scarring or tattoo (> 50%) on arms, shoulders, neck face and head. History of significant dermatologic disease in the last 6 months. Receipt or planned receipt of any vaccine in the 4 weeks preceding or following the Day 0 or 90 vaccinations. Any planned travel to dengue endemic areas including the Caribbean, Mexico, Central America, South America or Southeast Asia, during the study period and during the month prior to screening. Use of systemic corticosteroids therapy within the previous 6 months (at a dose of 0.5 mg/kg/day). Topical prednisone is not permitted if currently in use or used within the last month prior to the first vaccination. Use of any prescribed medication 7 days before the first injection. Previous vaccination in a clinical study or with an approved product against Dengue Fever, Yellow Fever and or Japanese Encephalitis. Known or suspected congenital or acquired immunodeficiency or receipt of immunosuppressive therapy in the last 6 months. Planned donation of blood during the period of the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1: TDV using PharmaJet® Injector<br>Takeda's Tetravalent Dengue Vaccine Candidate (TDV) [previously DENVax] one dose injection in arm 1 and placebo: phosphate buffered saline (PBS) one dose injection in arm 2, using needle-free PharmaJet® Injector, intradermal, on Day 0 and TDV, injection using needle-free PharmaJet® Injector, intradermal, one dose on Day 90. | Biological: TDV<br>* TDV suspension for intradermal administration<br>Drug: Placebo<br>* Phosphate buffered saline (PBS)<br>|
| Experimental: Group 2: TDV using PharmaJet® Injector<br>TDV injection, one dose in each arm, using needle-free PharmaJet® Injector, intradermal, on Day 0 and placebo: PBS, injection using needle-free PharmaJet® Injector, intradermal, one dose on Day 90. | Biological: TDV<br>* TDV suspension for intradermal administration<br>Drug: Placebo<br>* Phosphate buffered saline (PBS)<br>|
| Experimental: Group 3: TDV using Needle and Syringe<br>TDV one dose injection in arm 1 and placebo: PBS one dose injection in arm 2, using needle and syringe, intradermal, on Day 0 and TDV injection using needle and syringe, intradermal, one dose on Day 90. | Biological: TDV<br>* TDV suspension for intradermal administration<br>Drug: Placebo<br>* Phosphate buffered saline (PBS)<br>|
| Experimental: Group 4: TDV using PharmaJet® Injector<br>TDV injection, one dose in each arm, using needle-free PharmaJet® Injector, intradermal, on Day 0 and TDV, injection using needle-free PharmaJet® Injector, intradermal, one dose on Day 90. | Biological: TDV<br>* TDV suspension for intradermal administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Local (Injection Site) Adverse Events (AEs) After Either Vaccine Dose by Maximum Severity as Assessed by the Clinical Staff | An AE is defined as any untoward medical occurrence in a patient or clinical trial participant administered a pharmaceutical product regardless of its causal relationship to the study treatment. Local injection site reactions were evaluated by the blinded clinical staff and include: erythema (redness), edema/induration (swelling), pain and pruritus (itching). Severity grades for erythema and edema are derived based on the Division of Microbiology and Infectious Diseases (DMID) toxicity grading longest diameters using the scale 0=none, 1=<15 millimeters (mm), 2=15 to 30 mm and 3=>30 mm (severe). Pain and itching were graded using the scale: 0=none to 4=requires ER visit or hospitalization. Local injection site reactions are presented as the percentage of participants experiencing a reaction, by reaction type, overall and by severity, using the participant's worst reported severity grade. Only categories for which there was at least 1 participant are reported. | 28 Days after each dose | 
| Percentage of Participants With Unsolicited Adverse Events (AE) by Maximum Severity | An AE is defined as any untoward medical occurrence in a patient or clinical trial participant administered a pharmaceutical product regardless of its causal relationship to the study treatment. AEs are graded from Grade 0=None to Grade 4=Life threatening. AEs are presented as the percentage of participants experiencing an AE, overall and by severity, using the participant's worst reported severity grade. | 28 Days after each dose | 
| Percentage of Participants With Solicited Systemic AEs as Reported by the Participant Using a Memory Aid 14 Days After Either Vaccine Dose by Maximum Severity | An AE is defined as any untoward medical occurrence in a patient or clinical trial participant administered a pharmaceutical product regardless of its causal relationship to the study treatment. Systemic AEs solicited from the participant using a memory aid included: body temperature, headache, myalgia (muscle pain), arthralgia (joint pain), photophobia (sensitivity to light), fatigue (tiredness), body rash, nausea and vomiting. Systemic AEs were graded using the scale: Grade 0= none to Grade 4=Life threatening. Systemic reactions are presented as percentage of participants experiencing a reaction, by reaction type, overall and by severity, using the participant's worst reported severity grade. Only categories for which there was at least 1 participant are reported. | 14 days after each dose | 
| Percentage of Participants With Solicited Local AEs as Reported by the Participant Using a Memory Aid 14 Days After Either Vaccine Dose by Maximum Severity | An AE is defined as any untoward medical occurrence in a patient or clinical trial participant administered a pharmaceutical product regardless of its causal relationship to the study treatment. Local injection site AEs solicited from the participant using a memory aid included: erythema (redness), edema/induration (swelling), pain and pruritus (itching). Local injection site reactions are presented as the percentage of participants experiencing a reaction, by reaction type, overall and by severity, using the participant's worst reported severity grade. | 14 days after each dose | 
| Percentage of Participants With Unsolicited Vaccine-Related AEs Within 28 Days After Either Vaccine Dose by Maximum Severity | An AE is defined as any untoward medical occurrence in a patient or clinical trial participant administered a pharmaceutical product regardless of its causal relationship to the study treatment. AEs are graded from Grade 0=None to Grade 4=Life threatening. AEs are presented as the percentage of participants experiencing an AE causally related to the study treatment as assessed by the investigator, overall and by severity, using the participant's worst reported severity grade. Only categories for which there was at least 1 participant are reported. | 28 Days after each dose | 
| Percentage of Participants With Abnormal Laboratory Values Reported as Adverse Events (AEs) | The percentage of participants with any clinically relevant abnormal safety laboratory values (chemistry, hematology and urinalysis) collected from vaccine dose 1 (Day 0) through 28 days after dose 2 (Day 90) that were reported as AEs. Abnormal laboratory values were reported as AEs based on the following criteria: Grade 3 (Severe) or Grade 4 (Life threatening) laboratory abnormalities based on DMID toxicity tables or laboratory abnormalities which resulted in a medical intervention. | 118 Days | 
| Seroconversion Rates (SCR) for Each of the Four Dengue Serotypes After First Injection | Seroconversion rate is defined as the percentage of participants with PRNT50 titer ≥ 10 or, if the titer on Day 0 is greater than 10, a four-fold rise in antibody titer. | Day 28 | 
| Seroconversion Rates (SCR) for Each of the Four Dengue Serotypes After Second Injection | Seroconversion rate is defined as the percentage of participants with PRNT50 titer ≥ 10 or, if the titer on Day 0 is greater than 10, a four-fold rise in antibody titer. | Day 118 | 
| Percentage of Participants With Unsolicited Vaccine-Related SAEs | A serious adverse event (SAE) is any AE in the view of the investigator that results in any of the following outcomes: death, life threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that may require medical or surgical intervention to prevent one of the other serious outcomes. | Dose 1 until 28 days after Dose 2 (Up to Day 118) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Titers of Neutralizing Antibody Titers Against Each of the Four Dengue Serotypes |  | Days 0, 28, 90, 118 and 270 | 
| Seroconversion Rates (SCR) for Each of the Four Dengue Serotypes at Days 90 and 270 | Seroconversion rate is defined as the percentage of participants with PRNT50 titer ≥ 10 or, if the titer on Day 0 is greater than 10, a four-fold rise in antibody titer. | Days 90 and 270 | 
| Percentage of Participants With Serotype-Specific DENVax RNA Detected Due to Each of the Four Dengue Vaccine Components After Each Vaccination | A quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) assay was used for detection and serotype identification of dengue viral ribonucleic acid (RNA) that is present in serum. A test for viremia is considered positive if the assay value is >= 3.6, which is the limit of quantification (LOQ), negative if the assay value was zero, and undetermined if the assay value is >0 but <3.6. The percentage of participants with positive results is reported. | Day 0 to Day 104 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prophylactic vaccination