Clinical trial NCT03746015: Immunogenicity and Safety of Tetravalent Dengue Vaccine Candidate (TDV) in Flavivirus-Naïve and Dengue-Immune Adults
Official title: An Open-Label, Phase 2 Trial to Investigate the Humoral and Cell-Mediated Immune Responses and Safety of a Tetravalent Dengue Vaccine Candidate (TDV) Administered Subcutaneously in Flavivirus-Naïve and Dengue-Immune Healthy Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Dengue Fever
Keywords: Vaccine
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2018-11-19
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to assess the neutralizing antibody response against each dengue serotype post-vaccination.

Detailed description: The vaccine being tested in this study is Takeda's Tetravalent Dengue Vaccine Candidate (TDV). TDV is being tested to protect people against dengue fever. This study will look at the immunogenicity and safety of TDV in flavivirus-naïve and dengue-immune adults.

The study will enroll approximately 44 patients. Participants will be categorized into two groups based on results from serological testing performed by the trial center outside the scope of this trial (up to 70 days \[10 weeks\] prior to Day 1 \[Month 0\]):

Group 1: Flavivirus-Naïve Participants Group 2: Dengue-Immune Participants

All participants will receive subcutaneous injection of TDV on Day 1 (Month 0) and Day 90 (Month 3).

This trial will be conducted in the United States. The overall time to participate in this study is 12 months. Participants will make multiple visits to the clinic, and 9 months after last dose of study drug for a follow-up assessment.

Eligibility criteria: Inclusion Criteria:

1. Who are in good health at the time of entry into the trial as determined by medical history, physical examination (including vital signs) and clinical judgment of the investigator.
2. Group 1 only: immunologically naïve to dengue, Zika, Yellow Fever (YF), Japanese Encephalitis (JE), West Nile (WN) (based on negative results for detection of anti-DENV, anti-Zika, anti-YF, anti-JE, anti-WN antibodies) as documented by serological testing performed by the trial center outside the scope of this trial (up to 70 days \[10 weeks\] prior to Day 1 \[Month 0\]).
3. Group 2 only: serology consistent with primary infection with either DENV-1 or DENV-3 (defined as detectable neutralizing antibodies against DENV-1 or DENV-3 only, or titers for DENV-1 or DENV-3 ≥4-times higher than titers for the 2 other dengue serotypes) as documented by serological testing performed by the trial center outside the scope of this trial (up to 70 days \[10 weeks\] prior to Day 1 \[Month 0\]).

Exclusion Criteria:

1. Has clinically active significant infection (as assessed by the investigator) or body temperature ≥38°C (100.4°F) within 3 days of the intended date of vaccination.
2. Has history of progressive or severe neurologic disorder, seizure disorder or neuro-inflammatory disease (eg, Guillain-Barré syndrome).
3. Known or suspected impairment/alteration of immune function including:

   1. Chronic use of oral steroids (equivalent to 20 mg/day prednisone ≥12 weeks and/or ≥2 mg/kg body weight/day prednisone ≥2 weeks) within 60 days prior to Day 1 (Month 0) (use of inhaled, intranasal, or topical corticosteroids is allowed).
   2. Receipt of parenteral steroids (equivalent to 20 mg/day prednisone ≥12 weeks and/or ≥2 mg/kg body weight/day prednisone ≥2 weeks) within 60 days prior to Day 1 (Month 0).
   3. Administration of immunoglobulins and/or any blood products within 3 months prior to Day 1 (Month 0) or planned administration during the trial.
   4. Receipt of immunostimulants within 60 days prior to Day 1 (Month 0).
   5. Immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within 6 months prior to Day 1 (Month 0).
   6. Known Human Immunodeficiency Virus (HIV) infection or HIV-related disease.
   7. Hepatitis C virus infection.
   8. Genetic immunodeficiency.
4. Has planned vaccination (during the trial conduct) against any non-dengue flavivirus (eg, Zika, YF, JE, WN, tick-borne encephalitis, or Murray-Valley encephalitis).
5. Planned travel (during the trial conduct) to any area endemic for dengue.

Primary outcomes:
measure: Geometric Mean Titers (GMT) of Neutralizing Antibodies for Each of the Four Dengue Serotypes at Day 15
timeFrame: Day 15
measure: GMT of Neutralizing Antibodies for Each of the Four Dengue Serotypes at Day 30 (Month 1)
timeFrame: Day 30 (Month 1)
measure: GMT of Neutralizing Antibodies for Each of the Four Dengue Serotypes at Day 60 (Month 2)
timeFrame: Day 60 (Month 2)
measure: GMT of Neutralizing Antibodies for Each of the Four Dengue Serotypes at Day 90 (Month 3)
timeFrame: Day 90 (Month 3)
measure: GMT of Neutralizing Antibodies for Each of the Four Dengue Serotypes at Day 105
timeFrame: Day 105
measure: GMT of Neutralizing Antibodies for Each of the Four Dengue Serotypes at Day 120 (Month 4)
timeFrame: Day 120 (Month 4)
measure: GMT of Neutralizing Antibodies for Each of the Four Dengue Serotypes at Day 150 (Month 5)
timeFrame: Day 150 (Month 5)
measure: GMT of Neutralizing Antibodies for Each of the Four Dengue Serotypes at Day 180 (Month 6)
timeFrame: Day 180 (Month 6)
measure: GMT of Neutralizing Antibodies for Each of the Four Dengue Serotypes at Day 270 (Month 9)
timeFrame: Day 270 (Month 9)
measure: GMT of Neutralizing Antibodies for Each of the Four Dengue Serotypes at Day 360 (Month 12)
timeFrame: Day 360 (Month 12)
Secondary outcomes:
measure: Percentage of Participants With Interferon-gamma (IFN-γ) Enzyme-linked Immunospot (ELISpot) Responses to Tetravalent Dengue Vaccine (TDV)
timeFrame: Days 30 (Month 1), 90 (Month 3), 120 (Month 4), 180 (Month 6), 360 (Month 12)
measure: Magnitude of Cellular Immune Response Assessed by Number of Spot Forming Cells [SFC]/10^6 Peripheral Blood Mononuclear Cells (PBMCs) Measured by IFN-γ ELISpot Responses to TDV
timeFrame: Days 30 (Month 1), 90 (Month 3), 120 (Month 4), 180 (Month 6), 360 (Month 12)
measure: Phenotype Characterization of Cellular Immune Response to TDV Assessed as Percentage of Total CD4+ T Cells by Intracellular Cytokine Staining (ICS)
timeFrame: Days 15, 30 (Month 1), 90 (Month 3), 105, 120 (Month 4), and 360 (Month 12)
measure: Phenotype Characterization of Cellular Immune Response to TDV Assessed as Percentage of Total CD8+ T Cells by Intracellular Cytokine Staining (ICS)
timeFrame: Days 15, 30 (Month 1), 90 (Month 3), 105, 120 (Month 4), and 360 (Month 12)
measure: Percentage of Participants With Vaccine Viremia for Each of the Four Vaccine Strains After Vaccination
timeFrame: Days 6, 9, 12, 15, 30 (Month 1), 90 (Month 3), 96, 99, 102, 105, 120 (Month 4)
measure: Duration of Vaccine Viremia for Each of the Four Vaccine Strains After Vaccination
timeFrame: Up to Day 120 (Month 4)
measure: Level of Vaccine Viremia for Each of the Four Vaccine Strains After Vaccination
timeFrame: Days 6, 9, 12, and 15
measure: Percentage of Participants With Solicited Local (Injection Site) Reactions Following Each Vaccination
timeFrame: Within 7 days after each of the vaccine dose given on Day 1 (Month 0) and 90 (Month 3)
measure: Percentage of Participants With Solicited Systemic Reactions Following Each Vaccination
timeFrame: Within 14 days after each of the vaccine dose given on Day 1 (Month 0) and 90 (Month 3)
measure: Percentage of Participants With at Least One Unsolicited Adverse Events (AEs) Following Each Vaccination
timeFrame: Up to 28 days (day of vaccination + 27 days) after administration of each vaccine dose given on Day 1 (Month 0) and 90 (Month 3)
measure: Percentage of Participants With Serious Adverse Events (SAEs)
timeFrame: From first vaccination (Day 1) through end of study (Day 360 [Month 12])
measure: Percentage of Participants With Medically Attended AEs (MAAEs)
timeFrame: From first vaccination (Day 1) through end of study (Day 360 [Month 12])
Other outcomes:
Locations:
city: Peoria
country: United States
facility: Optimal Research
state: Illinois
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
Study officials:
affiliation: Takeda
name: Medical Director
role: STUDY_DIRECTOR
References: