Clinical Trial: Safety and Immunogenicity of Three Formulations of Takeda's Tetravalent Dengue Vaccine Candidate (TDV)

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Randomized, Double Blind, Phase 2 Study to Assess the Safety and Immunogenicity of Three Formulations of Takeda's Tetravalent Dengue Vaccine Candidate (TDV) in Healthy A

Brief Summary: The purpose of this study is to evaluate the equivalence of the lyophilized formulation of Takeda's Tetravalent Dengue Vaccine Candidate (TDV) compared with the liquid formulation of TDV.

Detailed Summary:

The vaccine being tested in this study is Takeda's Tetravalent Dengue Vaccine Candidate (TDV). This study is designed to determine whether the lyophilized formulation provides equivalent safety and immunogenicity as the original liquid formulation. An exploratory analysis has been added for the purpose of understanding whether there is a manufacturing or formulation effect on the vaccine.

The study will enroll approximately 1000 participants. Participants will be randomly assigned (by chance, like flipping a coin) to one of the four study groups—which will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need):

• Group A: TDV Liquid Formulation 1, subcutaneous (SC) injection on Day 1 and placebo (dummy) SC at Month 3 - this is a liquid that looks like the study drug but has no active ingredient
• Group B: TDV Liquid Formulation 1, SC injection Day 1 and Month 3
• Group C: TDV Liquid Formulation 2, SC injection Day 1 and Month 3
• Group D: TDV Lyophilized formulation SC injection Day 1 and Month 3

In order to keep the treatment arms undisclosed to the participant and the doctor, participants will receive a placebo injection at any study visit where TDV is not being administered (Month 3). Participants will be asked to record any adverse events that may be related to the vaccine or the injection in a diary card for 28 days after each vaccination.

This multi-center trial will be conducted in the United States. The overall time to participate in this study is up to 10 months. Participants will make 9 visits to the clinic including a
Sponsor: Takeda

Current Primary Outcome: Geometric Mean Titer (GMT) of Neutralizing Antibodies for Each of the Four Dengue Serotypes Comparing Group D To Groups A and B Combined [ Time Frame: Month 1 ]

Original Primary Outcome: Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the Four DENV Serotypes Comparing Treatment Group D with Treatment Groups A and B Combined [ Time Frame: Month 1 ]

Current Secondary Outcome:

• Geometric Mean Titers (GMT) of Neutralizing Antibodies for Each of the Four Dengue Serotypes Comparing Group D With Group B [ Time Frame: Months 1 and 4 ]
  Geometric mean titer (GMT) of neutralizing antibodies for each of the four dengue serotypes as measured by Plaque Reduction Neutralization Test resulting in 50% reduction in Plaques (PRNT50). The four dengue serotypes are DEN-1, DEN-2, DEN-3 and DEN-4. ANOVA model for the natural log-transformed GMT at month 1 with study group as a factor was used for analysis.
• Percentage of Participants With a Seropositive Response for Each of the Four Dengue Serotypes Comparing Group D With Groups A and B Combined [ Time Frame: Month 1 ]
  A seropositive response is defined as a reciprocal neutralizing titer ≥ 10. The four dengue serotypes are DEN-1, DEN-2, DEN-3 and DEN-4.
• Percentage of Participants With a Seropositive Response for Each of the Four Dengue Serotypes Comparing Group D With Group B [ Time Frame: Months 1 and 4 ]
  A seropositive response is defined as a reciprocal neutralizing titer ≥ 10. The four dengue serotypes are DEN-1, DEN-2, DEN-3 and DEN-4.
• Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) [ Time Frame: Days 1 through 7 after each vaccination ]
  Solicited local AEs at injection site are defined as pain, erythema and swelling that occurred at least once within 7 days after either vaccination, as recorded by the participants in a diary. Percentages are based on the number of participants with diary data available.
• Percentage of Participants With Solicited Systemic Adverse Events (AEs) [ Time Frame: Days 1 through 14 after each vaccination ]
  Solicited systemic AEs are defined as asthenia, fever, headache, malaise, and myalgia that occurred at least once within 14 days after either vaccination, as recorded by the participants in a diary. Percentages are based on the number of participants with diary data available.
• Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) by Severity [ Time Frame: Days 1 through 7 after each vaccination ]
  The percentage of participants with solicited local AEs at injection site of varying severity are reported. Solicited local AEs are defined as pain, erythema and swelling that occurred at least once within 7 days after either vaccination, as recorded by the participants in a diary. Participants with multiple episodes are categorized using the highest severity level. Percentages are based on the number of participants with diary data available.
• Percentage of Participants With Solicited Systemic Adverse Events (AEs) by Severity [ Time Frame: Days 1 through 14 after each vaccination ]
  The percentage of participants with solicited systemic AEs of varying severity are reported. Solicited systemic AEs are defined as asthenia, fever, headache, malaise, and myalgia that occurred at least once within 14 days after either vaccination, as recorded by the participants in a diary. Participants with multiple episodes are categorized using the highest severity level. Percentages are based on the number of participants with diary data available.
• Percentage of Participants With Any Unsolicited Adverse Events (AEs) [ Time Frame: Up to Day 28 after each vaccination ]
  Unsolicited AEs are any AEs that are not solicited local or systemic AEs, as defined by this study, that occurred at least once within 28 days after either vaccination. An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. The investigator assessed whether the AE was related to the study vaccination.
• Percentage of Participants With Serious Adverse Events (SAEs) [ Time Frame: Up to 6 Months after the last dose (9 months) ]
  A serious adverse event (SAE) is defined as any untoward medical occurrence or effect that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability / incapacity, is a congenital anomaly / birth defect or is medically important due to other reasons than the above mentioned criteria.
• Percentage of Participants With Markedly Abnormal Laboratory Values in the Safety Sub-Set [ Time Frame: Days 8, 15, 91, 97 and 104 ]
  Percentage of participants with markedly abnormal standard safety laboratory values collected at any time after the first vaccination.

Original Secondary Outcome:

• Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the Four DENV Serotypes Comparing Treatment Group D with Treatment Group B [ Time Frame: Months 1 and 4 ]
  GMTs of neutralizing antibodies will be measured via Plaque Reduction Neutralization Test 50% (PRNT50). The four DENV serotypes are DEN-1, DEN-2, DEN-3 and DEN-4.
• Percentage of Participants with a Seroresponse for Each of the Four DENV Serotypes Comparing Treatment Group D with Treatment Groups A and B Combined [ Time Frame: Month 1 ]
  Seroconversion is defined as a reciprocal neutralizing titer ≥ 10.
• Percentage of Participants with a Seroresponse for Each of the Four DENV Serotypes Comparing Treatment Group D with Treatment Group B [ Time Frame: Months 1 and 4 ]
  Seroconversion is defined as a reciprocal neutralizing titer ≥ 10.
• Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) [ Time Frame: Days 1 through 7 after each vaccination ]
  Solicited local AEs at injection site are defined as pain, erythema and swelling that occurred within 7 days after each vaccination.
• Percentage of Participants With Solicited Systemic Adverse Events (AEs) [ Time Frame: Days 1 through 14 after each vaccination ]
  Solicited systemic AEs at injection site are defined as headache, malaise, myalgia, asthenia and fever that occurred within 14 days after each vaccination.
• Severity of Solicited Local (Injection Site) Adverse Events (AEs) [ Time Frame: Days 1 through 7 after each vaccination ]
  Solicited local AEs at injection site are defined as pain, erythema and swelling that occurred within 7 days after each vaccination.
• Severity of Solicited Systemic Adverse Events (AEs) [ Time Frame: Days 1 through 14 after each vaccination ]
  Solicited systemic AEs at injection site are defined as headache, malaise, myalgia, asthenia and fever that occurred within 14 days after each vaccination.
• Percentage of Participants With Any Unsolicited Adverse Events (AEs) [ Time Frame: Up to Day 28 after each vaccination ]
  Unsolicited AEs are any AEs that are not solicited local or systemic AEs, as defined by this study.
• Percentage of Participants With Serious Adverse Events (SAEs) [ Time Frame: Up to 6 Months after the last vaccination ]
  A serious adverse event (SAE) is any untoward medical occurrence or effect that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability / incapacity, is a congenital anomaly / birth defect or is medically important due to other reasons than the above mentioned criteria.
• Percentage of Participants with Abnormal Lab Tests Assessed in Half of the Participants in Each Treatment Group [ Time Frame: Days 1, 8, 15, and Month 3, Month 3 + 6 days (Day 97) and Month 3 + 13 days (Day 104) ]
  Percentage of participants with any markedly abnormal standard safety hematology and chemistry laboratory values collected throughout study.
• Severity of Abnormal Lab Tests Assessed in Half of the Participants in Each Treatment Group [ Time Frame: Days 1, 8, 15, and Month 3, Month 3 + 6 days (Day 97) and Month 3 + 13 days (Day 104) ]
  Severity of any markedly abnormal standard safety hematology and chemistry laboratory values collected throughout study.

Dates:
Date Received: July 15, 2014
Date Started: July 2014
Date Completion:
Last Updated: May 19, 2016
Last Verified: May 2016