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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02193087
Recruitment Status : Completed
First Posted : July 17, 2014
Results First Posted : June 29, 2016
Last Update Posted : June 20, 2019
Sponsor:
Information provided by (Responsible Party):
Takeda

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.

Condition or disease Intervention/treatment Phase
Dengue Fever Drug: TDV Liquid Formulation 1 Drug: TDV Liquid Formulation 2 Drug: TDV IDT Lyophilized Drug: Placebo Phase 2

Detailed Description:

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 final visit 1 month after last dose of study drug for a follow-up assessment. A follow up phone call will be done 6 months after the last dose to assess serious adverse events.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1002 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
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 Adults
Actual Study Start Date : August 6, 2014
Actual Primary Completion Date : May 19, 2015
Actual Study Completion Date : May 19, 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Dengue

Arm Intervention/treatment
Active Comparator: Group A: TDV Liquid + Placebo
Takeda's Tetravalent Dengue Vaccine Candidate (TDV) Liquid Formulation 1, diluted 1:5 with vaccine diluent, subcutaneous injection on Day 1, and TDV Liquid Formulation placebo-matching solution, subcutaneous injection, once on Day 90 (Month 3).
Drug: TDV Liquid Formulation 1
TDV Liquid Formulation 1 for subcutaneous injection

Drug: Placebo
TDV liquid formulation placebo-matching solution for subcutaneous injection

Active Comparator: Group B: TDV Liquid
TDV Liquid Formulation 1, diluted 1:5 with vaccine diluent, subcutaneous injection on Day 1 and Day 90 (Month 3).
Drug: TDV Liquid Formulation 1
TDV Liquid Formulation 1 for subcutaneous injection

Experimental: Group C: TDV Liquid
TDV Liquid Formulation 2, subcutaneous injection on Day 1 and Day 90 (Month 3).
Drug: TDV Liquid Formulation 2
TDV Liquid Formulation 2 for subcutaneous injection

Experimental: Group D: TDV Lyophilized
TDV Lyophilized Formulation reconstituted with water, subcutaneous injection on Day 1 and Day 90 (Month 3).
Drug: TDV IDT Lyophilized
TDV Lyophilized Formulation for subcutaneous injection




Primary Outcome Measures :
  1. 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 ]

    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.

    A 90% Confidence Interval (CI) for the ratio of GMT (or equivalently the difference of the log transformed GMT) was provided, for each serotype, for the comparison of the lyophilized formulation (Group D) versus the liquid formulation 1 (Groups A+B combined). An Analysis of Variance (ANOVA) model for the natural log-transformed GMT at month 1 with study group as a factor was used for analysis.



Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 49 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Is aged 18 to 49 years, at the time of enrollment inclusive.
  2. Individuals 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.
  3. Signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any trial procedures, after the nature of the trial has been explained according to local regulatory requirements.
  4. Individuals who can comply with trial procedures and are available for the duration of follow-up.

Exclusion Criteria:

  1. Febrile illness (temperature ≥ 38°C or 100.4°F) or moderate or severe acute illness or infection at the time of enrollment. Trial entry should be delayed until the illness has improved.
  2. History or any illness that, in the opinion of the investigator, might interfere with the results of the trial or pose additional risk to the participants due to participation in the trial, including but not limited to: a. Known hypersensitivity or allergy to any of the vaccine components; b. Individuals with history of substance or alcohol abuse within the past 6 months; c. Female participants who are pregnant or breastfeeding; d. Individuals with any serious chronic or progressive disease according to judgment of the investigator (e.g., neoplasm, insulin dependent diabetes, cardiac, renal or hepatic disease, neurologic or seizure disorder or Guillain-Barré syndrome); e. Known or suspected impairment/alteration of immune function, including: i. Chronic use of oral steroids (equivalent to 20 mg/day prednisone ≥ 12 weeks / ≥ 2 mg/kg body weight / day prednisone ≥ 2 weeks) within 60 days prior to Day 1 (use of inhaled, intranasal, or topical corticosteroids is allowed); Receipt of parenteral steroids (equivalent to 20 mg/day prednisone ≥ 12 weeks / ≥ 2 mg/kg body weight / day prednisone ≥ 2 weeks) within 60 days prior to Day 1; iii. Administration of immunoglobulins and/or any blood products within the three months preceding the first administration of the investigational vaccine or planned administration during the trial; iv. Receipt of immunostimulants within 60 days prior to Day 1; v. Immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within 6 months preceding (first) vaccination; vi. human immunodeficiency virus (HIV) infection or HIV-related disease; vii. Genetic immunodeficiency.
  3. Individuals who received any other vaccines within 14 days (for inactivated vaccines) or 28 days (for live vaccines) prior to enrollment in this trial or who are planning to receive any vaccine within 28 days of investigational vaccine administration.
  4. Individuals participating in any clinical trial with another investigational product 30 days prior to first trial visit or intent to participate in another clinical trial at any time during the conduct of this trial.
  5. Individuals who are first degree relatives of individuals involved in trial conduct.
  6. If female of childbearing potential, sexually active, and has not used any of the acceptable contraceptive methods for at least 2 months prior to trial entry: a. Of childbearing potential is defined as status post onset of menarche and not meeting any of the following conditions: menopausal (for at least 2 years), bilateral tubal ligation (at least 1 year previously), bilateral oophorectomy (at least 1 year previously) or hysterectomy; b. Acceptable birth control methods are defined as one or more of the following: i. Hormonal contraceptive (such as oral, injection, transdermal patch, implant, cervical ring); ii. Barrier (condom with spermicide or diaphragm with spermicide) each and every time during intercourse; iii. Intrauterine device (IUD); iv. Monogamous relationship with vasectomized partner. Partner must have been vasectomized for at least six months prior to the participants' trial entry.
  7. If female of childbearing potential, sexually active and refuses to use an acceptable contraceptive method through to 6 weeks after the last dose of investigational vaccine.
  8. Individuals with body mass index (BMI) greater than or equal to 35.
  9. Participants who received previous vaccination (in a clinical trial or with an approved product) against flaviviruses including dengue, yellow fever (YF), West Nile (WN), Japanese Encephalitis (JE), and St. Louis encephalitis.
  10. Documented or suspected disease caused by dengue, JE, WN, YF virus, and/or St. Louis encephalitis.
  11. History of travel to dengue endemic areas including the Caribbean, Mexico, Central America, South America or Southeast Asia during the 6 months prior to screening or planned travel to a dengue endemic area during the study period.
  12. Clinically significant abnormality in the screening laboratory tests as judged by the Investigator.
  13. History of recurring headaches or migraines (more frequent than once per week) or on prescription medication for treatment of recurring headaches or migraines.
  14. Blood tests positive for antibodies to HIV-1/2, Hepatitis C and Hepatitis B surface antigen.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02193087


Locations
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United States, Arizona
Hope Research Institute
Phoenix, Arizona, United States, 85018
United States, California
Anaheim Clinical Trials, LLC
Anaheim, California, United States, 92805
United States, Georgia
Clinical Research Atlanta
Stockbridge, Georgia, United States, 30281
United States, Idaho
Advanced Clinical Research
Meridian, Idaho, United States, 83462
United States, Kansas
Johnson County Clin-Trials
Lenexa, Kansas, United States, 66219
United States, Nevada
Clinical Research Center of Nevada
Las Vegas, Nevada, United States, 89104
United States, Texas
Tekton Research
Austin, Texas, United States, 78745
Sponsors and Collaborators
Takeda
Investigators
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Study Director: Medical Director Clinical Science Takeda

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Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT02193087     History of Changes
Other Study ID Numbers: DEN-106
U1111-1154-9746 ( Other Identifier: World Health Organization )
First Posted: July 17, 2014    Key Record Dates
Results First Posted: June 29, 2016
Last Update Posted: June 20, 2019
Last Verified: June 2019

Keywords provided by Takeda:
Drug therapy

Additional relevant MeSH terms:
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Dengue
Arbovirus Infections
Virus Diseases
Flavivirus Infections
Flaviviridae Infections
RNA Virus Infections
Hemorrhagic Fevers, Viral
Vaccines
Immunologic Factors
Physiological Effects of Drugs