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Safety and Immunogenicity With Two Different Serotype 2 Potencies of Takeda's Tetravalent Dengue Vaccine Candidate (TDV) in Adults in Singapore

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: NCT02425098
Recruitment Status : Completed
First Posted : April 23, 2015
Results First Posted : August 27, 2019
Last Update Posted : August 27, 2019
Sponsor:
Information provided by (Responsible Party):
Takeda

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

Condition or disease Intervention/treatment Phase
Dengue Fever Biological: Takeda's Tetravalent Dengue Vaccine Candidate (TDV) Biological: Takeda's High-Dose Tetravalent Dengue Vaccine Candidate (HD-TDV) Phase 2

Detailed Description:

The vaccine being tested in this study was Takeda's Tetravalent Dengue Vaccine Candidate (TDV). TDV is being tested to protect people against dengue fever. This study looked at safety and the titers of antibodies to dengue fever induced in people who were administered a high-dose of TDV (HD-TDV) compared to TDV.

The study enrolled 351 patients. Before being assigned to a treatment group participants were screened for previous exposure to the dengue virus using a Dengue immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA). Participants were randomly assigned in 1:1 ratio (by chance) to one of the two treatment groups—which remained undisclosed to the participant and study doctor during the study (unless there is an urgent medical need):

  • HD-TDV 0.5 mL subcutaneous injection
  • TDV 0.5 mL subcutaneous injection

All participants received a single injection on Day 1. Participants were asked to record any symptoms that may or may not be related to the vaccine or the injection site in a diary card for 28 days after vaccination.

This multi-center trial was conducted in Singapore. The overall time of participation in this study was 12 months. Participants made multiple visits to the clinic, including a final visit 1 year after receiving their dose of TDV.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 351 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: A Phase II, Double-Blind, Randomized, Controlled Trial to Assess the Safety and Immunogenicity of a Tetravalent Dengue Vaccine With Two Different Serotype 2 Potencies in an Adult Population in Singapore
Actual Study Start Date : June 3, 2015
Actual Primary Completion Date : September 18, 2017
Actual Study Completion Date : September 18, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Dengue

Arm Intervention/treatment
Experimental: High-dose Tetravalent Dengue Vaccine (HD-TDV)
High-dose Tetravalent Dengue Vaccine [HD-TDV], 0.5 mL, subcutaneous injection on Day 1. TDV comprised one molecularly-characterized and cloned TDV-2 live attenuated dengue virus strain and three recombinant live attenuated dengue virus strains: TDV-1, TDV-3 and TDV-4. TDV contained 2*10^4 plaque forming units (PFU), 5*10^4 PFU, 1*10^5 PFU, and 3*10^5 PFU of TDV-1, TDV-2, TDV-3 and TDV-4 respectively.
Biological: Takeda's High-Dose Tetravalent Dengue Vaccine Candidate (HD-TDV)
High-dose TDV subcutaneous injection

Experimental: Tetravalent Dengue Vaccine (TDV)
Tetravalent Dengue Vaccine [TDV], 0.5 mL, subcutaneous injection on Day 1. TDV comprised one molecularly-characterized and cloned TDV-2 live attenuated dengue virus strain and three recombinant live attenuated dengue virus strains: TDV-1, TDV-3 and TDV-4. TDV contained 2*10^4 plaque forming units (PFU), 5*10^3 PFU, 1*10^5 PFU, and 3*10^5 PFU of TDV-1, TDV-2, TDV-3 and TDV-4 respectively.
Biological: Takeda's Tetravalent Dengue Vaccine Candidate (TDV)
TDV subcutaneous injection




Primary Outcome Measures :
  1. Geometric Mean Neutralizing Antibody Titer (GMT) for Each of the Four Dengue Serotypes at Day 15 [ Time Frame: Day 15 ]
    GMTs were assessed for the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4, by microneutralization test [MNT].

  2. Geometric Mean Neutralizing Antibody Titer (GMT) for Each of the Four Dengue Serotypes at Day 30 [ Time Frame: Day 30 ]
    GMTs were assessed for the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4, by MNT.

  3. Geometric Mean Neutralizing Antibody Titer (GMT) for Each of the Four Dengue Serotypes at Day 90 [ Time Frame: Day 90 ]
    GMTs were assessed for the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4, by MNT.

  4. Geometric Mean Neutralizing Antibody Titer (GMT) for Each of the Four Dengue Serotypes at Day 180 [ Time Frame: Day 180 ]
    GMTs were assessed for the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4, by MNT.

  5. Geometric Mean Neutralizing Antibody Titer (GMT) for Each of the Four Dengue Serotypes at Day 365 [ Time Frame: Day 365 ]
    GMTs were assessed for the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4, by MNT.

  6. Seropositivity Rate for Each of the Four Dengue Serotypes at Day 15 [ Time Frame: Day 15 ]
    Seropositivity rate was defined as the percentage of participants being seropositive, derived from titers of dengue-neutralizing antibodies. Seropositivity was defined as a reciprocal neutralizing titer ≥10 (for each serotype). Seropositivity rates were assessed for the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4.

  7. Seropositivity Rate for Each of the Four Dengue Serotypes at Day 30 [ Time Frame: Day 30 ]
    Seropositivity rate was defined as the percentage of participants being seropositive, derived from titers of dengue-neutralizing antibodies. Seropositivity was defined as a reciprocal neutralizing titer ≥10 (for each serotype). Seropositivity rates were assessed for the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4.

  8. Seropositivity Rate for Each of the Four Dengue Serotypes at Day 90 [ Time Frame: Day 90 ]
    Seropositivity rate was defined as the percentage of participants being seropositive, derived from titers of dengue-neutralizing antibodies. Seropositivity was defined as a reciprocal neutralizing titer ≥10 (for each serotype). Seropositivity rates were assessed for the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4.

  9. Seropositivity Rate for Each of the Four Dengue Serotypes at Day 180 [ Time Frame: Day 180 ]
    Seropositivity rate was defined as the percentage of participants being seropositive, derived from titers of dengue-neutralizing antibodies. Seropositivity was defined as a reciprocal neutralizing titer ≥10 (for each serotype). Seropositivity rates were assessed for the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4.

  10. Seropositivity Rate for Each of the Four Dengue Serotypes at Day 365 [ Time Frame: Day 365 ]
    Seropositivity rate was defined as the percentage of participants being seropositive, derived from titers of dengue-neutralizing antibodies. Seropositivity was defined as a reciprocal neutralizing titer ≥10 (for each serotype). Seropositivity rates were assessed for the four dengue serotypes: DENV-1, DENV-2, DENV-3, and DENV-4.


Secondary Outcome Measures :
  1. Number of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (Diary Recorded) Following Vaccination by Severity [ Time Frame: Within 7 days after Vaccination ]
    Solicited local AEs (at injection site) were collected by participants using diary cards within 7 days after vaccination and included pain [Grade 0 (no pain), 1 (mild: no interference with daily activity), 2 (moderate: interference with daily activity with or without treatment) and 3 (severe: prevents daily activity with or without treatment)], erythema [Grade 0 (<25 mm), 1 (25 − ≤ 50 mm), 2 (>50 − ≤ 100 mm), 3 (> 100 mm)] and swelling [Grade 0 (<25 mm), 1 (25 − ≤ 50 mm), 2 (>50 − ≤ 100 mm), 3 (> 100 mm)].

  2. Number of Participants With Solicited Systemic Adverse Events (AEs) (Diary Recorded) Following Vaccination by Severity [ Time Frame: Within 14 days after Vaccination ]
    Solicited systemic AEs were collected by participants using diary cards within 14 days after vaccination and included fever, headache, asthenia, malaise and myalgia. Severity grades were: Grade 0: none, Grade 1: mild (no interference with daily activity), Grade 2: moderate (interference with daily activity with or without treatment), Grade 3: severe (prevents normal daily activity with or without treatment). A systemic AE of fever (defined as ≥ 100.4°F) was derived from a daily temperature reading recorded within 14 days after vaccination.

  3. Number of Participants With at Least One Unsolicited Adverse Events (AEs) Following Vaccination [ Time Frame: Within 28 days after Vaccination ]
    An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a study vaccine; it does not necessarily have to have a causal relationship with study vaccine administration.

  4. Number of Participants With Serious Adverse Events (SAEs) [ Time Frame: From first vaccination through end of study (Day 365) ]
    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.

  5. Geometric Mean Neutralizing Antibody Titers (GMT) for Each of the Four Dengue Serotypes Assessed by Dengue Baseline Seropositivity (MNT) Status [ Time Frame: Days 15, 30, 90, 180 and 365 ]
    Baseline dengue seropositivity was based on the microneutralization test (MNT) result and was defined as a reciprocal neutralizing titer ≥10 for one or more dengue serotype at baseline. The four DENV serotypes are DENV-1, DENV-2, DENV-3, and DENV-4.

  6. Seropositivity Rate for Each of the Four Dengue Serotypes Assessed by Dengue Baseline Seropositivity (MNT) Status [ Time Frame: Days 15, 30, 90, 180, and 365 ]
    Baseline dengue seropositivity was based on the MNT result and was defined as a reciprocal neutralizing titer ≥10 for one or more dengue serotype at baseline. Seropositive rate was defined as a reciprocal neutralizing titer ≥ 10. Seropositivity was assessed for the four Dengue serotypes are DENV-1, DENV-2, DENV-3, and DEN-4.

  7. Percentage of Participants Positive for Vaccine Viremia for Each of the Four Vaccine Strains After Vaccination [ Time Frame: Days 5, 7, 9, 11, 15, 17, 21 and 30 ]
    Vaccine Viremia was assessed for each of the four vaccine strains: TDV-1, TDV-2, TDV-3 and TDV-4. Vaccine viral ribonucleic acid (RNA) was detected by reverse transcription-polymerase chain reaction (RT-PCR) assay.

  8. Duration of Vaccine Viremia for Each of the Four Vaccine Strains After Vaccination [ Time Frame: Days 5, 7, 9, 11, 15, 17, 21 and 30 ]
    The duration of vaccine viremia for each vaccine strain was defined as the date when vaccine viremia was last detected (positive result) to date when vaccine viremia was first detected (positive result) + 1 day. It was assessed for each of the four vaccine strains: TDV-1, TDV-2, TDV-3 and TDV-4. Vaccine viral ribonucleic acid (RNA) was detected by reverse transcription-polymerase chain reaction (RT-PCR) assay.

  9. Level of Vaccine Viremia for Each of the Four Vaccine Strains After Vaccination [ Time Frame: Days 5, 7, 9, 11, 15, 17, 21 and 30 ]
    Vaccine Viremia was assessed for each of the four vaccine strains: TDV-1, TDV-2, TDV-3 and TDV-4. Vaccine viral ribonucleic acid (RNA) was detected by reverse transcription-polymerase chain reaction (RT-PCR) assay.



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:   21 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Participant signs and dates a written informed consent form where applicable, 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.
  2. Is aged 21 to 45 years of age, inclusive.
  3. Is 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.
  4. Can comply with trial procedures and are available for the duration of follow-up.
  5. Has self-declared as never having been vaccinated against Yellow Fever or Japanese Encephalitis Virus.

Exclusion Criteria:

  1. Has febrile illness (temperature ≥38°C or ≥100.4°F) or moderate or severe acute illness or infection at the time of enrollment.
  2. Has history or any illness that, in the opinion of the Investigator, might interfere with the results of the trial or pose an additional risk to the participant due to participation in the trial, including but not limited to:

    1. Known hypersensitivity or allergy to any of the vaccine components.
    2. Female participants who are pregnant or breastfeeding.
    3. 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).
    4. 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 (Month 0) (use of inhaled, intranasal, or topical corticosteroids is allowed).
      • ii. 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 (Month 0).
      • iii. Administration of immunoglobulins and/or any blood products within the 3 months prior to Day 1 (Month 0) or planned administration during the trial.
      • iv. Receipt of immunostimulants within 60 days prior to Day 1(Month 0).
      • v. Immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within 6 months prior to Day 1 (Month 0).
      • vi. Human immunodeficiency virus (HIV) infection and HIV-related diseases.
      • vii. Hepatitis C virus (HCV) infection.
      • viii. Genetic immunodeficiency.
  3. Has received any other vaccine within 14 days (for inactivated vaccines) or 28 days (for live vaccines) prior to Day 1 (Month 0) or planning to receive any vaccine within 28 days after Day 1 (Month 0).
  4. Has participated in any clinical trial with another investigational product 30 days prior to Day 1 (Month 0) or intent to participate in another clinical trial at any time during the conduct of this trial.
  5. Has previously participated in any clinical trial of a dengue candidate vaccine, or previous receipt of a dengue vaccine.
  6. Is first-degree relative of individuals involved in trial conduct.
  7. For females of childbearing potential who are sexually active, and who have not used any of the acceptable contraceptive methods for at least 2 months prior to Day 1 (Month 0).

    1. Of childbearing potential is defined as status post onset of menarche and not meeting any of the following conditions: bilateral tubal ligation (at least 1 year previously), bilateral oophorectomy (at least 1 year previously) or hysterectomy.
    2. 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 Day 1 [Month 0]).
  8. Females of childbearing potential who are sexually active, and who refuse to use an acceptable contraceptive method from signing the informed consent up to 6 weeks post-vaccination.

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): NCT02425098


Locations
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Singapore
Singapore General Hospital
Singapore, Singapore, 169608
Tan Tock Seng Hospital
Singapore, Singapore, 308433
Changi General Hospital
Singapore, Singapore, 529889
Sponsors and Collaborators
Takeda
Investigators
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Study Director: Medical Director Clinical Science Takeda
  Study Documents (Full-Text)

Documents provided by Takeda:
Statistical Analysis Plan  [PDF] December 14, 2017
Study Protocol  [PDF] April 25, 2017


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Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT02425098     History of Changes
Other Study ID Numbers: DEN-205
U1111-1166-8884 ( Registry Identifier: WHO )
First Posted: April 23, 2015    Key Record Dates
Results First Posted: August 27, 2019
Last Update Posted: August 27, 2019
Last Verified: July 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Takeda:
Vaccine
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