Back to resultsLot-to-lot Consistency of 3 Lots of Tetravalent Dengue Vaccine (TDV) in Non-endemic Country(Ies) for Dengue
Primary Purpose
Dengue Fever
Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
TAK-003
Placebo
Sponsored by
About this trial
This is an interventional prevention trial for Dengue Fever focused on measuring Vaccine
Eligibility Criteria
Inclusion Criteria:
- Is in good health at the time of entry into the trial as determined by medical history, physical examination (including vital signs) and the clinical judgment of the Investigator.
- 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.
Exclusion Criteria:
- Has an elevated oral temperature (≥38°C or 100.4°F) within 3 days of the intended date of vaccination.
- Known hypersensitivity or allergy to any of the vaccine components (including excipients of the investigational vaccine or placebo).
- Has any history of progressive or severe neurologic disorder, seizure disorder or neuro-inflammatory disease (e.g., Guillain-Barré syndrome).
Known or suspected impairment/alteration of immune function, including:
- 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 (M0) (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 (M0).
- Administration of immunoglobulins and/or any blood products within the 3 months prior to Day 1 (M0) or planned administration during the trial.
- Receipt of immunostimulants within 60 days prior to Day 1 (M0).
- Hepatitis C virus infection.
- Genetic immunodeficiency.
- Has abnormalities of splenic or thymic function.
- Has a known bleeding diathesis, or any condition that may be associated with a prolonged bleeding time.
- Has any serious chronic or progressive disease according to judgment of the Investigator (e.g., neoplasm, insulin dependent diabetes, cardiac, renal or hepatic disease).
- Has body mass index (BMI) greater than or equal to 35 kg/m^2 (= weight in kg/[height in meters^2]).
- Has history of substance or alcohol abuse within the past 2 years.
- Had previous and planned vaccination (during the trial conduct) against any flavivirus including dengue, yellow fever (YF), Japanese encephalitis (JE) viruses or tick-borne encephalitis.
- Has a current or previous infection with a flavivirus such as dengue, Zika, YF, JE, West Nile (WN) fever, tick-borne encephalitis or Murray Valley encephalitis and participants with a history of prolonged (≥1 year) habitation in a dengue endemic area.
Sites / Locations
- Optimal Research
- Anaheim Clinical Trials, LLC
- Advanced Clinical Research
- Optimal Research
- Synexus Limited- Council Bluffs
- Heartland Research Associates LLC - Augusta
- Heartland Research Associates LLC
- Optimal Research
- Synexus Limited - Minneapolis
- Synexus Limited - St. Louis
- Clinical Research Center of Nevada
- Synexus Limited - Columbus
- Advanced Clinical Research
- Advanced Clinical Research
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Placebo Comparator
Experimental
Experimental
Experimental
Arm Label
Placebo
TDV Lot 1
TDV Lot 2
TDV Lot 3
Arm Description
TDV placebo matching injection, subcutaneously (SC) once on Day 1, and Day 90.
Participants were administered TDV lot 1, 0.5 ml (each TDV 0.5 mL dose contained TDV-1, TDV-2, TDV-3, and TDV-4), SC injection, once on Day 1, and Day 90.
Participants were administered TDV lot 2, 0.5 ml (each TDV 0.5 mL dose contained TDV-1, TDV-2, TDV-3, and TDV-4), SC injection, once on Day 1, and Day 90.
Participants were administered TDV lot 3, 0.5 ml (each TDV 0.5 mL dose contained TDV-1, TDV-2, TDV-3, and TDV-4), SC injection once on Day 1, and Day 90.
Outcomes
Primary Outcome Measures
Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at Day 120 in the Immunogenicity Subset
GMTs of neutralizing antibodies for each of the 4 Dengue Serotypes was measured by microneutralization test 50% [MNT50]. The 4 dengue virus serotypes were DENV-1, DENV-2, DENV-3 and DENV-4.
Secondary Outcome Measures
Percentage of Participants Who Are Seropositive for Each of the 4 Dengue Serotypes at Days 120 and 270 in the Immunogenicity Subset
Seropositivity was defined as a reciprocal neutralizing titer ≥ 10. The 4 dengue virus serotypes were DENV-1, DENV-2, DENV-3 and DENV-4.
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at Day 270 in the Immunogenicity Subset
GMTs of neutralizing antibodies for each of the 4 Dengue Serotypes was measured by microneutralization test 50% [MNT50]. The 4 dengue virus serotypes were DENV-1, DENV-2, DENV-3 and DENV-4.
Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) by Severity After Each Vaccination
Solicited local AEs (at injection site) were collected by participants using diary cards within 7 days after vaccination and included pain (none, mild: no interference with daily activity, moderate: interference with daily activity with or without treatment and severe: prevents daily activity with or without treatment), redness (erythema) (<25 mm, mild: >25 - ≤50 mm, moderate: >50 - ≤100 mm, severe: >100 mm) and swelling (edema/induration) (<25 mm, mild: >25 - ≤50 mm, moderate: >50 - ≤100 mm, severe: >100 mm ). The percentages were rounded off to the first decimal place.
Percentage of Participants With Solicited Systemic Adverse Events (AEs) by Severity After Each Vaccination
Solicited systemic AEs include fever, headache, asthenia, malaise and myalgia that occurred within 14 days after each vaccination. Solicited systemic AEs (headache, asthenia, malaise and myalgia) was graded from 0 to 3 by severity; where 0=None, 1=Mild: No interference with daily activity, 2=Moderate: Interference with daily activity, 3=Severe: Prevents daily activity; A systemic AE of fever (defined as ≥38°C or ≥100.4°F) was derived from a daily temperature reading recorded within 14 days after vaccination. Fever was excluded from the overall count as no severity grading was applied for it. The percentages were rounded off to the first decimal place.
Percentage of Participants With Any Unsolicited Adverse Events (AEs) After Each Vaccination
An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a trial vaccine; it does not necessarily have to have a causal relationship with trial vaccine administration.
Percentage of Participants With Serious Adverse Events (SAEs)
An SAE was defined as any untoward medical occurrence that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, leads to a congenital anomaly/birth defect in the offspring of a participant, is an important medical event that may require intervention to prevent any of the above mentioned criteria and/or may expose the participant to danger, even though the event is not immediately life threatening or fatal or does not result in hospitalization. The percentages were rounded off to the first decimal place.
Percentage of Participants With Medically Attended Adverse Events (MAAEs)
MAAEs are defined as AEs leading to an unscheduled visit to or by a healthcare professional, including visits to an emergency department, but not fulfilling seriousness criteria. The percentages were rounded off to the first decimal place.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03423173
Brief Title
Lot-to-lot Consistency of 3 Lots of Tetravalent Dengue Vaccine (TDV) in Non-endemic Country(Ies) for Dengue
Official Title
A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial to Demonstrate Lot-to-Lot Consistency of 3 Lots of a Tetravalent Dengue Vaccine Candidate in Healthy Adults in Non-Endemic Country(Ies) for Dengue
Study Type
Interventional
2. Study Status
Record Verification Date
October 2020
Overall Recruitment Status
Completed
Study Start Date
February 12, 2018 (Actual)
Primary Completion Date
August 3, 2018 (Actual)
Study Completion Date
January 14, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Takeda
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to investigate lot-to-lot consistency in terms of equivalence of the immune responses induced by 3 consecutive TDV lots in healthy participants aged 18 to 60 years in non-endemic country(ies) for dengue.
Detailed Description
The vaccine tested in this study is Takeda's Tetravalent Dengue Vaccine Candidate (TDV). The primary objective of this trial is to investigate lot-to-lot consistency in terms of equivalence of the immune responses induced by 3 consecutive lots of TDV in healthy participants in non-endemic country(ies) for dengue.
The study will enroll approximately 924 healthy participants. Participants will be randomized in 2:2:2:1 to one of 4 trial groups to receive TDV (Lots 1, 2 or 3) or placebo:
TDV 0.5 mL subcutaneous injection OR
Placebo normal saline solution (0.9% NaCl) for injection.
In each trial group, all participants will receive 2 doses of TDV or placebo by subcutaneous injection on Days 1 (Month 0) and 90 (Month 3). Immunogenicity will be assessed in participants included in the immunogenicity subset (TDV groups: 176 participants each and placebo group: 88 participants) and safety will be assessed in all participants in each group.
This multi-center trial will be conducted in the United States. The overall time to participate in this study is 270 days. Participants will make multiple visits to the clinic including a final visit at Day 270.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Dengue Fever
Keywords
Vaccine
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
A double-blind study.
Allocation
Randomized
Enrollment
923 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
TDV placebo matching injection, subcutaneously (SC) once on Day 1, and Day 90.
Arm Title
TDV Lot 1
Arm Type
Experimental
Arm Description
Participants were administered TDV lot 1, 0.5 ml (each TDV 0.5 mL dose contained TDV-1, TDV-2, TDV-3, and TDV-4), SC injection, once on Day 1, and Day 90.
Arm Title
TDV Lot 2
Arm Type
Experimental
Arm Description
Participants were administered TDV lot 2, 0.5 ml (each TDV 0.5 mL dose contained TDV-1, TDV-2, TDV-3, and TDV-4), SC injection, once on Day 1, and Day 90.
Arm Title
TDV Lot 3
Arm Type
Experimental
Arm Description
Participants were administered TDV lot 3, 0.5 ml (each TDV 0.5 mL dose contained TDV-1, TDV-2, TDV-3, and TDV-4), SC injection once on Day 1, and Day 90.
Intervention Type
Biological
Intervention Name(s)
TAK-003
Other Intervention Name(s)
TDV
Intervention Description
TDV subcutaneous injection
Intervention Type
Biological
Intervention Name(s)
Placebo
Intervention Description
TDV Placebo-matching normal saline (0.9% NaCl) subcutaneous injection
Primary Outcome Measure Information:
Title
Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at Day 120 in the Immunogenicity Subset
Description
GMTs of neutralizing antibodies for each of the 4 Dengue Serotypes was measured by microneutralization test 50% [MNT50]. The 4 dengue virus serotypes were DENV-1, DENV-2, DENV-3 and DENV-4.
Time Frame
1 month post second dose (Day 120)
Secondary Outcome Measure Information:
Title
Percentage of Participants Who Are Seropositive for Each of the 4 Dengue Serotypes at Days 120 and 270 in the Immunogenicity Subset
Description
Seropositivity was defined as a reciprocal neutralizing titer ≥ 10. The 4 dengue virus serotypes were DENV-1, DENV-2, DENV-3 and DENV-4.
Time Frame
1 month post second dose (Day 120) and 6 months post second dose (Day 270)
Title
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at Day 270 in the Immunogenicity Subset
Description
GMTs of neutralizing antibodies for each of the 4 Dengue Serotypes was measured by microneutralization test 50% [MNT50]. The 4 dengue virus serotypes were DENV-1, DENV-2, DENV-3 and DENV-4.
Time Frame
6 months post second dose (Day 270)
Title
Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) by Severity After Each Vaccination
Description
Solicited local AEs (at injection site) were collected by participants using diary cards within 7 days after vaccination and included pain (none, mild: no interference with daily activity, moderate: interference with daily activity with or without treatment and severe: prevents daily activity with or without treatment), redness (erythema) (<25 mm, mild: >25 - ≤50 mm, moderate: >50 - ≤100 mm, severe: >100 mm) and swelling (edema/induration) (<25 mm, mild: >25 - ≤50 mm, moderate: >50 - ≤100 mm, severe: >100 mm ). The percentages were rounded off to the first decimal place.
Time Frame
Within 7 Days of each Vaccination (day of vaccination + 6 days)
Title
Percentage of Participants With Solicited Systemic Adverse Events (AEs) by Severity After Each Vaccination
Description
Solicited systemic AEs include fever, headache, asthenia, malaise and myalgia that occurred within 14 days after each vaccination. Solicited systemic AEs (headache, asthenia, malaise and myalgia) was graded from 0 to 3 by severity; where 0=None, 1=Mild: No interference with daily activity, 2=Moderate: Interference with daily activity, 3=Severe: Prevents daily activity; A systemic AE of fever (defined as ≥38°C or ≥100.4°F) was derived from a daily temperature reading recorded within 14 days after vaccination. Fever was excluded from the overall count as no severity grading was applied for it. The percentages were rounded off to the first decimal place.
Time Frame
Within 14 Days of each Vaccination (day of vaccination + 13 days)
Title
Percentage of Participants With Any Unsolicited Adverse Events (AEs) After Each Vaccination
Description
An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a trial vaccine; it does not necessarily have to have a causal relationship with trial vaccine administration.
Time Frame
Within 28 days (day of vaccination + 27 days) after each vaccination
Title
Percentage of Participants With Serious Adverse Events (SAEs)
Description
An SAE was defined as any untoward medical occurrence that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, leads to a congenital anomaly/birth defect in the offspring of a participant, is an important medical event that may require intervention to prevent any of the above mentioned criteria and/or may expose the participant to danger, even though the event is not immediately life threatening or fatal or does not result in hospitalization. The percentages were rounded off to the first decimal place.
Time Frame
From the first vaccination on Day 1 until the end of the trial (Day 270)
Title
Percentage of Participants With Medically Attended Adverse Events (MAAEs)
Description
MAAEs are defined as AEs leading to an unscheduled visit to or by a healthcare professional, including visits to an emergency department, but not fulfilling seriousness criteria. The percentages were rounded off to the first decimal place.
Time Frame
From the first vaccination on Day 1 until the end of the trial (Day 270)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Is in good health at the time of entry into the trial as determined by medical history, physical examination (including vital signs) and the clinical judgment of the Investigator.
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.
Exclusion Criteria:
Has an elevated oral temperature (≥38°C or 100.4°F) within 3 days of the intended date of vaccination.
Known hypersensitivity or allergy to any of the vaccine components (including excipients of the investigational vaccine or placebo).
Has any history of progressive or severe neurologic disorder, seizure disorder or neuro-inflammatory disease (e.g., Guillain-Barré syndrome).
Known or suspected impairment/alteration of immune function, including:
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 (M0) (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 (M0).
Administration of immunoglobulins and/or any blood products within the 3 months prior to Day 1 (M0) or planned administration during the trial.
Receipt of immunostimulants within 60 days prior to Day 1 (M0).
Hepatitis C virus infection.
Genetic immunodeficiency.
Has abnormalities of splenic or thymic function.
Has a known bleeding diathesis, or any condition that may be associated with a prolonged bleeding time.
Has any serious chronic or progressive disease according to judgment of the Investigator (e.g., neoplasm, insulin dependent diabetes, cardiac, renal or hepatic disease).
Has body mass index (BMI) greater than or equal to 35 kg/m^2 (= weight in kg/[height in meters^2]).
Has history of substance or alcohol abuse within the past 2 years.
Had previous and planned vaccination (during the trial conduct) against any flavivirus including dengue, yellow fever (YF), Japanese encephalitis (JE) viruses or tick-borne encephalitis.
Has a current or previous infection with a flavivirus such as dengue, Zika, YF, JE, West Nile (WN) fever, tick-borne encephalitis or Murray Valley encephalitis and participants with a history of prolonged (≥1 year) habitation in a dengue endemic area.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director Clinical Science
Organizational Affiliation
Takeda
Official's Role
Study Director
Facility Information:
Facility Name
Optimal Research
City
Huntsville
State/Province
Alabama
ZIP/Postal Code
35802
Country
United States
Facility Name
Anaheim Clinical Trials, LLC
City
Anaheim
State/Province
California
ZIP/Postal Code
92805
Country
United States
Facility Name
Advanced Clinical Research
City
Boise
State/Province
Idaho
ZIP/Postal Code
83704
Country
United States
Facility Name
Optimal Research
City
Peoria
State/Province
Illinois
ZIP/Postal Code
61614
Country
United States
Facility Name
Synexus Limited- Council Bluffs
City
Council Bluffs
State/Province
Iowa
ZIP/Postal Code
51503
Country
United States
Facility Name
Heartland Research Associates LLC - Augusta
City
Augusta
State/Province
Kansas
ZIP/Postal Code
67010
Country
United States
Facility Name
Heartland Research Associates LLC
City
Park City
State/Province
Kansas
ZIP/Postal Code
67219
Country
United States
Facility Name
Optimal Research
City
Rockville
State/Province
Maryland
ZIP/Postal Code
20850
Country
United States
Facility Name
Synexus Limited - Minneapolis
City
Edina
State/Province
Minnesota
ZIP/Postal Code
55435
Country
United States
Facility Name
Synexus Limited - St. Louis
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63141
Country
United States
Facility Name
Clinical Research Center of Nevada
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89104
Country
United States
Facility Name
Synexus Limited - Columbus
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43212
Country
United States
Facility Name
Advanced Clinical Research
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84123
Country
United States
Facility Name
Advanced Clinical Research
City
West Jordan
State/Province
Utah
ZIP/Postal Code
84088
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
IPD Sharing Access Criteria
IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
IPD Sharing URL
https://vivli.org/ourmember/takeda/
Learn more about this trial
Lot-to-lot Consistency of 3 Lots of Tetravalent Dengue Vaccine (TDV) in Non-endemic Country(Ies) for Dengue
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