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Immunogenicity and Safety of Dengue Tetravalent Vaccine (TDV) and Recombinant 9-valent Human Papillomavirus Vaccine (9vHPV) in Participants Aged ≥9 to <15 Years

Primary Purpose

Dengue Fever

Status

Completed

Phase

Phase 3

Locations

Thailand

Study Type

Interventional

Intervention

9vHPV vaccine

Dengue Tetravalent Vaccine (TDV)

About this trial

This is an interventional prevention trial for Dengue Fever focused on measuring Drug therapy

Eligibility Criteria

9 Years - 14 Years (Child)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

Participants who are 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.
Participants who can comply with trial procedures and are available for the duration of follow-up.

Exclusion Criteria:

Has an elevated oral temperature ≥38°C (≥100.4°F) within 3 days of the intended date of vaccination.
Participants with contraindications, warnings and/or precautions to vaccination with Recombinant 9-valent Human Papillomavirus Vaccine (9vHPV) vaccine as specified within the prescribing information.
Has any history of progressive or severe neurologic disorder, seizure disorder or neuro-inflammatory disease.
Known or suspected impairment/alteration of immune function, including:
1. 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).
2. 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).
3. Administration of immunoglobulins and/or any blood products within the 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. Human immunodeficiency virus (HIV) infection or HIV-related disease.
7. Hepatitis B virus infection.
8. Hepatitis C virus infection.
9. Genetic immunodeficiency.
Abnormalities of splenic or thymic function.
Has a known bleeding diathesis, or any condition that may be associated with a prolonged bleeding time.
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 trial vaccine administration.
Who have used antipyretics and/or analgesic medications within 24 hours prior to vaccination. The reason for their use (prophylaxis versus treatment) must be documented. Trial entry should be delayed to allow for a full 24 hours to have passed since last use of antipyretics and/or analgesic medications.
Previous and planned vaccination (during the trial conduct), against any flavivirus (except Japanese encepahilitis [JE]) including dengue, yellow fever (YF) viruses or tick-borne encephalitis.
Previous and planned vaccination (during the trial conduct) against HPV.
Previous participation in any clinical trial of a dengue or other flavivirus (eg, West Nile [WN] virus) candidate vaccine, except for participants who received placebo in those trials.
Has a current or previous infection with a flavivirus such as Zika, YF, JE, WN fever, tick-borne encephalitis or Murray Valley encephalitis.

Sites / Locations

Siriraj Hospital
King Chulalongkorn Memorial Hospital
The Hospital for Tropical Diseases
Thammasat University Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Group 1

Group 2

Arm Description

0.5 mL Recombinant 9-valent Human Papillomavirus Vaccine (9vHPV) intramuscular (IM) will be co-administered with 0.5 mL Dengue Tetravalent Vaccine (TDV) subcutaneous (SC) once on Day 1 (Month 0) followed by 0.5 mL TDV SC once on Day 90 (Month 3) and 0.5 mL 9vHPV IM once on Day 180 (Month 6).

0.5 mL 9vHPV vaccine IM will be administered once on Day 1 (Month 0) followed by 0.5 mL 9vHPV vaccine IM once on Day 180 (Month 6).

Outcomes

Primary Outcome Measures

Geometric Mean Titers (GMTs) for Human Papillomavirus (HPV) Types 6, 11, 16, 18, 31, 33, 45, 52, 58

GMTs for HPV will be measured by immunoglobulin G binding assay (IgGBA) or equivalent assay.

Secondary Outcome Measures

Percentage of Participants with Seropositivity for HPV Types 6, 11, 16, 18, 31, 33, 45, 52 and 58 as Measured by Immunoglobulin G Binding Assay (IgGBA) or Equivalent Assay

Seropositivity for HPV is defined as an anti-HPV titer greater than or equal to the pre-specified serostatus cut-off for a given HPV type, measured by IgGBA.

GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes

GMTs of neutralizing antibodies for each of the 4 dengue serotypes will be measured by microneutralization test 50% (MNT50). The four dengue serotypes: DENV1, DENV2, DENV3 and DENV4.

Percentage of Participants with Seropositivity for Each of the 4 Dengue Serotypes

Seropositivity is defined as a reciprocal neutralizing antibody titer ≥10 for any of the 4 dengue serotypes. The four dengue serotypes: DENV1, DENV2, DENV3 and DENV4.

Percentage of Participants with Seropositivity for Multiple (2, 3 or 4) Dengue Serotypes

Seropositivity is defined as a reciprocal neutralizing antibody titer ≥10 for any of the 4 dengue serotypes. The four dengue serotypes: DENV1, DENV2, DENV3 and DENV4.

Percentage of Participants with Solicited Local Reactions for 7 Days Following Vaccination by Severity

Solicited local Adverse Events (AEs) (at injection site) will be collected by participants using diary cards within 7 days after vaccination and will include: 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 and swelling [Grade 0 (<25 mm), 1 (25 - ≤ 50 mm), 2 (>50 - ≤ 100 mm), 3 (> 100 mm)].

Percentage of Participants with Solicited Systemic Adverse Events (AEs) for 14 days Following Vaccination by Severity

Solicited systemic AEs will be collected by participants using diary cards within 14 days after vaccination and will include 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). Fever is defined as body temperature greater than or equal to 38°C (100.4°F).

Percentage of Participants with any Unsolicited AEs for 28 days Following 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.

Percentage of Participants with Serious Adverse Events (SAEs)

An SAE is defined as any untoward medical occurrence or effect that 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 which may require intervention to prevent the items listed above or may expose the participant to danger.

Full Information

NCT ID

NCT04313244

First Posted

March 16, 2020

Last Updated

January 18, 2023

Sponsor

Takeda

1. Study Identification

Unique Protocol Identification Number

NCT04313244

Brief Title

Immunogenicity and Safety of Dengue Tetravalent Vaccine (TDV) and Recombinant 9-valent Human Papillomavirus Vaccine (9vHPV) in Participants Aged ≥9 to <15 Years

Official Title

A Phase 3, Open-Label, Randomized Trial to Investigate the Immunogenicity and Safety of the Co-administration of a Subcutaneous Dengue Tetravalent Vaccine (Live, Attenuated) (TDV) and an Intramuscular Recombinant 9-Valent Human Papillomavirus (9vHPV) Vaccine in Subjects Aged ≥9 to <15 Years in an Endemic Country for Dengue

Study Type

Interventional

2. Study Status

Record Verification Date

January 2023

Overall Recruitment Status

Completed

Study Start Date

May 15, 2021 (Actual)

Primary Completion Date

January 19, 2022 (Actual)

Study Completion Date

July 19, 2022 (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

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The purpose of the study is to demonstrate the non-inferiority (NI) of the immune response to 2 doses of 9vHPV vaccine, 1 co-administered with TDV, compared with 2 doses of 9vHPV vaccine administered alone.

Detailed Description

The vaccine being tested in this study is called Tetravalent Dengue Vaccine (TDV). The study will assess the immunogenicity and safety on the co-administration of 9vHPV vaccine with TDV in healthy participants aged ≥9 to <15 years. The study will enroll approximately 614 healthy volunteers. Participants will be randomly assigned to one of the two treatment groups- Group 1 Group 2 All participants will receive recombinant 9-valent Human Papillomavirus Vaccine (9vHPV) intramuscular (IM) in combination with Dengue Tetravalent Vaccine (TDV) subcutaneous (SC) injection on Day 1 (Month 0 ) followed by 9vHPV on Day 90 (Month 3) and TDV on Day 180 (Month 6) in Group 1. Participants will receive 9vHPV on Day 1 (Month 0) and Day 180 (Month 6) IM in Group 2. This multi-center trial will be conducted in Thailand. The overall time to participate in this study is 12 months. Participants will make multiple visits to the clinic, after last dose of study drug for a follow-up assessment.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Dengue Fever

Keywords

Drug therapy

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

618 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Group 1

Arm Type

Experimental

Arm Description

Arm Title

Group 2

Arm Type

Experimental

Arm Description

0.5 mL 9vHPV vaccine IM will be administered once on Day 1 (Month 0) followed by 0.5 mL 9vHPV vaccine IM once on Day 180 (Month 6).

Intervention Type

Biological

Intervention Name(s)

9vHPV vaccine

Intervention Description

9vHPV intramuscular injection

Intervention Type

Biological

Intervention Name(s)

Dengue Tetravalent Vaccine (TDV)

Other Intervention Name(s)

TAK-003

Intervention Description

TDV subcutaneous injection

Primary Outcome Measure Information:

Title

Geometric Mean Titers (GMTs) for Human Papillomavirus (HPV) Types 6, 11, 16, 18, 31, 33, 45, 52, 58

Description

GMTs for HPV will be measured by immunoglobulin G binding assay (IgGBA) or equivalent assay.

Time Frame

Day 210 (Month 7)

Secondary Outcome Measure Information:

Title

Percentage of Participants with Seropositivity for HPV Types 6, 11, 16, 18, 31, 33, 45, 52 and 58 as Measured by Immunoglobulin G Binding Assay (IgGBA) or Equivalent Assay

Description

Seropositivity for HPV is defined as an anti-HPV titer greater than or equal to the pre-specified serostatus cut-off for a given HPV type, measured by IgGBA.

Time Frame

Day 210 (Month 7)

Title

GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes

Description

GMTs of neutralizing antibodies for each of the 4 dengue serotypes will be measured by microneutralization test 50% (MNT50). The four dengue serotypes: DENV1, DENV2, DENV3 and DENV4.

Time Frame

Day 120 (Month 4)

Title

Percentage of Participants with Seropositivity for Each of the 4 Dengue Serotypes

Description

Seropositivity is defined as a reciprocal neutralizing antibody titer ≥10 for any of the 4 dengue serotypes. The four dengue serotypes: DENV1, DENV2, DENV3 and DENV4.

Time Frame

Day 120 (Month 4)

Title

Percentage of Participants with Seropositivity for Multiple (2, 3 or 4) Dengue Serotypes

Description

Seropositivity is defined as a reciprocal neutralizing antibody titer ≥10 for any of the 4 dengue serotypes. The four dengue serotypes: DENV1, DENV2, DENV3 and DENV4.

Time Frame

Day 120 (Month 4)

Title

Percentage of Participants with Solicited Local Reactions for 7 Days Following Vaccination by Severity

Description

Time Frame

For Group 1 -Within 7 days after first doses of 9vHPV vaccine + TDV co-administered on Day 1 and within 7 days after second dose of TDV administered on Day 90; for Group 2 -Within 7 days after first dose of 9vHPV vaccine administered on Day 1

Title

Percentage of Participants with Solicited Systemic Adverse Events (AEs) for 14 days Following Vaccination by Severity

Description

Time Frame

For Group 1 -Within 14 days after first doses of 9vHPV vaccine + TDV co-administered on Day 1 and within 14 days after second dose of TDV administered on Day 90; for Group 2 -Within 14 days after first dose of 9vHPV vaccine administered on Day 1

Title

Percentage of Participants with any Unsolicited AEs for 28 days Following Vaccination

Description

Time Frame

For Group 1 -Within 28 days after first doses of 9vHPV vaccine + TDV co-administered on Day 1 and within 28 days after second dose of TDV administered on Day 90; for Group 2 -Within 28 days after first dose of 9vHPV vaccine administered on Day 1

Title

Percentage of Participants with Serious Adverse Events (SAEs)

Description

Time Frame

From first vaccination (Day 1) through end of study (Day 360 [Month 12])

10. Eligibility

Sex

All

Minimum Age & Unit of Time

9 Years

Maximum Age & Unit of Time

14 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Participants who are 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. Participants who can comply with trial procedures and are available for the duration of follow-up. Exclusion Criteria: Has an elevated oral temperature ≥38°C (≥100.4°F) within 3 days of the intended date of vaccination. Participants with contraindications, warnings and/or precautions to vaccination with Recombinant 9-valent Human Papillomavirus Vaccine (9vHPV) vaccine as specified within the prescribing information. Has any history of progressive or severe neurologic disorder, seizure disorder or neuro-inflammatory disease. 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 (Month 0) (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 (Month 0). Administration of immunoglobulins and/or any blood products within the 3 months prior to Day 1 (Month 0) or planned administration during the trial. Receipt of immunostimulants within 60 days prior to Day 1 (Month 0). Immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within 6 months prior to Day 1 (Month 0). Human immunodeficiency virus (HIV) infection or HIV-related disease. Hepatitis B virus infection. Hepatitis C virus infection. Genetic immunodeficiency. Abnormalities of splenic or thymic function. Has a known bleeding diathesis, or any condition that may be associated with a prolonged bleeding time. 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 trial vaccine administration. Who have used antipyretics and/or analgesic medications within 24 hours prior to vaccination. The reason for their use (prophylaxis versus treatment) must be documented. Trial entry should be delayed to allow for a full 24 hours to have passed since last use of antipyretics and/or analgesic medications. Previous and planned vaccination (during the trial conduct), against any flavivirus (except Japanese encephalitis [JE]) including dengue, yellow fever (YF) viruses or tick-borne encephalitis. Previous and planned vaccination (during the trial conduct) against HPV. Previous participation in any clinical trial of a dengue or other flavivirus (eg, West Nile [WN] virus) candidate vaccine, except for participants who received placebo in those trials. Has a current or previous infection with a flavivirus such as Zika, YF, JE, WN fever, tick-borne encephalitis or Murray Valley encephalitis.

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

Siriraj Hospital

City

Bangkoknoi

State/Province

Khet Bangkok Noi

ZIP/Postal Code

10700

Country

Thailand

Facility Name

King Chulalongkorn Memorial Hospital

City

Bangkok

ZIP/Postal Code

10330

Country

Thailand

Facility Name

The Hospital for Tropical Diseases

City

Bangkok

ZIP/Postal Code

10400

Country

Thailand

Facility Name

Thammasat University Hospital

City

Pathum Thani

ZIP/Postal Code

12121

Country

Thailand

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/

Links:

URL

https://clinicaltrials.takeda.com/study-detail/5f6b603d4db2bf003ab4a399?idFilter=%5B%22C16021CSC%22%2C%22DEN-308%22%5D

Description

To obtain more information about this study, click this link.

Learn more about this trial

Immunogenicity and Safety of Dengue Tetravalent Vaccine (TDV) and Recombinant 9-valent Human Papillomavirus Vaccine (9vHPV) in Participants Aged ≥9 to <15 Years

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