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

• ClinicalTrials.gov Identifier: NCT04313244
• Recruitment Status: Not yet recruiting
• First Posted: March 18, 2020
• Last Update Posted: December 10, 2020
• Sponsor: Takeda
• Information provided by (Responsible Party): Takeda

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.

Condition or disease	Intervention/treatment	Phase
Dengue Fever	Biological: 9vHPV vaccine; Biological: Dengue Tetravalent Vaccine (TDV)	Phase 3

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 614 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• 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
• Estimated Study Start Date: March 15, 2021
• Estimated Primary Completion Date: January 10, 2022
• Estimated Study Completion Date: July 25, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Group 1; 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).	Biological: 9vHPV vaccine; 9vHPV intramuscular injection; Biological: Dengue Tetravalent Vaccine (TDV); TDV subcutaneous injection; Other Name: TAK-003
Experimental: Group 2; 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).	Biological: 9vHPV vaccine; 9vHPV intramuscular injection

Outcome Measures

Primary Outcome Measures :

1. Geometric Mean Titers (GMTs) for Human Papillomavirus (HPV) Types 6, 11, 16, 18, 31, 33, 45, 52, 58 [ Time Frame: Day 210 (Month 7) ]
   GMTs for HPV will be measured by immunoglobulin G binding assay (IgGBA) or equivalent assay.

Secondary Outcome Measures :

1. 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 [ Time Frame: Day 210 (Month 7) ]
   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.
2. GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes [ Time Frame: Day 120 (Month 4) ]
   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.
3. Percentage of Participants with Seropositivity for Each of the 4 Dengue Serotypes [ Time Frame: Day 120 (Month 4) ]
   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.
4. Percentage of Participants with Seropositivity for Multiple (2, 3 or 4) Dengue Serotypes [ Time Frame: Day 120 (Month 4) ]
   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.
5. Percentage of Participants with Solicited Local Reactions for 7 Days Following Vaccination by Severity [ 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 ]
   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)].
6. Percentage of Participants with Solicited Systemic Adverse Events (AEs) for 14 days Following Vaccination by Severity [ 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 ]
   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).
7. Percentage of Participants with any Unsolicited AEs for 28 days Following Vaccination [ 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 ]
   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.
8. Percentage of Participants with Serious Adverse Events (SAEs) [ Time Frame: From first vaccination (Day 1) through end of study (Day 360 [Month 12]) ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 9 Years to 14 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

1. 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.
2. Participants who can comply with trial procedures and are available for the duration of follow-up.

Exclusion Criteria:

1. Has an elevated oral temperature ≥38°C (≥100.4°F) within 3 days of the intended date of vaccination.
2. Participants with contraindications, warnings and/or precautions to vaccination with Recombinant 9-valent Human Papillomavirus Vaccine (9vHPV) vaccine as specified within the prescribing information.
3. Has any history of progressive or severe neurologic disorder, seizure disorder or neuro-inflammatory disease.

4. 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.
5. Abnormalities of splenic or thymic function.
6. Has a known bleeding diathesis, or any condition that may be associated with a prolonged bleeding time.
7. 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.
8. 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.
9. 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.
10. Previous and planned vaccination (during the trial conduct) against HPV.
11. 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.
12. Has a current or previous infection with a flavivirus such as Zika, YF, JE, WN fever, tick-borne encephalitis or Murray Valley encephalitis.

Contacts and Locations

Contacts

Contact: Takeda Study Registration Call Center; +1-877-825-3327; medinfoUS@takeda.com

Locations

Thailand

Siriraj Hospital

Bangkoknoi, Bangkok, Thailand, 10700

King Chulalongkorn Memorial Hospital

Pathum Wan, Bangkok, Thailand, 10330

The Hospital for Tropical Diseases

Bangkok, Thailand, 10400

Thammasat University Hospital

Pathum Thani, Thailand, 12121

Sponsors and Collaborators

Takeda

Investigators

• Study Director: Medical Director Clinical Science; Takeda

More Information

• Responsible Party: Takeda
• ClinicalTrials.gov Identifier: NCT04313244
• Other Study ID Numbers: DEN-308
• First Posted: March 18, 2020
• Last Update Posted: December 10, 2020
• Last Verified: December 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Takeda makes patient-level, de-identified data sets and associated documents available for all interventional studies after applicable marketing approvals and commercial availability have been received (or program is completely terminated), an opportunity for the primary publication of the research and final report development has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by Takeda:

Drug therapy

Additional relevant MeSH terms:

Dengue; Arbovirus Infections; Virus Diseases; Flavivirus Infections; Flaviviridae Infections; RNA Virus Infections; Hemorrhagic Fevers, Viral; Vaccines; Immunologic Factors; Physiological Effects of Drugs