Clinical trial NCT04313244: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Dengue Fever
Keywords: Drug therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2020-03-18
Enrollment: 614
Sex: ALL
Minimum age (years): 9
Maximum age (years): 14
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility 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 encephalitis \[JE\]) 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.

Primary outcomes:
measure: Geometric Mean Titers (GMTs) for Human Papillomavirus (HPV) Types 6, 11, 16, 18, 31, 33, 45, 52, 58
timeFrame: Day 210 (Month 7)
Secondary outcomes:
measure: 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)
timeFrame: Day 210 (Month 7)
measure: GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes
timeFrame: Day 120 (Month 4)
measure: Percentage of Participants With Seropositivity for Each of the 4 Dengue Serotypes
timeFrame: Day 120 (Month 4)
measure: Percentage of Participants With Seropositivity for Multiple (2, 3 or 4) Dengue Serotypes
timeFrame: Day 120 (Month 4)
measure: Percentage of Participants With Solicited Local Adverse Events for 7 Days Following Vaccination by Severity
timeFrame: Up to 7 days (Day of vaccination + 6 subsequent days) after each vaccination
measure: Percentage of Participants With Solicited Systemic Adverse Events (AEs) for 14 Days Following Vaccination by Severity
timeFrame: Up to 14 days (Day of vaccination + 13 subsequent days) after each vaccination
measure: Percentage of Participants With Any Unsolicited AEs for 28 Days Following Vaccination
timeFrame: Up to 28 days (Day of vaccination + 27 subsequent days) after each vaccination
measure: Percentage of Participants With Serious Adverse Events (SAEs)
timeFrame: From first vaccination (Day 1 [Month 0]) through end of study (Day 360 [Month 12])
Other outcomes:
Locations:
city: Bangkoknoi
country: Thailand
facility: Siriraj Hospital
state: Khet Bangkok Noi
city: Bangkok
country: Thailand
facility: King Chulalongkorn Memorial Hospital
city: Bangkok
country: Thailand
facility: The Hospital for Tropical Diseases
city: Pathum Thani
country: Thailand
facility: Thammasat University Hospital
Study officials:
affiliation: Takeda
name: Medical Director
role: STUDY_DIRECTOR
References: