A Study of Dengue Tetravalent Vaccine (TDV) in Adults (Age 45 to 60 and >60 to 79 Years)

Official title

A Phase 3, Randomized, Double-Blind, Placebo-Controlled (Older Adults, Aged >60 to 79 Years) and Open-Label (Adults, Aged 45 to 60 Years), Multicenter Trial to Investigate the Safety and Immunogenicity of a Dengue Tetravalent Vaccine (TDV) Administered Subcutaneously to Adults and Older Adults With or Without Comorbidities in Endemic Areas for Dengue

Overview

Dengue fever is caused by an infection with the dengue virus. Vaccination with Dengue Tetravalent Vaccine (TDV) can help prevent dengue fever. Researchers have seen that dengue fever now also happens more often in elderly persons. The main aim of this study is to learn more about the side effects of TDV in adult (45 - 60 years) and elderly (60 - 79 years) persons and about TDV's ability to create an immune response in adult and elderly persons. Another aim is to learn about the side effects of TDV in adult and elderly persons in endemic countries who have one or more additional medical conditions (called comorbidities) such as diabetes mellitus, hypertension or a chronic kidney condition. In this study, participants will receive 2 vaccinations with TDV (the second 3 months after the first). During the study, participants will visit their study clinic 5 times.

Interventions

• Biological TDV
  TDV SC injection.
• Other Placebo
  Placebo SC injection.

Primary outcome measures

• Number of Participants with Solicited Local (Injection Site) Adverse Events (AEs) Within 7 Days Post Vaccination at Day 1 [Time frame: Within 7 days post-vaccination at Day 1]
• Number of Participants with Solicited Local (Injection Site) Adverse Events (AEs) Within 7 Days Post Vaccination at Day 90 [Time frame: Within 7 days post-vaccination at Day 90]
• Number of Participants with Solicited Systemic AEs Within 14 Days Post Vaccination at Day 1 [Time frame: Within 14 days post-vaccination at Day 1]
• Number of Participants with Solicited Systemic AEs Within 14 Days Post Vaccination at Day 90 [Time frame: Within 14 days post-vaccination at Day 90]
• Percentage of Participants with Solicited Local (Injection Site) AEs by Severity Within 7 Days Post Vaccination at Day 1 [Time frame: Within 7 days post-vaccination at Day 1]
• Percentage of Participants with Solicited Local (Injection Site) AEs by Severity Within 7 Days Post Vaccination at Day 90 [Time frame: Within 7 days post-vaccination at Day 90]
• Percentage of Participants with Solicited Systemic AEs by Severity Within 14 Days Post Vaccination at Day 1 [Time frame: Within 14 days post-vaccination at Day 1]
• Percentage of Participants with Solicited Systemic AEs by Severity Within 14 Days Post Vaccination at Day 90 [Time frame: Within 14 days post-vaccination at Day 90]
• Percentage of Participants with Any Unsolicited AEs Within 28 Days Post Vaccination at Day 1 [Time frame: Within 28 days post-vaccination at Day 1]
• Percentage of Participants with Any Unsolicited AEs Within 28 Days Post Vaccination at Day 90 [Time frame: Within 28 days post-vaccination at Day 90]

Secondary outcome measures (12)

• Number of Participants with Solicited Local (Injection Site) AEs Within 7 Days Post Vaccination at Day 1 and Day 90 (With Comorbidities) [Time frame: Within 7 days post-vaccination at Day 1 and Day 90]
• Number of Participants with Solicited Systemic AEs Within 14 Days Post Vaccination at Day 1 and Day 90 (With Comorbidities) [Time frame: Within 14 days post-vaccination at Day 1 and Day 90]
• Percentage of Participants with Solicited Local (Injection Site) AEs by Severity Within 7 days Post Vaccination at Day 1 and Day 90 (With Comorbidities) [Time frame: Within 7 days post-vaccination at Day 1 and Day 90]
• Percentage of Participants with Solicited Systemic AEs by Severity (With Comorbidities) [Time frame: Within 14 days post-vaccination at Day 1 and Day 90]
• Percentage of Participants with Any Unsolicited AEs Within 28 Days Post Vaccination (With Comorbidities) [Time frame: Within 28 days post-vaccination at Day 1 and Day 90]
• Percentage of Participants with a SAE (With Comorbidities) [Time frame: From first vaccination on Day 1 through the end of trial (up to Day 270)]
• Geometric Mean Titers by MNT for Each of the 4 Dengue Virus Serotypes [Time frame: Day 1, Day 30, Day 90 and Day 270]
• Geometric Mean Titers by MNT for Each of the 4 Dengue Virus Serotypes (With Comorbidities) [Time frame: Day 1, Day 30, Day 90, Day 120 and Day 270]
• Seropositivity Rate for Each of the 4 Dengue Virus Serotypes [Time frame: Day 1, Day 30, Day 90, Day 120 and Day 270]
• Seropositivity Rate for Each of the 4 Dengue Virus Serotypes (With Comorbidities) [Time frame: Day 1, Day 30, Day 90, Day 120 and Day 270]
• Seropositivity Rate for Multiple (2, 3, or 4) Dengue Virus Serotypes [Time frame: Day 1, Day 30, Day 90, Day 120 and Day 270]
• Seropositivity Rate for Multiple (2, 3, or 4) Dengue Virus Serotypes (With Comorbidities) [Time frame: Day 1, Day 30, Day 90, Day 120 and Day 270]

Eligibility criteria

Inclusion criteria

• Participant is aged 45 to 79 years at the time of entry into the trial.
• Participant is male or female.
• Participant is in good health or has a medical diagnosis of one or more of diabetes mellitus, hypertension, or chronic kidney disease (that is, comorbidities) and are medically stable in the opinion of the investigator at the time of entry into the trial, as determined by medical history and targeted physical examination. Medically stable is defined as no change in diagnoses or chronic medications (dose or class) for medical reasons in the 3 months prior to participating in the trial.
• Participant has signed and dated a written informed consent form and any required privacy authorization prior to the initiation of any trial procedure, and after the nature of the trial has been explained according to local regulatory requirements.
• Participant can comply with trial procedures and is available for the duration of follow-up.

Exclusion criteria

• Participant has contraindication(s), warning(s), and/or precaution(s) applicable to vaccination with TDV as specified in the Investigator's Brochure and/or approved product label (as applicable) in the participating country.
• Participant has a known hypersensitivity or allergy to any of the TDV or placebo components (including excipients).
• Participant has behavioral or cognitive impairment or psychiatric disease that, in the opinion of the investigator, could interfere with the participant's ability to take part in the trial.
• Participant has a history of progressive or severe neurologic disorder, seizure disorder or neuro-inflammatory disease (example, Guillain-Barré syndrome).
• Participant has an illness, or history of any illness that, in the opinion of the investigator, might interfere with the results of the trial or pose additional risk to the participant due to involvement in this trial.
• Participant has a known or suspected altered immunocompetence, including:

• Chronic administration of oral and/or parenteral steroids at doses considered sufficiently immunosuppressive (example, greater than or equal to \[>=\] 2 milligram per kilogram \[mg/kg\] body weight prednisone \[or equivalent\] for >=14 consecutive days, or >=20 milligram per day \[mg/day\] prednisone \[or equivalent\] administered for >=14 consecutive days) within 60 days prior to Day 1 (month \[M0\]) (note: use of corticosteroids by inhaled, intranasal, intra-articular, bursal, tendon injection, or topical routes is allowed).
• Receipt 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).
• Immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within 6 months prior to Day 1 (M0).
• Human Immunodeficiency Virus (HIV) infection or HIV-related disease.
• Hepatitis B virus infection.
• Hepatitis C virus infection.
• Genetic immunodeficiency.
• Participant has known or suspected abnormalities of splenic or thymic function.
• Participant has a known bleeding diathesis, or any condition/medication that may be associated with a prolonged bleeding time.
• Participant has a serious chronic or progressive disease deemed to be preclusive to trial entry, that is, not medically stable according to the judgment of the investigator.
• Participant has previously received a vaccination against dengue virus (investigational or licensed).
• Participant had a clinically significant active infection (as assessed by the investigator) or body temperature >38.0 degree Celsius (>100.4 degree Fahrenheit) within 3 days of intended TDV or placebo administration.
• Participant has used antipyretics and/or analgesic medications within 24 hours prior to vaccination. The reason for their use (prophylaxis vs treatment) must be documented. Trial entry must be delayed to allow for a full 24 hours to have passed since the last use of antipyretics and/or analgesic medications.
• Participant has a history of substance or alcohol abuse within the past 2 years.
• Female participants who are pregnant (that is, a positive or indeterminate pregnancy test).
• Female participants who are breastfeeding.
• Female participants 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 (M0).
• Female participants of childbearing potential who are sexually active and who refuse to use an acceptable contraceptive method up to 6 weeks post final vaccination on Day 90 (M3). In addition, they must also be advised not to donate ova during this period.
• Participant has received any of the following:

• A licensed vaccine within 14 days (for inactivated vaccines) or 28 days (for live vaccines) prior to TDV or placebo administration on Day 1 (M0). This includes co-administration with routine vaccines.
• A coronavirus vaccine within 14 days prior to TDV or placebo administration.
• A vaccine authorized for emergency use within 28 days prior to TDV or placebo administration.
• Participant is scheduled to receive any other vaccine within 28 days after TDV or placebo administration.
• Participant is participating in any clinical trial with another investigational product 30 days prior to Day 1 (M0) or intending to participate in another clinical trial at any time during the conduct of this trial.
• Participant has taken part in any clinical trial of a dengue or other flavivirus (example, West Nile virus) candidate vaccine, except if it is known that the participant received placebo in those trials.
• Participant or their first-degree relatives are involved in the trial conduct.
• Participant identified as an employee of the investigator or trial center, with direct involvement in the proposed trial or other trials under the direction of that investigator or trial center.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Prevention

Study locations

Brazil · 2 centers

• Associacao Obras Sociais Irma Dulce Hospital Santo Antonio — Salvador
• Fundacao Faculdade Regional de Medicina de Sao Jose Do Rio Preto Hospital de Base - PPDS — São José do Rio Preto

Singapore · 2 centers

• Singapore General Hospital (SGH) — Singapore
• Tan Tock Seng Hospital — Singapore

Thailand · 2 centers

• Ramathibodi Hospital — Ratchathewi
• Hospital for Tropical Diseases — Ratchathewi

Argentina · 1 center

• Fundacion Huesped - PPDS — Buenos Aires

Identifiers

NCT: NCT06579755 · DEN-321

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗