Clinical trial NCT06891950: Butantan-DV Vaccine in Elderly Populations (DEN-04-IB)
Official title: Phase 3B, Double-blind, Randomized Study to Evaluate the Safety and Non-inferiority of the Humoral Immune Response of the Butantan Dengue Vaccine in Participants Aged 60 to 79 Years Compared to Participants Aged 40 to 59 Years
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Dengue
Keywords: dengue vaccine
elderly population
Lead sponsor: Butantan Institute
Sponsor class: OTHER_GOV
Collaborators: name: Fundação Butantan
First posted: 2025-03-24
Enrollment: 997
Sex: ALL
Minimum age (years): 40
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a randomized, double-blind (60-79 years old) and open-label (40-59 years), three-arm parallel Phase 3b, multicenter study to evaluate the safety and non-inferiority of the humoral immune response of the Butantan Dengue vaccine (Dengue 1,2,3,4 (attenuated)) in participants aged 60 - 79 years (elderly) compared to participants aged 40 to 59 years (adults), with or without previous dengue and healthy based on clinical examination. The 997 participants will be randomized with a 9:3:1 allocation, so that the largest group (60 - 79 years) will be allocated to receive Dengue 1,2,3,4 (attenuated) in a blinded regimen (n=690), the next group (40-59 years) will be allocated to receive Dengue 1,2,3,4 (attenuated) in an open regimen (n=230) and the last (60-79 years) will be allocated to receive placebo (n=77), respectively.
Primary purpose: PREVENTION

Brief summary: This is a randomized, double-blind (60 -79 years) and open-label (40-59 years), three-arm parallel Phase 3b, multicenter study to evaluate the safety and non-inferiority of the humoral immune response of the Butantan Dengue vaccine (Dengue 1,2,3,4 (attenuated)) in participants aged 60 -79 years (elderly) compared to participants aged 40 to 59 years (adults), with or without previous dengue and healthy based on clinical examination.

Detailed description: The study aims to evaluate the non-inferiority of the immune response induced by the Dengue 1,2,3,4 (attenuated) vaccine in participants aged 60 - 79 years old (elderly) compared to participants aged 40 to 59 years on Day 42 + 7 days after vaccination. The primary analysis will include the immunogenicity cohort (n=460 participants, allocated 1:1). The primary outcome is the proportion of neutralizing antibody seroconversion measured by plaque reduction neutralization test (PRNT50), for each dengue serotype, of participants aged 60 - 79 years (elderly) compared with participants aged 40 to 59 years (adults), with or without previous exposure to dengue, on Day 42 + 7 days after vaccination. The primary safety outcome will be the frequency and intensity of solicited and unsolicited adverse reactions from vaccination to Day 22 post-vaccination among participants aged 60 - 79 years and in participants aged 40 to 59 years, with or without prior exposure to dengue. The study will last one year in order to assess the duration of the immune response and serious adverse events (SAE) and events of special interest (SIAE). Throughout the study period, there will be surveillance of suspected and confirmed cases of dengue, chikungunya fever and Zika virus fever. Therefore, if the null hypothesis is rejected, the immunogenicity and safety results of immunobridging will be used to expand the use of Dengue 1,2,3,4 (attenuated) for the age group of 60 - 79 years old.

Eligibility criteria: Inclusion Criteria:

* a. Healthy participants aged between 40 and 79 years at the time of study entry, with or without a history of exposure to dengue fever;

  b. Agree to periodic contact by telephone, electronic means, and home visits and to the research center;

  c. Participants with reproductive potential must be using some effective contraceptive method at screening and continue using it for up to 90 days after the intervention; except in cases where the volunteer declares that she is not at risk of becoming pregnant, either by not engaging in sexual activities or by engaging in them in a non-reproductive manner, up to 90 days after vaccination;

  d. Demonstrate intent to participate in the study, documented by the participant's signature of the informed consent form, as well as the study procedures, including completing the Participant Diaries, blood collection, and being available for scheduled study visits and contacts.

Exclusion Criteria:

* a. For female participants with reproductive potential: pregnancy (confirmed by positive β-hCG test), breastfeeding or manifest intention to have sexual practices with reproductive potential without using a contraceptive method in the 90 days following vaccination;

  b. Planned donation of blood, semen or eggs in the 90 days following vaccination;

  c. Evidence of active uncontrolled neurological, cardiac, pulmonary, hepatic or renal disease according to anamnesis or physical examination, at the discretion of the investigator;

  d. Diseases that compromise the immune system, including: decompensated diabetes mellitus, active neoplasms or history of neoplasms in the last five years (except basal cell carcinoma), congenital or acquired immunodeficiencies (including HIV/AIDS), solid organ transplants (heart, liver, pancreas, lung, kidney) or uncontrolled autoimmune diseases according to anamnesis or physical examination, as well as a history of liver failure, heart failure or terminal chronic kidney disease or dialysis;

  e. Behavioral, cognitive, or psychiatric illness that, in the opinion of the principal investigator or his/her medical representative, affects the potential participant's ability to understand and comply with the requirements of the study protocol;

  f. Any abuse of alcohol or drugs in the last 12 months prior to enrollment in the study that has caused medical, professional, or family problems, as indicated by the clinical history;

  g. History of severe allergic reaction or anaphylaxis to the vaccine or components of the study vaccine;

  h. History of asplenia;

  i. Participation in another clinical trial with administration of an investigational product during the six months prior to enrollment in the study or scheduled participation in another clinical trial in the 12 months following enrollment;

  j. Previous participation in a dengue vaccine evaluation study or previous exposure to dengue vaccine;

  k. Use of immunosuppressive therapies six months prior to enrollment in the study or their scheduled use in the 12 months following enrollment. The following immunosuppressive therapies will be considered: antineoplastic chemotherapy, radiotherapy, immunosuppressants to induce tolerance to transplants, monoclonal antibody therapy for the treatment of rheumatological diseases, among others;

  l.Having received an immunosuppressive dose of corticosteroid in the last three months prior to inclusion in the study or administration of an immunosuppressive dose of corticosteroid for the 12 months following inclusion in the study. The dose of corticosteroid considered immunosuppressive is the equivalent of prednisone at a dose of 20 mg/day, for adults, for 14 days (cumulative dose equivalent to at least 280 mg of prednisone). Continuous use of topical or nasal corticosteroid is not considered immunosuppressive;

  m. Having received blood products (transfusions or immunoglobulins) in the last three months prior to inclusion in the study, or scheduled administration of blood products or immunoglobulin in the 12 months following inclusion in the study;

  n. Fever, suspected or measured, in the 72 hours prior to vaccination or axillary temperature ≥ 37.8°C on the day of vaccination (inclusion may be postponed until the potential participant has been fever-free for 72 hours);

  o. Having received a live attenuated virus vaccine in the last 28 days or an inactivated vaccine in the last 14 days prior to inclusion in the study, or having been immunized within 12 months of inclusion in the study;

  p. Any other condition that, in the opinion of the principal investigator or his/her medical representative, may jeopardize the safety or rights of a potential participant or that prevents him/her from complying with this protocol.

Primary outcomes:
measure: Immunogenicity Primary
timeFrame: Day 42+7 days post-vaccination.
measure: Safety Primary 1.
timeFrame: From vaccination to Day 22 + 3 days post-vaccination.
measure: Safety Primary 2.
timeFrame: From vaccination to Day 22 + 3 days post-vaccination.
Secondary outcomes:
measure: Immunogenicity Secondary 1.
timeFrame: Day 1, Day 42 + 7 days and Day 364 + 28 days after vaccination.
measure: Immunogenicity Secondary 2.
timeFrame: Day 42 + 7 days after vaccination.
measure: Immunogenicity Secondary 3.
timeFrame: Day 364 + 28 days after vaccination.
measure: Immunogenicity Secondary 4.
timeFrame: Days 42 + 7 days and Day 364 + 28 days after vaccination.
measure: Safety Secondary 1.
timeFrame: From Day 22 + 3 days post-vaccination until the end of study.
measure: Safety Secondary 2.
timeFrame: Throughout the study period.
measure: Safety Secondary 3.
timeFrame: Throughout the study period.
measure: Safety Secondary 4.
timeFrame: Days 1, 6, 9, 12, 22 and 30.
measure: Safety Secondary 5.
timeFrame: Day 29 and throughout the study period.
measure: Safety Secondary 6.
timeFrame: Day 22 + 3 days after vaccination.
Other outcomes:
Locations:
city: Porto Alegre
country: Brazil
facility: Centro de Pesquisa 1 (POA01): Hospital São Lucas - PUCRS
state: Rio Grande do Sul
Study officials:
affiliation: Instituto Butantan
name: Fernanda C Boulos, MD, PhD
role: STUDY_DIRECTOR
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