Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    NCT02406729
Previous Study | Return to List | Next Study

Phase III Trial to Evaluate Efficacy and Safety of a Tetravalent Dengue Vaccine

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02406729
Recruitment Status : Recruiting
First Posted : April 2, 2015
Last Update Posted : January 16, 2019
Sponsor:
Information provided by (Responsible Party):
Butantan Institute

Tracking Information
First Submitted Date  ICMJE March 30, 2015
First Posted Date  ICMJE April 2, 2015
Last Update Posted Date January 16, 2019
Actual Study Start Date  ICMJE February 2016
Estimated Primary Completion Date June 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 18, 2015)
  • Efficacy (incidence density of symptomatic dengue cases, virologically confirmed) [ Time Frame: at 52 weeks post vaccination, all cases after 28 days post-vaccination ]
    • The primary efficacy outcome is incidence density of symptomatic dengue cases, virologically confirmed, after 28 days post-vaccination. Virological confirmation might be done by viral isolation, RT-PCR and/or detection of NS1.
  • Safety (adverse reactions) [ Time Frame: in the first 21 days post-vaccination ]
    • The primary safety outcome is the frequency of local and systemic adverse reactions, solicited and non-solicited in the three age groups, within the first 21 days post-vaccination. Adverse reactions are defined as adverse events that have a reasonable causal relationship with vaccination.
Original Primary Outcome Measures  ICMJE
 (submitted: April 1, 2015)
  • Efficacy (ncidence density of symptomatic dengue cases, virologically confirmed) [ Time Frame: at 52 weeks post vaccination, all cases after 28 days post-vaccination ]
    • The primary efficacy outcome is incidence density of symptomatic dengue cases, virologically confirmed, after 28 days post-vaccination. Virological confirmation might be done by viral isolation, RT-PCR and/or detection of NS1.
  • Safety (adverse reactions) [ Time Frame: in the first 21 days post-vaccination ]
    • The primary safety outcome is the frequency of local and systemic adverse reactions, solicited and non-solicited in the three age groups, within the first 21 days post-vaccination. Adverse reactions are defined as adverse events that have a reasonable causal relationship with vaccination.
Change History Complete list of historical versions of study NCT02406729 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase III Trial to Evaluate Efficacy and Safety of a Tetravalent Dengue Vaccine
Official Title  ICMJE Phase III Trial to Evaluate Efficacy and Safety of a Dengue 1,2,3,4 (Attenuated) Vaccine
Brief Summary

This is a randomized, multicenter, double-blind, placebo-controlled Phase III study that will evaluate efficacy and safety of a live attenuated, tetravalent, lyophilized dengue vaccine produced by Butantan Institute.

The study will be carried out in multiple sites in Brazil. The study will be community-based in select urban areas where there's dengue transmission.

Study's intervention will be a single dose of the tetravalent dengue vaccine or placebo in a ratio 2:1. For efficacy analysis will be considered all dengue cases occurring after 28 days post-vaccination in the entire population of 16944 participants.

For safety analysis participants will be divided in three age groups: 18 to 59 ys, 7-17 ys and 2 to 6 ys. In each of these age groups there will be a minimum of 4992 participants. The age groups of 18 to 59 ys and 7 to 17 ys will start first. Once safety data for the first 21 days after vaccination is analysed for 450 participants in 7-to17-ys age group, the following group, of 2 to 6 ys, will start.

The study's hypothesis is that the vaccine under investigation and produced by Butantan Institute is safe and provides protection against dengue symptomatic disease of 80% or more with a lower bound of the 95% confidence interval of 25%. This way, the expected number of dengue cases virologically confirmed is 24 or more which will provide a response in terms of vaccine efficacy.

All participants will be followed up for five years to verify dengue incidence, regardless severity.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Condition  ICMJE Dengue
Intervention  ICMJE
  • Biological: Dengue 1,2,3,4 (attenuated) vaccine
    Dose 1000 PFU per virus (1,2,3,4) Route:subcutaneous
    Other Names:
    • Butantan DV
    • TetraVax-DV-TV003
  • Other: Placebo
    Route:subcutaneous
Study Arms  ICMJE
  • Experimental: Dengue 1,2,3,4 (attenuated) vaccine
    Dengue 1,2,3,4 (attenuated) vaccine Single dose, SC
    Intervention: Biological: Dengue 1,2,3,4 (attenuated) vaccine
  • Placebo Comparator: Placebo
    Placebo Single dose, SC
    Intervention: Other: Placebo
Publications * Precioso AR, Palacios R, Thomé B, Mondini G, Braga P, Kalil J. Clinical evaluation strategies for a live attenuated tetravalent dengue vaccine. Vaccine. 2015 Dec 10;33(50):7121-5. doi: 10.1016/j.vaccine.2015.09.105. Epub 2015 Oct 14. Review.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 1, 2015)
16944
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2025
Estimated Primary Completion Date June 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Children who have completed 24 months of age, adolescents and adults who have not completed 60 years of age;
  2. Agree with periodic contacts, either/or by phone, electronic means, and home visits.
  3. Show voluntary intention to participate in the study, documented by the participant's or participant's legal representative's signature of the informed consent form.

Exclusion Criteria:

  1. For women: Pregnancy (confirmed by positive beta-hCG test) or breastfeeding;
  2. Evidence of active neurological, cardiac, pulmonary, hepatic or renal disease as per clinical history and/or physical examination;
  3. Compromised immune system diseases including: decompensated diabetes mellitus, cancer (except basal cell carcinoma), congenital or acquired immune deficiencies and not controlled autoimmune, as per clinical history and/or physical examination;
  4. Behavioral, cognitive or psychiatric disease that in the opinion of the principal investigator or his representative physician, affects the participant ability to understand and cooperate with all study protocol requirements;
  5. Abusive usage of alcohol or drugs in the past 12 months that has caused medical, professional or family problems, indicated by clinical history;
  6. History of severe allergic reactions or anaphylaxis to the vaccine or to components of the vaccine in study;
  7. History of asplenia;
  8. Use of any investigational product within 28 days before or after receiving this study vaccination;
  9. Has participated in another clinical trial six months prior to inclusion in the study or planning to participate in another clinical trial within 2 years following inclusion;
  10. Use of immunosuppressant drugs such as: antineoplastic chemotherapy, radiation therapy, immunosuppressants to induce tolerance to transplants, and corticosteroids use (except topical or nasal). For this protocol will be considered for exclusion use of corticosteroids 3 months prior to the inclusion in the study and 6 months prior to the inclusion for the other therapies mentioned, and planned use of any immunosuppressant therapy within 2 years following inclusion in the study. It will be considered immunosuppressive dose of corticosteroids the equivalent to a dose ≥20 mg of prednisone per day for adults and the equivalent of prednisone at 2 mg/kg/day for children for over 7 days;
  11. Have received blood products in the past three months, including transfusions or immunoglobulin, or scheduled administration of blood products or immunoglobulin for the following 2 years after vaccination;
  12. Fever or suspected fever within 72 hours prior to vaccination or axillary temperature greater than 37,8°C on the day of vaccination (inclusion might be postponed until participant has completed 72 hours of no fever);
  13. Have received live virus vaccine within 28 days or killed virus vaccine in the last 14 days prior to vaccination, or have a scheduled immunization during the first 28 days after receiving the investigational product;
  14. Any other condition that might put in risk the safety/rights of a potential participant or hurdle his/her compliance with this protocol in investigator's opinion or his representative physician.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 24 Months to 59 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Alexander R Precioso, MD, PhD +55(11)26279372 alexander.precioso@butantan.gov.br
Contact: Ricardo Palacios, MD, PhD +55(11)26279372 ricardo.palacios@butantan.gov.br
Listed Location Countries  ICMJE Brazil
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02406729
Other Study ID Numbers  ICMJE DEN-03-IB
U1111-1168-8679 ( Registry Identifier: UTN )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Butantan Institute
Study Sponsor  ICMJE Butantan Institute
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Alexander R Precioso, MD, PhD Butantan Institute
Study Chair: Ricardo Palacios, MD, PHD Butantan Institute
Principal Investigator: Esper G Kallas, MD, PhD School of Medicine, University of São Paulo
PRS Account Butantan Institute
Verification Date January 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP