- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01696422
Phase II Trial to Evaluate Safety and Immunogenicity of a Dengue 1,2,3,4 (Attenuated) Vaccine
January 15, 2019 updated by: Butantan Institute
Phase II, Step-wise, Randomized, Double-blind, Controlled Clinical Trial for Safety and Immunogenicity Evaluation of a Lyophilized Formulation of Dengue 1,2,3,4 (Attenuated) Vaccine in Healthy Adults
This is a phase II step-wise, randomized, multicenter, double-blind and controlled clinical trial to evaluate the safety and immunogenicity of a attenuated tetravalent lyophilized dengue vaccine manufactured by Butantan Institute.
Three Clinical Sites at University of Sao Paulo - Brazil will participate in the study.
A total of 300 volunteers will be recruited and divided into two steps: Step A (with no previous exposure to dengue) and Step B (with and without previous exposure to dengue).
In step A the participants will be assigned to receive either the lyophilized vaccine, or the liquid vaccine(developed at NIH and produced and formulated at Butantan according to the NIH-Protocol), or the placebo.
In Step B participants will be assigned to receive either the lyophilized vaccine, or the placebo.
Both vaccine formulations (lyophilized and liquid) are composed of the same attenuated viruses: rDEN1∆30, rDEN2/4∆30(ME), rDEN3∆30/31, and rDEN4∆30.
At the end of the study, 20 volunteers will have received the liquid formulation (NIH), 210 the lyophilized formulation (Butantan), and 70 will have received the placebo.
All participants included in both steps will be followed by a period of five years after their inclusion in the study.
The study hypothesis is that the investigational lyophilized dengue vaccine manufactured by Butantan Institute is safe and confers balanced immune response, after one dose of 1000PFU, to all for vaccine viruses.
Study Overview
Status
Unknown
Conditions
Detailed Description
This is a phase II step-wise, randomized, multicenter, double-blind and controlled clinical trial to evaluate the safety and immunogenicity of an attenuated tetravalent lyophilized dengue vaccine manufactured by Butantan Institute.
A total of 300 volunteers will be recruited including men and no pregnant/breastfeeding women between 18 and 59 years of age complete, with and without previous exposure to dengue that will be randomized into Step A and Step B. Step A will include 50 volunteers with no previous exposure and they will be randomly assigned to receive one dose of either the lyophilized formulation (Butantan), or the liquid formulation (TetraVax-DV Vaccine - Admixture TV003 developed by NIH/NIAID and produced and formulated at Butantan according the NIH-Protocol), or the placebo.
A second dose will be administered six months after the first vaccination as part of an exploratory assessment.
Step B will include 250 participants(50 without previous exposure to dengue,and 200 with previous exposure to dengue) who will be randomly assigned to receive one dose of either the lyophilized formulation (Butantan),or the placebo.
All participants included in both steps will be followed by a period of five years after their inclusion in the study.
The vaccines will be administered at dose of 1000 PFU (for each of the vaccine viruses),and both vaccines and the placebo will be administered subcutaneously.
Study Type
Interventional
Enrollment (Actual)
300
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Sao Paulo, Brazil, 01246- 903
- Instituto da Criança do Hospital das Clínicas da Faculdade de Medicina da USP
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São Paulo, Brazil, 05403-010
- Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
16 years to 57 years (Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Healthy adults (men and non-pregnant women), from 18 to 59 years old;
- Willingness to participate throughout the study period (approximately five years);
- Willingness to participate documented by the signature of ICF;
- Females with childbearing potential must be willing to avoid pregnancies up to three weeks after the last vaccine dose. All female volunteers will be considered with childbearing potential unless they have documented history of hysterectomy, tubal ligation or are postmenopausal (12 months of amenorrhea after the last menstrual period).
Exclusion Criteria:
- Pregnancy (confirmed by positive beta-hCG test) or breastfeeding;
- Evidence of active neurological, cardiac, pulmonary, hepatic or renal disease as clinical history, physical examination and/or laboratory results;
- Compromised immune system diseases including: diabetes mellitus, cancer (except basal cell carcinoma) and autoimmune diseases;
- 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;
- Values of absolute neutrophil, alanine aminotransferase (ALT) or serum creatinine count greater than or equal to Grade 1, as defined in the protocol;
- Abusive usage of alcohol or drugs in the past 12 months that has caused medical, professional or family problems, indicated by clinical history;
- History of severe allergic reactions or anaphylaxis;
- Diagnosis of asthma with a history of hospitalization in the last six months due to illness;
- Fever or suspect fever within 72 hours prior to vaccination or axillary temperature greater than 37,8°C on the day of vaccination;
- Positive result of HIV-1 serology by screening or confirmed tests;
- Screening or confirmed positive test for hepatitis C virus (HCV);
- Positive test of hepatitis B virus antigen surface (AgHBs) alone or against hepatitis B "core" antigen antibody (anti-HBc);
- Use of corticosteroids (except topical or nasal) or other immunosuppressive drugs within 42 days before study initiation/baseline. It will be considered immunosuppressive dose of corticosteroids the equivalent to a dose ≥10 mg of prednisone per day for over 14 days;
- Use of anticoagulant medication;
- 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 42 days after receiving the investigational product;
- History of asplenia;
- Have received blood products in the past six months, including transfusions or immunoglobulin, or scheduled administration of blood products or immunoglobulin for the first 42 days after vaccination;
- Use of any investigational product within 42 days before or after receiving this study vaccination;
- Has participated in another clinical trial six months prior to vaccination;
- Denies permission for biological material storage for future research as defined in ICF;
- 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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Step A: dengue lyophilized vaccine
Dengue 1,2,3,4 (attenuated) vaccine Two doses with a six-months interval, SC
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Dose 1000 PFU per virus (1,2,3,4) Route:subcutaneous
Other Names:
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Active Comparator: Step A:dengue liquid vaccine
TetraVax-DV Vaccine - Admixture TV003 Two doses with a six-months interval, SC
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Dose 1000 PFU per virus (1,2,3,4) Route: subcutaneous
Other Names:
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Placebo Comparator: Step A: Placebo
Placebo comparator Two doses with a six-months interval, SC
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Route:subcutaneous
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Experimental: Step B: dengue lyophilized vaccine
Dengue 1,2,3,4 (attenuated) vaccine Single dose, SC
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Dose 1000 PFU per virus (1,2,3,4) Route:subcutaneous
Other Names:
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Placebo Comparator: Step B: Placebo
Placebo comparator Single dose, SC
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Route:subcutaneous
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Safety
Time Frame: Up to day 21 after vaccination
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Frequency of solicited and unsolicited local and systemic adverse reactions up to Day 21 after vaccination.
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Up to day 21 after vaccination
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Immunogenicity
Time Frame: Up to day 91 after vaccination
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Seroconversion rate for each of the four vaccine viruses defined by PRNT50 ≥1:10 for each vaccine virus serotype on Days 28, 56 or 91.
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Up to day 91 after vaccination
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Safety
Time Frame: up to Day 182 after the first vaccination
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up to Day 182 after the first vaccination
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Immunogenicity
Time Frame: Annualy up to five years
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Annualy up to five years
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Exploratory
Time Frame: Up to Day 182 after the second vaccination
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Up to Day 182 after the second vaccination
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Study Director: Alexander R Precioso, MD, PhD, Instituto Butantan
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- Blaney JE Jr, Durbin AP, Murphy BR, Whitehead SS. Development of a live attenuated dengue virus vaccine using reverse genetics. Viral Immunol. 2006 Spring;19(1):10-32. doi: 10.1089/vim.2006.19.10.
- Durbin AP, Kirkpatrick BD, Pierce KK, Schmidt AC, Whitehead SS. Development and clinical evaluation of multiple investigational monovalent DENV vaccines to identify components for inclusion in a live attenuated tetravalent DENV vaccine. Vaccine. 2011 Sep 23;29(42):7242-50. doi: 10.1016/j.vaccine.2011.07.023. Epub 2011 Jul 21.
- Durbin AP, Kirkpatrick BD, Pierce KK, Elwood D, Larsson CJ, Lindow JC, Tibery C, Sabundayo BP, Shaffer D, Talaat KR, Hynes NA, Wanionek K, Carmolli MP, Luke CJ, Murphy BR, Subbarao K, Whitehead SS. A single dose of any of four different live attenuated tetravalent dengue vaccines is safe and immunogenic in flavivirus-naive adults: a randomized, double-blind clinical trial. J Infect Dis. 2013 Mar 15;207(6):957-65. doi: 10.1093/infdis/jis936. Epub 2013 Jan 17.
- Silveira CGT, Magnani DM, Costa PR, Avelino-Silva VI, Ricciardi MJ, Timenetsky MDCST, Goulart R, Correia CA, Marmorato MP, Ferrari L, Nakagawa ZB, Tomiyama C, Tomiyama H, Kalil J, Palacios R, Precioso AR, Watkins DI, Kallas EG. Plasmablast Expansion Following the Tetravalent, Live-Attenuated Dengue Vaccine Butantan-DV in DENV-Naive and DENV-Exposed Individuals in a Brazilian Cohort. Front Immunol. 2022 Jun 28;13:908398. doi: 10.3389/fimmu.2022.908398. eCollection 2022.
- Kallas EG, Precioso AR, Palacios R, Thome B, Braga PE, Vanni T, Campos LMA, Ferrari L, Mondini G, da Graca Salomao M, da Silva A, Espinola HM, do Prado Santos J, Santos CLS, Timenetsky MDCST, Miraglia JL, Gallina NMF, Weiskopf D, Sette A, Goulart R, Salles RT, Maestri A, Sallum AME, Farhat SCL, Sakita NK, Ferreira JCOA, Silveira CGT, Costa PR, Raw I, Whitehead SS, Durbin AP, Kalil J. Safety and immunogenicity of the tetravalent, live-attenuated dengue vaccine Butantan-DV in adults in Brazil: a two-step, double-blind, randomised placebo-controlled phase 2 trial. Lancet Infect Dis. 2020 Jul;20(7):839-850. doi: 10.1016/S1473-3099(20)30023-2. Epub 2020 Mar 24.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
October 1, 2013
Primary Completion (Actual)
April 1, 2016
Study Completion (Anticipated)
December 1, 2020
Study Registration Dates
First Submitted
September 27, 2012
First Submitted That Met QC Criteria
September 27, 2012
First Posted (Estimate)
October 1, 2012
Study Record Updates
Last Update Posted (Actual)
January 16, 2019
Last Update Submitted That Met QC Criteria
January 15, 2019
Last Verified
January 1, 2019
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- DEN-01-IB
- U1111-1135-4553 (Registry Identifier: UTN)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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