Phase II Trial to Evaluate Safety and Immunogenicity of a Dengue 1,2,3,4 (Attenuated) Vaccine

NCT01696422 | Unknown Phase 2 DMC

• 2 other identifiers: DEN-01-IBU1111-1135-4553
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Dengue

Keywords

Dengue; tetravalent attenuated Vaccine; Healthy adults

Outcome Measures

Primary Outcomes (2)

• Safety

  Frequency of solicited and unsolicited local and systemic adverse reactions up to Day 21 after vaccination.

  Up to day 21 after vaccination

• Immunogenicity

  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.

  Up to day 91 after vaccination

Secondary Outcomes (2)

• Safety

  up to Day 182 after the first vaccination

• Immunogenicity

  Annualy up to five years

Other Outcomes (1)

• Exploratory

  Up to Day 182 after the second vaccination

Study Arms (5)

Step A: dengue lyophilized vaccine

EXPERIMENTAL

Dengue 1,2,3,4 (attenuated) vaccine Two doses with a six-months interval, SC

Biological: Dengue 1,2,3,4 (attenuated) vaccine

Step A:dengue liquid vaccine

ACTIVE COMPARATOR

TetraVax-DV Vaccine - Admixture TV003 Two doses with a six-months interval, SC

Biological: TetraVax-DV Vaccine - Admixture TV003

Step A: Placebo

PLACEBO COMPARATOR

Placebo comparator Two doses with a six-months interval, SC

Other: Placebo

Step B: dengue lyophilized vaccine

EXPERIMENTAL

Dengue 1,2,3,4 (attenuated) vaccine Single dose, SC

Biological: Dengue 1,2,3,4 (attenuated) vaccine

Step B: Placebo

PLACEBO COMPARATOR

Placebo comparator Single dose, SC

Other: Placebo

Interventions

Dengue 1,2,3,4 (attenuated) vaccine BIOLOGICAL

Dose 1000 PFU per virus (1,2,3,4) Route:subcutaneous

Also known as: Butantan DV, Dengue Tetravalent Vaccine - Lyophilized formulation

Step A: dengue lyophilized vaccine; Step B: dengue lyophilized vaccine

TetraVax-DV Vaccine - Admixture TV003 BIOLOGICAL

Dose 1000 PFU per virus (1,2,3,4) Route: subcutaneous

Also known as: Dengue Tetravalent Vaccine - Liquid formulation

Step A:dengue liquid vaccine

Placebo OTHER

Route:subcutaneous

Step A: Placebo; Step B: Placebo

Eligibility Criteria

• Age: 18 Years - 59 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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).

You may not qualify if:

• 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;

Sponsors & Collaborators

• Butantan Institute: lead
• Banco Nacional de Desenvolvimento Economico e Social: collaborator
• Fundação de Amparo à Pesquisa do Estado de São Paulo: collaborator
• Butantan Foundation: collaborator

Study Sites (2)

Instituto da Criança do Hospital das Clínicas da Faculdade de Medicina da USP

São Paulo, 01246- 903, Brazil

Location

Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo

São Paulo, 05403-010, Brazil

Location

Related Publications (5)

• 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.

  PMID: 16553547 BACKGROUND

• 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.

  PMID: 21781997 BACKGROUND

• 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.

  PMID: 23329850 BACKGROUND

• 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.

  PMID: 35837409 DERIVED

• 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.

  PMID: 32220283 DERIVED

MeSH Terms

Conditions

Dengue

Interventions

Vaccines

Condition Hierarchy (Ancestors)

Mosquito-Borne Diseases; Vector Borne Diseases; Infections; Arbovirus Infections; Virus Diseases; Flavivirus Infections; Flaviviridae Infections; RNA Virus Infections; Hemorrhagic Fevers, Viral

Intervention Hierarchy (Ancestors)

Biological Products; Complex Mixtures

Study Officials

• Alexander R Precioso, MD, PhD

  Instituto Butantan

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 27, 2012
• First Posted: October 1, 2012
• Study Start: October 1, 2013
• Primary Completion: April 1, 2016
• Study Completion: December 1, 2020
• Last Updated: January 16, 2019

Record last verified: 2019-01

Locations

BR (2)