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Trial record 40 of 158 for:    Diseases | ( Map: Costa Rica )

VRC 705: A Zika Virus DNA Vaccine in Healthy Adults and Adolescents (DNA)

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03110770
Recruitment Status : Active, not recruiting
First Posted : April 12, 2017
Last Update Posted : July 25, 2019
Sponsor:
Collaborators:
The Emmes Company, LLC
Leidos Biomedical Research, Inc.
FHI 360
PPD
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Brief Summary:
This is a multicenter, randomized, study to evaluate the safety, immunogenicity, and efficacy of VRC-ZKADNA090-00-VP (Zika virus wildtype DNA vaccine) or placebo. In Part A, the primary objective is to evaluate the safety and tolerability of the vaccine. In Part B, the primary objectives are to evaluate the safety and efficacy of the vaccine compared to placebo.

Condition or disease Intervention/treatment Phase
Zika Virus Zika Virus Infection Virus Diseases Flavivirus Infections Flaviviral Diseases Flaviviridae Infections RNA Virus Infections Biological: VRC-ZKADNA090-00-VP Other: VRC-PBSPLA043-00-VP Phase 2

Detailed Description:

This is a multicenter, randomized study to evaluate safety, immunogenicity, and efficacy of a 3-dose vaccination regimen with the Zika virus wildtype (ZIKVwt) DNA vaccine, VRC-ZKADNA090-00-VP or placebo (VRC-PBSPLA043-00-VP). The placebo is a sterile phosphate-buffered saline (PBS). The hypotheses are that the ZIKVwt DNA vaccine will be safe and will elicit a ZIKV-specific immune response.

Participants will receive study product intramuscularly (IM) in the limbs as specified by the group assignment by PharmaJet needle-free device. In Part A, 90 participants will be randomized to vaccine at a 1:1:1 ratio to receive a 4 mg or 8 mg dose of vaccine split between 2 or 4 injections. In Part B, about 2400 participants will be randomized to vaccine or placebo in a 1:1 ratio to receive a 4 mg dose of vaccine or 1 mL of placebo split between 2 injections.

Vaccine safety and tolerability will be assessed by monitoring of clinical and laboratory parameters throughout the study. Solicited reactogenicity symptoms will be collected for 7 days after each product administration. The study schedule will include clinic visits with safety and immunogenicity blood samples collected at particular time points.

The vaccine dose and administration plan for Part B was selected based on Part A and Phase 1 data. Vaccine efficacy will be evaluated in Part B by comparing incidence of ZIKV cases between vaccine and placebo groups. During the study, when participants exhibit any possible symptom of ZIKV infection, they will be evaluated by blood and urine ZIKV polymerase chain reaction (PCR). Stored blood and urine samples will also be assessed retrospectively by ZIKV PCR to identify possible asymptomatic cases. A Data and Safety Monitoring Board (DSMB) will oversee the study.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 2338 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Part A participants (n=90) will be randomized to vaccine at a 1:1:1 ratio to receive a 4 mg or 8 mg dose of vaccine split between 2 or 4 injections. In Part B, about 2400 participants will be randomized to vaccine or placebo in a 1:1 ratio to receive a 4 mg dose of vaccine or 1 mL of placebo split between 2 injections. The concentration and number of injections in Part B was determined by preliminary data from the Phase 1 trial and Part A.
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Masking Description:

Part A is open-label. For Part A, the participant, investigator and outcome assessor will know what the participant received.

Part B injections will be prepared by an unblinded site pharmacist, designee, or otherwise qualified personnel who will not be involved in any participants assessments and who will not discuss randomizations with study clinicians. Subjects, study personnel, site data entry personnel, and laboratory personnel performing immunologic assays will be blinded to the treatment assignment of all product administrations. The IND Sponsor intends to unblind treatment assignments for Part B of the study once 90 cases of ZIKV infection are detected. The DSMB will be consulted prior to unblinding.

Primary Purpose: Prevention
Official Title: VRC 705: A Phase 2/2B, Randomized Trial to Evaluate the Safety, Immunogenicity and Efficacy of a Zika Virus DNA Vaccine in Healthy Adults and Adolescents
Actual Study Start Date : March 29, 2017
Estimated Primary Completion Date : January 2020
Estimated Study Completion Date : January 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Zika Virus

Arm Intervention/treatment
Experimental: Part A, Group 1
ZIKV vaccine (VRC-ZKADNA090-00-VP), in 2 limbs (both arms) on Day 0, Day 28 (+/-7 days), and Day 56 (-7/+14 days), 4 mg of vaccine.
Biological: VRC-ZKADNA090-00-VP
VRC-ZKADNA090-00-VP is composed of a single closed-circular DNA plasmid (VRC 5283) that encodes with wild type (wt) precursor transmembrane M (prM) and envelope (E) proteins from the H/PF/2013 strain of ZIKV

Experimental: Part A, Group 2
ZIKV vaccine (VRC-ZKADNA090-00-VP), in 4 limbs (both arms and legs) on Day 0, Day 28 (+/-7 days), and Day 56 (-7/+14 days), 4 mg of vaccine.
Biological: VRC-ZKADNA090-00-VP
VRC-ZKADNA090-00-VP is composed of a single closed-circular DNA plasmid (VRC 5283) that encodes with wild type (wt) precursor transmembrane M (prM) and envelope (E) proteins from the H/PF/2013 strain of ZIKV

Experimental: Part A, Group 3
ZIKV vaccine (VRC-ZKADNA090-00-VP), in 4 limbs (both arms and legs) on Day 0, Day 28 (+/-7 days), and Day 56 (-7/+14 days), 8 mg of vaccine.
Biological: VRC-ZKADNA090-00-VP
VRC-ZKADNA090-00-VP is composed of a single closed-circular DNA plasmid (VRC 5283) that encodes with wild type (wt) precursor transmembrane M (prM) and envelope (E) proteins from the H/PF/2013 strain of ZIKV

Experimental: Part B, Group 4
ZIKV vaccine (VRC-ZKADNA090-00-VP), in 2 limbs (both arms) on Day 0, Day 28 (+/-7 days), and Day 56 (-7/+14 days), 4 mg of vaccine.
Biological: VRC-ZKADNA090-00-VP
VRC-ZKADNA090-00-VP is composed of a single closed-circular DNA plasmid (VRC 5283) that encodes with wild type (wt) precursor transmembrane M (prM) and envelope (E) proteins from the H/PF/2013 strain of ZIKV

Placebo Comparator: Part B, Group 5
Sterile phosphate-buffered saline (PBS) (VRC-PBSPLA043-00-VP), the placebo, in 2 limbs (both arms) on Day 0, Day 28 (+/-7 days), and Day 56 (-7/+14 days), 1 mL of placebo.
Other: VRC-PBSPLA043-00-VP
A sterile phosphate-buffered saline (PBS) prepared for human administration as a placebo
Other Name: Placebo




Primary Outcome Measures :
  1. Local Reactogenicity (Part A and B) [ Time Frame: 7 days after each product administration ]
    Occurrence of local reactogenicity signs and symptoms

  2. Systemic Reactogenicity (Part A and B) [ Time Frame: 7 days after each product administration ]
    Occurrence of systemic reactogenicity signs and symptoms

  3. Laboratory measures (Part A) [ Time Frame: Day 0 through Day 112 ]
    Occurrence of laboratory safety measures

  4. Laboratory measures (Part B) [ Time Frame: Day 0 through Day 308 ]
    Occurrence of laboratory safety measures

  5. Serious adverse events (Part A) [ Time Frame: Day 0 through Day 224 ]
    Occurrence of serious adverse events

  6. Serious adverse events (Part B) [ Time Frame: Day 0 through Day 672 ]
    Occurrence of serious adverse events

  7. New chronic medical conditions (Part A) [ Time Frame: Day 0 through Day 224 ]
    Occurrence of new-onset of chronic medical conditions

  8. New chronic medical conditions (Part B) [ Time Frame: Day 0 through Day 672 ]
    Occurrence of new-onset of chronic medical conditions

  9. Confirmed cases of Dengue virus infection (Part A) [ Time Frame: Day 0 through Day 224 ]
    Occurrence of confirmed cases of Dengue virus infection

  10. Confirmed cases of Dengue virus infection (Part B) [ Time Frame: Day 0 through Day 672 ]
    Occurrence of confirmed cases of Dengue virus infection

  11. Unsolicited adverse events (Part A and B) [ Time Frame: Day 0 through 28 days post product administration ]
    Occurrence of unsolicited non-serious adverse events

  12. Confirmed cases of Zika with symptoms (Part B only) [ Time Frame: Day 0 through Day 672 ]
    Occurrence of confirmed cases of Zika incidence with symptoms


Secondary Outcome Measures :
  1. Antibody response to VRC-ZKADNA090-00-VP (Part A and B) [ Time Frame: Day 0 to 28 days post product administration ]
    Antibody response as measured by ZIKV neutralization antibodies

  2. Confirmed cases of Zika (Part B only) [ Time Frame: Day 0 through Day 672 ]
    Occurrence of confirmed cases of Zika irrespective of symptoms



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   15 Years to 35 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

A subject must meet all of the following criteria:

Part A:

  • 18 to 35 years of age
  • Available for clinical follow-up through Study Week 32
  • Accessible injection sites on each limb as follows: 1 injection site in the deltoid muscle of each arm and 1 injection site in the vastus lateralis muscle of each anterolateral thigh

Part B:

  • 15 to 35 years of age
  • Available for clinical follow-up through Study Week 96
  • Accessible injection sites on the deltoid muscle of each arm. Injections sites on the vastus lateralis muscle of the anterolateral thighs may be allowed with IND Sponsor approval if an injection site on each deltoid muscle is not available.

Part A and B:

  • Able to provide proof of identity to the satisfaction of the clinician completing the enrollment process
  • Able and willing to complete the informed consent/assent process
  • Able and willing to complete the Assessment of Understanding and to verbalize understanding of all questions answered incorrectly prior to signing consent/assent
  • Willing to donate blood and urine to be stored and used for future research
  • In good general health without clinically significant medical history
  • Physical examination and laboratory results without clinically significant findings within the 56 days prior to randomization
  • Weight >30 kilograms (kg)
  • Agree not to receive any licenses or investigational flavivirus vaccines through 4 weeks after last product administration
  • Accessible injection sites on each limb as follows: 1 injections site in the deltoid muscle of each arm and 1 injection site in the vastus lateralis muscle of each anterolateral thigh.

Laboratory Criteria within 56 days prior to enrollment:

  • Hemoglobin within site institutional normal limits
  • Absolute neutrophil count (ANC) within site institutional normal limits
  • Total lymphocyte count ≥800 cells/mm3
  • Platelets = 125,000-510,000 cells/mm3
  • Alanine aminotransferase (ALT) ≤1.5 x upper limit of normal (ULN) based on site institutional normal range for respective age group
  • Serum creatinine ≤1.2 x ULN based on site institutional normal range for respective age group
  • Negative result on an human immunodeficiency virus (HIV) test that meets local standards for identification of HIV infection

Criteria applicable to women and adolescents of childbearing potential:

  • Negative result on a human chorionic gonadotropin pregnancy test (urine or serum) on day of randomization before receiving study product
  • Agree to use effective means of birth control from at least 21 days before randomization through 12 weeks after the last product administration

Criteria applicable to adolescents:

  • Capability of the parent/guardian of the minor to understand and comply with planned study procedures
  • Capability of the minor and their parent/guardian to provide informed consent/assent

Exclusion Criteria:

Criteria applicable to women and adolescents of childbearing potential:

  • Breast-feeding or planning to become pregnant while participating through 12 weeks after the last product administration

Participant has received any of the following:

  • More than 10 days of systemic immunosuppressive medications or cytotoxic medications within the 4 weeks prior to randomization
  • Any systemic immunosuppressive medications or cytotoxic medications within the 14 days prior to randomization
  • Blood products within 16 weeks prior to randomization
  • Immunoglobulin within 8 weeks prior to randomization
  • Investigational research agents within 4 weeks prior to randomization or planning to receive investigational products while on the study
  • Any vaccination within 2 weeks prior to randomization
  • Any live attenuated vaccination within 4 weeks prior to randomization
  • Current anti-tuberculosis (TB) prophylaxis or therapy

Participant has any of the following:

  • Confirmed history of ZIKV infection (as reported by participant)
  • Serious reactions to vaccines
  • Chronic angioedema or chronic urticaria
  • Asthma that is not well-controlled
  • Diabetes mellitus (type I or II)
  • Clinically significant autoimmune disease or immunodeficiency
  • Hypertension that is not well-controlled
  • Bleeding disorder diagnosed by a doctor (e.g., factor deficiency, coagulopathy, or platelet disorder requiring special precautions)
  • Significant bruising or bleeding difficulties with IM injections or blood draws
  • Malignancy that is active or history of a malignancy that is likely to recur during the period of the study
  • Seizure or treatment for a seizure disorder within the last 3 years
  • Asplenia, functional asplenia or any condition resulting in the absence or removal of the spleen
  • History of Guillain-Barré Syndrome
  • Psychiatric condition that may preclude compliance with the protocol; past or present psychoses; or a history of suicide plan or attempt within 5 years prior to randomization
  • Any medical psychiatric, or social condition that, in the judgment of the investigator, is a contraindication to protocol participation or impairs a participant's ability to give informed consent

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03110770


Locations
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United States, Florida
QPS-Miami Research Associates
Miami, Florida, United States, 33143
United States, Texas
Doctors Hospital at Renaissance
Edinburg, Texas, United States, 78539
Baylor College of Medicine
Houston, Texas, United States, 77030
Brazil
Hospital Das Clinicas Da Universidade Federal de Minas Gerais
Belo Horizonte, MG, Brazil, 30130-100
Centro de Pesquisas Clínicas Do Instituto Central Do Hospital Das Clínicas Da FMUSP
São Paulo, SP, Brazil, 05403-010
Colombia
Clinica de la Costa Ltda
Barranquilla, Atlantico, Colombia, 080020
Centro de Atencion y Diagnostico de Enfermedades Infecciosas
Bucaramanga, Santander, Colombia, 680003
Costa Rica
CCIM Costa Rican Center Center of Medical Research, Sociedad Anonima
San José, Los Yoses, Costa Rica
Ecuador
AGA Clinical Centro de Investigaciones
Guayaquil, Guayas, Ecuador, 090506
Mexico
Hospital Civil Fray Antonio Alcalde
Guadalajara, Jalisco, Mexico, 44280
Panama
Instituto Conmemorativo Gorgas
Panamá, San Miguelito Province, Panama
Peru
Asociacion Civil Selva Amazonica
Iquitos, Maynas/Loreto, Peru, 16001
Unidad de Ensayos (UNIDEC) del Policlinico Universidad Nacional Mayor de San Marcos
Lima, Peru, 15081
Puerto Rico
Ponce Medical School Foundation Inc./CAIMED Center
Ponce, Puerto Rico, 00716
Fundación de Investigación de Diego
San Juan, Puerto Rico, 00927
San Juan Hospital Research Unit
San Juan, Puerto Rico, 00935
Puerto Rico Clinical and Translational Research Consortium
San Juan, Puerto Rico, 00936-5067
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
The Emmes Company, LLC
Leidos Biomedical Research, Inc.
FHI 360
PPD
Investigators
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Study Chair: Julie Ledgerwood, DO VRC, NIAID, NIH
Study Chair: Grace Chen, MD VRC, NIAID, NIH

Additional Information:
Publications:

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Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT03110770     History of Changes
Other Study ID Numbers: VRC 705
First Posted: April 12, 2017    Key Record Dates
Last Update Posted: July 25, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Flavivirus
Zika
Vaccine
Physiological Effects of Drugs
Immunologic Factors
Virus-like Particles
Zika vaccine
Additional relevant MeSH terms:
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Communicable Diseases
Virus Diseases
Infection
Zika Virus Infection
RNA Virus Infections
Flaviviridae Infections
Flavivirus Infections
Arbovirus Infections
Vaccines
Immunologic Factors
Physiological Effects of Drugs