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

This study is currently recruiting participants.
Verified November 2017 by National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor:
ClinicalTrials.gov Identifier:
NCT03110770
First Posted: April 12, 2017
Last Update Posted: November 17, 2017
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.
Collaborators:
The EMMES Corporation
Leidos Biomedical Research, Inc.
FHI 360
PPD
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
  Purpose
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 Intervention 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

Study Type: Interventional
Study Design: 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, 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

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

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

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

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

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

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

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

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

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

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

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

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

  • 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:
  • 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

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


Estimated Enrollment: 2500
Actual Study Start Date: March 29, 2017
Estimated Study Completion Date: January 2020
Estimated Primary Completion Date: January 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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, 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 symptomatic ZIKV infections 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.

  Eligibility

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.


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

Part B:

  • 15 to 35 years of age
  • Available for clinical follow-up through Study Week 96

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 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

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 urticarial
  • 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-Barre 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
  Contacts and Locations
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


Contacts
Contact: Phyllis Renehan 301-251-1161 vrc705@emmes.com
Contact: Kim Linton 301-251-1161 vrc705@emmes.com

Locations
United States, Florida
QPS-Miami Research Associates Recruiting
Miami, Florida, United States, 33143
Contact: Maria Soto, CCRC    305-279-0015 ext 4206    maria.soto@qps.com   
Contact: Lourdes Arnillas, CRC    305-279-0015 ext 4221    lourdes.arnillas@qps.com   
Principal Investigator: Diane Krieger, MD         
United States, Texas
Doctors Hospital at Renaissance Recruiting
Edinburg, Texas, United States, 78539
Contact: John Rodriguez    956-362-2378    john.rodriguez@dhr-rgv.com   
Contact: Maria E Herrera, RN    956-362-2380    m.herrera@dhr-rgv.com   
Baylor College of Medicine Recruiting
Houston, Texas, United States, 77030
Contact: Shital M Patel, MD    713-798-3793    shitalp@bcm.edu   
Contact: Annette Nagel, RN    713-798-4912    bnagel@bcm.edu   
Principal Investigator: Shital Patel, MD         
Sub-Investigator: Hana El Sahly, MD         
Sub-Investigator: Wendy Keital, MD         
Sub-Investigator: Robert Atmar, MD         
Mexico
Hospital Civil Fray Antonio Alcalde Recruiting
Guadalajara, Jalisco, Mexico, 44280
Contact: Alejandro Castillo Mondragon, MD    52 33 36145568    alcastillom@gmail.com   
Contact: Maria Del Rayo Morfin Otero, MD    52 33 36145568    rayomorfin@gmail.com   
Principal Investigator: Maria Del Rayo Morfin Otero, MD         
Peru
Asociacion Civil Selva Amazonica Recruiting
Iquitos, Maynas/Loreto, Peru, 16001
Contact: Norma L Pezo, MPH    +51-965682004    lpezo@acsaperu.org   
Contact: Wilfredo M Casapia, MD, MPH    +51-965621830    mcasapia@acsaperu.org   
Principal Investigator: Wilfredo M Casapia, MD, MPH         
Puerto Rico
Ponce Medical School Foundation Inc./CAIMED Center Recruiting
Ponce, Puerto Rico, 00716
Contact: Imaris Arroyo    787-840-2505    iarroyo@psm.edu   
Contact: Elizabeth A Barranco-Santana    787-840-2505    crc@psm.edu   
Principal Investigator: Elizabeth A Barranco-Santana, MD         
Sub-Investigator: Rafael O Mendoza-Rodriguez, MD         
Fundación de Investigación de Diego Recruiting
San Juan, Puerto Rico, 00927
Contact: Michelle Echeandia-Ortiz, MT, MS    787-722-1248    mecheandia@fdipr.com   
Contact: Nydia Lazaro    787-722-1248    nlazaro@fdipr.com   
Principal Investigator: Grisell Ortiz-Lasanta, MD         
Sub-Investigator: Caroline A Nazario-Lugo, MD         
San Juan Hospital Research Unit Recruiting
San Juan, Puerto Rico, 00935
Contact: Elvia Pérez, MEd, MA, MPH    787-765-4186    eperez@sanjuanciudadpatria.com   
Contact: Lizbeth M Fábregas, BS, MS    787-764-3083    lfabregas@sanjuanciudadpatria.com   
Principal Investigator: Nicolas Rosario, MD, MSc         
Sub-Investigator: Midnela Acevedo-Flores, MT, MD         
Puerto Rico Clinical and Translational Research Consortium Recruiting
San Juan, Puerto Rico, 00936-5067
Contact: Clemente Diaz, MD    787-759-0306    clemente.diaz@upr.edu   
Principal Investigator: Clemente Diaz, MD         
Sub-Investigator: Irma Febo, MD         
Sub-Investigator: Maribel Campos, MD         
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
The EMMES Corporation
Leidos Biomedical Research, Inc.
FHI 360
PPD
Investigators
Study Chair: Julie Ledgerwood, DO VRC, NIAID, NIH
Study Chair: Grace Chen, MD VRC, NIAID, NIH
  More Information

Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT03110770     History of Changes
Other Study ID Numbers: VRC 705
First Submitted: March 28, 2017
First Posted: April 12, 2017
Last Update Posted: November 17, 2017
Last Verified: November 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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:
Infection
Communicable Diseases
Virus Diseases
Zika Virus Infection
RNA Virus Infections
Flaviviridae Infections
Flavivirus Infections
Arbovirus Infections
Vaccines
Immunologic Factors
Physiological Effects of Drugs