VRC 705: A Zika Virus DNA Vaccine in Healthy Adults and Adolescents
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
Overall Status
Completed
CT.gov ID
NCT03110770
Collaborator
(none)
2,428
17
5
30.2
142.8
4.7
Study Details
Study Description
Brief Summary
This was 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 was to evaluate the safety and tolerability of the vaccine in different vaccination regimens. In Part B, the primary objectives were to evaluate the safety and efficacy of the vaccine compared to placebo.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
This was 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 was a sterile phosphate-buffered saline (PBS). The hypotheses were that the ZIKVwt DNA vaccine would be safe and would elicit a ZIKV-specific immune response.
Participants received study product intramuscularly (IM) in the limbs as specified by the group assignment by PharmaJet needle-free device. In Part A, 90 participants were randomized to vaccine at a 1:1:1 ratio to receive a 4 mg dose split between 2 injections, 4 mg dose split between 4 injections or 8 mg dose split between 4 injections. In Part B, 2338 participants were randomized to vaccine or placebo in a 1:1 ratio to receive a 4 mg (1 mL) dose of vaccine or 1 mL of placebo split between 2 injections. The vaccine dose and administration plan for Part B was selected based on Part A and Phase 1 data.
Vaccine safety and tolerability were assessed by monitoring of clinical and laboratory parameters throughout the study. Solicited reactogenicity symptoms were collected for 7 days after each product administration. The study schedule included clinic visits with safety and immunogenicity blood samples collected at particular time points.
Vaccine efficacy was evaluated in Part B by comparing incidence of virologic ZIKV cases between vaccine and placebo groups. During the study, when participants exhibited any possible symptom of ZIKV infection, they were evaluated by blood and urine ZIKV polymerase chain reaction (PCR). Stored blood samples were also assessed retrospectively by ZIKV PCR to identify possible asymptomatic cases. A Data and Safety Monitoring Board (DSMB) oversaw the study.
Study Design
Study Type:
Interventional
Actual Enrollment
:
2428 participants
Allocation:
Randomized
Intervention Model:
Sequential Assignment
Intervention Model Description:
Part A participants (n=90) were randomized to study groups 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, participants (n=2338) were randomized to vaccine or placebo in a 1:1 ratio to receive a 4 mg (1 mL) dose of vaccine or 1 mL of placebo split between 2 injections. The vaccine dose and number of injections in Part B was determined by preliminary data from the Phase 1 trial and from Part A.Part A participants (n=90) were randomized to study groups 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, participants (n=2338) were randomized to vaccine or placebo in a 1:1 ratio to receive a 4 mg (1 mL) dose of vaccine or 1 mL of placebo split between 2 injections. The vaccine dose and number of injections in Part B was determined by preliminary data from the Phase 1 trial and from Part A.
Masking:
Triple (Participant, Investigator, Outcomes Assessor)
Masking Description:
Part A was open-label. For Part A, the participant, investigator and outcome assessor knew what the participant received.
Part B injections were prepared by an unblinded site pharmacist or designee who was not involved in any participant assessments and did not discuss randomizations with study clinicians. Participants, study personnel, site data entry personnel, and laboratory personnel performing immunologic assays were blinded to the treatment assignment of all product administrations. The investigational new drug (IND) Sponsor unblinded treatment assignments for Part B at the end of the study.
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
:
Mar 29, 2017
Actual Primary Completion Date
:
Oct 4, 2019
Actual Study Completion Date
:
Oct 4, 2019
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Part A, Group 1: VRC-ZKADNA090-00-VP (4 mg), 2 injections Zika virus wildtype (ZIKVwt) DNA 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 administered intramuscularly (IM) by a needle-free injection device |
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: VRC-ZKADNA090-00-VP (4 mg), 4 injections ZIKVwt DNA 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 administered IM by a needle-free injection device |
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: VRC-ZKADNA090-00-VP (8 mg), 4 injections ZIKVwt DNA 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 administered IM by a needle-free injection device |
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: VRC-ZKADNA090-00-VP (4 mg), 2 injections ZIKVwt DNA 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 administered IM by a needle-free injection device |
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: Placebo (VRC-PBSPLA043-00-VP), 2 injections 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 administered IM by a needle-free injection device |
Other: VRC-PBSPLA043-00-VP
A sterile phosphate-buffered saline (PBS) prepared for human administration as a placebo
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Number of Participants Reporting Local Reactogenicity Signs and Symptoms for 7 Days After Each Product Administration (Part A and Part B) [7 days after each product administration]
Participants recorded the occurrence of solicited symptoms on a diary card for 7 days after each study product administration and reviewed the diary card with clinic staff at a follow up visit. Participants were counted once for each symptom at the worst severity if they indicated experiencing the symptom more than one time at any severity during the reporting period. The number reported for "Any Local Symptom" is the number of participants reporting any local symptom at the worst severity. Reactogenicity grading (Mild, Moderate, Severe) was done using the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (FDA Guidance - September 2007).
- Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms for 7 Days After Each Product Administration (Part A and Part B) [7 days after each product administration]
Participants recorded the occurrence of solicited symptoms on a diary card for 7 days after each study product administration and reviewed the diary card with clinic staff at a follow up visit. Participants were counted once for each symptom at the worst severity if they indicated experiencing the symptom more than once at any severity during the reporting period. The number reported for "Any Systemic Symptom" is the number of participants reporting any systemic symptom at the worst severity. Reactogenicity grading (Mild, Moderate, Severe) was done using the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (FDA Guidance - September 2007).
- Number of Participants With Abnormal Laboratory Measures of Safety (Part A) [Day 0 after first product administration through Day 112]
Any abnormal laboratory results recorded as unsolicited AEs are summarized. Safety laboratory parameters included: alanine aminotransferase (ALT), white blood cells (WBC), red blood cells (RBC), hemoglobin, hematocrit, mean corpuscular volume (MCV), platelets, neutrophils, lymphocytes, monocytes, eosinophils, and basophils. Laboratory safety evaluations were scheduled at baseline and weeks 4, 6, 8, 10, 12, and 16. Institutional laboratory normals as well as the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventative Vaccine Clinical Trials FDA Guidance, September 2007 were used.
- Number of Participants With Abnormal Laboratory Measures of Safety (Part B) [Day 0 after first product administration through Day 308]
Any abnormal laboratory results recorded as unsolicited AEs are summarized. Safety laboratory parameters included: alanine aminotransferase (ALT), white blood cells (WBC), red blood cells (RBC), hemoglobin, hematocrit, mean corpuscular volume (MCV), platelets, neutrophils, lymphocytes, monocytes, eosinophils, and basophils. Laboratory safety evaluations were scheduled at baseline and weeks 4, 8, 16, and 44. Institutional laboratory normals as well as the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventative Vaccine Clinical Trials FDA Guidance, September 2007 were used.
- Number of Participants With Serious Adverse Events (SAEs) Following Product Administration (Part A) [Day 0 through Day 224]
Any SAEs recorded from receipt of first study product administration through the last expected study visit at Day 224 are summarized. The relationship between a SAE and the study product was assessed by the investigator on the basis of his or her clinical judgment and the definitions outlined in the protocol.
- Number of Participants With Serious Adverse Events (SAEs) Following Product Administration (Part B) [Day 0 through Day 672]
Any SAEs recorded from receipt of first study product administration through the last expected study visit at Day 672 are summarized. The relationship between a SAE and the study product was assessed by the investigator on the basis of his or her clinical judgment and the definitions outlined in the protocol.
- Number of Participants With New Chronic Medical Conditions Following Product Administration (Part A) [Day 0 through Day 224]
New onset chronic medical conditions were reported from receipt of first study product administration through the last expected study visit at Day 224.The relationship between a chronic medical condition and the study product was assessed by the investigator on the basis of his or her clinical judgment and the definitions outlined in the protocol.
- Number of Participants With New Chronic Medical Conditions Following Product Administration (Part B) [Day 0 through Day 672]
New onset chronic medical conditions were reported from receipt of first study product administration through the last expected study visit at Day 672.The relationship between a chronic medical condition and the study product was assessed by the investigator on the basis of his or her clinical judgment and the definitions outlined in the protocol.
- Number of Participants With One or More Unsolicited Non-Serious Adverse Events (AEs) Following Product Administration (Part A and Part B) [Day 0 through the one month visit that follows the last product administration (Visit 05), 84 days for both Parts A and B]
Unsolicited AEs and attribution assessments were recorded in the study database from receipt of the first study product administration through the one month visit that followed the last study product administration (Visit 05), 84 days for both Parts A and B for participants who received all three study product administrations. If a participant received the first and second product administrations but not the third, then the time frame was through 56 days (Visit 04). If a participant only received the first product administration but not the second or third, then the time frame was through 28 days (Visit 03). The relationship between an AE and the study product was assessed by the investigator on the basis of his or her clinical judgment and the definitions outlined in the protocol. A participant with multiple experiences of the same event is counted once using the event of worst severity.
- Number of Participants With Virologically Confirmed Cases of ZIKV (Part B Only) [Day 0 through Day 672]
Virologically confirmed Zika infection, irrespective of symptoms, by polymerase chain reaction (PCR) in blood or in urine were recorded from receipt of first study product administration through the last expected study visit.
Secondary Outcome Measures
- Zika Antigen-specific Neutralizing Antibody Geometric Mean Titer (GMT) - (Part A) [Day 0 to 28 days after the final product administration]
Antibody response as measured by ZIKV neutralization antibody (NAb) assay. Neutralizing activity is reported as the dilution of sera required to neutralize eighty percent of infection events (EC80).
- Number of Participants With Positive Response to Zika Antigen-specific Neutralizing Antibody (Part A) [Day 0 to 28 days after the final product administration]
A participant was a responder or met the threshold of a positive response if the post vaccination anti-ZIKV antibody titer was 30 or greater.
- Number of Participants With Subclinical Cases of ZIKV (Part B Only) [Day 0 through Day 672]
Virologically confirmed cases of Zika infection without clinical signs or symptoms were recorded from receipt of first study product administration through the last expected study visit by PCR virus detection in blood of participants at regularly defined intervals. Subclinical cases of ZIKV infection were identified by retrospective PCR.
- Zika Antigen-specific Neutralizing Antibody Geometric Mean Titer (GMT) - (Part B) [Day 0 to 28 days after the final product administration]
Antibody response as measured by ZIKV neutralization antibody (NAb) assay. Neutralizing activity is reported as the dilution of sera required to neutralize eighty percent of infection events (EC80). Data is not yet available for this outcome measure as this particular outcome is based on the results from retrospective ZIKV neutralizing antibody assays which are still being performed on the samples. Outcome measure data will be provided once testing is complete. Testing is anticipated to be completed in 2022 and data will be reported as soon as it is available.
- Number of Participants With Positive Response to Zika Antigen-specific Neutralizing Antibody (Part B) [Day 0 to 28 days after the final product administration]
A participant is a responder or met the threshold of a positive response if the post vaccination anti-ZIKV antibody titer was 30 or greater. Data is not yet available for this outcome measure as it is based on the results from retrospective ZIKV PCR assays which are still being performed on the samples. There are tens of thousands of samples that are still being tested for this outcome measure and outcome measure data will be provided once testing is complete. Testing is anticipated to be completed in 2022 and data will be reported as soon as it is available.
Eligibility Criteria
Criteria
Ages Eligible for Study:
15 Years
to 35 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
Inclusion Criteria:
A participant 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. Injection in the vastus lateralis muscle of the anterolateral thighs may have been allowed with IND Sponsor approval if an injection site on each deltoid muscle was 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 licensed or investigational flavivirus vaccines through 4 weeks after last product administration
Laboratory Criteria within 56 days prior to randomization:
-
Hemoglobin within site institutional normal limits
-
Absolute neutrophil count (ANC) within site institutional normal limits
-
Total lymphocyte count ≥800 cells/mm^3
-
Platelets = 125,000-510,000 cells/mm^3
-
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 a 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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | QPS-Miami Research Associates | Miami | Florida | United States | 33143 |
| 2 | Doctors Hospital at Renaissance | Edinburg | Texas | United States | 78539 |
| 3 | Baylor College of Medicine | Houston | Texas | United States | 77030 |
| 4 | Hospital Das Clinicas Da Universidade Federal de Minas Gerais | Belo Horizonte | MG | Brazil | 30130-100 |
| 5 | Centro de Pesquisas Clínicas Do Instituto Central Do Hospital Das Clínicas Da FMUSP | São Paulo | SP | Brazil | 05403-010 |
| 6 | Clinica de la Costa Ltda | Barranquilla | Atlantico | Colombia | 080020 |
| 7 | Centro de Atencion y Diagnostico de Enfermedades Infecciosas | Bucaramanga | Santander | Colombia | 680003 |
| 8 | CCIM Costa Rican Center Center of Medical Research, Sociedad Anonima | San José | Los Yoses | Costa Rica | |
| 9 | AGA Clinical Centro de Investigaciones | Guayaquil | Guayas | Ecuador | 090506 |
| 10 | Hospital Civil Fray Antonio Alcalde | Guadalajara | Jalisco | Mexico | 44280 |
| 11 | Instituto Conmemorativo Gorgas | Panamá | San Miguelito Province | Panama | |
| 12 | Asociacion Civil Selva Amazonica | Iquitos | Maynas/Loreto | Peru | 16001 |
| 13 | Unidad de Ensayos (UNIDEC) del Policlinico Universidad Nacional Mayor de San Marcos | Lima | Peru | 15081 | |
| 14 | Ponce Medical School Foundation Inc./CAIMED Center | Ponce | Puerto Rico | 00716 | |
| 15 | Fundación de Investigación de Diego | San Juan | Puerto Rico | 00927 | |
| 16 | San Juan Hospital Research Unit | San Juan | Puerto Rico | 00935 | |
| 17 | Puerto Rico Clinical and Translational Research Consortium | San Juan | Puerto Rico | 00936-5067 |
Sponsors and Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
- Study Chair: Julie Ledgerwood, DO, VRC, NIAID, NIH
Study Documents (Full-Text)
More Information
Additional Information:
Publications
- Dowd KA, Ko SY, Morabito KM, Yang ES, Pelc RS, DeMaso CR, Castilho LR, Abbink P, Boyd M, Nityanandam R, Gordon DN, Gallagher JR, Chen X, Todd JP, Tsybovsky Y, Harris A, Huang YS, Higgs S, Vanlandingham DL, Andersen H, Lewis MG, De La Barrera R, Eckels KH, Jarman RG, Nason MC, Barouch DH, Roederer M, Kong WP, Mascola JR, Pierson TC, Graham BS. Rapid development of a DNA vaccine for Zika virus. Science. 2016 Oct 14;354(6309):237-240. Epub 2016 Sep 22.
- Gaudinski MR, Houser KV, Morabito KM, Hu Z, Yamshchikov G, Rothwell RS, Berkowitz N, Mendoza F, Saunders JG, Novik L, Hendel CS, Holman LA, Gordon IJ, Cox JH, Edupuganti S, McArthur MA, Rouphael NG, Lyke KE, Cummings GE, Sitar S, Bailer RT, Foreman BM, Burgomaster K, Pelc RS, Gordon DN, DeMaso CR, Dowd KA, Laurencot C, Schwartz RM, Mascola JR, Graham BS, Pierson TC, Ledgerwood JE, Chen GL; VRC 319; VRC 320 study teams. Safety, tolerability, and immunogenicity of two Zika virus DNA vaccine candidates in healthy adults: randomised, open-label, phase 1 clinical trials. Lancet. 2018 Feb 10;391(10120):552-562. doi: 10.1016/S0140-6736(17)33105-7. Epub 2017 Dec 5.
- Ledgerwood JE, Pierson TC, Hubka SA, Desai N, Rucker S, Gordon IJ, Enama ME, Nelson S, Nason M, Gu W, Bundrant N, Koup RA, Bailer RT, Mascola JR, Nabel GJ, Graham BS; VRC 303 Study Team. A West Nile virus DNA vaccine utilizing a modified promoter induces neutralizing antibody in younger and older healthy adults in a phase I clinical trial. J Infect Dis. 2011 May 15;203(10):1396-404. doi: 10.1093/infdis/jir054. Epub 2011 Mar 11.
- Martin JE, Pierson TC, Hubka S, Rucker S, Gordon IJ, Enama ME, Andrews CA, Xu Q, Davis BS, Nason M, Fay M, Koup RA, Roederer M, Bailer RT, Gomez PL, Mascola JR, Chang GJ, Nabel GJ, Graham BS. A West Nile virus DNA vaccine induces neutralizing antibody in healthy adults during a phase 1 clinical trial. J Infect Dis. 2007 Dec 15;196(12):1732-40. doi: 10.1086/523650.
Responsible Party:
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT03110770
Other Study ID Numbers:
- VRC 705
First Posted:
Apr 12, 2017
Last Update Posted:
May 24, 2021
Last Verified:
Apr 1, 2021
Individual Participant Data (IPD) Sharing Statement:
No
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)
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Part A targeted healthy adults only. Part B included adolescents in the study population. Part B sites had the option to enroll adolescents and adults, or choose to enroll only adults. The study was conducted at sites located in areas of confirmed or projected active transmission of Zika virus (ZIKV) infection. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Part A, Group 1: VRC-ZKADNA090-00-VP (4 mg), 2 Injections | Part A, Group 2: VRC-ZKADNA090-00-VP (4 mg), 4 Injections | Part A, Group 3: VRC-ZKADNA090-00-VP (8 mg), 4 Injections | Part B, Group 4: VRC-ZKADNA090-00-VP (4 mg), 2 Injections | Part B, Group 5: Placebo (VRC-PBSPLA043-00-VP), 2 Injections |
|---|---|---|---|---|---|
| Arm/Group Description | Zika virus wildtype (ZIKVwt) DNA 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 administered intramuscularly (IM) by a needle-free injection device 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 | ZIKVwt DNA 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 administered IM by a needle-free injection device 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 | ZIKVwt DNA 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 administered IM by a needle-free injection device 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 | ZIKVwt DNA 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 administered IM by a needle-free injection device 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 | 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 administered IM by a needle-free injection device VRC-PBSPLA043-00-VP: A sterile phosphate-buffered saline (PBS) prepared for human administration as a placebo |
| Period Title: Overall Study | |||||
| STARTED | 30 | 30 | 30 | 1170 | 1168 |
| Received First Product Administration | 30 | 30 | 30 | 1162 | 1161 |
| Received Second Product Administration | 30 | 29 | 29 | 1126 | 1127 |
| Received Third Product Administration | 29 | 27 | 28 | 1107 | 1107 |
| COMPLETED | 24 | 30 | 28 | 1037 | 1045 |
| NOT COMPLETED | 6 | 0 | 2 | 133 | 123 |
Baseline Characteristics
| Arm/Group Title | Part A, Group 1: VRC-ZKADNA090-00-VP (4 mg), 2 Injections | Part A, Group 2: VRC-ZKADNA090-00-VP (4 mg), 4 Injections | Part A, Group 3: VRC-ZKADNA090-00-VP (8 mg), 4 Injections | Part B, Group 4: VRC-ZKADNA090-00-VP (4 mg), 2 Injections | Part B, Group 5: Placebo (VRC-PBSPLA043-00-VP), 2 Injections | Total |
|---|---|---|---|---|---|---|
| Arm/Group Description | Zika virus wildtype (ZIKVwt) DNA 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 administered intramuscularly (IM) by a needle-free injection device 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 | ZIKVwt DNA 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 administered IM by a needle-free injection device 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 | ZIKVwt DNA 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 administered IM by a needle-free injection device 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 | ZIKVwt DNA 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 administered IM by a needle-free injection device 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 | 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 administered IM by a needle-free injection device VRC-PBSPLA043-00-VP: A sterile phosphate-buffered saline (PBS) prepared for human administration as a placebo | Total of all reporting groups |
| Overall Participants | 30 | 30 | 30 | 1170 | 1168 | 2428 |
| Age, Customized (Count of Participants) | ||||||
| 15-17 years |
NA
NaN
|
NA
NaN
|
NA
NaN
|
17
1.5%
|
17
1.5%
|
NA
NaN
|
| 18-20 years |
0
0%
|
0
0%
|
2
6.7%
|
223
19.1%
|
222
19%
|
447
18.4%
|
| 21-30 years |
19
63.3%
|
24
80%
|
22
73.3%
|
740
63.2%
|
734
62.8%
|
1539
63.4%
|
| 31-35 years |
11
36.7%
|
6
20%
|
6
20%
|
190
16.2%
|
195
16.7%
|
408
16.8%
|
| Sex: Female, Male (Count of Participants) | ||||||
| Female |
14
46.7%
|
22
73.3%
|
13
43.3%
|
595
50.9%
|
601
51.5%
|
1245
51.3%
|
| Male |
16
53.3%
|
8
26.7%
|
17
56.7%
|
575
49.1%
|
567
48.5%
|
1183
48.7%
|
| Ethnicity (NIH/OMB) (Count of Participants) | ||||||
| Hispanic or Latino |
15
50%
|
18
60%
|
17
56.7%
|
1150
98.3%
|
1139
97.5%
|
2339
96.3%
|
| Not Hispanic or Latino |
15
50%
|
12
40%
|
13
43.3%
|
17
1.5%
|
25
2.1%
|
82
3.4%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
3
0.3%
|
4
0.3%
|
7
0.3%
|
| Race (NIH/OMB) (Count of Participants) | ||||||
| American Indian or Alaska Native |
6
20%
|
7
23.3%
|
5
16.7%
|
6
0.5%
|
6
0.5%
|
30
1.2%
|
| Asian |
4
13.3%
|
2
6.7%
|
1
3.3%
|
2
0.2%
|
3
0.3%
|
12
0.5%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
1
0.1%
|
0
0%
|
1
0%
|
| Black or African American |
4
13.3%
|
2
6.7%
|
2
6.7%
|
52
4.4%
|
41
3.5%
|
101
4.2%
|
| White |
13
43.3%
|
15
50%
|
17
56.7%
|
270
23.1%
|
278
23.8%
|
593
24.4%
|
| More than one race |
3
10%
|
4
13.3%
|
5
16.7%
|
834
71.3%
|
837
71.7%
|
1683
69.3%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
5
0.4%
|
3
0.3%
|
8
0.3%
|
| Weight (kilograms) [Mean (Standard Deviation) ] | ||||||
| Mean (Standard Deviation) [kilograms] |
86.31
(28.22)
|
79.57
(19.84)
|
78.55
(23.82)
|
70.80
(16.94)
|
70.05
(17.49)
|
70.84
(17.65)
|
Outcome Measures
| Title | Number of Participants Reporting Local Reactogenicity Signs and Symptoms for 7 Days After Each Product Administration (Part A and Part B) |
|---|---|
| Description | Participants recorded the occurrence of solicited symptoms on a diary card for 7 days after each study product administration and reviewed the diary card with clinic staff at a follow up visit. Participants were counted once for each symptom at the worst severity if they indicated experiencing the symptom more than one time at any severity during the reporting period. The number reported for "Any Local Symptom" is the number of participants reporting any local symptom at the worst severity. Reactogenicity grading (Mild, Moderate, Severe) was done using the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (FDA Guidance - September 2007). |
| Time Frame | 7 days after each product administration |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants in the study who received at least one study product administration with available data for at least one post-administration assessment for the symptom being summarized. |
| Arm/Group Title | Part A, Group 1: VRC-ZKADNA090-00-VP (4 mg), 2 Injections | Part A, Group 2: VRC-ZKADNA090-00-VP (4 mg), 4 Injections | Part A, Group 3: VRC-ZKADNA090-00-VP (8 mg), 4 Injections | Part B, Group 4: VRC-ZKADNA090-00-VP (4 mg), 2 Injections | Part B, Group 5: Placebo (VRC-PBSPLA043-00-VP), 2 Injections |
|---|---|---|---|---|---|
| Arm/Group Description | Zika virus wildtype (ZIKVwt) DNA 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 administered intramuscularly (IM) by a needle-free injection device 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 | ZIKVwt DNA 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 administered IM by a needle-free injection device 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 | ZIKVwt DNA 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 administered IM by a needle-free injection device 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 | ZIKVwt DNA 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 administered IM by a needle-free injection device 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 | 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 administered IM by a needle-free injection device VRC-PBSPLA043-00-VP: A sterile phosphate-buffered saline (PBS) prepared for human administration as a placebo |
| Measure Participants | 30 | 30 | 30 | 1153 | 1148 |
| None |
5
16.7%
|
2
6.7%
|
2
6.7%
|
291
24.9%
|
566
48.5%
|
| Mild |
21
70%
|
21
70%
|
14
46.7%
|
600
51.3%
|
482
41.3%
|
| Moderate |
4
13.3%
|
7
23.3%
|
14
46.7%
|
257
22%
|
96
8.2%
|
| Severe |
0
0%
|
0
0%
|
0
0%
|
5
0.4%
|
4
0.3%
|
| None |
26
86.7%
|
25
83.3%
|
23
76.7%
|
1059
90.5%
|
1124
96.2%
|
| Mild |
4
13.3%
|
5
16.7%
|
6
20%
|
82
7%
|
22
1.9%
|
| Moderate |
0
0%
|
0
0%
|
1
3.3%
|
12
1%
|
2
0.2%
|
| Severe |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| None |
24
80%
|
26
86.7%
|
23
76.7%
|
1037
88.6%
|
1085
92.9%
|
| Mild |
5
16.7%
|
3
10%
|
7
23.3%
|
103
8.8%
|
52
4.5%
|
| Moderate |
1
3.3%
|
1
3.3%
|
0
0%
|
13
1.1%
|
11
0.9%
|
| Severe |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| None |
5
16.7%
|
2
6.7%
|
2
6.7%
|
282
24.1%
|
552
47.3%
|
| Mild |
21
70%
|
20
66.7%
|
14
46.7%
|
598
51.1%
|
485
41.5%
|
| Moderate |
4
13.3%
|
8
26.7%
|
14
46.7%
|
268
22.9%
|
107
9.2%
|
| Severe |
0
0%
|
0
0%
|
0
0%
|
5
0.4%
|
4
0.3%
|
| Title | Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms for 7 Days After Each Product Administration (Part A and Part B) |
|---|---|
| Description | Participants recorded the occurrence of solicited symptoms on a diary card for 7 days after each study product administration and reviewed the diary card with clinic staff at a follow up visit. Participants were counted once for each symptom at the worst severity if they indicated experiencing the symptom more than once at any severity during the reporting period. The number reported for "Any Systemic Symptom" is the number of participants reporting any systemic symptom at the worst severity. Reactogenicity grading (Mild, Moderate, Severe) was done using the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (FDA Guidance - September 2007). |
| Time Frame | 7 days after each product administration |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants in the study who received at least one study product administration with available data for at least one post-administration assessment for the symptom being summarized. |
| Arm/Group Title | Part A, Group 1: VRC-ZKADNA090-00-VP (4 mg), 2 Injections | Part A, Group 2: VRC-ZKADNA090-00-VP (4 mg), 4 Injections | Part A, Group 3: VRC-ZKADNA090-00-VP (8 mg), 4 Injections | Part B, Group 4: VRC-ZKADNA090-00-VP (4 mg), 2 Injections | Part B, Group 5: Placebo (VRC-PBSPLA043-00-VP), 2 Injections |
|---|---|---|---|---|---|
| Arm/Group Description | Zika virus wildtype (ZIKVwt) DNA 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 administered intramuscularly (IM) by a needle-free injection device 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 | ZIKVwt DNA 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 administered IM by a needle-free injection device 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 | ZIKVwt DNA 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 administered IM by a needle-free injection device 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 | ZIKVwt DNA 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 administered IM by a needle-free injection device 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 | 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 administered IM by a needle-free injection device VRC-PBSPLA043-00-VP: A sterile phosphate-buffered saline (PBS) prepared for human administration as a placebo |
| Measure Participants | 30 | 30 | 30 | 1153 | 1148 |
| None |
20
66.7%
|
20
66.7%
|
17
56.7%
|
748
63.9%
|
772
66.1%
|
| Mild |
8
26.7%
|
6
20%
|
12
40%
|
306
26.2%
|
286
24.5%
|
| Moderate |
2
6.7%
|
3
10%
|
1
3.3%
|
97
8.3%
|
86
7.4%
|
| Severe |
0
0%
|
1
3.3%
|
0
0%
|
2
0.2%
|
4
0.3%
|
| None |
26
86.7%
|
22
73.3%
|
20
66.7%
|
793
67.8%
|
842
72.1%
|
| Mild |
3
10%
|
6
20%
|
8
26.7%
|
270
23.1%
|
227
19.4%
|
| Moderate |
1
3.3%
|
2
6.7%
|
2
6.7%
|
86
7.4%
|
77
6.6%
|
| Severe |
0
0%
|
0
0%
|
0
0%
|
4
0.3%
|
2
0.2%
|
| None |
20
66.7%
|
15
50%
|
17
56.7%
|
696
59.5%
|
713
61%
|
| Mild |
8
26.7%
|
13
43.3%
|
13
43.3%
|
320
27.4%
|
298
25.5%
|
| Moderate |
2
6.7%
|
2
6.7%
|
0
0%
|
131
11.2%
|
124
10.6%
|
| Severe |
0
0%
|
0
0%
|
0
0%
|
6
0.5%
|
13
1.1%
|
| None |
27
90%
|
25
83.3%
|
29
96.7%
|
1015
86.8%
|
1029
88.1%
|
| Mild |
3
10%
|
4
13.3%
|
1
3.3%
|
109
9.3%
|
84
7.2%
|
| Moderate |
0
0%
|
1
3.3%
|
0
0%
|
28
2.4%
|
33
2.8%
|
| Severe |
0
0%
|
0
0%
|
0
0%
|
1
0.1%
|
2
0.2%
|
| None |
26
86.7%
|
26
86.7%
|
26
86.7%
|
971
83%
|
991
84.8%
|
| Mild |
2
6.7%
|
3
10%
|
4
13.3%
|
136
11.6%
|
118
10.1%
|
| Moderate |
2
6.7%
|
1
3.3%
|
0
0%
|
44
3.8%
|
34
2.9%
|
| Severe |
0
0%
|
0
0%
|
0
0%
|
2
0.2%
|
5
0.4%
|
| None |
26
86.7%
|
23
76.7%
|
28
93.3%
|
964
82.4%
|
982
84.1%
|
| Mild |
3
10%
|
5
16.7%
|
2
6.7%
|
149
12.7%
|
121
10.4%
|
| Moderate |
1
3.3%
|
2
6.7%
|
0
0%
|
36
3.1%
|
41
3.5%
|
| Severe |
0
0%
|
0
0%
|
0
0%
|
4
0.3%
|
4
0.3%
|
| None |
30
100%
|
30
100%
|
29
96.7%
|
1090
93.2%
|
1082
92.6%
|
| Mild |
0
0%
|
0
0%
|
1
3.3%
|
37
3.2%
|
31
2.7%
|
| Moderate |
0
0%
|
0
0%
|
0
0%
|
22
1.9%
|
24
2.1%
|
| Severe |
0
0%
|
0
0%
|
0
0%
|
4
0.3%
|
11
0.9%
|
| None |
16
53.3%
|
13
43.3%
|
8
26.7%
|
508
43.4%
|
542
46.4%
|
| Mild |
10
33.3%
|
12
40%
|
19
63.3%
|
421
36%
|
394
33.7%
|
| Moderate |
4
13.3%
|
4
13.3%
|
3
10%
|
210
17.9%
|
190
16.3%
|
| Severe |
0
0%
|
1
3.3%
|
0
0%
|
14
1.2%
|
22
1.9%
|
| Title | Number of Participants With Abnormal Laboratory Measures of Safety (Part A) |
|---|---|
| Description | Any abnormal laboratory results recorded as unsolicited AEs are summarized. Safety laboratory parameters included: alanine aminotransferase (ALT), white blood cells (WBC), red blood cells (RBC), hemoglobin, hematocrit, mean corpuscular volume (MCV), platelets, neutrophils, lymphocytes, monocytes, eosinophils, and basophils. Laboratory safety evaluations were scheduled at baseline and weeks 4, 6, 8, 10, 12, and 16. Institutional laboratory normals as well as the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventative Vaccine Clinical Trials FDA Guidance, September 2007 were used. |
| Time Frame | Day 0 after first product administration through Day 112 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants in the study who received at least one study product administration, and had at least one post-administration safety assessment, analyzed according to the study product received. |
| Arm/Group Title | Part A, Group 1: VRC-ZKADNA090-00-VP (4 mg), 2 Injections | Part A, Group 2: VRC-ZKADNA090-00-VP (4 mg), 4 Injections | Part A, Group 3: VRC-ZKADNA090-00-VP (8 mg), 4 Injections |
|---|---|---|---|
| Arm/Group Description | Zika virus wildtype (ZIKVwt) DNA 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 administered intramuscularly (IM) by a needle-free injection device 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 | ZIKVwt DNA 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 administered IM by a needle-free injection device 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 | ZIKVwt DNA 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 administered IM by a needle-free injection device 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 |
| Measure Participants | 30 | 30 | 30 |
| ALT |
3
10%
|
1
3.3%
|
3
10%
|
| WBC |
2
6.7%
|
1
3.3%
|
3
10%
|
| Hemoglobin |
2
6.7%
|
2
6.7%
|
2
6.7%
|
| Platelets |
0
0%
|
1
3.3%
|
1
3.3%
|
| Neutrophil |
0
0%
|
1
3.3%
|
2
6.7%
|
| Lymphocyte |
1
3.3%
|
0
0%
|
1
3.3%
|
| Eosinophil |
1
3.3%
|
0
0%
|
1
3.3%
|
| Title | Number of Participants With Abnormal Laboratory Measures of Safety (Part B) |
|---|---|
| Description | Any abnormal laboratory results recorded as unsolicited AEs are summarized. Safety laboratory parameters included: alanine aminotransferase (ALT), white blood cells (WBC), red blood cells (RBC), hemoglobin, hematocrit, mean corpuscular volume (MCV), platelets, neutrophils, lymphocytes, monocytes, eosinophils, and basophils. Laboratory safety evaluations were scheduled at baseline and weeks 4, 8, 16, and 44. Institutional laboratory normals as well as the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventative Vaccine Clinical Trials FDA Guidance, September 2007 were used. |
| Time Frame | Day 0 after first product administration through Day 308 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants in the study who received at least one study product administration, and had at least one post-administration safety assessment, analyzed according to the study product received. |
| Arm/Group Title | Part B, Group 4: VRC-ZKADNA090-00-VP (4 mg), 2 Injections | Part B, Group 5: Placebo (VRC-PBSPLA043-00-VP), 2 Injections |
|---|---|---|
| Arm/Group Description | ZIKVwt DNA 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 administered IM by a needle-free injection device 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 | 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 administered IM by a needle-free injection device VRC-PBSPLA043-00-VP: A sterile phosphate-buffered saline (PBS) prepared for human administration as a placebo |
| Measure Participants | 1162 | 1161 |
| ALT |
87
290%
|
90
300%
|
| WBC |
53
176.7%
|
70
233.3%
|
| Hemoglobin |
49
163.3%
|
53
176.7%
|
| Platelets |
7
23.3%
|
3
10%
|
| Neutrophil |
19
63.3%
|
15
50%
|
| Lymphocyte |
13
43.3%
|
6
20%
|
| Eosinophil |
72
240%
|
68
226.7%
|
| Title | Number of Participants With Serious Adverse Events (SAEs) Following Product Administration (Part A) |
|---|---|
| Description | Any SAEs recorded from receipt of first study product administration through the last expected study visit at Day 224 are summarized. The relationship between a SAE and the study product was assessed by the investigator on the basis of his or her clinical judgment and the definitions outlined in the protocol. |
| Time Frame | Day 0 through Day 224 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants in the study who received at least one study product administration, and had at least one post-administration safety assessment, analyzed according to the study product received. |
| Arm/Group Title | Part A, Group 1: VRC-ZKADNA090-00-VP (4 mg), 2 Injections | Part A, Group 2: VRC-ZKADNA090-00-VP (4 mg), 4 Injections | Part A, Group 3: VRC-ZKADNA090-00-VP (8 mg), 4 Injections |
|---|---|---|---|
| Arm/Group Description | Zika virus wildtype (ZIKVwt) DNA 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 administered intramuscularly (IM) by a needle-free injection device 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 | ZIKVwt DNA 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 administered IM by a needle-free injection device 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 | ZIKVwt DNA 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 administered IM by a needle-free injection device 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 |
| Measure Participants | 30 | 30 | 30 |
| Related to Study Product |
0
0%
|
0
0%
|
0
0%
|
| Unrelated to Study Product |
1
3.3%
|
2
6.7%
|
0
0%
|
| Title | Number of Participants With Serious Adverse Events (SAEs) Following Product Administration (Part B) |
|---|---|
| Description | Any SAEs recorded from receipt of first study product administration through the last expected study visit at Day 672 are summarized. The relationship between a SAE and the study product was assessed by the investigator on the basis of his or her clinical judgment and the definitions outlined in the protocol. |
| Time Frame | Day 0 through Day 672 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants in the study who received at least one study product administration, and had at least one post-administration safety assessment, analyzed according to the study product received. |
| Arm/Group Title | Part B, Group 4: VRC-ZKADNA090-00-VP (4 mg), 2 Injections | Part B, Group 5: Placebo (VRC-PBSPLA043-00-VP), 2 Injections |
|---|---|---|
| Arm/Group Description | ZIKVwt DNA 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 administered IM by a needle-free injection device 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 | 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 administered IM by a needle-free injection device VRC-PBSPLA043-00-VP: A sterile phosphate-buffered saline (PBS) prepared for human administration as a placebo |
| Measure Participants | 1162 | 1161 |
| Related to Study Product |
0
0%
|
0
0%
|
| Unrelated to Study Product |
17
56.7%
|
18
60%
|
| Title | Number of Participants With New Chronic Medical Conditions Following Product Administration (Part A) |
|---|---|
| Description | New onset chronic medical conditions were reported from receipt of first study product administration through the last expected study visit at Day 224.The relationship between a chronic medical condition and the study product was assessed by the investigator on the basis of his or her clinical judgment and the definitions outlined in the protocol. |
| Time Frame | Day 0 through Day 224 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants in the study who received at least one study product administration, and had at least one post-administration safety assessment, analyzed according to the study product received. |
| Arm/Group Title | Part A, Group 1: VRC-ZKADNA090-00-VP (4 mg), 2 Injections | Part A, Group 2: VRC-ZKADNA090-00-VP (4 mg), 4 Injections | Part A, Group 3: VRC-ZKADNA090-00-VP (8 mg), 4 Injections |
|---|---|---|---|
| Arm/Group Description | Zika virus wildtype (ZIKVwt) DNA 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 administered intramuscularly (IM) by a needle-free injection device 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 | ZIKVwt DNA 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 administered IM by a needle-free injection device 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 | ZIKVwt DNA 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 administered IM by a needle-free injection device 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 |
| Measure Participants | 30 | 30 | 30 |
| Related to Study Product |
0
0%
|
0
0%
|
0
0%
|
| Unrelated to Study Product |
0
0%
|
1
3.3%
|
0
0%
|
| Title | Number of Participants With New Chronic Medical Conditions Following Product Administration (Part B) |
|---|---|
| Description | New onset chronic medical conditions were reported from receipt of first study product administration through the last expected study visit at Day 672.The relationship between a chronic medical condition and the study product was assessed by the investigator on the basis of his or her clinical judgment and the definitions outlined in the protocol. |
| Time Frame | Day 0 through Day 672 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants in the study who received at least one study product administration, and had at least one post-administration safety assessment, analyzed according to the study product received. |
| Arm/Group Title | Part B, Group 4: VRC-ZKADNA090-00-VP (4 mg), 2 Injections | Part B, Group 5: Placebo (VRC-PBSPLA043-00-VP), 2 Injections |
|---|---|---|
| Arm/Group Description | ZIKVwt DNA 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 administered IM by a needle-free injection device 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 | 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 administered IM by a needle-free injection device VRC-PBSPLA043-00-VP: A sterile phosphate-buffered saline (PBS) prepared for human administration as a placebo |
| Measure Participants | 1162 | 1161 |
| Related to Study Product |
0
0%
|
0
0%
|
| Unrelated to Study Product |
15
50%
|
9
30%
|
| Title | Number of Participants With One or More Unsolicited Non-Serious Adverse Events (AEs) Following Product Administration (Part A and Part B) |
|---|---|
| Description | Unsolicited AEs and attribution assessments were recorded in the study database from receipt of the first study product administration through the one month visit that followed the last study product administration (Visit 05), 84 days for both Parts A and B for participants who received all three study product administrations. If a participant received the first and second product administrations but not the third, then the time frame was through 56 days (Visit 04). If a participant only received the first product administration but not the second or third, then the time frame was through 28 days (Visit 03). The relationship between an AE and the study product was assessed by the investigator on the basis of his or her clinical judgment and the definitions outlined in the protocol. A participant with multiple experiences of the same event is counted once using the event of worst severity. |
| Time Frame | Day 0 through the one month visit that follows the last product administration (Visit 05), 84 days for both Parts A and B |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants in the study who received at least one study product administration, and had at least one post-administration safety assessment, analyzed according to the study product received. |
| Arm/Group Title | Part A, Group 1: VRC-ZKADNA090-00-VP (4 mg), 2 Injections | Part A, Group 2: VRC-ZKADNA090-00-VP (4 mg), 4 Injections | Part A, Group 3: VRC-ZKADNA090-00-VP (8 mg), 4 Injections | Part B, Group 4: VRC-ZKADNA090-00-VP (4 mg), 2 Injections | Part B, Group 5: Placebo (VRC-PBSPLA043-00-VP), 2 Injections |
|---|---|---|---|---|---|
| Arm/Group Description | Zika virus wildtype (ZIKVwt) DNA 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 administered intramuscularly (IM) by a needle-free injection device 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 | ZIKVwt DNA 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 administered IM by a needle-free injection device 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 | ZIKVwt DNA 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 administered IM by a needle-free injection device 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 | ZIKVwt DNA 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 administered IM by a needle-free injection device 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 | 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 administered IM by a needle-free injection device VRC-PBSPLA043-00-VP: A sterile phosphate-buffered saline (PBS) prepared for human administration as a placebo |
| Measure Participants | 30 | 30 | 30 | 1162 | 1161 |
| Related to Study Product |
4
13.3%
|
5
16.7%
|
6
20%
|
77
6.6%
|
58
5%
|
| Unrelated to Study Product |
18
60%
|
14
46.7%
|
20
66.7%
|
500
42.7%
|
530
45.4%
|
| Title | Number of Participants With Virologically Confirmed Cases of ZIKV (Part B Only) |
|---|---|
| Description | Virologically confirmed Zika infection, irrespective of symptoms, by polymerase chain reaction (PCR) in blood or in urine were recorded from receipt of first study product administration through the last expected study visit. |
| Time Frame | Day 0 through Day 672 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants in the study, analyzed according to the randomized study product. One placebo participant, who had a virologically confirmed case of ZIKV from a sample collected prior to first product administration, is not counted as a virologically confirmed case. |
| Arm/Group Title | Part B, Group 4: VRC-ZKADNA090-00-VP (4 mg), 2 Injections | Part B, Group 5: Placebo (VRC-PBSPLA043-00-VP), 2 Injections |
|---|---|---|
| Arm/Group Description | ZIKVwt DNA 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 administered IM by a needle-free injection device 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 | 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 administered IM by a needle-free injection device VRC-PBSPLA043-00-VP: A sterile phosphate-buffered saline (PBS) prepared for human administration as a placebo |
| Measure Participants | 1170 | 1168 |
| Count of Participants [Participants] |
1
3.3%
|
2
6.7%
|
| Title | Zika Antigen-specific Neutralizing Antibody Geometric Mean Titer (GMT) - (Part A) |
|---|---|
| Description | Antibody response as measured by ZIKV neutralization antibody (NAb) assay. Neutralizing activity is reported as the dilution of sera required to neutralize eighty percent of infection events (EC80). |
| Time Frame | Day 0 to 28 days after the final product administration |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants, analyzed according to the randomized study product. All participants with samples at the protocol-defined immunogenicity timepoint were analyzed. The two subjects missing from Group 1 missed their Day 28 visit and thus there was no sample to analyze. |
| Arm/Group Title | Part A, Group 1: VRC-ZKADNA090-00-VP (4 mg), 2 Injections | Part A, Group 2: VRC-ZKADNA090-00-VP (4 mg), 4 Injections | Part A, Group 3: VRC-ZKADNA090-00-VP (8 mg), 4 Injections |
|---|---|---|---|
| Arm/Group Description | Zika virus wildtype (ZIKVwt) DNA 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 administered intramuscularly (IM) by a needle-free injection device 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 | ZIKVwt DNA 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 administered IM by a needle-free injection device 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 | ZIKVwt DNA 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 administered IM by a needle-free injection device 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 |
| Measure Participants | 28 | 30 | 30 |
| Day 0 (Baseline, Pre-administration) |
22.288
|
34.836
|
22.25
|
| Day 28 |
77.468
|
187.629
|
130.497
|
| Title | Number of Participants With Positive Response to Zika Antigen-specific Neutralizing Antibody (Part A) |
|---|---|
| Description | A participant was a responder or met the threshold of a positive response if the post vaccination anti-ZIKV antibody titer was 30 or greater. |
| Time Frame | Day 0 to 28 days after the final product administration |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants, analyzed according to the randomized study product. All participants with samples at the protocol-defined immunogenicity timepoint were analyzed. The two subjects missing from Group 1 missed their Day 28 visit and thus there was no sample to analyze. |
| Arm/Group Title | Part A, Group 1: VRC-ZKADNA090-00-VP (4 mg), 2 Injections | Part A, Group 2: VRC-ZKADNA090-00-VP (4 mg), 4 Injections | Part A, Group 3: VRC-ZKADNA090-00-VP (8 mg), 4 Injections |
|---|---|---|---|
| Arm/Group Description | Zika virus wildtype (ZIKVwt) DNA 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 administered intramuscularly (IM) by a needle-free injection device 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 | ZIKVwt DNA 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 administered IM by a needle-free injection device 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 | ZIKVwt DNA 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 administered IM by a needle-free injection device 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 |
| Measure Participants | 28 | 30 | 30 |
| Day 0 (Baseline, Pre-administration) |
5
16.7%
|
8
26.7%
|
4
13.3%
|
| Day 28 |
20
66.7%
|
27
90%
|
29
96.7%
|
| Title | Number of Participants With Subclinical Cases of ZIKV (Part B Only) |
|---|---|
| Description | Virologically confirmed cases of Zika infection without clinical signs or symptoms were recorded from receipt of first study product administration through the last expected study visit by PCR virus detection in blood of participants at regularly defined intervals. Subclinical cases of ZIKV infection were identified by retrospective PCR. |
| Time Frame | Day 0 through Day 672 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants in the study, analyzed according to the randomized study product. One placebo participant had a subclinical case of ZIKV from a sample collected prior to first product administration. Two placebo participants had subclinical cases of ZIKV but also reported symptomatic ZIKV cases close in time to the positive subclinical result, consistent with a clinical picture of one symptomatic ZIKV infection event for each. These 3 are not counted as subclinical cases. |
| Arm/Group Title | Part B, Group 4: VRC-ZKADNA090-00-VP (4 mg), 2 Injections | Part B, Group 5: Placebo (VRC-PBSPLA043-00-VP), 2 Injections |
|---|---|---|
| Arm/Group Description | ZIKVwt DNA 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 administered IM by a needle-free injection device 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 | 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 administered IM by a needle-free injection device VRC-PBSPLA043-00-VP: A sterile phosphate-buffered saline (PBS) prepared for human administration as a placebo |
| Measure Participants | 1170 | 1168 |
| Count of Participants [Participants] |
1
3.3%
|
0
0%
|
| Title | Zika Antigen-specific Neutralizing Antibody Geometric Mean Titer (GMT) - (Part B) |
|---|---|
| Description | Antibody response as measured by ZIKV neutralization antibody (NAb) assay. Neutralizing activity is reported as the dilution of sera required to neutralize eighty percent of infection events (EC80). Data is not yet available for this outcome measure as this particular outcome is based on the results from retrospective ZIKV neutralizing antibody assays which are still being performed on the samples. Outcome measure data will be provided once testing is complete. Testing is anticipated to be completed in 2022 and data will be reported as soon as it is available. |
| Time Frame | Day 0 to 28 days after the final product administration |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Number of Participants With Positive Response to Zika Antigen-specific Neutralizing Antibody (Part B) |
|---|---|
| Description | A participant is a responder or met the threshold of a positive response if the post vaccination anti-ZIKV antibody titer was 30 or greater. Data is not yet available for this outcome measure as it is based on the results from retrospective ZIKV PCR assays which are still being performed on the samples. There are tens of thousands of samples that are still being tested for this outcome measure and outcome measure data will be provided once testing is complete. Testing is anticipated to be completed in 2022 and data will be reported as soon as it is available. |
| Time Frame | Day 0 to 28 days after the final product administration |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
Adverse Events
| Time Frame | Solicited adverse events (AEs) were reported for 7 days after each study injection. Unsolicited AEs were recorded from receipt of the first study injection through the one month visit that followed the last product administration. At other time periods, only SAEs, new chronic medical conditions and confirmed cases of Dengue (DENV) infection were recorded through the last expected study visit (Part A: Day 224 and Part B: Day 672). | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Solicited AEs collected through systematic assessment and unsolicited AEs collected through non-systematic assessment were recorded for subjects who received at least one study injection and provided safety data following the injection, and represent the number and percentage of subjects reporting the event. A subject with multiple experiences of the same event is counted once using the event of worst severity. | |||||||||
| Arm/Group Title | Part A, Group 1: VRC-ZKADNA090-00-VP (4 mg), 2 Injections | Part A, Group 2: VRC-ZKADNA090-00-VP (4 mg), 4 Injections | Part A, Group 3: VRC-ZKADNA090-00-VP (8 mg), 4 Injections | Part B, Group 4: VRC-ZKADNA090-00-VP (4 mg), 2 Injections | Part B, Group 5: Placebo (VRC-PBSPLA043-00-VP), 2 Injections | |||||
| Arm/Group Description | Zika virus wildtype (ZIKVwt) DNA 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 administered intramuscularly (IM) by a needle-free injection device 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 | ZIKVwt DNA 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 administered IM by a needle-free injection device 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 | ZIKVwt DNA 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 administered IM by a needle-free injection device 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 | ZIKVwt DNA 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 administered IM by a needle-free injection device 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 | 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 administered IM by a needle-free injection device VRC-PBSPLA043-00-VP: A sterile phosphate-buffered saline (PBS) prepared for human administration as a placebo | |||||
All Cause Mortality |
||||||||||
| Part A, Group 1: VRC-ZKADNA090-00-VP (4 mg), 2 Injections | Part A, Group 2: VRC-ZKADNA090-00-VP (4 mg), 4 Injections | Part A, Group 3: VRC-ZKADNA090-00-VP (8 mg), 4 Injections | Part B, Group 4: VRC-ZKADNA090-00-VP (4 mg), 2 Injections | Part B, Group 5: Placebo (VRC-PBSPLA043-00-VP), 2 Injections | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/30 (3.3%) | 0/30 (0%) | 0/30 (0%) | 1/1162 (0.1%) | 0/1161 (0%) | |||||
Serious Adverse Events |
||||||||||
| Part A, Group 1: VRC-ZKADNA090-00-VP (4 mg), 2 Injections | Part A, Group 2: VRC-ZKADNA090-00-VP (4 mg), 4 Injections | Part A, Group 3: VRC-ZKADNA090-00-VP (8 mg), 4 Injections | Part B, Group 4: VRC-ZKADNA090-00-VP (4 mg), 2 Injections | Part B, Group 5: Placebo (VRC-PBSPLA043-00-VP), 2 Injections | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/30 (3.3%) | 2/30 (6.7%) | 0/30 (0%) | 17/1162 (1.5%) | 18/1161 (1.6%) | |||||
| Congenital, familial and genetic disorders | ||||||||||
| Atrial septal defect | 0/30 (0%) | 0/30 (0%) | 0/30 (0%) | 1/1162 (0.1%) | 0/1161 (0%) | |||||
| Congenital hydronephrosis | 0/30 (0%) | 0/30 (0%) | 0/30 (0%) | 1/1162 (0.1%) | 0/1161 (0%) | |||||
| Gastrointestinal disorders | ||||||||||
| Gastritis | 0/30 (0%) | 0/30 (0%) | 0/30 (0%) | 1/1162 (0.1%) | 0/1161 (0%) | |||||
| Hepatobiliary disorders | ||||||||||
| Cholecystitis | 0/30 (0%) | 0/30 (0%) | 0/30 (0%) | 0/1162 (0%) | 1/1161 (0.1%) | |||||
| Cholecystitis chronic | 0/30 (0%) | 0/30 (0%) | 0/30 (0%) | 0/1162 (0%) | 1/1161 (0.1%) | |||||
| Cholelithiasis | 0/30 (0%) | 0/30 (0%) | 0/30 (0%) | 0/1162 (0%) | 1/1161 (0.1%) | |||||
| Hepatitis acute | 0/30 (0%) | 0/30 (0%) | 0/30 (0%) | 0/1162 (0%) | 1/1161 (0.1%) | |||||
| Infections and infestations | ||||||||||
| Appendicitis | 0/30 (0%) | 0/30 (0%) | 0/30 (0%) | 2/1162 (0.2%) | 4/1161 (0.3%) | |||||
| Cellulitis | 0/30 (0%) | 0/30 (0%) | 0/30 (0%) | 1/1162 (0.1%) | 1/1161 (0.1%) | |||||
| Cellulitis orbital | 0/30 (0%) | 0/30 (0%) | 0/30 (0%) | 0/1162 (0%) | 1/1161 (0.1%) | |||||
| Gastroenteritis | 0/30 (0%) | 0/30 (0%) | 0/30 (0%) | 1/1162 (0.1%) | 0/1161 (0%) | |||||
| Influenza | 0/30 (0%) | 0/30 (0%) | 0/30 (0%) | 1/1162 (0.1%) | 0/1161 (0%) | |||||
| Pelvic inflammatory disease | 0/30 (0%) | 0/30 (0%) | 0/30 (0%) | 2/1162 (0.2%) | 0/1161 (0%) | |||||
| Skin infection | 0/30 (0%) | 0/30 (0%) | 0/30 (0%) | 1/1162 (0.1%) | 0/1161 (0%) | |||||
| Injury, poisoning and procedural complications | ||||||||||
| Gun shot wound | 1/30 (3.3%) | 0/30 (0%) | 0/30 (0%) | 1/1162 (0.1%) | 0/1161 (0%) | |||||
| Multiple injuries | 0/30 (0%) | 0/30 (0%) | 0/30 (0%) | 1/1162 (0.1%) | 0/1161 (0%) | |||||
| Road traffic accident | 0/30 (0%) | 0/30 (0%) | 0/30 (0%) | 1/1162 (0.1%) | 0/1161 (0%) | |||||
| Musculoskeletal and connective tissue disorders | ||||||||||
| Rhabdomyolysis | 0/30 (0%) | 0/30 (0%) | 0/30 (0%) | 0/1162 (0%) | 2/1161 (0.2%) | |||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||
| Mucinous cystadenocarcinoma ovary | 0/30 (0%) | 0/30 (0%) | 0/30 (0%) | 0/1162 (0%) | 1/1161 (0.1%) | |||||
| Nervous system disorders | ||||||||||
| Seizure | 0/30 (0%) | 0/30 (0%) | 0/30 (0%) | 0/1162 (0%) | 1/1161 (0.1%) | |||||
| Pregnancy, puerperium and perinatal conditions | ||||||||||
| Abortion spontaneous | 0/30 (0%) | 0/30 (0%) | 0/30 (0%) | 1/1162 (0.1%) | 0/1161 (0%) | |||||
| Ectopic pregnancy | 0/30 (0%) | 0/30 (0%) | 0/30 (0%) | 0/1162 (0%) | 1/1161 (0.1%) | |||||
| Psychiatric disorders | ||||||||||
| Bipolar disorder | 0/30 (0%) | 1/30 (3.3%) | 0/30 (0%) | 0/1162 (0%) | 0/1161 (0%) | |||||
| Conversion disorder | 0/30 (0%) | 0/30 (0%) | 0/30 (0%) | 0/1162 (0%) | 1/1161 (0.1%) | |||||
| Depression | 0/30 (0%) | 0/30 (0%) | 0/30 (0%) | 2/1162 (0.2%) | 0/1161 (0%) | |||||
| Renal and urinary disorders | ||||||||||
| Calculus urinary | 0/30 (0%) | 1/30 (3.3%) | 0/30 (0%) | 0/1162 (0%) | 1/1161 (0.1%) | |||||
| Nephrolithiasis | 0/30 (0%) | 0/30 (0%) | 0/30 (0%) | 1/1162 (0.1%) | 0/1161 (0%) | |||||
| Reproductive system and breast disorders | ||||||||||
| Metrorrhagia | 0/30 (0%) | 0/30 (0%) | 0/30 (0%) | 0/1162 (0%) | 1/1161 (0.1%) | |||||
| Ovarian cyst ruptured | 0/30 (0%) | 0/30 (0%) | 0/30 (0%) | 0/1162 (0%) | 1/1161 (0.1%) | |||||
Other (Not Including Serious) Adverse Events |
||||||||||
| Part A, Group 1: VRC-ZKADNA090-00-VP (4 mg), 2 Injections | Part A, Group 2: VRC-ZKADNA090-00-VP (4 mg), 4 Injections | Part A, Group 3: VRC-ZKADNA090-00-VP (8 mg), 4 Injections | Part B, Group 4: VRC-ZKADNA090-00-VP (4 mg), 2 Injections | Part B, Group 5: Placebo (VRC-PBSPLA043-00-VP), 2 Injections | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 28/30 (93.3%) | 29/30 (96.7%) | 30/30 (100%) | 990/1162 (85.2%) | 859/1161 (74%) | |||||
| Blood and lymphatic system disorders | ||||||||||
| Anaemia | 2/30 (6.7%) | 2/30 (6.7%) | 2/30 (6.7%) | 51/1162 (4.4%) | 56/1161 (4.8%) | |||||
| Leukocytosis | 2/30 (6.7%) | 1/30 (3.3%) | 1/30 (3.3%) | 49/1162 (4.2%) | 67/1161 (5.8%) | |||||
| Leukopenia | 0/30 (0%) | 0/30 (0%) | 2/30 (6.7%) | 4/1162 (0.3%) | 3/1161 (0.3%) | |||||
| Neutropenia | 0/30 (0%) | 1/30 (3.3%) | 2/30 (6.7%) | 19/1162 (1.6%) | 15/1161 (1.3%) | |||||
| Eosinophilia | 1/30 (3.3%) | 0/30 (0%) | 1/30 (3.3%) | 72/1162 (6.2%) | 69/1161 (5.9%) | |||||
| Cardiac disorders | ||||||||||
| Bradycardia | 1/30 (3.3%) | 1/30 (3.3%) | 2/30 (6.7%) | 21/1162 (1.8%) | 24/1161 (2.1%) | |||||
| Gastrointestinal disorders | ||||||||||
| Nausea | 4/30 (13.3%) | 4/30 (13.3%) | 4/30 (13.3%) | 182/1162 (15.7%) | 157/1161 (13.5%) | |||||
| General disorders | ||||||||||
| Administration site erythema | 6/30 (20%) | 4/30 (13.3%) | 7/30 (23.3%) | 116/1162 (10%) | 63/1161 (5.4%) | |||||
| Administration site pain | 25/30 (83.3%) | 28/30 (93.3%) | 28/30 (93.3%) | 862/1162 (74.2%) | 582/1161 (50.1%) | |||||
| Administration site swelling | 4/30 (13.3%) | 5/30 (16.7%) | 7/30 (23.3%) | 94/1162 (8.1%) | 24/1161 (2.1%) | |||||
| Chills | 3/30 (10%) | 5/30 (16.7%) | 1/30 (3.3%) | 139/1162 (12%) | 119/1161 (10.2%) | |||||
| Injection site bruising | 5/30 (16.7%) | 10/30 (33.3%) | 13/30 (43.3%) | 31/1162 (2.7%) | 26/1161 (2.2%) | |||||
| Injection site pruritus | 1/30 (3.3%) | 1/30 (3.3%) | 2/30 (6.7%) | 12/1162 (1%) | 3/1161 (0.3%) | |||||
| Malaise | 10/30 (33.3%) | 10/30 (33.3%) | 13/30 (43.3%) | 405/1162 (34.9%) | 376/1161 (32.4%) | |||||
| Pyrexia | 0/30 (0%) | 0/30 (0%) | 1/30 (3.3%) | 63/1162 (5.4%) | 66/1161 (5.7%) | |||||
| Infections and infestations | ||||||||||
| Gastroenteritis | 2/30 (6.7%) | 0/30 (0%) | 1/30 (3.3%) | 11/1162 (0.9%) | 17/1161 (1.5%) | |||||
| Pharyngitis | 2/30 (6.7%) | 0/30 (0%) | 0/30 (0%) | 28/1162 (2.4%) | 22/1161 (1.9%) | |||||
| Sinusitis | 0/30 (0%) | 0/30 (0%) | 2/30 (6.7%) | 3/1162 (0.3%) | 5/1161 (0.4%) | |||||
| Upper respiratory tract infection | 4/30 (13.3%) | 1/30 (3.3%) | 5/30 (16.7%) | 36/1162 (3.1%) | 35/1161 (3%) | |||||
| Viral infection | 2/30 (6.7%) | 1/30 (3.3%) | 0/30 (0%) | 21/1162 (1.8%) | 26/1161 (2.2%) | |||||
| Nasopharyngitis | 0/30 (0%) | 0/30 (0%) | 0/30 (0%) | 72/1162 (6.2%) | 75/1161 (6.5%) | |||||
| Investigations | ||||||||||
| Alanine aminotransferase increased | 3/30 (10%) | 1/30 (3.3%) | 3/30 (10%) | 87/1162 (7.5%) | 92/1161 (7.9%) | |||||
| Musculoskeletal and connective tissue disorders | ||||||||||
| Arthralgia | 4/30 (13.3%) | 7/30 (23.3%) | 2/30 (6.7%) | 189/1162 (16.3%) | 167/1161 (14.4%) | |||||
| Myalgia | 4/30 (13.3%) | 8/30 (26.7%) | 10/30 (33.3%) | 362/1162 (31.2%) | 306/1161 (26.4%) | |||||
| Nervous system disorders | ||||||||||
| Headache | 10/30 (33.3%) | 14/30 (46.7%) | 13/30 (43.3%) | 444/1162 (38.2%) | 432/1161 (37.2%) | |||||
| Headache | 0/30 (0%) | 1/30 (3.3%) | 2/30 (6.7%) | 21/1162 (1.8%) | 7/1161 (0.6%) | |||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||
| Nasal congestion | 0/30 (0%) | 0/30 (0%) | 2/30 (6.7%) | 4/1162 (0.3%) | 3/1161 (0.3%) | |||||
| Skin and subcutaneous tissue disorders | ||||||||||
| Dermatitis contact | 2/30 (6.7%) | 0/30 (0%) | 1/30 (3.3%) | 2/1162 (0.2%) | 3/1161 (0.3%) | |||||
| Vascular disorders | ||||||||||
| Hypertension | 0/30 (0%) | 1/30 (3.3%) | 3/30 (10%) | 26/1162 (2.2%) | 27/1161 (2.3%) | |||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Allison Beck, PA-C, MPAS, Deputy Chief of Clinical Affairs, Clinical Development Unit, CTP |
|---|---|
| Organization | Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health |
| Phone | (301) 761-7158 |
| allison.beck@nih.gov |
Responsible Party:
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT03110770
Other Study ID Numbers:
- VRC 705
First Posted:
Apr 12, 2017
Last Update Posted:
May 24, 2021
Last Verified:
Apr 1, 2021