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

NCT03110770 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: VRC 705
• Study Type: interventional
• Target: 2,428
• Locations: 8 countries
• Sites: 16

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.

Conditions

Zika Virus; Zika Virus Infection; Virus Diseases; Flavivirus Infections; Flaviviral Diseases; Flaviviridae Infections; RNA Virus Infections

Keywords

Flavivirus; Zika; Vaccine; Physiological Effects of Drugs; Immunologic Factors; Virus-like Particles; Zika vaccine

Outcome Measures

Primary Outcomes (10)

• Number of Participants Reporting Local Reactogenicity Signs and Symptoms for 7 Days After Each Product Administration (Part A and Part B)

  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).

  7 days after each product administration

• Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms for 7 Days After Each Product Administration (Part A and Part B)

  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).

  7 days after each product administration

• Number of Participants With Abnormal Laboratory Measures of Safety (Part A)

  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.

  Day 0 after first product administration through Day 112

• Number of Participants With Abnormal Laboratory Measures of Safety (Part B)

  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.

  Day 0 after first product administration through Day 308

• Number of Participants With Serious Adverse Events (SAEs) Following Product Administration (Part A)

  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.

  Day 0 through Day 224

• Number of Participants With Serious Adverse Events (SAEs) Following Product Administration (Part B)

  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.

  Day 0 through Day 672

• Number of Participants With New Chronic Medical Conditions Following Product Administration (Part A)

  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.

  Day 0 through Day 224

• Number of Participants With New Chronic Medical Conditions Following Product Administration (Part B)

  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.

  Day 0 through Day 672

• Number of Participants With One or More Unsolicited Non-Serious Adverse Events (AEs) Following Product Administration (Part A and Part 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.

  Day 0 through the one month visit that follows the last product administration (Visit 05), 84 days for both Parts A and B

• Number of Participants With Virologically Confirmed Cases of ZIKV (Part B Only)

  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.

  Day 0 through Day 672

Secondary Outcomes (5)

• Zika Antigen-specific Neutralizing Antibody Geometric Mean Titer (GMT) - (Part A)

  Day 0 to 28 days after the third product administration

• Number of Participants With Positive Response to Zika Antigen-specific Neutralizing Antibody (Part A)

  Day 0 to 28 days after the third product administration

• Number of Participants With Subclinical Cases of ZIKV (Part B Only)

  Day 0 through Day 672

• Zika Antigen-specific Neutralizing Antibody Geometric Mean Titer (GMT) - (Part B)

  Day 0 to 28 days after the third product administration

• Number of Participants With Positive Response to Zika Antigen-specific Neutralizing Antibody (Part B)

  Day 0 to 28 days after the third product administration

Study Arms (5)

Part A, Group 1: VRC-ZKADNA090-00-VP (4 mg), 2 injections

EXPERIMENTAL

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

Part A, Group 2: VRC-ZKADNA090-00-VP (4 mg), 4 injections

EXPERIMENTAL

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

Part A, Group 3: VRC-ZKADNA090-00-VP (8 mg), 4 injections

EXPERIMENTAL

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

Part B, Group 4: VRC-ZKADNA090-00-VP (4 mg), 2 injections

EXPERIMENTAL

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

Part B, Group 5: Placebo (VRC-PBSPLA043-00-VP), 2 injections

PLACEBO COMPARATOR

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

Interventions

VRC-ZKADNA090-00-VP BIOLOGICAL

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

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

VRC-PBSPLA043-00-VP OTHER

A sterile phosphate-buffered saline (PBS) prepared for human administration as a placebo

Also known as: Placebo

Part B, Group 5: Placebo (VRC-PBSPLA043-00-VP), 2 injections

Eligibility Criteria

• Age: 15 Years - 35 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• A participant must meet all of the following criteria:
• Part A:
• 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:
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (17)

QPS-Miami Research Associates

Miami, Florida, 33143, United States

Location

Doctors Hospital at Renaissance

Edinburg, Texas, 78539, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Hospital Das Clinicas Da Universidade Federal de Minas Gerais

Belo Horizonte, Minas Gerais, 30130-100, Brazil

Location

Centro de Pesquisas Clínicas Do Instituto Central Do Hospital Das Clínicas Da FMUSP

São Paulo, São Paulo, 05403-010, Brazil

Location

Clinica de la Costa Ltda

Barranquilla, Atlántico, 080020, Colombia

Location

Centro de Atencion y Diagnostico de Enfermedades Infecciosas

Bucaramanga, Santander Department, 680003, Colombia

Location

CCIM Costa Rican Center Center of Medical Research, Sociedad Anonima

San José, Los Yoses, Costa Rica

Location

AGA Clinical Centro de Investigaciones

Guayaquil, Guayas, 090506, Ecuador

Location

Hospital Civil Fray Antonio Alcalde

Guadalajara, Jalisco, 44280, Mexico

Location

Instituto Conmemorativo Gorgas

Panama City, San Miguelito Province, Panama

Location

Asociacion Civil Selva Amazonica

Iquitos, Maynas/Loreto, 16001, Peru

Location

Unidad de Ensayos (UNIDEC) del Policlinico Universidad Nacional Mayor de San Marcos

Lima, 15081, Peru

Location

Ponce Medical School Foundation Inc./CAIMED Center

Ponce, 00716, Puerto Rico

Location

Fundación de Investigación de Diego

San Juan, 00927, Puerto Rico

Location

San Juan Hospital Research Unit

San Juan, 00935, Puerto Rico

Location

Puerto Rico Clinical and Translational Research Consortium

San Juan, 00936-5067, Puerto Rico

Location

Related Publications (4)

• 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.

  PMID: 21398392 BACKGROUND

• 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.

  PMID: 18190252 BACKGROUND

• 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. doi: 10.1126/science.aai9137. Epub 2016 Sep 22.

  PMID: 27708058 BACKGROUND

• 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.

  PMID: 29217376 BACKGROUND

MeSH Terms

Conditions

Zika Virus Infection; Virus Diseases; Flavivirus Infections; Flaviviridae Infections; RNA Virus Infections

Condition Hierarchy (Ancestors)

Mosquito-Borne Diseases; Vector Borne Diseases; Infections; Arbovirus Infections

Results Point of Contact

• Title: VRC Clinical Trials Program Leadership
• Organization: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health

ctpleadership@mail.nih.gov

301-451-8715

Study Officials

• Julie Ledgerwood, DO

  VRC, NIAID, NIH

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: March 28, 2017
• First Posted: April 12, 2017
• Study Start: March 29, 2017
• Primary Completion: October 4, 2019
• Study Completion: October 4, 2019
• Last Updated: January 31, 2024
• Results First Posted: December 4, 2020

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

CO (2); BR (2); US (3); PR (4); EC (1); PA (1); ME (1); PE (2)