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

NCT ID: NCT03110770

Last Updated: 2024-01-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 2428 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-03-29
• Study Completion Date: 2019-10-04

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.

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.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: TRIPLE

Study Groups

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

Group Type: EXPERIMENTAL

VRC-ZKADNA090-00-VP

Intervention Type: 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 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

Group Type: EXPERIMENTAL

VRC-ZKADNA090-00-VP

Intervention Type: 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 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

Group Type: EXPERIMENTAL

VRC-ZKADNA090-00-VP

Intervention Type: 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 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

Group Type: EXPERIMENTAL

VRC-ZKADNA090-00-VP

Intervention Type: 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 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

Group Type: PLACEBO_COMPARATOR

VRC-PBSPLA043-00-VP

Intervention Type: OTHER

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

Interventions

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

Intervention Type: BIOLOGICAL

VRC-PBSPLA043-00-VP

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

Intervention Type: OTHER

Other Intervention Names

Placebo

Eligibility Criteria

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

• Minimum Eligible Age: 15 Years
• Maximum Eligible Age: 35 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Julie Ledgerwood, DO

Role: STUDY_CHAIR

VRC, NIAID, NIH

Locations

QPS-Miami Research Associates

Miami, Florida, United States

Doctors Hospital at Renaissance

Edinburg, Texas, United States

Baylor College of Medicine

Houston, Texas, United States

Hospital Das Clinicas Da Universidade Federal de Minas Gerais

Belo Horizonte, Minas Gerais, Brazil

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

São Paulo, São Paulo, Brazil

Clinica de la Costa Ltda

Barranquilla, Atlántico, Colombia

Centro de Atencion y Diagnostico de Enfermedades Infecciosas

Bucaramanga, Santander Department, Colombia

CCIM Costa Rican Center Center of Medical Research, Sociedad Anonima

San José, Los Yoses, Costa Rica

AGA Clinical Centro de Investigaciones

Guayaquil, Guayas, Ecuador

Hospital Civil Fray Antonio Alcalde

Guadalajara, Jalisco, Mexico

Instituto Conmemorativo Gorgas

Panama City, San Miguelito Province, Panama

Asociacion Civil Selva Amazonica

Iquitos, Maynas/Loreto, Peru

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

Lima, , Peru

Ponce Medical School Foundation Inc./CAIMED Center

Ponce, , Puerto Rico

Fundación de Investigación de Diego

San Juan, , Puerto Rico

San Juan Hospital Research Unit

San Juan, , Puerto Rico

Puerto Rico Clinical and Translational Research Consortium

San Juan, , Puerto Rico

Countries

United States; Brazil; Colombia; Costa Rica; Ecuador; Mexico; Panama; Peru; Puerto Rico

References

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.

Reference Type: BACKGROUND

PMID: 21398392 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 18190252 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 27708058 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 29217376 (View on PubMed)

Provided Documents

Document Type: Study Protocol, Statistical Analysis Plan, and Informed Consent Form

View Document

Other Identifiers

VRC 705

Identifier Type: -

Identifier Source: org_study_id